ATC code PSI A10A Insulin - All labels state that insulin doses should be adjusted on an individual basis (usually in the context of more intensive monitoring) in patients with renal impairment. A10A Insulin - Partly renally excreted; may need reduced dose when GFR is < 30 mL/min/1.73 m2 A10 Guidelines for patients with diabetic nephropathy: Start treatment in patients with sustained urinary albumin excretion of >30 mg/day. In patients with overt proteinuria treatment goal is <0.5 g/day A10BX Nateglinide - CKD 3-4 no dose adjustment necessary; CKD-5 therapy should be started at the lowest dose possible (60 mg/ day). To be avoided in dialysis patients A10BX Nateglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 60 mg with meals if eGFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed A10BX Repaglinide - careful dose titration recommended in advanced stages of CKD A10BX Repaglinide - CKD 3-4 no dose adjustment necessary; CKD-5 to be avoided A10BX Repaglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 0.5 mg with meals if GFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed A10BX Repaglinide - Needs no initial dose adjustment in renal impairment (Canada). Caution advised when titrating doses in renal impairment (EU, Canada). In severe renal impairment, initiate at a dose of 0.5 mg/day and subsequently, carefully titrate doses (US) A10BA Avoidance of metformin in renal impairment (SCr ≥1.5 mg/dL male and SCr ≥1.4 mg/dL female patients) A10BA Medications to use with extreme caution in elderly patients with kdiney disease: Metformin - Risk of lactic acidosis if eGFR <30 mL/min A10BA Metformin - Avoid when GFR is <30 mL/min/1.73 m2, but consider risk-benefit if GFR is stable. Review use when GFR is <45 mL/min/1.73 m2 Hold during acute illness or prior to intravenous radiocontrast A10BA Metformin - Contraindicated if CrCl <60 mL/min (EU, Canada) or abnormal CrCl (US) A10BA Metformin - CrCl 60-90ml/min 2000mg daily; CrCl 30-60ml/min 1000mg daily; CrCl <30ml/min avoid use A10BA Metformin - In CKD-3 the dosage should not exceed 1.5 g/day with eGFR > 45 mL/min and 850 mg/day with eGFR 30–45 mL/min.; In CKD-4: maximum 500 mg daily but the drug should be temporarily withheld in periods of unstable GFR; In CKD-5 Consider carefully especially in the presence of acidosis, hypoxia, dehydration A10BA Metformin - not recommended in patients with eGFR <45 and contraindicated in patients with eGFR <30 A10BA Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity. A10BA Regular monitoring of renal function is necessary (when taking metformin) A10BA Renal failure or renal dysfuntion (creatinine clearance < 60ml/ min) is considered a contraindication (to metformin) A10BB Drugs that need special attention in chronic kidney disease: Sulfonylureas A10BB Sulfonylureas - Avoid mainly renally excreted agents (eg, glyburide) Agents mainly metabolized by the liver may need reduced dose when GFR is < 30 mL/min/1.73 m2 A10BB Sulfoylureas - Avoid usage as much as possible. Consider a DPP-4 inhibitor as an alternative drug. A10BB Acetohexamide - CKD 3-5 contraindicated A10BB Chlorpropamide - CKD-3: 100 to 125 mg daily; CKD-4 avoid; CKD-5 contraindicated A10BB Glibenclamide - Clcr < 50 mL/min: not recommended A10BD Glibenclamide/metformin - Use is contraindicated in patients with serum creatinine ≥1.5 mg/dL in males, or ≥1.4 mg/dL in females or abnormal creatinine clearance A10BB Gliclazide - CKD 3-5 started at low doses and the dose titrated up every 1–4weeks A10BB Gliclazide - contraindicated in cases of severe renal insufficiency A10BB Gliclazide - NKF-KDOQI guidelines: no dose adjustments required if CKD stages 3, 4, and 5. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; consider alternative agent if eGFR<15 mL/ min/ A10BB Glimepiride - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated A10BB Glimepiride - NKF-KDOQI guidelines: start treatment conservatively with 1 mg daily. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; maximum dose 1 mg, consider alternative agent if eGFR <15 mL/min. A10BB Glimepiride - should be used with caution if eGFR <60 A10BB Medications requiring dose adjustments at variable GFR thresholds: Glimepiride A10BB Glimipramide - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated A10BB Glipizide - in renal impairment conservative dosing recommended to avoid hypoglycaemia A10BB Glyburide - Combined ADA/EASD 2012 position statement: totally avoid if any renal impairment. NKF-KDOQI guidelines: totally avoid if CKD stages 3, 4, and 5. CDA guidelines: use alternative agent if eGFR <60 mL/ min A10BB Glyburide - not recommended in CrCl <50ml/min A10BB Tolazamide - CKD 3-5 contraindicated A10BB Tolbutammide - CKD 3-4 Preferably dose titration to 250 mg one to three times/ day (especially in elderly patients); CKD-5 contraindicated A10BK SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) - reduced efficacy and increased toxicity in patients with moderate or severe renal impairment and contraindicated in those with eGFR <45 A10BK Canagliflozin - 2013 AACE/ACE guidelines: not to be used if eGFR <45 mL/min/1.73 m2 A10BK Canagliflozin - Careful monitoring in patients with GFR < 60 mL/ min; CKD-5 to be avoided A10BK Canagliflozin - for eGFR 45-60ml/min give 100mg once daily A10BK Canagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/1.73 m2) (US, EU, Canada). Not recommended if CrCl or eGFR <60 mL/min/1.73 m2 (EU, Canada), or eGFR <45 mL/min/1.73 m2 (US), or contraindicated if eGFR <45 mL/min/1.73 m2 (Canada). A10BK Dapagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/ 1.73 m2) (US, EU). Not recommended (US, EU) or contraindicated (Canada) if CrCl or eGFR <60 mL/min/1.73 m. Contraindicated in severe renal impairment (US, Canada). A10BK Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2 A10BH DPP-4 inhibitors (alogliptin, saxagliptin, sitagliptin) - require dose adjustments in with patients with moderate or severe CKD A10BH Medicines that may accumulate and require renal function monitoring: Gliptins A10BH Alogliptin - 2013 AACE/ACE guidelines: decrease dose based on GFR: ≽30–\60 mL/min (12.5 mg daily); <30 mL/min (6.25 mg daily). Not in combined ADA/EASD 2012 position statement. Not in NKF-KDOQI guidelines. A10BH Alogliptin - eGFR ≽50 use at full dose (25mg/day); eGFR <50 reduce dose (12.5mg/day); eGFR <30 6.25mg/day; patients with ESRD and haemodialysis use with caution (6.25mg/day) A10BH Saxagliptin - can be used in full dose (2.5mg QDS or 5mg QDS) in mild renal insufficiency; reduce dose to 2.5mg QDS in moderatre-severe renal sufficiency and in those receiving haemodialysis A10BH Saxagliptin - CKD 3-5 halve dose to 2.5mg once daily; administer after HD session. A10BH Saxagliptin - eGFR ≽50 use at full dose (5mg/day); eGFR <50 half dose (2.5mg/day); eGFR <30 use with caution; patients with ESRD and haemodialysis do not use A10BH Sitagliptin - CKD-3 50mg; CKD-4 25mg; CKD-5 reduce dose to 25mg and administer irrespective of HD timing A10BH Sitagliptin - eGFR ≽50 use at full dose(100mg/day); eGFR 30-50 half dose (50mg/day); eGFR <30 quarter dose (25mg/day); patients with ESRD and haemodialysis use with caution (25mg/day) A10BH Vildagliptin - eGFR ≽50 use at full dose (2x50mg/day); eGFR <50 half dose (1x50mg/day); patients with ESRD and haemodialysis use with caution (1x50mg/day) A10BH Gemigliptin - use without dose adjustment (50mg/day); patients with ESRD and haemodialysis can possibily use but no data A10BH Linagliptin - use without dose adjustment (5mg/day); patients with ESRD and haemodialysis can possibily use but no data A10BJ Albiglutide - No dose adjustment in mild (eGFR 60–89 mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment (US, EU). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m2) or in dialysis due to limited data (EU). No dose adjustment in severe renal impairment (eGFR 15 to <30 mL/min/ 1.73 m2) (US). A10BJ Contraindicated medications at variable GFR thresholds: Exenatide A10BJ Drugs requiring dosing adjustments in impaired renal function: Exenatide A10BJ Exenatide - Combined ADA/EASD 2012 position statement: contraindicated if GFR <30 mL/min. NKF-KDOQI guidelines: not recommended if GFR <30 mL/min/1.73 m2. 2015 AACE/ACE guidelines: contraindicated if GFR <30 mL/min. CDA guidelines: reduce dosage if eGFR 30–59 mL/min (5 lg BID); use alternative agent if eGFR <30 mL/min A10BJ Exenatide - eGFR ≽60 use at full dose (2x10mcg/day; eGFR 30-60 use with caution (2x10mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use A10BJ Exenatide - Use with caution in moderate renal impairment (CrCl 30–50 mL/min) (US, EU, Canada). Contraindicated (Canada)/not recommended (US, EU) in severe renal impairment (CrCl <30 mL/min)/ESRD. Use with caution in renal transplantation (US, Canada) A10BJ Contraindicated medications at variable GFR thresholds: Liraglutide A10BJ Liraglutide - Combined ADA/EASD 2012 position statement: safety not established, although drug levels are unaffected by CKD as not renally cleared. NKF-KDOQI guidelines: not recommended if GFR <60 mL/min/1.73 m2. 2013 AACE/ACE guidelines: no restrictions on use. CDA guidelines: use alternative agent if eGFR <50 mL/ min. A10BJ Liraglutide - eGFR ≽50 use at full dose (1.2-1.8mg/day); eGFR <50 do not use; patients with ESRD and haemodialysis do not use A10BJ Dulaglutide - No dose adjustment required in mild to moderate renal impairment (US, EU). Not recommended in severe CKD (eGFR <30 mL/min/1.73 m2) due to limited clinical data (EU) A10BJ Lixisenatide - eGFR ≽50 use at full dose (1x20mcg/day); eGFR 30-50 use with caution (1x20mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use A10BJ Lixisenatide - No dose adjustment in patients with GFR 50–80 mL/min. Careful use in patients with GFR 50–15 mL/min. A10BG TZDs (pioglitazone and rosiglitazone) - often avoided in non-dialysis pateints with T2Dm and CKD due to risk of fluid retention, heart failure and increased bone fracture risk A10BG Pioglitazone - Combined ADA/EASD 2012 position statement: no restrictions for use in CKD; be aware of risk of fluid retention. NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed. A10BF Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Alpha glucosidase inhibitors A10BF Acarbose - Contraindicated (EU) or not recommended (Canada) if CrCl<25 mL/ min, and not recommended if serum creatinine >2 mg/dL (US) due to lack of information A10BF Acarbose - No evidence of dose adjustment required for GFR values higher than 25 mL/min; CKD-5 to be avoided A10BF Miglitol - Needs no dosage adjustment if CrCl >25 mL/min (EU). Contraindicated if CrCl <25 mL/min (EU). Not recommended if serum creatinine>2 mg/dL due to lack of information (US). A10BG Rosiglitazone - Needs no dose adjustment in renal impairment (US, Canada). Caution recommended if CrCl <30 mL/min, due to limited data (Canada). A10BG Rosiglitazone - NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed A02A Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiacids and other dtrugs for acid related disorders A02BA Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: H2 receptor antagonists A02BA H-2 blockers in renal dysfunction; ≤1200 mg/d cimetidine, 20 mg/d famotidine, 150 mg/d nizatidine, 150 mg/d ranitidine if CrClf <50 mL/min A02BA Cimetidine if CrCl <50 - mental status change - reduce dose A02BA Ranitidine if CrCl <50 - mental status change - reduce dose A02BA Medications requiring dose adjustments at variable GFR thresholds: Famotidine A02BA Niatidine if CrCl <50 - mental status change - reduce dose A02BX Medications to use with extreme caution in elderly patients with kdiney disease: PPIs - Increased risk of fractures, infections, and cognitive decline; hypomagnesemia A03F Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Propulsives A03F Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Metoclopramide A03F Metoclopramide - GFR 10-29 reduce dose 50% A06AD Oral sodium phosphate containing bowel preparations - Can cause acute kidney injury by phosphate crystal deposition and volume depletion Risk factors are CKD, > 60 years of age, female gender, HTN, diabetes, CHF, volume depletion, active colitis, and medications that may predispose to AKI (RAAS blockers, diuretics, lithium, and NSAIDs) A06AD Sodium Phosphate should not be used as bowel preparation in patients with CKD, heart failure, cirrhosis or hypertension A07E Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Intestinal anti-inflammatory agents A11CC Calcitriol/VDRA (and calcimimetics) can be used to lower PTH in patients with CKD stage 5D where PTH is elevated or rising A11CC Calcitriol/VDRA should be reduced or stopped if (i) PTH levels fall below two times the upper limit of normal in CKD stage 5D (2C), and/or (ii) patients develop hypercalcaemia A11CC In patients with CKD stage 3–5 not on dialysis, where serum PTH is rising and remains persistently elevated despite the correction of modifiable factors, treatment with calcitriol or VDRA should be used A11CC In patients with CKD stage 5D, PTH levels should be maintained in the range of two to nine times the upper normal limit of the assay A11CC Initial drug selection for the treatment of elevated PTH should be based on serum calcium and phosphate levels and other aspects of CKD-MBD A11CA Medications to use with extreme caution in elderly patients with kdiney disease: Vitamin A - Increased serum levels of RBP4 and apoRBP4 A11G Medications to use with extreme caution in elderly patients with kdiney disease: Vitamin C - Organ accumulation of insoluble oxalate A11CC The percentage of patients ≽18 years with CKD 3-5 and elevated calcium levels who are prescribed active vitamin D A16AX Drugs requiring dosing adjustments in impaired renal function: Miglustat B01A Drugs that need special attention in chronic kidney disease: Anticoagulants B01A Evaluate renal function prior to initiation of direct thrombin or factor Xa inhibitors, and reevaluate when clinically indicated and at least annually B01AA Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Vitamin K antagonists and heparin group B02AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Tranexamic acid B01AE Drugs requiring dosing adjustments in impaired renal function: Bivalirudin B01A For patients with CKD and AF the following recommendations apply: If renal function is impaired, the European Heart Rhythm Association’s practical guide recom- mends renal function to be monitored every 6 months for GFR 30–60mL/min and every 3 months for GFR<30mL/min in patients with AF receiving an NOAC B03A Recommendations for treatment of anaemia of CKD: We suggest that Hb concentration should be monitored every 2–4 weeks in the correction phase and every 1– 3 months for stable patients in the maintenance phase. B01AB Therapeutic drug monitoring of antifactor Xa levels in patients with CKD stage 4 or 5 requring full anticoagulation is strongly recommended B01AA Warfarin - Increased risk of bleeding when GFR is < 30 mL/min/1.73 m2 B01AA With CHA2DS2-VASc score ! 2 and end-stage CKD (CrCl < 15 mL/min) or on hemodialysis, it is reasonable to prescribe warfarin for OAC B03A Recommendations for treatment of anaemia of CKD: We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an op- tion, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation. B01A With moderate-to-severe CKD and CHA2DS2-VASc scores ! 2, reduced doses of direct thrombin or factor Xa inhibitors may be considered B01AF Apixaban - 5 mg bid in patients with CrCl ≽30 mL/minute; 2.5 mg bid if CrCl 15–29 mL/minute; 2.5 mg bid in the presence of 2 or more of the following characteristics: • Age $80 years • Body weight #60 kg • Serum creatinine $1.5 mg/dL (133 μmo B01AF Apixaban - Age ≥80 years and body weight ≤60 kg or serum creatinine ≥1.5 mg/dl: reduce dose to 2.5 mg b.i.d B01AF Apixaban - Body weight ≤60 kg and age ≥80 years or serum creatinine ≥1.5 mg/dl: reduce dose to 2.5 mg b.i.d. B01AF Apixaban - CrCl <15ml/min or on dialysis use has not been studied B01AF Apixaban - CrCl 15-29 mL/min 2.5 mgBD; CrCl < 15 ml/min, or dialysis not recommended B01AF Apixaban - CrCl 30-49ml/min 5mg twice daily; CrCl 15-29ml/min 2,5mg twice daily; CrCl <15ml/min contraindicated B01AF Apixaban - not recommended in: Pregnant women; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatment • Severe hepatic impairment B01AF Apixaban if CrCl <25 - increased risk of bleeding - avoid B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - amiodarone - at least 6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - antiplatelets/NSAIDs - at least 6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - carbamazepine/phenytoin/phenobarbital - 3-6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - dronederone - 3-6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - HIV protease inhibitors - 3-6 months (dose adjustment with apixaban) B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - loop diuretics/thizide-like diuretics/ACEI/ARB - 3-6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - verapamil/quinidine - at least 6 months (dose adjustment with edoxaban) B01AF For patients with CKD and AF the following recommendations apply: Rivaroxaban (20 mg once a day), edoxaban (60 mg once a day) and apixaban (5 mg twice a day) do not require any dose adjustment in patients with a GFR>50mL/min B01AF In patients with CrCl <50ml/min apixaban should be stopped 48 hours before surgery or invasive procedures B01AE Consider dose reduction if: Prescribed dabigatran and eGFR <30 B01AE Dabigatran - 150 mg bid in patients with CrCl ≽30 mL/minute 110 mg bid may be considered in patients with the following factors: • Age ≽80 years (or 75–80 years with high risk of bleeding) • CrCl 30–50 mL/minute with a high risk of bleeding B01AE Dabigatran - age <75 150mg BD; age 75-80 150mg BD (110mg BD should be considered when the risk of stroke is low and bleeding risk is high); age 80 and over 110mg BD B01AE Dabigatran - contraindicated in patients with CrCl <30ml/min B01AE Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment B01AE Dabigatran - CrCl <15ml/min use has not been studied B01AE Dabigatran - CrCl ≥50 mL/min no dose adjustment is necessary; CrCl 30-50 mL/min the recommended dose is 150 mg BD (110 mg BD for patients with high risk of bleeding); CrCl < 30 ml/min contraindicated B01AE Dabigatran - CrCl 15-30ml/min give 75mg BD B01AE Dabigatran - dose adjustments: 10 mg bid in patients 75–80 years with low thromboembolic risk and high risk of bleeding, or 80 years or older with CrCl 30–50 mL/min and high risk of bleeding, or receiving the strong P-gp inhibitor verapamil B01AE Dabigatran - drugs requiring caution during concomitant treatment in patients with renal impairment: Close clinical surveillance is recommended in patients with mild to moderate renal impairment when dabigatran is combined with mild to moderate P-gp inhibitors (eg, amiodarone, quinidine, verapamil, and clarithromycin) B01AE Dabigatran - increased risk of GI bleeding compared with warfarin and oter target specific oral anticoagulants in adults aged 75 and older, lack of evidence of efficacy and safety in individuals with CrCl <30ml/min B01AE Dabigatran - no dose adjustment is necessary according to body weight. However, close clinical follow-up is required for patients with a body weight <50 kg. B01AE Dabigatran - treatment of VTE - Avoid if CrCl <50 mL/min B01AE Dabigatran if CrCl <30 - increased risk of bleeding - avoid B01AE Dabigatran should not be used in patients with a CrCl of <30 mL/min and other NOACs should be used in reduced doses in patients with CrCl 15 – 29 mL/min B01AE Direct thrombin dabigatran and factor Xa inhibitor rivaroxaban are not recommended in patients with AF and end-stage chronic kidney disease (CKD) or on dialysis because of a lack of evidence from clinical trials regarding the balance of risks and benefits B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - amiodarone - 3-6 months B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - dronederone - 3-6 months with dose adjustment based on renal function B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - HIV protease inhibitors - 6 months B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - loop diuretics/thiazide-like diuretics/ACEI/ARB - 3-6 months B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - verapamil/quinidine - 3-6 months with dose adjustment based on renal function B01AE For patients prescribed dabigatran renal function should be monitored at least once a year if their kidney function is mildy to moderately reduced or if they are over 75 years old B01AE For patients with CKD and AF the following recommendations apply: European Medicines Agency - approved a lower dose of dabigatran 75 mg twice daily in patients with a GFR of 15–30mL/min B01AE In patients with CrCl <50ml/min dabigatran should be withdrawn at least 3 days before surgery B01AE Switching from dabigatran to warfarin: if CrCl <15 no recommendations provided B01AE Switching from dabigatran to warfarin: if CrCl >50 start warfarin 3 days before stopping dabigatran B01AE Switching from dabigatran to warfarin: if CrCl 15-30 start warfarin 1 day before stopping dabigatran B01AE Switching from dabigatran to warfarin: if CrCl 31-50 start warfarin 2 days before stopping dabigatran B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - antiplatelets/NSAIDs - at least 6 months B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - carbamazepine/phenytoin/phenobarbital - 3-6 months B01AF Edoxaban - 30 --> 15mg OD if CrC; 30-50ml/min or weight 60kg or less B01AF Edoxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 60 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg) B01AF Edoxaban - CrCl ≥50 mL/min 60 mg OD; CrCl 15-49 mL/min 30 mg OD; CrCl <15 mL/min not recommended. B01AF Edoxaban if CrCl <30 or >95 - increased risk of bleeding - avoid B01AF Edoxaban if CrCl 30-50 - increased risk of bleeding - reduce dose B01AF If CrCl <15ml/min rivaroxaban is not approved B01AF Medicines that may accumulate and require renal function monitoring: Rivaroxaban B01AF Rivaroxaban - 20 --> 15mg OD if CrCl 30-49ml/min B01AF Rivaroxaban - avoid use to treat/prevent VTE if CrCl <30ml/min B01AF Rivaroxaban - Caution in case of CrCl 15–30 ml/min Dose reduction to 15 mg/ day B01AF Rivaroxaban - CrCl >50 ml/min: 20 mg orally, QD with evening meal B01AF Rivaroxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 20 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg) B01AF Rivaroxaban - CrCl 15–50 ml/min: 15 mg orally, QD with evening meal B01AF Rivaroxaban - drugs requiring caution during concomitant treatment in patients with renal impairment: Moderate or potent inhibitors of CYP3A4 (eg, fluconazole, clarithromycin); Moderate inhibitors of both CYP3A4 and P-gp (eg, erythromycin) B01AF Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided B01AF Rivaroxaban - prevention of VTE - Avoid if CrCl <50 mL/min B01AF Rivaroxaban if CrCl <30 - increased risk of bleeding - avoid B01AF Rivaroxaban if CrCl 30-50 - increased risk of bleeding - reduce dose B01AF Rivaroxaban may be used at a reduced dose of 15mg OD for anti-coagulation management of atrial fibrillation in patients with severe renal impairment (CrCl 15-29 ml/min) B01AC Aspirin - use with caution eGFR <10ml/min B01AC Patients with eGFR <60 should be taking: Aspirin to prevent cardiovascular events B01AX Fondaparinux - GFR 30-49 reduc dse to 1.5mg daily B01AX Fondaparinux if CrCl <30 - increased risk of bleeding - avoid B01AB If CrCl <30ml/min recommend 1 mg/kg/day of enoxaparin for treatment of venous thromboembolism B01AB If CrCl <30ml/min recommend 30 mg of enoxaparin for prophylaxis of venous thromboembolism B01AB Medicines that may accumulate and require renal function monitoring: Enoxaparin B01AB For patients with renal impairment prophylatic dose of LMWH is 20 mg/24 h B01AB For patients with renal impairment treatment dose of LMWH is 1 mg/kg/24 h B01AB Low molecular weight heparins - Reduce dose by 50% when GFR is <30 mL/min/1.73 m2. Consider switch to conventional heparin or monitor plasma antiefactor Xa in those at high risk for bleeding B01A CrCl (ml/min) - preferred oral anticoagulant class <15 - VKA or NOAC (use with caution) B01A CrCl (ml/min) - preferred oral anticoagulant class ≽50 - NOAC B01A CrCl (ml/min) - preferred oral anticoagulant class 15-29 - VKA or NOAC B01A CrCl (ml/min) - preferred oral anticoagulant class 30-49 - NOAC B01A Not using of any one of the three DOACs in patients with a CrCl \30 ml/min is recommended B03XA Recommendations for treatment of anaemia of CKD: We recommend that adjustments to ESA doses should be considered when Hb is <105 or >115 g/L in adults, young people and children aged 2 years and older B03XA Recommendations for treatment of anaemia of CKD: We recommend that blood pressure should be moni- tored in all patients receiving ESAs and, if present, hypertension be treated by volume removal and/or anti- hypertensive drugs B03XA Recommendations for treatment of anaemia of CKD: We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the tar- get Hb level despite SC epoetin dose >300 IU/kg/ week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week B03XA Recommendations for treatment of anaemia of CKD: We suggest exerting extreme caution while prescribing ESA therapy in CKD patients with a history of stroke, or malignancy, particularly in those with active malignancy when cure is the anticipated outcome B03XA Recommendations for treatment of anaemia of CKD: We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension B03XA The percentage of patients ≽18 years with CKD 3-5 and Hb ≽7.5 who are prescribed an ESA B03XA Do not initiate erythropoiesis-stimulating agents in patients with chronic kidney disease (CKD) with hemoglobin levels greater than or equal to 100 g/L without symptoms of anemia B03A Recommendations for treatment of anaemia of CKD: We recommend that serum ferritin should not exceed 800 microgram/L in patients treated with iron, and to achieve this iron management should be reviewed when the ferritin is >500 microgram/L. B01AC Acetylsalicylic acid - increase dosing interval to every six hours if GFR equals 10-50 mL/minute; avoid use if GFR is less than 10 mL/minute B01AC Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Asprin and derivatives B01AC Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Aspirin C01B CrCl <10ml/min - Flecainide, milrinone, procainamide, quinidine, sotalol C01B CrCl <30ml/min - Disopyramide, enoxaparin sodium, milrinone, sotalol, tirofiban C01B CrCl <40ml/min - Disopyramide, dofetilide, milrinone C01B CrCl <50ml/min - Eptifibatide, milrinone, procainamide C01BA Drugs that need special attention in chronic kidney disease: Procainamide C10AD Acipimox - Acipimox is eliminated almost exclusively via the kidneys. Dosage reduction in patients with renal failure is recommended. For patients with a creatinine clearance of 30 to 60 mL/min, the suggested dose is 150 mg C02DB Cadralazine - GFR < 40 max 10 mg daily, GFR > 40 max 15 mg daily C03DA Contraindicated medications at variable GFR thresholds: Eplerenone C01B CrCl <20ml/min - Dofetilide, milrinone C01B CrCl <60ml/min - Dofetilide, sotalol C02A Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiadrenegic agents, centrally acting C02C Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiadrenegic agents, peripherally acting C10AX Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Other lipid modifying agents C01C Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Adrenergics for systemic use C01B Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiarrhythmics (class Ia and Ic) C04 Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Peipheral vasodilators C02AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Methyldopa C01BD Drugs requiring dosing adjustments in impaired renal function: Dofetilide C02CA Drugs that need special attention in chronic kidney disease: Alpha adrenergic blockes eg methyldopa, doxazosin, prazosin, reserpine C03EA Epitizide - eGFR <30 contraindicated C10AB Gemfibrozil - Severe impairment: use is contraindicated C10 Guidelines for patients with diabetic nephropathy: For management of dyslipidaemia: eGFR >15 ml/min/1.73m2: advise lipid-lowering treatment for reduction of cardiovascular events; eGFR <15 ml/min/1.73m2: lipid-lowering treatment not advised C02CA Medications to use with extreme caution in elderly patients with kdiney disease: alpha-Adrenergic inhibitors - Bradycardia and orthostatic hypotension C01B Medications to use with extreme caution in elderly patients with kdiney disease: Antiarrhythmic drugs (amiodarone, propafenone, sotalol, quinidine, and dronedarone) - Thyroid disease, pulmonary disorders, and QT interval prolongation C08CA Medications to use with extreme caution in elderly patients with kdiney disease: Nifedipine (immediate release) - Risk of hypotension and cerebral or myocardial ischemia C02AC Moxonidine - Moxonidine should be used with caution and under close medical supervision in patients with moderate renal insufficiency (glomerular filtration rate 30 to 60 mL/min, serum creatinine 1.2 to 1.8mg/dL C03DB Triamterene - eGFR <30 contraindicated C03DB Triamterene - eGFR 30-50 dose 50%, monitor potassium C03DB Triamterene if CrCl <30 - increased potassium and decreased sodium - avoid C10AB Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Fibrates C10AB Fenofibrate - Associated with AKI C10AB Fenofibrate - CrCl 20-60ml/min 96mg once daily; CrCl 10-20ml/min 48mg once daily; CrCl <10 avoid use C10AB Fenofibrate - Not recommended in severely impaired renal function C10AB Medicines that may accumulate and require renal function monitoring: Fenofibrate C10 Recommendations in adults with chronic kidney disease: If triglycerides ≽500 mg/dL - initiate therapeutic lifestyle changes and if fails add fibrate or niacin C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Lovastatin - <15 - decrease to 50% C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Lovastatin - 15-59 - decrease to 50% C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Pravastatin - 15-59 - Start at 10 mg/day for GFR <60 ml/min/1.73 m2 C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Rosuvastatin - <15 - 5-10mg /day C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Rosuvastatin - 15-59 - 5-10mg /day C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Simvastatin - <15 - start at 5mg/day C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Simvastatin - Reduce by 50% in patients with GFR b30 ml/min/1.73 m C10AA Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Statin C10AA Drugs requiring dosing adjustments in impaired renal function: Rosuvastatin calcium C10AA Fluvastatin - caution when exceed doses >40mg/day C10AA For patients aged 65 and over: If CrCl <30ml/min dose of simvastatin >10mg/day should be carefully considered and if deemed necessary, implemented cautiously C10AA Guidelines recommend statin or statin/ezetimibe treatment in adults age 50 years or older with an estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 but not treated with chronic dialysis or kidney transplantation C10AA In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction C10AA In CKD patients lifestyle and/or statin therapy are recommended to reduce levels of LDL-C to <100mg/dL and non-HDL-LDL-C to <130mg/dL C10AA Lovastatin - Renal impairment, severe (CrCl ≤ 30 mL/min): doses ≥20 mg/day should be undertaken with caution if deemed necessary; Aronoff no adjustmen C10AA Pitavastatin - in severe renal impairment (GFR 15-29ml/min not receiving dialysis) initally 1mg orally daly with max 2mg daily C10AA Pravastatin - if significant kidney impairment 10mg/day intially C10AA Recommendations in adults with chronic kidney disease: If LDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is bile acid sequestrant or niacin) C10AA Recommendations in adults with chronic kidney disease: If LDL 100-129 mg/dL - initiate therapeutic lifestyle changes and if fails add low dose statin (alternative is bile acid sequestrant or niacin) C10AA Recommendations in adults with chronic kidney disease: If triglycerides ≽200 mg/dL and non-HDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is fibrate or niacin) C10AA Rosuvastatin - Clcr <30 mL/min/1.73 m2: initial: 5 mg/day; do not exceed 10 mg once daily C10AA Rosuvastatin - GFR 25ml/min avoid C10AA Simvastatin - GFR 10-29 reduce dose 50-75% C10AA Simvastatin - if severe kidney impairment 5mg/day initially C10BA Simvastatin/ezetimibe - GFR ≥ 60 mL/min/1.73 m2: no dosage adjustment necessary. GFR < 60 mL/min/ 1.73 m2: ezetimibe 10 mg and simvastatin 20 mg once daily in the evening (higher doses should be used with caution) C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Atorvastatin - 20 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Fluvastatin - 80 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Pitavastatin - 2 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Pravastatin - 40 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Rosuvastatin - 10 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Simvastatin - 40 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Simvastatin/ezetimibe - 20/10 C10AA Statin therapy or combination therapy is recommended in patients with CKD2-4 and treatment to LDL-C levels of <70mg/dL C10AA Statins - No increased toxicity for simvastatin 20 mg/day when GFR is < 30 mL/min/1.73 m2 or on dialysis. Dose reduction/increased toxicity for GFR < 30 mL/min/1.73 m2 for lovastatin, rosuvastatin, and pravastatin C07AB Atenolol - GFR >35 no change; GFR 15-35 maximum 50mg/day; GFR <15 maximum 25mg/day C07AB Atenolol - GFR 10-29 reduce dose 50-75% C07AB Atenolol - GFR 32ml/min recommended maximum dose 50mg/day C07AB Bisoprolol - 2.5 mg initially 10 mg maximum C07AB Bisoprolol - eGFR 10-30ml/min starting dose 50% of normal dose and if necessary increase to a maximum of 10mg per day C07AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Atenolol C07AB Medicines that may accumulate and require renal function monitoring: Atenolol C07AB Medicines that may accumulate and require renal function monitoring: Bisoprolol C07BB Metoprolol/hydrochlorothiazide - Clcr > 30 mL/min: no dosage adjustment necessary. Clcr 61–8 mL/min: loop diuretics preferred; the use of hydrochlorothiazide may not be effective. Anuria: use is contraindicated C07A Beta blockers - Reduce dose by 50% when GFR is < 30 mL/min/1.73 m2 C07B Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Beta blocking agents and thiazides or other diuretics C07A Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Beta blocking agents C07AA Sotalol - eGFR 10-30 max dose 80mg/day C07AA Sotalol - eGFR 30-50 max dose 160mg/day C03 Caution warranted if combining diuretics and duloxetine, due to increased risk of orthostatic hypotension C03 Diuretic - Coprescription of thiazide and loop diuretic (without valid indication); Overdosing due to lack of monitoring of fluid balance, renal function, electrolytes, etc. C03 Drug-drug interaction - adverse event in older patients with renal functon impairment Thiazides and loop diuretics - Hyponatremia and hypokalemia C02L Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antihypertensives and diuretics in combination C03E Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Diuretics and potassium sparing agents in combination C03 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Low-ceiling diuretics and thiazides C03C Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: High ceilin diuretics C03 Drugs that need special attention in chronic kidney disease: Diuretics C03AA Hydrochlorothiazide - Clcr < 10 mL/min: avoid use. Usually ineffective with GFR < 30 mL/min. Effective at lower GFR in combination with a loop diuretic C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - AT1 antagonists C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - eplerenone C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - potassium C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - potassium sparing diuretic C03D Hypokalaemia - Use of a non-potassium sparing diuretic; No use of a potassium supplement; No electrolyte test in the 6 months prior to admission C03D Medications to use with extreme caution in elderly patients with kdiney disease: Potassium-sparing diuretics - Hyperkalemia C09 Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic C03 Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - AT1 antagonists + NSAID C03CA Furosemide - eGFR 10-30 dose higher C03CA Furosemide - in chronic renal failure initially 80-120mg orally daily with a maximum of 1500mg orally daily C03DA Contraindicated medications at variable GFR thresholds: Spironolactone C03DA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Spironolactone C03DA Medications to use with extreme caution in elderly patients with kdiney disease: Spironolactone and triamterene - Hyperkalemia; cautious if eGFR <30 mL/min C03DA Reduce spironolactone if >25-mg daily in elderly patients with congestive heart failure or with creatinine clearance less than 30 mL/min C03DA Spironolactone - eGFR 10-50 monitor potassium C03DB Amiloride - eGFR <30 contraindicated C03DB Amiloride - eGFR 30-50 monitor potassium C03DB Amiloride if CrCL <30 - increased potassium and decreased sodium - avoid C03D Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Potassium sparing agents C03AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Chlorothiazide C03AA For patients aged 65 and over: Thiazides likely to be ineffective at CrCl <30ml/min C03AA Hydrochlorothiazide - eGFR <30 contraindicated C03AA Hydrochlorothiazide - eGFR 10-30ml/min avoid C03AA Hydrochlorothiazide - eGFR 30-50 initial dose 12.5mg C03DA Spirinolactone - eGFR 10-50ml/min monitor serum potassium levels regularly C03DA Spirinolactone >25mg/day - Risk of hyperkalemia C03DA Spirinolactone if CrCl <30 - increased potassium - avoid C03AA Bendroflumethiazde with potassium chloride - GFR 10-29 avoid C03CA Bumetanide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose to maximum of 10mg per day C03DA Spirinololactone - Renal impairment: mild renal failure (GFR ≥ 50 mL/min), dosing interval of 6–12 h; moderate renal failure (GFR 10–50 mL/min), dosing interval of 12 to 24 h; severe renal failure (GFR ≤ 10 mL/min), avoid the use of spinololactone C03D If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) C03CA Furosemide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose guided by effect and indication. In case the effect is inadequate, replace furosemide by bumetanide. C01AA Digoxin - eGFR 10-50 intial dose 50% C01AA Digoxin - Keep the dose down to 0.125 mg/day or lower. Since even 0.125 mg/ day or lower has a risk of digitalis toxicity in the elderly, consider discontinuing it if monitoring blood levels and electrocardiography is difficult. C01AA Digoxin - Overdosing due to lack of GFR/digoxin level monitoring C01AA Digoxin >125 mcg/day if low GFR C01AA Digoxin toxicity - Use of digoxin; No BUNC09CA or serum creatinine test in the 6 months prior to admission; No digoxin level test in the 6 months prior to admission C01AA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Digoxin C01AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Digoxin C01AA Has read code for chronic kidney disease stage 3B, 4 or 5 at least 3 month before audit date - prescribed digoxin at daily dose > 125 nanograms within 3 months leading up to audit date C03D Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years) C01AA Potential hazard - at risk patient group; Prescribed digoxin at a daily dose of >125 - patients with a diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 C01AA The percentage of patients ≽18 years with eGFR <50ml/min who are prescribed digoxin >0.125mg/day C01AA When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year C09DA Candesartan/hydrochlorothiazide - Contraindicated with severe renal impairment (Clcr < 30 mL/min) C09CA Drug - CrCl - maximum dosing recommendation (mg) Olmesartan - <30 - avoid use C09CA Drug - CrCl - maximum dosing recommendation (mg) Valsartan - <30 - 80 once daily C09CA Eprosartan - in moderate-severe impairment no initial starting dosage adjustment is necessary hoewever carefully monitor the patient, maximum dose 600mg daily C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - valsartan C09B Lisinopril–irbesartan - hyperkalaemia, renal deterioration C09DA Losartan with hydrochlorothiazide - GFR 10-29 reduce dose of hydrocholorthiazde C09DA Losartan/hydrochlorothiazide - Clcr ≤ 30 mL/min: use of combination formulation is not recommended C09DA Telmisartan/hydrochlorothiazide - Clcr ≤ 30 mL/min: not recommended C09DA Valsartan/hydrochlorothiazide - Clcr ≥ 30 mL/min: no dosage adjustment necessary, Clcr < 30 mL/min: no dosage adjustment provided in manufacturer’s labelling; safety and efficacy has not been established. Use is contraindicated in patients with anuria C09D Do not prescribe angiotensin-converting-enzyme inhibitors in combination with angiotensin II receptor blockers for the treatment of hypertension, diabetic nephropathy or heart failure C09D Drug-drug interaction - adverse event in older patients with renal functon impairment 2 or more renin-angiotensin-aldosterone inhibitors - Hyperkalemia, hypotension, and increase in serum creatinine C09D Drug-drug interaction - adverse event in older patients with renal functon impairment Renin-angiotensin inhibitors and aldosterone antagonist - Hyperkalemia, gynaecomastia, and increase in serum creatinine C09D Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Angiotensin II antagonists and diuretics C03DA Aldosterone antagonists - Monitor electrolytes and renal function as deemed necessary. Limit to low-dose usage in patients with high potassium level or renal impairment. C09CA Drugs that need special attention in chronic kidney disease: ARBs C09CA Medicines that may accumulate and require renal function monitoring: ARBs C09 If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic; C09D ACE inhibitor - ARB - kidney failure/hypotension C09D ACE inhibitor/ARB/diuretic - Coprescription of potassium sparing diuretic (without valid indication) C09AA ACEI in diabetics with nephropathy C09 AKI (i.e. estimated GFR reduced by 50 % and/or a twofold increase in serum creatinine concentration and/or urine output B0.5 mL/kg/h for 12 h) - NSAIDs, diuretics, ACE inhibitors, angiotensin receptor antagonists C09AA Alacepril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09AA Altiopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09B Attention: higher risk of hyperkalaemia with concomitant use of higher doses of ACEIs (captopril ‡75 mg/day; enalapril, lisinopril ‡10 mg/day) C09B Avoidance of (ACEI or ARB) with K-sparing diuretic in patients with CrClf <50 mL/min C09AA Benazepril- mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose C09AA Captopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose to be administered in 2 daily doses C09AA Cilazapril - CrCl >40 maximum 5mg; CrCl 10-40 maximum 2.5mg; GFR <10 maximum 0.25-0.5mg once or twice weekly per response C09AA Cilazepril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09 CKD patients on ACEi/ARBs should have close and indefinite monitoring C09AA Delapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09 Diabetes - use of ACEI/ARB if micro-albuminuria C09 Diabetes and proteinuria/microalbuminuria and eGFR <50ml/min - ACEI or ARB C09 Discontinue ACE-Is/ARBs if there is confirmed progressive and continuous loss of kidney function after all other causes have been ruled out C09AA Drug - CrCl - maximum dosing recommendation (mg) Perindopril - <15 - 2.5/2 on day of dialysis C09AA Drug - CrCl - maximum dosing recommendation (mg) Perindopril - 15-30 - 2.5/2 alternate days C09AA Drug - CrCl - maximum dosing recommendation (mg) Perindopril - 30-60 - 2.5/2 once daily C09AA Drug-drug interaction - adverse event in older patients with renal functon impairment ACEis and lithium - Acute kidney injury in 1.5/100 persons per year. C09AA Drugs contraindicated in patients with impaired kidney function and aged 65 and over: ACE inhibitors, plain and combinations C09AA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Captopril C09AA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Enalapril C09AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Captopril C09AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Perindopril C09AA Enalapril - eGFR 10-30 initial dose 2.5mg C09AA Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher) C09AA Enalapril - maximum 40mg daily C09AA Enalapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09 For patients aged 65 and over: ACEIs and ARBs should be used with caution in reduced kidney function (<30ml/min) C09AA Fosinopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 100% C09 Guidelines for patients with diabetic nephropathy: To reduce BP and albuminuria start RAAS blockade with ACEi or AT1 receptor blockade; aim for maximal dosage C09BA Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - ACEI C09BA Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - ACEI + loop diuretic C09 Hyperkalaemia - Use of an ACEI or ARB; No electrolyte or potassium test in the 6 months prior to admission C09AA Hypertensive patients with chronic renal failure should receive, unless contraindicated, an ACE-I C09AA In patients with existing renal insufficiency, one should take into consideration that most ACE inhibitors may further compromise renal function through accumulation of an active metabolite. Dose adjustment is not necessary for fosinopril and for most AT1 antagonists (with the exception of olmesartan) C09 K in the past 6 months for ACEI or ARB with K-sparing diuretic in patients with CrClf < 50 mL/min C09AA Lisinopril - Maximum of 40 mg daily C09AA Lisinopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09AA Moexipril - CrCl ≤ 40: maximum 15 mg/day C09 Patients with CKD should be prescribed preventative medication with ACEIs or ARBs to slow the progression of renal dysfunction C09 Patients with CKD stages 3 or 4 should be prescribed an ACEI/ARB C09 Patients with eGFR <60 should be taking: ACEI/ARB to slow progression of renal disfunction C09AA Pentopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure no data C09AA Perindopril - CrCl > 30 max 8 mg/day, CrCl < 30 mL/min, not recommended C09AA Perindopril - CrCl 30-60ml/min 2.5/2mg once daily; CrCl 15-30ml/min 2.5/2mg alternate days; CrCl <15ml/min 2.5/2mg on day of dialysis C09AA Perindopril - eGFR 30-50ml/min if prescriber is a GP maximum dose is 2mg and if a specialised physician the dose may be higher; eGFR 10-30ml/min if prescriber is a GP maximum dose is 2mg every 48 hours and if a specialised physician the dose may be higher C09AA Perindopril - GFR 48ml/min recommended maximum dose 2mg/day C09AA Perindopril - mild renal failure 150-00% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09BA Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - ACEI C03 Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - acetylsalicylic acid C09AA Quinapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09 RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective C09AA Ramipril - GFR 10-29 maximal dose 5mg daily C09AA Ramipril - GFR 30-49 maximal dose 5mg daily C09AA Ramipril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09AA Ramipril - starting dose 1.25mg orally daily, titrate to effect with maximum 5mg daily C09 SCr in the past 6 months for ACEI or ARB with K-sparing diuretic in patients with CrClf <50 mL/min C09 The percentage of patients ≽18 years with CKD 3-5 and a prescription of RAS blockers wo are prescribed at least 2 RAS blockers simultaneously C09 Triple blockade with ACE inhibitors and ARBs [with mineralocorticoid receptor antagonists] should be avoided, as should the use of other potassium sparing diuretics C09 When initiating ACE-I/ARB/combination, do not stop drug unless creatinine rises >30% C09 When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). C09AA Zofenopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose G04BD Drugs requiring dosing adjustments in impaired renal function: Solifenacin succinate G04BE Drugs requiring dosing adjustments in impaired renal function: Tadalafil G04BD Drugs requiring dosing adjustments in impaired renal function: Trospium chloride G04BX Medications requiring dose adjustments at variable GFR thresholds: Phenazopyrdine G04BE Medicines that may accumulate and require renal function monitoring: Sildenafil G04BD Medicines that may accumulate and require renal function monitoring: Solifenacin G04BE Medicines that may accumulate and require renal function monitoring: Tadalafil G04BD Medicines that may accumulate and require renal function monitoring: Tolterodine G04BE Medicines that may accumulate and require renal function monitoring: Vardenafil G04BD Solifenacin - CrCl <30ml/min 5mg once daily G04BD Tolterodine - CrCl <30ml/min 1mg once daily G04BD Tolterodine tartate - GFR 10-29 reduce dose 50% G04BD Trospium chloride - GFR 30-49 reduce dose 25% G03 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Sex hormones H01CB Drugs requiring dosing adjustments in impaired renal function: Lanreotide H02AB When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) H05AA Teriparatide - CrCl <30ml/min avoid use H05AA Medicines that may accumulate and require renal function monitoring: Teriparatide J01XE Drugs that need special attention in chronic kidney disease: Nitrofurantoin J01XE Nitrofurantoin - Long-term use associated with pulmonary side-effects, renal impairment, liver damage J01XE Contraindicated medications at variable GFR thresholds: Nitrofurantoin J01XE Patient with a creatinine clearance <60 mL/min is not receiving nitrofurantoin for UTI J01XE Potentially dangerous or contraindicated in patients with eGFR <50:Nitrofurantoin J01XE For patients aged 65 and over: Nitrofurantoin likely to be ineffective at CrCl <45ml/min J01XE Medications to use with extreme caution in elderly patients with kdiney disease: Nitrofurantoin - Pulmonary toxicity; do not use if eGFR <30 mL/min J01XE Nitrofurantoin - potential for pulmonary toxicity, hepatotoxicity and peripheral neuropathy - avoid in individuals with creatinine clearance <30ml/min J01MB Chronic renal failure - nalidixic acid J01XX Methenamine - GFR 10-29 avoid J01XX Patient with a creatinine clearance <50 mL/min is not receiving methenamine (hexamine) for UTI prophylaxis J01A Tetracyclines - Reduce dose when GFR is < 45 mL/min/1.73 m2; can exacerbate uremia J01EA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): TMP/SMX J01EA Trimethoprim - Reduce dose by 50% when GFR is < 30 mL/min/1.73 m2. Risk factors for hyperkalemia include high doses, the elderly, CKD, orwith ACE-Is or NSAIDs J01CA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Amoxicillin J01CR Medications requiring dose adjustments at variable GFR thresholds: Amoxicillin/clavulanata J01CA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Ampicillin/sulbactam J01CA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Penicillin G J01CA Drugs that need special attention in chronic kidney disease: Penicillins J01CA Medications requiring dose adjustments at variable GFR thresholds: Piperacillin/tazobactam J01XA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Vancomycin J01XA Vancomycin - GFR 10-29 150-500mg daily J01GB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Gentamicin J01G Medications to use with extreme caution in elderly patients with kdiney disease: Aminoglycosides - Nephrotoxicity; otovestibular toxicity J01FA Macrolides - Reduce dose by 50% when GFR is < 30 mL/min/1.73 m2 J01FA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Clarithyromycin J01FA Drugs requiring dosage adjustment in renal impairment: Erythromycin J01XX Drugs requiring dosage adjustment in renal impairment: Fosfomycin J01GB Drugs requiring dosage adjustment in renal impairment: Tobramycin J01FA Drugs requiring dosing adjustments in impaired renal function: Telithromycin J01GB Nephrotoxic Medications: Kanamycin sulfate J01MA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ciprofloxacin J01MA Medications requiring dose adjustments at variable GFR thresholds: Gemifloxacin J01MA Medications requiring dose adjustments at variable GFR thresholds: Levofloxacin J01MA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Norfloxacin J01DB Drugs that need special attention in chronic kidney disease: Cephalosporins J01DD Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Cefotaxime J01DD Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ceftazidime J01DB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Cephalexin J01DC Drugs requiring dosage adjustment or contraindicated in patients with CKD: Cefuroxime J01DB Drugs requiring dosing adjustments in impaired renal function: Cefditorn pivoxil J01M Medications to use with extreme caution in elderly patients with kdiney disease: Quinolones - Tendinitis; acute kidney injury J01MA Fluroquinolones - Reduce dose by 50% when GFR is < 15 mL/min/1.73 m2 J01GB Drugs requiring dosage adjustment in renal impairment: Amikacin J01CR Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Augmentin J01XB Nephrotoxic Medications: Colistimethate sodium J01XD Medications requiring dose adjustments at variable GFR thresholds: Metronidazole J05AF Drugs requiring dosing adjustments in impaired renal function: Emtricitabine J01DH Drugs requiring dosing adjustments in impaired renal function: Ertapenem J04AK Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ethambutol J04AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Rifampin J04AC Drugs requiring dosage adjustment in renal impairment: Isoniazid J07 Clinicians should vaccinate against chronic hepatitis B virus (HBV) in all unvaccinated adults at risk for infection, including: Adults with end-stage renal disease, including those receiving predialysis care, hemodialysis, peritoneal dialysis, and home dialysis. J07 Hepatitis B vaccine is usually given as a 3- or 4-dose series, but higher dosages may be required for immunocompromised persons and those with end-stage renal disease. These persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg level <10 mIU/mL) should be revaccinated J07 Vaccination guidelines for kidney transplant recipients: Influenza - annially J05AF CrCl - dosing recommendation for tenofovir CrCl ≽50 - tenofovir disoproxil fumarate 300mg every 24 hours J05AF CrCl - dosing recommendation for tenofovir CrCl 10-29 - tenofovir disoproxil fumarate 300mg every 72-96 hours J05AF CrCl - dosing recommendation for tenofovir CrCl 30-49 - tenofovir disoproxil fumarate 300mg every 48 hours J05AF CrCl - dosing recommendation for tenofovir Haemodialysis patients - tenofovir disoproxil fumarate 300mg every 7 days or after approximately 12 hours of haemodialyis J05AF For adults starting tenofovir disproxil fumarate with a baseline eGFR <90 mL/min, who are on other nephrotoxic medications, or who have hypertension or diabetes, guidelines recommend that physicians check a baseline blood pressure, serum creatinine, and urine protein J05AF For adults taking tenofovir disproxil fumarate monitor kidney function with biannual serum creatinine, serum phosphorous, and urinalysis for proteinuria and glycosuria J05AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Acyclovir J05AB Drug - CrCl at which dosage reduction recommended Acyclovir - creatinine clearance <25 mL/min J05AB Drug - CrCl at which dosage reduction recommended Famciclovir - creatinine clearance <60 mL/min J05AB Drug - CrCl at which dosage reduction recommended Valacyclovir - creatinine clearance <50 mL/min J05AB Valganciclovir - GFR 10-29 50% of standard dose vevery 48 hours J05AF For patients with eGFR 30-50 E/C/F/TAF (single pill antiretroviral regimen) has been approved J05AR Ledipasvir/sofosbuvir - Contraindicated in patients with GFR < 30 mL/min J05AR Velpatasvir/sofosbuvir - Contraindicated in patients with GFR < 30 mL/min J05AP Sofosbuvir - Contraindicated in patients with GFR < 30 mL/min J05AF Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Lamivudine J05AF Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Stavudine J05AF Drugs requiring dosing adjustments in impaired renal function: Telbivudine J05AF Drugs requiring dosing adjustments in impaired renal function: Adefovir dipivoxil J05AF Drugs requiring dosing adjustments in impaired renal function: Entecavir J05AH Drugs requiring dosing adjustments in impaired renal function: Oseltamivir phosphate J02AC Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Fluconazole J02AC Antifungals - Reduce maintenance dose of fluconazole by 50% when GFR is < 45 mL/min/1.73 m2 J02AC Drugs requiring dosing adjustments in impaired renal function: Voriconazole J01XB Nephrotoxic Medications: Polymyxin B sulfate J02AA Nephrotoxic Medications: Amphotericin B J02AA Drugs that need special attention in chronic kidney disease: Amphoteracin B J01FA Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and calcium channel blockers - Bradycardia, shock, heart block, multiorgan failure J01FA Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and digoxin - Strong increase in digoxin cardiac and neurological toxicity J01FA Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and statins - Myopathy J01EE Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and phenytoin- Phenytoin intoxication J01EE Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and renin-angiotensin-aldosterone inhibitor - Hyperkalemia J01EE Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole or amiodarone and warfarin - Increase in warfarin effect J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <10ml/min - Amoxicillin, amoxicillin–clavulanic acid, cefazolin, cefepime, cefoxitin, ceftazidime, cephalexin, imipenem– cilastatin J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <20ml/min - Amikacin, cefixime, gentamicin, imipenem–cilastatin, levofloxacin, piperacillin– tazobactam, tobramycin J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <30ml/min - Amoxicillin, ampicillin–sulbactam, cefazolin, cefepime, cefoxitin, ceftazidime, ticarcillin– clavulanic acid J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <40ml/min - Amikacin, gemifloxacin, gentamicin, imipenem, piperacillin–tazobactam, tobramycin, vancomycin J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <50ml/min - Cefoxitin, ceftazidime, cephalexin, ciprofloxacin, levofloxacin, meropenem, penicillin J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <60ml/min - Amikacin, cefepime, cefixime, gentamicin, ticarcillin– clavulanic acid, tobramycin, vancomycin J Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antibacterials and antivirals for systemic use L01XE Afatinib dimaleate - djustments to the starting dose were not considered necessary for mild RI (CLcr = 60–89 ml/min). Closely monitor patients with moderate (CLcr = 30–59 ml/min) to severe (CLcr < 30 ml/min) RI and adjust afatinib dose if not tolerated. L01XE Axitinib - No dose adjustment was needed for mild to severe RI (CLcr ≥ 15 ml/min). Use caution for end-stage renal disease (CLcr < 15 ml/min). L01DC Bleomycin - CrCl <30 - do not adminster L01DC Bleomycin - CrCl 90-60ml/min 10 to 20 mg/m2; CrCl 60-30ml/min 7.5 to 15 mg/m2; CrCl 30-15ml/min 7.5 to 15 mg/m2; CrCl <15ml/min +/or haemodialysis 5 to 10 mg/m2 L01CD Cabazitaxel - No dose adjustment was provided. Population PK indicated no significant difference in CL in patients with mild (CLcr = 50–80 ml/min) and moderate (CLcr = 30–50 ml/min) RI. Caution should be used in patients with severe RI or ESRD. L01BC Capecitabine - CrCl <30 - do not administer L01BC Capecitabine - CrCl 90-60ml/min 1250 mg/m2 every 12 h; CrCl 60-30ml/min 950 mg/m2 every 12 h; CrCl <30ml/min +/or haemodilysis contraindicated L01XA Carboplatin - Adjust according to patient using a formula such as the Calvert formula. L01XA Carboplatin - CrCl <10 - 25% of full dose L01XA Carboplatin - CrCl >50 - 100% full dose L01XA Carboplatin - CrCl 10-50 - 50% of full dose L01XA Cisplatin - CrCl <30 - do not use; use an alternative drug L01XA Cisplatin - CrCl <60ml/min contraindicated L01XA Cisplatin - CrCl 31-45 - 25% of full dose L01XA Cisplatin - CrCl 46-60 - 50% of full dose L01XA Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients) L04AD Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function. L01XE Crizotinib - No dose adjustment was needed for mild (CLcr = 60–90 ml/min) and moderate (CLcr = 30–60 ml/min) RI. Dose adjustment for severe RI (CLcr < 30 ml/min) was not determined (use caution). L01AA Cyclophosphamide - CrCl <10 - 50% of full dose L04AD Cyclosporin - perindopril - hyprkalaemia/kidney failure L01BC Cytarabine - An initial dose 100 mg/m2/day for 7 to 10 days, or 200 mg/m2/day for 5 to 10 days followed by 20 mg/m2/day for 5 to 10 days.; CrCl 90-60ml/min 2 to 3 g/m2 every 12 h; CrCl 60-30ml/min 1 to 2 g/m2 every 12 h; CrCl 30-15ml/min 1 g/m2 every 12 to 24 h; CrCl <15ml/min +/or haemodialysis 1 g/m2 every 24 h L01BC Cytarabine - CrCl <40 - if dose >0.75g/m2/dose decrease to <200mg/m2/dose L01BC Cytarabine - CrCl 40-60 - if dose >2g/m2/dose decrease to 1g/m2/dose; if dose 0.75-1g/m2/dose decrease to 0.5g/m2/dose L01AX Dacarbazine - CrCl <10 - omit L01AX Dacarbazine - CrCl 10-30 - 50% of full dose L01AX Dacarbazine - CrCl 30-60 - 75% of full dose L01DB Daunorubicin - SCr >3mg/dL - 50% of full dose L01DB Doxorubicin - CrCl <10 - 75% of full dose L04AC Drugs requiring dosing adjustments in impaired renal function: Anakinra L03AB Drugs requiring dosing adjustments in impaired renal function: Peginterferon alfa-2a L03AB Drugs requiring dosing adjustments in impaired renal function: Peginterferon alfa-2b L01BA Drugs requiring dosing adjustments in impaired renal function: Pemetrexed disodium L01 Drugs that need special attention in chronic kidney disease: Antineoplastic agents eg carboplatin, cisplatin, cyclophosphamide, etoposide, fludarabine, hydroxyurea, methotrexate L01DB Epirubicin - SCr >5mg/dL - lower doses should be considered L01XX Eribulin mesylate - No dose adjustment was needed mild RI (1.4 mg/m2). Dose reduction for moderate RI (CLcr = 30–50 ml/min) to 1.1 mg/m2. No data for severe RI (CLcr < 30 ml/min) L01CB Etoposide - CrCl <10 - 50% of full dose L01CB Etoposide - CrCl 10-50 - 75% of full dose L01CB Etoposide - CrCl 15-50ml/min require dose to be reduced; CrCl <15ml/min contraindicated L01CB Etoposide - SCr >1.4mg/dL - 70% of full dose L01CB Etoposide (oral) - CrCl 90-60ml/min 80 to 300 mg/m2/day for 3 to 5 days, followed by 50 to 100 mg/m2/day; CrCl 60-15ml/min 60 to 225 mg/m2/day for 3 to 5 days, followed by 37.5 to 75 mg/m2/day; CrCl <15ml/min +/or haemodialysis 40 to 150 mg/m2/day for 3 to 5 days, followed by 25 to 50 mg/m2/day L01BB Fludarabine - CrCl <10 - omit L01BB Fludarabine - CrCl 10-30 - 50% of full dose L01BB Fludarabine - CrCl 30-60 - 75% of full dose L01DB Idarubicin - SCr ≽2.5mg/dL - dose reduction is recommended L01XX Idelalisib - No dose adjustment was necessary for CLcr ≥ 15 ml/min L01AA Ifosfamide - CrCl <10 - omit L01AA Ifosfamide - CrCl 10-30 - 50% of full dose L01AA Ifosfamide - CrCl 30-60 - 75% of full dose L01AA Ifosfamide - should not be used in patients with impaired renal function L01AA Ifosfamide (continuous) - CrCl 90-15ml/min dose/day 5 to 8 g/m2; CrCl <15ml/min +/or haemodialysis dose/day: 3.75 to 6 g/m2 L01AA Ifosfamide (intermittent) - CrCl 90-15ml/min dose/day: 1.5 to 3 g/m2; dose/cycle: 5 to 10 g/m2; CrCl <15ml/min +/or haemodialysis: dose/day: 1.13 to 2.25 g/m2 dose/cycle: 3.75 to 7.5 g/m2 L01XE Lenvatinib mesylate - No dose adjustment was recommended for mile or moderate RI. Dose reduction to 14 mg daily was recommended for severe RI. Patients with ESRD were not studied. L01AX Medications to use with extreme caution in elderly patients with kdiney disease: Azathioprine - Bone marrow suppression and leukopenia L01AA Melphalan - CrCl <10 - 50% of full dose L01AA Melphalan - CrCl 10-50 - 75% of full dose L01AA Melphalan (oral for breast cancer) - CrCl 90-60ml/min 0.15 mg/kg/day or 6 mg/m2 per os for 4 to 6 days; CrCl 60-15ml/min 0.11 mg/kg/day or 4.5 mg/m2 per os for 4 to 6 days; CrCl <15ml/min +/or haemodialysis 0.075 mg/kg/day or 3 mg/m2 per os for4to6days L01AA Melphalan (oral for ovarian cancer) - CrCl 90-60ml/min 0.2 mg/kg/day per os for 5 days; CrCl 60-15ml/min 0.15 mg/kg/day for 5 days; CrCl <15ml/min +/or haemodialysis 0.1 mg/kg/day per os for 5 days L01BA Methotrexate - CrCl <30 - omit L01BA Methotrexate - CrCl 30-60 - 50% of full dose L01BA Methotrexate (IM, IV or SC) - CrCl 90-60ml/min 30 to 50 mg/m2; CrCl 60-30ml/min 24 to 40 mg/m2; CrCl 30-15ml/min 15 to 525 mg/m2; CrCl <15ml/min +/or haemodialysis contraindicated L01BA Methotrexate (oral) - CrCl 90-60ml/min 15 to 30 mg/m2; CrCl 60-30ml/min 12 to 24 mg/m2; CrCl 30-10ml/min 7.5 to 24 mg/m2; CrCl <15ml/min +/0r haemodialysis contraindicated L01DC Mitomycin C - CrCl <10 - omit L01DC Mitomycin C - CrCl 10-30 - 50% of full dose L01DC Mitomycin C - CrCl 30-60 - 75% of full dose L01XX Olaparib - No dose adjustment was required for mild RI (CLcr = 50–80 ml/min). Patients should be monitored. L01XA Oxaliplatin - CrCl 90-15ml/min 85 or 100 mg/m2 every 2 weeks, or 130 mg/m2 every 3 weeks; CrCl <15ml/min +/or haemodialysis contraindicated L01XX Pentostatin - CrCl <30 - consider to use alternative drugs if possible L01XX Pentostatin - CrCl 30-45 - 60% of full dose L01XX Pentostatin - CrCl 45-60 - 70% of full dose L04AX Pomalidomide - No dose established for RI. Safety, efficacy, and PK were not evaluated in RI. Avoid POMALYST in patients with serum creatinine>3.0mg/dl. L01XB Procarbazine - SCr >2mg/dL - dose reduction should be considered L01BA Raltitrexed - 60–60 mL/min: 3 mg/m2 every 3 weeks; 65–55 mL/min: 2.25 mg/m2 every 4 weeks; 54–25 mL/min: 1.5 mg/m2 every 4 weeks; <25 mL/min and haemodialysis: contraindicated L01XE Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. L01AX Temozolomide - Pharmacokinetics appear unchanged in patients with mild-moderate renal dysfunction. Patients with severe renal failure should be monitored closely and consideration given to dose modification. L01XX Topotecan - CrCl <10 - omit L01XX Topotecan - CrCl 10-30 - 50% of full dose L01XX Topotecan - CrCl 30-60 - 75% of full dose L01XX Topotecan - CrCl 90-60ml/min 1.5 mg/m2/day; 60–40 mL/min: 1.5 mg/m2/day; 39–20 mL/min: <20 mL/min and haemodialysis: not available L01XE Vandetinib - Dose reduced to 200 mg for moderate (CLcr = 30–50 ml/min) and severe (CLcr < 30 ml/min) RI. L04AD Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus azoles, macrolides, calcium channel antagonists, or grapefruit juice - Increased serum levels and toxicity of CNI (nephrotoxicity, hypertension, etc) L04AD Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus rifampicin or anticonvulsant - Decreased serum levels of CNI M04 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antigout preparations M01CC Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Other (including gold salt and penicillamine) M01AE Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Propionic acid derivatives M05BA Alendronate - if GFR <35ml/min not recommended M05BA Drug - CrCl - maximum dosing recommendation (mg) Alendronate - <35 - avoid use M05BA Ibandronate - CrCl 90-15ml/min 6 mg every 3 to 4 weeks; CrCl <15ml/min +/or haemodialysis 2 mg every 3 to 4 weeks M05BA Ibandronic acid - CrCl <30ml/min not recommended M05BA Ibandronic acid - CrCl 30-50 50mg every second day if oral or 4mg every 4 weeks if IV; CrCl <30ml/min 50mg once each week if oral or 2mg every 4 weeks if IV; CrCl <10ml/min avoid use M05BA Zoledronic acid - CrCl <40ml/min not recommended M05BA Zoledronic acid - GFR 40-49 3.3mg M05BA Zolendronic acid - CrCl <30ml/min avoid use M05BA Zolendronic acid - CrCl 30-60ml/min graded dose reduction M05BA Zolendronic acid - CrCl 90-60ml/min 4 mg every 3 to 4 weeks; 60–50 mL/min: 3.5 mg every 3 to 4 weeks 50–40 mL/min: 3.3 mg every 3 to 4 weeks 40–30 mL/min: 3 mg every 3 to 4 weeks; CrCl <30ml/min +/or haemodialysis not recommended M05BA Clodronate - CrCl 50-80ml/min 1600mg daily; CrCl 30-50 1200mg daily; CrCl 10-30ml/min 800mg daily; CrCl <10ml/min avoid use M04AA Allopurinol in renal dysfunction: ≤200 mg/d if CrClf 20 to 60 mL/min, 100 mg/d if CrCl ≤20 mL/min M04AA Allopurinol without baseline urea, electrolytes, creatinine and eGFR M04AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Allopurinol M04AA Drugs that need special attention in chronic kidney disease: Allopurinol M04AA IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg. M04AA Medicines that may accumulate and require renal function monitoring: Allopurinol M04AA Patients with creatinine clearance < 60 ml/min, initial allopurinol dose to be < 300 mg/day M04AA Potentially dangerous or contraindicated in patients with eGFR <50: Allopurinol exceeding recommended standard dose M04AC Colchicine if CrCl <30 - GI, neuromuscular, bone marro toxicity - reduce dose M04AC Drugs requiring dosage adjustment or contraindicated in patients with CKD: Colchicine M04AC Medicines that may accumulate and require renal function monitoring: Colchicine M01A Avoid NSAID use in individuals with hypertension, heart failure, or chronic kidney disease of all causes, including diabetes M01A Avoidance of NSAID or Cox 2 Inhibitor in CHF, HTN or renal dysfunction: pts with dx of CHF, HTN or CrCl £20 ml/min M01A Drugs that need special attention in chronic kidney disease: NSAIDs M01A For patients aged 65 and over: NSAIDs should be used with caution in reduced kidney function (<30ml/min) M01A If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) M01A Medications to use with extreme caution in elderly patients with kdiney disease: NSAIDs, nondihydropyridine CCBs, antidiabetic glitazones - Fluid retention M01A NSAID - methotrexate - reduce renal clearing of methotrexate M01A NSAID prescribed in patients aged 65 and over with estimated glomerular filtration rate <60 M01A NSAIDs - Avoid when GFR is < 30 mL/min/1.73 m2 Prolonged therapy is not recommended when GFR is <60mL/min/1.73m2 Avoid when taking RAAS-blocking agents or lithium. M01A NSAIDS - with chronic kidney disease (eGFR<50ml/min) - risk of renal impairment M01A Patient with risk factors for impaired renal function (l) is not taking an NSAID M01A Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 M01A Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI M01A Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI and a loop diuretic M01A Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiinflammatory and antirheumatic products (non steroids) M01AB Diclofenac - GFR 39-57ml/min recommended maximum dose 75mg/day M01AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Diclofenac M01AB Nephrotoxic Medications: Diclofenac sodium M01AE Nephrotoxic Medications: Ibuprofen M01AB Nephrotoxic Medications: Indomethacin M01AE Nephrotoxic Medications: Naproxen M01AC Drugs requiring dosing adjustments in impaired renal function: Meloxicam M01AH Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Coxibs M01AC Nephrotoxic Medications: Piroxicam M01AB Ketorolac - increased risk of GI bleeding, peptic ulcer and AKI M01AG Mefenamic acid–lisinopril - hypertension, nephrotoxicity M01AB Nephrotoxic Medications: Sulindac M05BA Risedronate dosium - CrCl <30ml/min contraindicated M05BA Bisphosphonates - Most are not recommended when GFR is < 30 mL/min/1.73 m2 Refer to bone specialist if GFR is < 30 mL/min/1.73 m2 and no evidence of CKD-MBD (calcium, phosphate, alkaline phosphatase, and intact PTH normal) M05BA Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Bisphosphonates M05BA Medicines that may accumulate and require renal function monitoring: Bisphosphonates M05BA Disodium etidronate - in mild renal impairment reduce dose M05BA Drug - CrCl - maximum dosing recommendation (mg) Tiludronate - <30 - avoid use M05BA Pamidronate - CrCl 90-30ml/min 90mg every 4weeks; CrCl <30ml/min +/or haemodialysis not recommended M05BA CKD stage 3a (eGFR 45-59) - Dose of BP is the same as in non-renal patients, but ensure that patient is vitamin D replete. M05BA CKD stage 5 (eGFR <15) or patients on dialysis - Avoid BP. Bone biopsy may be required to distinguish from other forms of metabolic bone diseases (renal osteodystrophy) that are associated with CKD. M05BA CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. M05BX Drug - CrCl - maximum dosing recommendation (mg) Strontium - <30 - avoid use M05BX Medicines that may accumulate and require renal function monitoring: Strontium ranelate M04AB Contraindicated medications at variable GFR thresholds: Probenecid M04AB Probenecid if CrCl <30 - loss of effectiveness - avoid M03BX Baclofen - GFR 30-49 reduce dose 75% M03BX Medicines that may accumulate and require renal function monitoring: Baclofen N06AA Amitriptylinoxide - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR 15-30; 15-150mg daily if eGFR <15 or in RRT N05CC Chloral hydrate - avoid use if GFR is less than 50 mL/minute N05BA Clorazepate - reduce doses by 33% to 50% if GFR is less than 30 mL/minute N06AA Dibenzepine - no adjustment if eGFR 30-60; initially 240mg with careful increase if eGFR <30 or in RRT N06AA Dosulepine - no adjustment if eGFR 30-60; initially 75mg with careful increase if eGFR <30 or in RRT N02CA Drug - CrCl - maximum dosing recommendation (mg) Methysergide - <50 - avoid use N06 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Psychoanaleptics N03 Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiepileptics N04B Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Dopaminergic agents N02CC Drugs requiring dosing adjustments in impaired renal function: Almotriptan malate N03AF Drugs requiring dosing adjustments in impaired renal function: Oxacarbazepine N02A Drugs that need special attention in chronic kidney disease: Narcotic analgesics N03AB Drugs that need special attention in chronic kidney disease: Phenytoin N06AB Escitalopram - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT N06AA Maprotiline - no adjustment if eGFR 30-60; initially 50mg with careful increase if eGFR <30 or in RRT N05AL Medicines that may accumulate and require renal function monitoring: Amisulpride N06AX Medicines that may accumulate and require renal function monitoring: Buproprion N06DA Medicines that may accumulate and require renal function monitoring: Galantamine N02CA Medicines that may accumulate and require renal function monitoring: Methysergide N06AX Medicines that may accumulate and require renal function monitoring: Reboxetine N03AX Medicines that may accumulate and require renal function monitoring: Topiramate N05BC Meprobamate - double the dosing interval if GFR is 10-50 mL/minute N02BB Metamizol - GFR 29-30ml/min avoid high doses N06AX Mianserin - initially 30mg with careful increase if eGFR <60 or in RRT N06AX Milnacipran - initially 25mg with careful increase if eGFR 30-60; 25-50mg if eGFR <30 or in RRT N06AX Nefazodone - initially 100mg with careful increase if eGFR <60 or in RRT N06AB Paroxetine - initially 10mg with careful increase if eGFR <60 or in RRT N05BE Patients with anuria a 25 to 50% dosage reduction of buspirone indicated N02AC Propoxyphene - avoid use if GFR is less than 10 mL/minute N06AA Protryptiline - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR <30 or in RRT N06AX Reboxetine - 4-6mg daily if eGFR <60 or in RRT N04BD Selegiline - initally 5mg with careful increase if eGFR 30-60; 5mg daily if eGFR <30 or in RRT N06AB Sertraline - no adjustment if eGFR 30-60; initially 50mg with careful increase if eGFR 15-30; 25mg and consider reducing max dose if eGFR <15 or in RRT N06AX Tianeptine - initially 12.5mg with careful increase if eGFR 30-60; 12.5-25mg if eGFR <30 or in RRT N06AF Tranylcypromine - no adjustment if eGFR 30-60; initially 30mg with careful increase if eGFR <30 or in RRT N06AX Trazadone - no adjustment if eGFR 15-60; initially 150mg with careful increase if eGFR <15 or in RRT N03AG Valproate - ascertain haematological and hepatic history and measre serum valproate levels at start of treatment; 3 monthly weight; 6 monthly FBC, LFTs, and serum valproate levels; measure blood pressure, lipid profile and fasting glucose in patients with risk factors, monitor for menstrual irregularities N03AX For patients aged 65 and over: Gabapentin and pregabalin should have reduced doses at specified levels of CrCl N03AX Gabapentin - Can cause altered mental status, myoclonus and asterixis with severe CKD/ESRD. GFR 30-59 mL/min: 200-700 mg twice daily, GFR 15-29 mL/min: 200-700 mg once per day, GFR <15 mL/min: 300 every other day, hemodialysis: 200-300 mg after each dialysis. Extended release: GFR 30-59 mL/min: 600-1,800 mg once per day, GFR < 30 mL/min to ESRD—not recommended N03AX Gabapentin - CrCl 50-79ml/min 600-1800mg daily in 3 doses; CrCl 30-49ml/min 300-900 in 2/3 doses; CrCl 15-29ml/min 600mg daily in 2/3 doses; CrCl <15ml/min 300mg daily N03AX Gabapentin if CrCl <60 - CNS adverse effects - reduce dose N03AX Medicines that may accumulate and require renal function monitoring: Gabapentin N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); >15-29 - 200-700mg/day - 200, 300, 400, 500, 700 given qd N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); >30-59 - 400-1400mg/day - 200, 300, 400, 500, 700 given bid N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); ≽60 - 900-3600mg/day - 300, 400, 600, 800, 1200 given tid N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); 15 - 100-300mg/day - 100, 125, 150, 200, 300 given qd N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); Haemodialysis (Patients on hemodialysis should receive maintenance doses based on estimates of Clcr and supplemental doses after 4 hours of hemodialysis ) - 125, 150, 200, 250, 350 [post dialysis supplemental dose] N03AX Drug - CrCl - maximum dosing recommendation (mg) Gabapentin - <15 - 300 daily N02A In patients with renal insufficiency: Avoid: Codeine, morphine, pethidine, dextropropoxyphene and tramadol. N02AX Medicines that may accumulate and require renal function monitoring: Tramadol N02AX Recommendations for opioid prescribing in renal failure: Recommended with caution - tramadol; methadone N02AX Tramadol - GFR 30-49 reduce dose 25% N02AX Tramadol if CrCl <30 - CNS adverse effects - immediate release reduce dose and extended release avoid N06AX Duloxetine - CrCl <30ml/min 30mg once daily N06AX Duloxetine - no adjustment if eGFR 30-60; initially 40mg with careful increase if eGFR <30 or in RRT N06AX Duloxetine if CrCl <30 - increased GI adverse effects - avoid N06AX Medicines that may accumulate and require renal function monitoring: Duloxetine N06AX Use of doluxetine is not normally recommended for patients with ESRD or for patients with a creatinine clearance <30 N06AX Mirtazapine - GFR 10-29 reduce dose 50% N06AX Mirtazapine - GFR 30-49 reduce dose 25% N06AX Mirtazapine - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR <30 or in RRT N02BE Acetaminophen - Increase dosing interval to every six hours if GFR* equals 10-50 milliliters/minute; increase dosing interval to every eight hours if GFR is less than 10 mL/minute N02BE Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Acetaminophen and derivatives N02BE Paracetamol - GFR 25-59ml/min recommended maximum dose 2500mg/day N03AX Medicines that may accumulate and require renal function monitoring: Pregabalin N03AX Pregabalin - CrCl 30-60ml/min 300mg in 1 or 2 doses; CrCl 15-30ml/min 150mg in 1 or 2 doses; CrCl <15ml/min 75mg as single dose N03AX Levetiracetam - CrCl 50-79ml/min 500-1000mg twice daily; CrCl 30-49ml/min 250-750mg twice daily; CrCl <30ml/min 250-500mh twice daily N03AX Levetiracetam if CrCl < or equal to 80 - CNS adverse effects - reduce dose N03AX Medicines that may accumulate and require renal function monitoring: Levetiracetam N02A In patients with renal insufficiency: Least likely to cause harm: Fentanyl, buprenorphine and oxymorphone. N02A In patients with renal insufficiency: Use with caution: Hydromorphone and oxycodone. N02AA Medicines that may accumulate and require renal function monitoring: Hydromorphone N02A Recommendations for opioid prescribing in renal failure: Limited information available - buprenorphine; hydrmorphone; oxycodone; oxymorphone; tapentadol N02AA Codeine - GFR 30-49 reduce dose 50% N02AA Medicines that may accumulate and require renal function monitoring: Codeine N02AA Paracetamol with codeine - GFR 10-29 avoid use of codeine N02A Recommendations for opioid prescribing in renal failure: Not recommended - codeine; hydrocodone; morphine N02AA Medicines that may accumulate and require renal function monitoring: Oxycodone N02A Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Opioids N02A Opioids - Reduce dose if GFR is < 60 mL/min/1.73 m2. Use with caution when GFR is < 15 mL/min/1.73 m2 N04BC Drugs requiring dosing adjustments in impaired renal function: Apomorphine N02AA Medicines that may accumulate and require renal function monitoring: Morphine N05AX Medicines that may accumulate and require renal function monitoring: Paliperidone N05AX Paliperidone - CrCl 50-80ml/min 6mg once daily; CrCl 30-50ml/min 3mg once daily/avoid injection; CrCl 10-30ml/min 3mg once daily; CrCl <10ml/min avoid use N04BC Medicines that may accumulate and require renal function monitoring: Pramipexole N04BC Pramipexole - CrCl 20-50ml/min 2.25mg once daily; CrCl <20 1.5mg once daily N06DX Medicines that may accumulate and require renal function monitoring: Memantine N06DX Memantine - CrCl 5-29ml/min 10mg once daily N05 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Psycholeptics (including lithium) N05AN Lithium - measure calcium and serum lithium levels at start of treatment; 3 monthly renal function; 6 monthly thyroid function, calcium, weight and serum lithium levels N05AN Medicines that may accumulate and require renal function monitoring: Lithium N05AN Nephrotoxic Medications: Lithium N05AN Patients on lithium therapy for bipolar disorder should have plasma creatinine cncentrations measured at least annually N06AX Desvenlafaxine - initially 25mg with careful increase if eGFR 30-60; 25g daily if GFR <30 or in RRT N06AX Medicines that may accumulate and require renal function monitoring: Desvenlafaxine N06AX Medicines that may accumulate and require renal function monitoring: Venlafaxine N06AX Venlafaxine - no adjustment if eGFR 30-60; 37.5-112.5mg if eGFR <30 N07BB Drugs requiring dosing adjustments in impaired renal function: Acamprosate calcium N07BB Medicines that may accumulate and require renal function monitoring: Acamprosate N05BA Diazepam - reduce doses by 33% to 50% if GFR is less than 30 mL/minute N05CD Flurazepam - reduce doses by 33% to 50% if GFR is less than 30 mL/minute N05BA Chlordiazepoxide - reduce doses by 33% to 50% if GFR is less than 30 mL/minute N05BA Medicines that may accumulate and require renal function monitoring: Benzidiazepines N07BA Medications requiring dose adjustments at variable GFR thresholds: Varenciline N07BA Medicines that may accumulate and require renal function monitoring: Varenicline N07BA Varenicline - CrCl <30ml/min 1mg daily N06AA Clomipramine - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT N06AA Desipramine - no adjustment if eGFR 15-60; initially 25mg with carfeul increase if eGFR <15 or in RRT N06AA Imipramine - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT N06AA Lofepramine - no adjustment if eGFR 15-60; initially 140mg with careful increase if eGFR <15 or in RRT N06AA Trimipramine - no adjustment if eGFR 15-60; initially 50g with careful increase if eGFR <15 or in RRT N06AX Bupropion - CrCl ≼50ml/min 150mg once daily N06AX Buproprion - 150mg daily if eGFR <60 or in RRT P01 Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiprotazoals P01BA Group 1 - chloroquine - 100mg/day if CrCl 60-89ml/min P01BA Group 1 - chloroquine - 25mg every 48 hours if CrCl <15ml/min or HD P01BA Group 1 - chloroquine - 25mg/day if CrCl 15-29ml/min P01BA Group 1 - chloroquine - 50mg/day if CrCl 30-59ml/min P01BA Group 2 - chloroquine - 100mg/day if CrCl 60-89ml/min P01BA Group 2 - chloroquine base/proguanil - 1 tablet per day if CrCl 60-69ml/min P01BA Group 2 - chloroquine base/proguanil - both require dosage adjutsment if CrCl <60ml/min and because tablet is not divisible drugs must be administered seprately P01BB Group 2 - proguanil - 100mg/day if normal CrCl 30-59ml/min P01BB Group 2 - proguanil - 200mg/day if normal CrCl 60-89ml/min P01BB Group 2 - proguanil - 50mg every 48 hours if normal CrCl 15-29ml/min P01BB Group 2 - proguanil - 50mg per week if normal CrCl <15ml/min or HD P01BB Group 2 - proguanil/atovaquone - 1 tablet per day if CrCl 60-89ml/min P01BB Group 2 - proguanil/atovaquone - impossible to use if CrCl <60ml/min so choose therapeutic alternative P01CX Nephrotoxic Medications: Pentamidine R06 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antihistamines for systemic use R06AE Cetirizine - GFR 10-29 reduce dose 50% R06AE Cetirizine - GFR 30-49 reduce dose 50% R06AX Loratadine - GFR 10-29 reduce dose 50% R06AX Drugs requiring dosing adjustments in impaired renal function: Desloratadine R03BB Drugs requiring dosing adjustments in impaired renal function: Tiotropium bromide monohydrate S01E Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiglaucome preparations and miotics V03AE Drug-drug interaction - adverse event in older patients with renal functon impairment Oral phosphate binders - Calcium accumulation; decreased absorption of other drugs V03AE The percentage of patients between 18-80 with CKD 3-5 and an elevated phosphate level who are prescribed a phosphate binder V03AE The percentage of patients between 18-80 with CKD 3-5 treated with phosphate binders and with a low calcium level who are prescribed a calcium-containing phosphate binder V03AE The percentage of patients between 18-80 with CKD 3-5 treated with phosphate binders and with an elevated calcium level who are prescribed a non-calcium-containing phosphate binder V03AE Patiromer - Monitor serum potassium and adjust the dose of patiromer based on the serum potassium level and the desired target range. The dose can be up-titrated based on serum potassium level at 1-week or longer intervals, in increments of 8.4 g. V09CX Nephrotoxic Medications: Edetate disodium CrCl <10ml/min - Acyclovir, didanosine, entecavir, meperidine, methadone, morphine, propoxyphene, zalcitabine CrCl <20ml/min - Adefovir, allopurinol, citalopram, escitalopram, nevirapine CrCl <30ml/min - Didanosine, emtricitabine, entecavir, gabapentin, lamivudine, memantine, paroxetine, pregabalin, telbivudine CrCl <40ml/min - Allopurinol, zalcitabine CrCl <50ml/min - Acyclovir, adefovir, emtricitabine, entecavir, fluconazole, lamivudine, meperidine, methadone, morphine, stavudine, telbivudine, voriconazole CrCl <60ml/min - Allopurinol, didanosine, gabapentin, paroxetine, pregabalin Hydroxyurea - CrCl <10 - 50% of full dose Hydroxyurea - CrCl >60- 100% full dose Hydroxyurea - CrCl 10-60 - 75% of full dose Meperidine - avoid especially in individuals with chronic kidney disease Patients with CKD should be prescribed preventative medication with aspirin to prevent cardiovascular events Drugs requiring dosing adjustments in impaired renal function: Dapromycin Phenoprocoumon - Kidney insufficiency is a contraindication according to current product information Hydroxyurea - 2.5 to 25 mg/kg depending on the indication Insulin - All labels state that insulin doses should be adjusted on an individual basis (usually in the context of more intensive monitoring) in patients with renal impairment. Insulin - Partly renally excreted; may need reduced dose when GFR is < 30 mL/min/1.73 m2 Guidelines for patients with diabetic nephropathy: Start treatment in patients with sustained urinary albumin excretion of >30 mg/day. In patients with overt proteinuria treatment goal is <0.5 g/day Nateglinide - CKD 3-4 no dose adjustment necessary; CKD-5 therapy should be started at the lowest dose possible (60 mg/ day). To be avoided in dialysis patients Nateglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 60 mg with meals if eGFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed

Repaglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 0.5 mg with meals if GFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed Repaglinide - Needs no initial dose adjustment in renal impairment (Canada). Caution advised when titrating doses in renal impairment (EU, Canada). In severe renal impairment, initiate at a dose of 0.5 mg/day and subsequently, carefully titrate doses (US) Avoidance of metformin in renal impairment (SCr ≥1.5 mg/dL male and SCr ≥1.4 mg/dL female patients) Medications to use with extreme caution in elderly patients with kdiney disease: Metformin - Risk of lactic acidosis if eGFR <30 mL/min Metformin - Avoid when GFR is <30 mL/min/1.73 m2, but consider risk-benefit if GFR is stable. Review use when GFR is <45 mL/min/1.73 m2 Hold during acute illness or prior to intravenous radiocontrast Metformin - Contraindicated if CrCl <60 mL/min (EU, Canada) or abnormal CrCl (US) Metformin - CrCl 60-90ml/min 2000mg daily; CrCl 30-60ml/min 1000mg daily; CrCl <30ml/min avoid use Metformin - In CKD-3 the dosage should not exceed 1.5 g/day with eGFR > 45 mL/min and 850 mg/day with eGFR 30–45 mL/min.; In CKD-4: maximum 500 mg daily but the drug should be temporarily withheld in periods of unstable GFR; In CKD-5 Consider carefully especially in the presence of acidosis, hypoxia, dehydration Metformin - not recommended in patients with eGFR <45 and contraindicated in patients with eGFR <30 Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity.

Renal failure or renal dysfuntion (creatinine clearance < 60ml/ min) is considered a contraindication (to metformin)

Sulfonylureas - Avoid mainly renally excreted agents (eg, glyburide) Agents mainly metabolized by the liver may need reduced dose when GFR is < 30 mL/min/1.73 m2 Sulfoylureas - Avoid usage as much as possible. Consider a DPP-4 inhibitor as an alternative drug.

Chlorpropamide - CKD-3: 100 to 125 mg daily; CKD-4 avoid; CKD-5 contraindicated

Glibenclamide/metformin - Use is contraindicated in patients with serum creatinine ≥1.5 mg/dL in males, or ≥1.4 mg/dL in females or abnormal creatinine clearance Gliclazide - CKD 3-5 started at low doses and the dose titrated up every 1–4weeks

Gliclazide - NKF-KDOQI guidelines: no dose adjustments required if CKD stages 3, 4, and 5. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; consider alternative agent if eGFR<15 mL/ min/ Glimepiride - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated Glimepiride - NKF-KDOQI guidelines: start treatment conservatively with 1 mg daily. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; maximum dose 1 mg, consider alternative agent if eGFR <15 mL/min.

Medications requiring dose adjustments at variable GFR thresholds: Glimepiride Glimipramide - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated Glipizide - in renal impairment conservative dosing recommended to avoid hypoglycaemia Glyburide - Combined ADA/EASD 2012 position statement: totally avoid if any renal impairment. NKF-KDOQI guidelines: totally avoid if CKD stages 3, 4, and 5. CDA guidelines: use alternative agent if eGFR <60 mL/ min

Tolbutammide - CKD 3-4 Preferably dose titration to 250 mg one to three times/ day (especially in elderly patients); CKD-5 contraindicated SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) - reduced efficacy and increased toxicity in patients with moderate or severe renal impairment and contraindicated in those with eGFR <45 Canagliflozin - 2013 AACE/ACE guidelines: not to be used if eGFR <45 mL/min/1.73 m2 Canagliflozin - Careful monitoring in patients with GFR < 60 mL/ min; CKD-5 to be avoided

Canagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/1.73 m2) (US, EU, Canada). Not recommended if CrCl or eGFR <60 mL/min/1.73 m2 (EU, Canada), or eGFR <45 mL/min/1.73 m2 (US), or contraindicated if eGFR <45 mL/min/1.73 m2 (Canada). Dapagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/ 1.73 m2) (US, EU). Not recommended (US, EU) or contraindicated (Canada) if CrCl or eGFR <60 mL/min/1.73 m. Contraindicated in severe renal impairment (US, Canada). Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2 DPP-4 inhibitors (alogliptin, saxagliptin, sitagliptin) - require dose adjustments in with patients with moderate or severe CKD Medicines that may accumulate and require renal function monitoring: Gliptins Alogliptin - 2013 AACE/ACE guidelines: decrease dose based on GFR: ≽30–\60 mL/min (12.5 mg daily); <30 mL/min (6.25 mg daily). Not in combined ADA/EASD 2012 position statement. Not in NKF-KDOQI guidelines. Alogliptin - eGFR ≽50 use at full dose (25mg/day); eGFR <50 reduce dose (12.5mg/day); eGFR <30 6.25mg/day; patients with ESRD and haemodialysis use with caution (6.25mg/day) Saxagliptin - can be used in full dose (2.5mg QDS or 5mg QDS) in mild renal insufficiency; reduce dose to 2.5mg QDS in moderatre-severe renal sufficiency and in those receiving haemodialysis Saxagliptin - CKD 3-5 halve dose to 2.5mg once daily; administer after HD session. Saxagliptin - eGFR ≽50 use at full dose (5mg/day); eGFR <50 half dose (2.5mg/day); eGFR <30 use with caution; patients with ESRD and haemodialysis do not use Sitagliptin - CKD-3 50mg; CKD-4 25mg; CKD-5 reduce dose to 25mg and administer irrespective of HD timing Sitagliptin - eGFR ≽50 use at full dose(100mg/day); eGFR 30-50 half dose (50mg/day); eGFR <30 quarter dose (25mg/day); patients with ESRD and haemodialysis use with caution (25mg/day) Vildagliptin - eGFR ≽50 use at full dose (2x50mg/day); eGFR <50 half dose (1x50mg/day); patients with ESRD and haemodialysis use with caution (1x50mg/day) Gemigliptin - use without dose adjustment (50mg/day); patients with ESRD and haemodialysis can possibily use but no data Linagliptin - use without dose adjustment (5mg/day); patients with ESRD and haemodialysis can possibily use but no data Albiglutide - No dose adjustment in mild (eGFR 60–89 mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment (US, EU). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m2) or in dialysis due to limited data (EU). No dose adjustment in severe renal impairment (eGFR 15 to <30 mL/min/ 1.73 m2) (US).

Exenatide - Combined ADA/EASD 2012 position statement: contraindicated if GFR <30 mL/min. NKF-KDOQI guidelines: not recommended if GFR <30 mL/min/1.73 m2. 2015 AACE/ACE guidelines: contraindicated if GFR <30 mL/min. CDA guidelines: reduce dosage if eGFR 30–59 mL/min (5 lg BID); use alternative agent if eGFR <30 mL/min Exenatide - eGFR ≽60 use at full dose (2x10mcg/day; eGFR 30-60 use with caution (2x10mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use Exenatide - Use with caution in moderate renal impairment (CrCl 30–50 mL/min) (US, EU, Canada). Contraindicated (Canada)/not recommended (US, EU) in severe renal impairment (CrCl <30 mL/min)/ESRD. Use with caution in renal transplantation (US, Canada)

Liraglutide - Combined ADA/EASD 2012 position statement: safety not established, although drug levels are unaffected by CKD as not renally cleared. NKF-KDOQI guidelines: not recommended if GFR <60 mL/min/1.73 m2. 2013 AACE/ACE guidelines: no restrictions on use. CDA guidelines: use alternative agent if eGFR <50 mL/ min. Liraglutide - eGFR ≽50 use at full dose (1.2-1.8mg/day); eGFR <50 do not use; patients with ESRD and haemodialysis do not use Dulaglutide - No dose adjustment required in mild to moderate renal impairment (US, EU). Not recommended in severe CKD (eGFR <30 mL/min/1.73 m2) due to limited clinical data (EU) Lixisenatide - eGFR ≽50 use at full dose (1x20mcg/day); eGFR 30-50 use with caution (1x20mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use Lixisenatide - No dose adjustment in patients with GFR 50–80 mL/min. Careful use in patients with GFR 50–15 mL/min. TZDs (pioglitazone and rosiglitazone) - often avoided in non-dialysis pateints with T2Dm and CKD due to risk of fluid retention, heart failure and increased bone fracture risk Pioglitazone - Combined ADA/EASD 2012 position statement: no restrictions for use in CKD; be aware of risk of fluid retention. NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed. Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Alpha glucosidase inhibitors Acarbose - Contraindicated (EU) or not recommended (Canada) if CrCl<25 mL/ min, and not recommended if serum creatinine >2 mg/dL (US) due to lack of information Acarbose - No evidence of dose adjustment required for GFR values higher than 25 mL/min; CKD-5 to be avoided Miglitol - Needs no dosage adjustment if CrCl >25 mL/min (EU). Contraindicated if CrCl <25 mL/min (EU). Not recommended if serum creatinine>2 mg/dL due to lack of information (US). Rosiglitazone - Needs no dose adjustment in renal impairment (US, Canada). Caution recommended if CrCl <30 mL/min, due to limited data (Canada). Rosiglitazone - NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiacids and other dtrugs for acid related disorders Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: H2 receptor antagonists H-2 blockers in renal dysfunction; ≤1200 mg/d cimetidine, 20 mg/d famotidine, 150 mg/d nizatidine, 150 mg/d ranitidine if CrClf <50 mL/min

Medications requiring dose adjustments at variable GFR thresholds: Famotidine

Medications to use with extreme caution in elderly patients with kdiney disease: PPIs - Increased risk of fractures, infections, and cognitive decline; hypomagnesemia Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Propulsives Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Metoclopramide

Oral sodium phosphate containing bowel preparations - Can cause acute kidney injury by phosphate crystal deposition and volume depletion Risk factors are CKD, > 60 years of age, female gender, HTN, diabetes, CHF, volume depletion, active colitis, and medications that may predispose to AKI (RAAS blockers, diuretics, lithium, and NSAIDs) Sodium Phosphate should not be used as bowel preparation in patients with CKD, heart failure, cirrhosis or hypertension Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Intestinal anti-inflammatory agents Calcitriol/VDRA (and calcimimetics) can be used to lower PTH in patients with CKD stage 5D where PTH is elevated or rising Calcitriol/VDRA should be reduced or stopped if (i) PTH levels fall below two times the upper limit of normal in CKD stage 5D (2C), and/or (ii) patients develop hypercalcaemia In patients with CKD stage 3–5 not on dialysis, where serum PTH is rising and remains persistently elevated despite the correction of modifiable factors, treatment with calcitriol or VDRA should be used In patients with CKD stage 5D, PTH levels should be maintained in the range of two to nine times the upper normal limit of the assay Initial drug selection for the treatment of elevated PTH should be based on serum calcium and phosphate levels and other aspects of CKD-MBD Medications to use with extreme caution in elderly patients with kdiney disease: Vitamin A - Increased serum levels of RBP4 and apoRBP4 Medications to use with extreme caution in elderly patients with kdiney disease: Vitamin C - Organ accumulation of insoluble oxalate The percentage of patients ≽18 years with CKD 3-5 and elevated calcium levels who are prescribed active vitamin D

Evaluate renal function prior to initiation of direct thrombin or factor Xa inhibitors, and reevaluate when clinically indicated and at least annually Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Vitamin K antagonists and heparin group Drugs requiring dosage adjustment or contraindicated in patients with CKD: Tranexamic acid

For patients with CKD and AF the following recommendations apply: If renal function is impaired, the European Heart Rhythm Association’s practical guide recom- mends renal function to be monitored every 6 months for GFR 30–60mL/min and every 3 months for GFR<30mL/min in patients with AF receiving an NOAC Recommendations for treatment of anaemia of CKD: We suggest that Hb concentration should be monitored every 2–4 weeks in the correction phase and every 1– 3 months for stable patients in the maintenance phase. Therapeutic drug monitoring of antifactor Xa levels in patients with CKD stage 4 or 5 requring full anticoagulation is strongly recommended

With CHA2DS2-VASc score ! 2 and end-stage CKD (CrCl < 15 mL/min) or on hemodialysis, it is reasonable to prescribe warfarin for OAC Recommendations for treatment of anaemia of CKD: We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an op- tion, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation. With moderate-to-severe CKD and CHA2DS2-VASc scores ! 2, reduced doses of direct thrombin or factor Xa inhibitors may be considered Apixaban - 5 mg bid in patients with CrCl ≽30 mL/minute; 2.5 mg bid if CrCl 15–29 mL/minute; 2.5 mg bid in the presence of 2 or more of the following characteristics: • Age $80 years • Body weight #60 kg • Serum creatinine $1.5 mg/dL (133 μmo Apixaban - Age ≥80 years and body weight ≤60 kg or serum creatinine ≥1.5 mg/dl: reduce dose to 2.5 mg b.i.d Apixaban - Body weight ≤60 kg and age ≥80 years or serum creatinine ≥1.5 mg/dl: reduce dose to 2.5 mg b.i.d.

Apixaban - CrCl 15-29 mL/min 2.5 mgBD; CrCl < 15 ml/min, or dialysis not recommended Apixaban - CrCl 30-49ml/min 5mg twice daily; CrCl 15-29ml/min 2,5mg twice daily; CrCl <15ml/min contraindicated Apixaban - not recommended in: Pregnant women; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatment • Severe hepatic impairment

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - amiodarone - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - antiplatelets/NSAIDs - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - carbamazepine/phenytoin/phenobarbital - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - dronederone - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - HIV protease inhibitors - 3-6 months (dose adjustment with apixaban) Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - loop diuretics/thizide-like diuretics/ACEI/ARB - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - verapamil/quinidine - at least 6 months (dose adjustment with edoxaban) For patients with CKD and AF the following recommendations apply: Rivaroxaban (20 mg once a day), edoxaban (60 mg once a day) and apixaban (5 mg twice a day) do not require any dose adjustment in patients with a GFR>50mL/min In patients with CrCl <50ml/min apixaban should be stopped 48 hours before surgery or invasive procedures

Dabigatran - 150 mg bid in patients with CrCl ≽30 mL/minute 110 mg bid may be considered in patients with the following factors: • Age ≽80 years (or 75–80 years with high risk of bleeding) • CrCl 30–50 mL/minute with a high risk of bleeding Dabigatran - age <75 150mg BD; age 75-80 150mg BD (110mg BD should be considered when the risk of stroke is low and bleeding risk is high); age 80 and over 110mg BD

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment

Dabigatran - CrCl ≥50 mL/min no dose adjustment is necessary; CrCl 30-50 mL/min the recommended dose is 150 mg BD (110 mg BD for patients with high risk of bleeding); CrCl < 30 ml/min contraindicated

Dabigatran - dose adjustments: 10 mg bid in patients 75–80 years with low thromboembolic risk and high risk of bleeding, or 80 years or older with CrCl 30–50 mL/min and high risk of bleeding, or receiving the strong P-gp inhibitor verapamil Dabigatran - drugs requiring caution during concomitant treatment in patients with renal impairment: Close clinical surveillance is recommended in patients with mild to moderate renal impairment when dabigatran is combined with mild to moderate P-gp inhibitors (eg, amiodarone, quinidine, verapamil, and clarithromycin) Dabigatran - increased risk of GI bleeding compared with warfarin and oter target specific oral anticoagulants in adults aged 75 and older, lack of evidence of efficacy and safety in individuals with CrCl <30ml/min Dabigatran - no dose adjustment is necessary according to body weight. However, close clinical follow-up is required for patients with a body weight <50 kg. Dabigatran should not be used in patients with a CrCl of <30 mL/min and other NOACs should be used in reduced doses in patients with CrCl 15 – 29 mL/min Direct thrombin dabigatran and factor Xa inhibitor rivaroxaban are not recommended in patients with AF and end-stage chronic kidney disease (CKD) or on dialysis because of a lack of evidence from clinical trials regarding the balance of risks and benefits Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - amiodarone - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - dronederone - 3-6 months with dose adjustment based on renal function Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - HIV protease inhibitors - 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - loop diuretics/thiazide-like diuretics/ACEI/ARB - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - verapamil/quinidine - 3-6 months with dose adjustment based on renal function For patients prescribed dabigatran renal function should be monitored at least once a year if their kidney function is mildy to moderately reduced or if they are over 75 years old For patients with CKD and AF the following recommendations apply: European Medicines Agency - approved a lower dose of dabigatran 75 mg twice daily in patients with a GFR of 15–30mL/min In patients with CrCl <50ml/min dabigatran should be withdrawn at least 3 days before surgery Switching from dabigatran to warfarin: if CrCl <15 no recommendations provided Switching from dabigatran to warfarin: if CrCl >50 start warfarin 3 days before stopping dabigatran Switching from dabigatran to warfarin: if CrCl 15-30 start warfarin 1 day before stopping dabigatran Switching from dabigatran to warfarin: if CrCl 31-50 start warfarin 2 days before stopping dabigatran Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - antiplatelets/NSAIDs - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - carbamazepine/phenytoin/phenobarbital - 3-6 months

Edoxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 60 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg) Edoxaban - CrCl ≥50 mL/min 60 mg OD; CrCl 15-49 mL/min 30 mg OD; CrCl <15 mL/min not recommended.

Medicines that may accumulate and require renal function monitoring: Rivaroxaban

Rivaroxaban - Caution in case of CrCl 15–30 ml/min Dose reduction to 15 mg/ day

Rivaroxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 20 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg)

Rivaroxaban - drugs requiring caution during concomitant treatment in patients with renal impairment: Moderate or potent inhibitors of CYP3A4 (eg, fluconazole, clarithromycin); Moderate inhibitors of both CYP3A4 and P-gp (eg, erythromycin) Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided

Rivaroxaban may be used at a reduced dose of 15mg OD for anti-coagulation management of atrial fibrillation in patients with severe renal impairment (CrCl 15-29 ml/min)

Patients with eGFR <60 should be taking: Aspirin to prevent cardiovascular events

If CrCl <30ml/min recommend 1 mg/kg/day of enoxaparin for treatment of venous thromboembolism If CrCl <30ml/min recommend 30 mg of enoxaparin for prophylaxis of venous thromboembolism Medicines that may accumulate and require renal function monitoring: Enoxaparin

Low molecular weight heparins - Reduce dose by 50% when GFR is <30 mL/min/1.73 m2. Consider switch to conventional heparin or monitor plasma antiefactor Xa in those at high risk for bleeding CrCl (ml/min) - preferred oral anticoagulant class <15 - VKA or NOAC (use with caution) Not using of any one of the three DOACs in patients with a CrCl \30 ml/min is recommended Recommendations for treatment of anaemia of CKD: We recommend that adjustments to ESA doses should be considered when Hb is <105 or >115 g/L in adults, young people and children aged 2 years and older Recommendations for treatment of anaemia of CKD: We recommend that blood pressure should be moni- tored in all patients receiving ESAs and, if present, hypertension be treated by volume removal and/or anti- hypertensive drugs Recommendations for treatment of anaemia of CKD: We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the tar- get Hb level despite SC epoetin dose >300 IU/kg/ week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week Recommendations for treatment of anaemia of CKD: We suggest exerting extreme caution while prescribing ESA therapy in CKD patients with a history of stroke, or malignancy, particularly in those with active malignancy when cure is the anticipated outcome Recommendations for treatment of anaemia of CKD: We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension The percentage of patients ≽18 years with CKD 3-5 and Hb ≽7.5 who are prescribed an ESA Do not initiate erythropoiesis-stimulating agents in patients with chronic kidney disease (CKD) with hemoglobin levels greater than or equal to 100 g/L without symptoms of anemia Recommendations for treatment of anaemia of CKD: We recommend that serum ferritin should not exceed 800 microgram/L in patients treated with iron, and to achieve this iron management should be reviewed when the ferritin is >500 microgram/L. Acetylsalicylic acid - increase dosing interval to every six hours if GFR equals 10-50 mL/minute; avoid use if GFR is less than 10 mL/minute Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Asprin and derivatives Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Aspirin

CrCl <30ml/min - Disopyramide, enoxaparin sodium, milrinone, sotalol, tirofiban

Acipimox - Acipimox is eliminated almost exclusively via the kidneys. Dosage reduction in patients with renal failure is recommended. For patients with a creatinine clearance of 30 to 60 mL/min, the suggested dose is 150 mg

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiadrenegic agents, centrally acting Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiadrenegic agents, peripherally acting Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Other lipid modifying agents Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Adrenergics for systemic use Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiarrhythmics (class Ia and Ic) Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Peipheral vasodilators Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Methyldopa

Drugs that need special attention in chronic kidney disease: Alpha adrenergic blockes eg methyldopa, doxazosin, prazosin, reserpine

Guidelines for patients with diabetic nephropathy: For management of dyslipidaemia: eGFR >15 ml/min/1.73m2: advise lipid-lowering treatment for reduction of cardiovascular events; eGFR <15 ml/min/1.73m2: lipid-lowering treatment not advised Medications to use with extreme caution in elderly patients with kdiney disease: alpha-Adrenergic inhibitors - Bradycardia and orthostatic hypotension Medications to use with extreme caution in elderly patients with kdiney disease: Antiarrhythmic drugs (amiodarone, propafenone, sotalol, quinidine, and dronedarone) - Thyroid disease, pulmonary disorders, and QT interval prolongation Medications to use with extreme caution in elderly patients with kdiney disease: Nifedipine (immediate release) - Risk of hypotension and cerebral or myocardial ischemia Moxonidine - Moxonidine should be used with caution and under close medical supervision in patients with moderate renal insufficiency (glomerular filtration rate 30 to 60 mL/min, serum creatinine 1.2 to 1.8mg/dL

Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Fibrates

Fenofibrate - CrCl 20-60ml/min 96mg once daily; CrCl 10-20ml/min 48mg once daily; CrCl <10 avoid use

Medicines that may accumulate and require renal function monitoring: Fenofibrate Recommendations in adults with chronic kidney disease: If triglycerides ≽500 mg/dL - initiate therapeutic lifestyle changes and if fails add fibrate or niacin Drug - GFR (ml/min) - dose adjustments (mg/day) Lovastatin - <15 - decrease to 50% Drug - GFR (ml/min) - dose adjustments (mg/day) Lovastatin - 15-59 - decrease to 50% Drug - GFR (ml/min) - dose adjustments (mg/day) Pravastatin - 15-59 - Start at 10 mg/day for GFR <60 ml/min/1.73 m2 Drug - GFR (ml/min) - dose adjustments (mg/day) Rosuvastatin - <15 - 5-10mg /day Drug - GFR (ml/min) - dose adjustments (mg/day) Rosuvastatin - 15-59 - 5-10mg /day Drug - GFR (ml/min) - dose adjustments (mg/day) Simvastatin - <15 - start at 5mg/day Drug - GFR (ml/min) - dose adjustments (mg/day) Simvastatin - Reduce by 50% in patients with GFR b30 ml/min/1.73 m Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Statin Drugs requiring dosing adjustments in impaired renal function: Rosuvastatin calcium

For patients aged 65 and over: If CrCl <30ml/min dose of simvastatin >10mg/day should be carefully considered and if deemed necessary, implemented cautiously Guidelines recommend statin or statin/ezetimibe treatment in adults age 50 years or older with an estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 but not treated with chronic dialysis or kidney transplantation In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction In CKD patients lifestyle and/or statin therapy are recommended to reduce levels of LDL-C to <100mg/dL and non-HDL-LDL-C to <130mg/dL Lovastatin - Renal impairment, severe (CrCl ≤ 30 mL/min): doses ≥20 mg/day should be undertaken with caution if deemed necessary; Aronoff no adjustmen Pitavastatin - in severe renal impairment (GFR 15-29ml/min not receiving dialysis) initally 1mg orally daly with max 2mg daily

Recommendations in adults with chronic kidney disease: If LDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is bile acid sequestrant or niacin) Recommendations in adults with chronic kidney disease: If LDL 100-129 mg/dL - initiate therapeutic lifestyle changes and if fails add low dose statin (alternative is bile acid sequestrant or niacin) Recommendations in adults with chronic kidney disease: If triglycerides ≽200 mg/dL and non-HDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is fibrate or niacin) Rosuvastatin - Clcr <30 mL/min/1.73 m2: initial: 5 mg/day; do not exceed 10 mg once daily

Simvastatin/ezetimibe - GFR ≥ 60 mL/min/1.73 m2: no dosage adjustment necessary. GFR < 60 mL/min/ 1.73 m2: ezetimibe 10 mg and simvastatin 20 mg once daily in the evening (higher doses should be used with caution) Statin - recommended dose in patients with eGFR 45-59 (mg/day) Atorvastatin - 20 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Fluvastatin - 80 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Pitavastatin - 2 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Pravastatin - 40 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Rosuvastatin - 10 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Simvastatin - 40 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Simvastatin/ezetimibe - 20/10 Statin therapy or combination therapy is recommended in patients with CKD2-4 and treatment to LDL-C levels of <70mg/dL Statins - No increased toxicity for simvastatin 20 mg/day when GFR is < 30 mL/min/1.73 m2 or on dialysis. Dose reduction/increased toxicity for GFR < 30 mL/min/1.73 m2 for lovastatin, rosuvastatin, and pravastatin Atenolol - GFR >35 no change; GFR 15-35 maximum 50mg/day; GFR <15 maximum 25mg/day

Bisoprolol - eGFR 10-30ml/min starting dose 50% of normal dose and if necessary increase to a maximum of 10mg per day Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Atenolol Medicines that may accumulate and require renal function monitoring: Atenolol Medicines that may accumulate and require renal function monitoring: Bisoprolol Metoprolol/hydrochlorothiazide - Clcr > 30 mL/min: no dosage adjustment necessary. Clcr 61–8 mL/min: loop diuretics preferred; the use of hydrochlorothiazide may not be effective. Anuria: use is contraindicated

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Beta blocking agents and thiazides or other diuretics Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Beta blocking agents Caution warranted if combining diuretics and duloxetine, due to increased risk of orthostatic hypotension Diuretic - Coprescription of thiazide and loop diuretic (without valid indication); Overdosing due to lack of monitoring of fluid balance, renal function, electrolytes, etc. Drug-drug interaction - adverse event in older patients with renal functon impairment Thiazides and loop diuretics - Hyponatremia and hypokalemia Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antihypertensives and diuretics in combination Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Diuretics and potassium sparing agents in combination Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Low-ceiling diuretics and thiazides Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: High ceilin diuretics

Hydrochlorothiazide - Clcr < 10 mL/min: avoid use. Usually ineffective with GFR < 30 mL/min. Effective at lower GFR in combination with a loop diuretic Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - AT1 antagonists Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - eplerenone Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - potassium Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - potassium sparing diuretic Hypokalaemia - Use of a non-potassium sparing diuretic; No use of a potassium supplement; No electrolyte test in the 6 months prior to admission Medications to use with extreme caution in elderly patients with kdiney disease: Potassium-sparing diuretics - Hyperkalemia Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - AT1 antagonists + NSAID

Furosemide - in chronic renal failure initially 80-120mg orally daily with a maximum of 1500mg orally daily

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Spironolactone Medications to use with extreme caution in elderly patients with kdiney disease: Spironolactone and triamterene - Hyperkalemia; cautious if eGFR <30 mL/min Reduce spironolactone if >25-mg daily in elderly patients with congestive heart failure or with creatinine clearance less than 30 mL/min

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Potassium sparing agents Drugs requiring dosage adjustment or contraindicated in patients with CKD: Chlorothiazide For patients aged 65 and over: Thiazides likely to be ineffective at CrCl <30ml/min

Bumetanide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose to maximum of 10mg per day Spirinololactone - Renal impairment: mild renal failure (GFR ≥ 50 mL/min), dosing interval of 6–12 h; moderate renal failure (GFR 10–50 mL/min), dosing interval of 12 to 24 h; severe renal failure (GFR ≤ 10 mL/min), avoid the use of spinololactone If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) Furosemide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose guided by effect and indication. In case the effect is inadequate, replace furosemide by bumetanide.

Digoxin - Keep the dose down to 0.125 mg/day or lower. Since even 0.125 mg/ day or lower has a risk of digitalis toxicity in the elderly, consider discontinuing it if monitoring blood levels and electrocardiography is difficult.

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Digoxin Drugs requiring dosage adjustment or contraindicated in patients with CKD: Digoxin Has read code for chronic kidney disease stage 3B, 4 or 5 at least 3 month before audit date - prescribed digoxin at daily dose > 125 nanograms within 3 months leading up to audit date Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years) Potential hazard - at risk patient group; Prescribed digoxin at a daily dose of >125 - patients with a diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 The percentage of patients ≽18 years with eGFR <50ml/min who are prescribed digoxin >0.125mg/day When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year Candesartan/hydrochlorothiazide - Contraindicated with severe renal impairment (Clcr < 30 mL/min) Drug - CrCl - maximum dosing recommendation (mg) Olmesartan - <30 - avoid use Drug - CrCl - maximum dosing recommendation (mg) Valsartan - <30 - 80 once daily Eprosartan - in moderate-severe impairment no initial starting dosage adjustment is necessary hoewever carefully monitor the patient, maximum dose 600mg daily Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - valsartan

Losartan with hydrochlorothiazide - GFR 10-29 reduce dose of hydrocholorthiazde Losartan/hydrochlorothiazide - Clcr ≤ 30 mL/min: use of combination formulation is not recommended

Valsartan/hydrochlorothiazide - Clcr ≥ 30 mL/min: no dosage adjustment necessary, Clcr < 30 mL/min: no dosage adjustment provided in manufacturer’s labelling; safety and efficacy has not been established. Use is contraindicated in patients with anuria Do not prescribe angiotensin-converting-enzyme inhibitors in combination with angiotensin II receptor blockers for the treatment of hypertension, diabetic nephropathy or heart failure Drug-drug interaction - adverse event in older patients with renal functon impairment 2 or more renin-angiotensin-aldosterone inhibitors - Hyperkalemia, hypotension, and increase in serum creatinine Drug-drug interaction - adverse event in older patients with renal functon impairment Renin-angiotensin inhibitors and aldosterone antagonist - Hyperkalemia, gynaecomastia, and increase in serum creatinine Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Angiotensin II antagonists and diuretics Aldosterone antagonists - Monitor electrolytes and renal function as deemed necessary. Limit to low-dose usage in patients with high potassium level or renal impairment.

If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic;

ACE inhibitor/ARB/diuretic - Coprescription of potassium sparing diuretic (without valid indication)

AKI (i.e. estimated GFR reduced by 50 % and/or a twofold increase in serum creatinine concentration and/or urine output B0.5 mL/kg/h for 12 h) - NSAIDs, diuretics, ACE inhibitors, angiotensin receptor antagonists Alacepril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose Altiopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose Attention: higher risk of hyperkalaemia with concomitant use of higher doses of ACEIs (captopril ‡75 mg/day; enalapril, lisinopril ‡10 mg/day) Avoidance of (ACEI or ARB) with K-sparing diuretic in patients with CrClf <50 mL/min Benazepril- mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose Captopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose to be administered in 2 daily doses Cilazapril - CrCl >40 maximum 5mg; CrCl 10-40 maximum 2.5mg; GFR <10 maximum 0.25-0.5mg once or twice weekly per response Cilazepril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose

Delapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose

Diabetes and proteinuria/microalbuminuria and eGFR <50ml/min - ACEI or ARB Discontinue ACE-Is/ARBs if there is confirmed progressive and continuous loss of kidney function after all other causes have been ruled out Drug - CrCl - maximum dosing recommendation (mg) Perindopril - <15 - 2.5/2 on day of dialysis Drug - CrCl - maximum dosing recommendation (mg) Perindopril - 15-30 - 2.5/2 alternate days Drug - CrCl - maximum dosing recommendation (mg) Perindopril - 30-60 - 2.5/2 once daily Drug-drug interaction - adverse event in older patients with renal functon impairment ACEis and lithium - Acute kidney injury in 1.5/100 persons per year. Drugs contraindicated in patients with impaired kidney function and aged 65 and over: ACE inhibitors, plain and combinations Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Captopril Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Enalapril Drugs requiring dosage adjustment or contraindicated in patients with CKD: Captopril Drugs requiring dosage adjustment or contraindicated in patients with CKD: Perindopril

Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher)

Enalapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose For patients aged 65 and over: ACEIs and ARBs should be used with caution in reduced kidney function (<30ml/min) Fosinopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 100% Guidelines for patients with diabetic nephropathy: To reduce BP and albuminuria start RAAS blockade with ACEi or AT1 receptor blockade; aim for maximal dosage Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - ACEI Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - ACEI + loop diuretic Hyperkalaemia - Use of an ACEI or ARB; No electrolyte or potassium test in the 6 months prior to admission Hypertensive patients with chronic renal failure should receive, unless contraindicated, an ACE-I In patients with existing renal insufficiency, one should take into consideration that most ACE inhibitors may further compromise renal function through accumulation of an active metabolite. Dose adjustment is not necessary for fosinopril and for most AT1 antagonists (with the exception of olmesartan) K in the past 6 months for ACEI or ARB with K-sparing diuretic in patients with CrClf < 50 mL/min

Lisinopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose

Patients with CKD should be prescribed preventative medication with ACEIs or ARBs to slow the progression of renal dysfunction

Patients with eGFR <60 should be taking: ACEI/ARB to slow progression of renal disfunction Pentopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure no data

Perindopril - CrCl 30-60ml/min 2.5/2mg once daily; CrCl 15-30ml/min 2.5/2mg alternate days; CrCl <15ml/min 2.5/2mg on day of dialysis Perindopril - eGFR 30-50ml/min if prescriber is a GP maximum dose is 2mg and if a specialised physician the dose may be higher; eGFR 10-30ml/min if prescriber is a GP maximum dose is 2mg every 48 hours and if a specialised physician the dose may be higher

Perindopril - mild renal failure 150-00% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - ACEI Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - acetylsalicylic acid Quinapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective

Ramipril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose Ramipril - starting dose 1.25mg orally daily, titrate to effect with maximum 5mg daily SCr in the past 6 months for ACEI or ARB with K-sparing diuretic in patients with CrClf <50 mL/min The percentage of patients ≽18 years with CKD 3-5 and a prescription of RAS blockers wo are prescribed at least 2 RAS blockers simultaneously Triple blockade with ACE inhibitors and ARBs [with mineralocorticoid receptor antagonists] should be avoided, as should the use of other potassium sparing diuretics When initiating ACE-I/ARB/combination, do not stop drug unless creatinine rises >30% When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). Zofenopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose Drugs requiring dosing adjustments in impaired renal function: Solifenacin succinate

Drugs requiring dosing adjustments in impaired renal function: Trospium chloride Medications requiring dose adjustments at variable GFR thresholds: Phenazopyrdine Medicines that may accumulate and require renal function monitoring: Sildenafil Medicines that may accumulate and require renal function monitoring: Solifenacin Medicines that may accumulate and require renal function monitoring: Tadalafil Medicines that may accumulate and require renal function monitoring: Tolterodine Medicines that may accumulate and require renal function monitoring: Vardenafil

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Sex hormones

When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy)

Medicines that may accumulate and require renal function monitoring: Teriparatide

Nitrofurantoin - Long-term use associated with pulmonary side-effects, renal impairment, liver damage

Patient with a creatinine clearance <60 mL/min is not receiving nitrofurantoin for UTI Potentially dangerous or contraindicated in patients with eGFR <50:Nitrofurantoin For patients aged 65 and over: Nitrofurantoin likely to be ineffective at CrCl <45ml/min Medications to use with extreme caution in elderly patients with kdiney disease: Nitrofurantoin - Pulmonary toxicity; do not use if eGFR <30 mL/min Nitrofurantoin - potential for pulmonary toxicity, hepatotoxicity and peripheral neuropathy - avoid in individuals with creatinine clearance <30ml/min

Patient with a creatinine clearance <50 mL/min is not receiving methenamine (hexamine) for UTI prophylaxis Tetracyclines - Reduce dose when GFR is < 45 mL/min/1.73 m2; can exacerbate uremia Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): TMP/SMX Trimethoprim - Reduce dose by 50% when GFR is < 30 mL/min/1.73 m2. Risk factors for hyperkalemia include high doses, the elderly, CKD, orwith ACE-Is or NSAIDs Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Amoxicillin Medications requiring dose adjustments at variable GFR thresholds: Amoxicillin/clavulanata Drugs requiring dosage adjustment or contraindicated in patients with CKD: Ampicillin/sulbactam Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Penicillin G

Medications requiring dose adjustments at variable GFR thresholds: Piperacillin/tazobactam Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Vancomycin

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Gentamicin Medications to use with extreme caution in elderly patients with kdiney disease: Aminoglycosides - Nephrotoxicity; otovestibular toxicity

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Clarithyromycin

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ciprofloxacin Medications requiring dose adjustments at variable GFR thresholds: Gemifloxacin Medications requiring dose adjustments at variable GFR thresholds: Levofloxacin Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Norfloxacin

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Cefotaxime Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ceftazidime Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Cephalexin Drugs requiring dosage adjustment or contraindicated in patients with CKD: Cefuroxime Drugs requiring dosing adjustments in impaired renal function: Cefditorn pivoxil Medications to use with extreme caution in elderly patients with kdiney disease: Quinolones - Tendinitis; acute kidney injury

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Augmentin

Medications requiring dose adjustments at variable GFR thresholds: Metronidazole

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ethambutol Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Rifampin

Clinicians should vaccinate against chronic hepatitis B virus (HBV) in all unvaccinated adults at risk for infection, including: Adults with end-stage renal disease, including those receiving predialysis care, hemodialysis, peritoneal dialysis, and home dialysis. Hepatitis B vaccine is usually given as a 3- or 4-dose series, but higher dosages may be required for immunocompromised persons and those with end-stage renal disease. These persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg level <10 mIU/mL) should be revaccinated

CrCl - dosing recommendation for tenofovir CrCl ≽50 - tenofovir disoproxil fumarate 300mg every 24 hours CrCl - dosing recommendation for tenofovir CrCl 10-29 - tenofovir disoproxil fumarate 300mg every 72-96 hours CrCl - dosing recommendation for tenofovir CrCl 30-49 - tenofovir disoproxil fumarate 300mg every 48 hours CrCl - dosing recommendation for tenofovir Haemodialysis patients - tenofovir disoproxil fumarate 300mg every 7 days or after approximately 12 hours of haemodialyis For adults starting tenofovir disproxil fumarate with a baseline eGFR <90 mL/min, who are on other nephrotoxic medications, or who have hypertension or diabetes, guidelines recommend that physicians check a baseline blood pressure, serum creatinine, and urine protein For adults taking tenofovir disproxil fumarate monitor kidney function with biannual serum creatinine, serum phosphorous, and urinalysis for proteinuria and glycosuria Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Acyclovir Drug - CrCl at which dosage reduction recommended Acyclovir - creatinine clearance <25 mL/min Drug - CrCl at which dosage reduction recommended Famciclovir - creatinine clearance <60 mL/min Drug - CrCl at which dosage reduction recommended Valacyclovir - creatinine clearance <50 mL/min

For patients with eGFR 30-50 E/C/F/TAF (single pill antiretroviral regimen) has been approved

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Lamivudine Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Stavudine

Drugs requiring dosing adjustments in impaired renal function: Adefovir dipivoxil

Drugs requiring dosing adjustments in impaired renal function: Oseltamivir phosphate Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Fluconazole Antifungals - Reduce maintenance dose of fluconazole by 50% when GFR is < 45 mL/min/1.73 m2

Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and calcium channel blockers - Bradycardia, shock, heart block, multiorgan failure Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and digoxin - Strong increase in digoxin cardiac and neurological toxicity Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and statins - Myopathy Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and phenytoin- Phenytoin intoxication Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and renin-angiotensin-aldosterone inhibitor - Hyperkalemia Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole or amiodarone and warfarin - Increase in warfarin effect Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <10ml/min - Amoxicillin, amoxicillin–clavulanic acid, cefazolin, cefepime, cefoxitin, ceftazidime, cephalexin, imipenem– cilastatin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <20ml/min - Amikacin, cefixime, gentamicin, imipenem–cilastatin, levofloxacin, piperacillin– tazobactam, tobramycin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <30ml/min - Amoxicillin, ampicillin–sulbactam, cefazolin, cefepime, cefoxitin, ceftazidime, ticarcillin– clavulanic acid Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <40ml/min - Amikacin, gemifloxacin, gentamicin, imipenem, piperacillin–tazobactam, tobramycin, vancomycin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <50ml/min - Cefoxitin, ceftazidime, cephalexin, ciprofloxacin, levofloxacin, meropenem, penicillin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <60ml/min - Amikacin, cefepime, cefixime, gentamicin, ticarcillin– clavulanic acid, tobramycin, vancomycin Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antibacterials and antivirals for systemic use Afatinib dimaleate - djustments to the starting dose were not considered necessary for mild RI (CLcr = 60–89 ml/min). Closely monitor patients with moderate (CLcr = 30–59 ml/min) to severe (CLcr < 30 ml/min) RI and adjust afatinib dose if not tolerated. Axitinib - No dose adjustment was needed for mild to severe RI (CLcr ≥ 15 ml/min). Use caution for end-stage renal disease (CLcr < 15 ml/min).

Bleomycin - CrCl 90-60ml/min 10 to 20 mg/m2; CrCl 60-30ml/min 7.5 to 15 mg/m2; CrCl 30-15ml/min 7.5 to 15 mg/m2; CrCl <15ml/min +/or haemodialysis 5 to 10 mg/m2 Cabazitaxel - No dose adjustment was provided. Population PK indicated no significant difference in CL in patients with mild (CLcr = 50–80 ml/min) and moderate (CLcr = 30–50 ml/min) RI. Caution should be used in patients with severe RI or ESRD.

Capecitabine - CrCl 90-60ml/min 1250 mg/m2 every 12 h; CrCl 60-30ml/min 950 mg/m2 every 12 h; CrCl <30ml/min +/or haemodilysis contraindicated Carboplatin - Adjust according to patient using a formula such as the Calvert formula.

Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients) Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function. Crizotinib - No dose adjustment was needed for mild (CLcr = 60–90 ml/min) and moderate (CLcr = 30–60 ml/min) RI. Dose adjustment for severe RI (CLcr < 30 ml/min) was not determined (use caution).

Cytarabine - An initial dose 100 mg/m2/day for 7 to 10 days, or 200 mg/m2/day for 5 to 10 days followed by 20 mg/m2/day for 5 to 10 days.; CrCl 90-60ml/min 2 to 3 g/m2 every 12 h; CrCl 60-30ml/min 1 to 2 g/m2 every 12 h; CrCl 30-15ml/min 1 g/m2 every 12 to 24 h; CrCl <15ml/min +/or haemodialysis 1 g/m2 every 24 h

Cytarabine - CrCl 40-60 - if dose >2g/m2/dose decrease to 1g/m2/dose; if dose 0.75-1g/m2/dose decrease to 0.5g/m2/dose

Drugs requiring dosing adjustments in impaired renal function: Peginterferon alfa-2a Drugs requiring dosing adjustments in impaired renal function: Peginterferon alfa-2b Drugs requiring dosing adjustments in impaired renal function: Pemetrexed disodium Drugs that need special attention in chronic kidney disease: Antineoplastic agents eg carboplatin, cisplatin, cyclophosphamide, etoposide, fludarabine, hydroxyurea, methotrexate

Eribulin mesylate - No dose adjustment was needed mild RI (1.4 mg/m2). Dose reduction for moderate RI (CLcr = 30–50 ml/min) to 1.1 mg/m2. No data for severe RI (CLcr < 30 ml/min)

Etoposide - CrCl 15-50ml/min require dose to be reduced; CrCl <15ml/min contraindicated Etoposide (oral) - CrCl 90-60ml/min 80 to 300 mg/m2/day for 3 to 5 days, followed by 50 to 100 mg/m2/day; CrCl 60-15ml/min 60 to 225 mg/m2/day for 3 to 5 days, followed by 37.5 to 75 mg/m2/day; CrCl <15ml/min +/or haemodialysis 40 to 150 mg/m2/day for 3 to 5 days, followed by 25 to 50 mg/m2/day

Ifosfamide (continuous) - CrCl 90-15ml/min dose/day 5 to 8 g/m2; CrCl <15ml/min +/or haemodialysis dose/day: 3.75 to 6 g/m2 Ifosfamide (intermittent) - CrCl 90-15ml/min dose/day: 1.5 to 3 g/m2; dose/cycle: 5 to 10 g/m2; CrCl <15ml/min +/or haemodialysis: dose/day: 1.13 to 2.25 g/m2 dose/cycle: 3.75 to 7.5 g/m2 Lenvatinib mesylate - No dose adjustment was recommended for mile or moderate RI. Dose reduction to 14 mg daily was recommended for severe RI. Patients with ESRD were not studied. Medications to use with extreme caution in elderly patients with kdiney disease: Azathioprine - Bone marrow suppression and leukopenia

Melphalan (oral for breast cancer) - CrCl 90-60ml/min 0.15 mg/kg/day or 6 mg/m2 per os for 4 to 6 days; CrCl 60-15ml/min 0.11 mg/kg/day or 4.5 mg/m2 per os for 4 to 6 days; CrCl <15ml/min +/or haemodialysis 0.075 mg/kg/day or 3 mg/m2 per os for4to6days Melphalan (oral for ovarian cancer) - CrCl 90-60ml/min 0.2 mg/kg/day per os for 5 days; CrCl 60-15ml/min 0.15 mg/kg/day for 5 days; CrCl <15ml/min +/or haemodialysis 0.1 mg/kg/day per os for 5 days

Methotrexate (IM, IV or SC) - CrCl 90-60ml/min 30 to 50 mg/m2; CrCl 60-30ml/min 24 to 40 mg/m2; CrCl 30-15ml/min 15 to 525 mg/m2; CrCl <15ml/min +/or haemodialysis contraindicated Methotrexate (oral) - CrCl 90-60ml/min 15 to 30 mg/m2; CrCl 60-30ml/min 12 to 24 mg/m2; CrCl 30-10ml/min 7.5 to 24 mg/m2; CrCl <15ml/min +/0r haemodialysis contraindicated

Olaparib - No dose adjustment was required for mild RI (CLcr = 50–80 ml/min). Patients should be monitored. Oxaliplatin - CrCl 90-15ml/min 85 or 100 mg/m2 every 2 weeks, or 130 mg/m2 every 3 weeks; CrCl <15ml/min +/or haemodialysis contraindicated

Pomalidomide - No dose established for RI. Safety, efficacy, and PK were not evaluated in RI. Avoid POMALYST in patients with serum creatinine>3.0mg/dl.

Raltitrexed - 60–60 mL/min: 3 mg/m2 every 3 weeks; 65–55 mL/min: 2.25 mg/m2 every 4 weeks; 54–25 mL/min: 1.5 mg/m2 every 4 weeks; <25 mL/min and haemodialysis: contraindicated Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. Temozolomide - Pharmacokinetics appear unchanged in patients with mild-moderate renal dysfunction. Patients with severe renal failure should be monitored closely and consideration given to dose modification.

Topotecan - CrCl 90-60ml/min 1.5 mg/m2/day; 60–40 mL/min: 1.5 mg/m2/day; 39–20 mL/min: <20 mL/min and haemodialysis: not available Vandetinib - Dose reduced to 200 mg for moderate (CLcr = 30–50 ml/min) and severe (CLcr < 30 ml/min) RI. Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus azoles, macrolides, calcium channel antagonists, or grapefruit juice - Increased serum levels and toxicity of CNI (nephrotoxicity, hypertension, etc) Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus rifampicin or anticonvulsant - Decreased serum levels of CNI Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antigout preparations Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Other (including gold salt and penicillamine) Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Propionic acid derivatives

Drug - CrCl - maximum dosing recommendation (mg) Alendronate - <35 - avoid use Ibandronate - CrCl 90-15ml/min 6 mg every 3 to 4 weeks; CrCl <15ml/min +/or haemodialysis 2 mg every 3 to 4 weeks

Ibandronic acid - CrCl 30-50 50mg every second day if oral or 4mg every 4 weeks if IV; CrCl <30ml/min 50mg once each week if oral or 2mg every 4 weeks if IV; CrCl <10ml/min avoid use

Zolendronic acid - CrCl 90-60ml/min 4 mg every 3 to 4 weeks; 60–50 mL/min: 3.5 mg every 3 to 4 weeks 50–40 mL/min: 3.3 mg every 3 to 4 weeks 40–30 mL/min: 3 mg every 3 to 4 weeks; CrCl <30ml/min +/or haemodialysis not recommended Clodronate - CrCl 50-80ml/min 1600mg daily; CrCl 30-50 1200mg daily; CrCl 10-30ml/min 800mg daily; CrCl <10ml/min avoid use Allopurinol in renal dysfunction: ≤200 mg/d if CrClf 20 to 60 mL/min, 100 mg/d if CrCl ≤20 mL/min

Drugs requiring dosage adjustment or contraindicated in patients with CKD: Allopurinol

IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg. Medicines that may accumulate and require renal function monitoring: Allopurinol Patients with creatinine clearance < 60 ml/min, initial allopurinol dose to be < 300 mg/day Potentially dangerous or contraindicated in patients with eGFR <50: Allopurinol exceeding recommended standard dose

Drugs requiring dosage adjustment or contraindicated in patients with CKD: Colchicine Medicines that may accumulate and require renal function monitoring: Colchicine Avoid NSAID use in individuals with hypertension, heart failure, or chronic kidney disease of all causes, including diabetes Avoidance of NSAID or Cox 2 Inhibitor in CHF, HTN or renal dysfunction: pts with dx of CHF, HTN or CrCl £20 ml/min

For patients aged 65 and over: NSAIDs should be used with caution in reduced kidney function (<30ml/min) If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) Medications to use with extreme caution in elderly patients with kdiney disease: NSAIDs, nondihydropyridine CCBs, antidiabetic glitazones - Fluid retention

NSAID prescribed in patients aged 65 and over with estimated glomerular filtration rate <60 NSAIDs - Avoid when GFR is < 30 mL/min/1.73 m2 Prolonged therapy is not recommended when GFR is <60mL/min/1.73m2 Avoid when taking RAAS-blocking agents or lithium. NSAIDS - with chronic kidney disease (eGFR<50ml/min) - risk of renal impairment

Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI and a loop diuretic Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiinflammatory and antirheumatic products (non steroids)

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Diclofenac

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Coxibs Bisphosphonates - Most are not recommended when GFR is < 30 mL/min/1.73 m2 Refer to bone specialist if GFR is < 30 mL/min/1.73 m2 and no evidence of CKD-MBD (calcium, phosphate, alkaline phosphatase, and intact PTH normal) Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Bisphosphonates Medicines that may accumulate and require renal function monitoring: Bisphosphonates

Drug - CrCl - maximum dosing recommendation (mg) Tiludronate - <30 - avoid use Pamidronate - CrCl 90-30ml/min 90mg every 4weeks; CrCl <30ml/min +/or haemodialysis not recommended CKD stage 3a (eGFR 45-59) - Dose of BP is the same as in non-renal patients, but ensure that patient is vitamin D replete. CKD stage 5 (eGFR <15) or patients on dialysis - Avoid BP. Bone biopsy may be required to distinguish from other forms of metabolic bone diseases (renal osteodystrophy) that are associated with CKD. CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. Drug - CrCl - maximum dosing recommendation (mg) Strontium - <30 - avoid use Medicines that may accumulate and require renal function monitoring: Strontium ranelate

Medicines that may accumulate and require renal function monitoring: Baclofen Amitriptylinoxide - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR 15-30; 15-150mg daily if eGFR <15 or in RRT

Dibenzepine - no adjustment if eGFR 30-60; initially 240mg with careful increase if eGFR <30 or in RRT Dosulepine - no adjustment if eGFR 30-60; initially 75mg with careful increase if eGFR <30 or in RRT Drug - CrCl - maximum dosing recommendation (mg) Methysergide - <50 - avoid use Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Psychoanaleptics Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiepileptics Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Dopaminergic agents Drugs requiring dosing adjustments in impaired renal function: Almotriptan malate Drugs requiring dosing adjustments in impaired renal function: Oxacarbazepine Drugs that need special attention in chronic kidney disease: Narcotic analgesics

Escitalopram - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT Maprotiline - no adjustment if eGFR 30-60; initially 50mg with careful increase if eGFR <30 or in RRT Medicines that may accumulate and require renal function monitoring: Amisulpride Medicines that may accumulate and require renal function monitoring: Buproprion Medicines that may accumulate and require renal function monitoring: Galantamine Medicines that may accumulate and require renal function monitoring: Methysergide Medicines that may accumulate and require renal function monitoring: Reboxetine Medicines that may accumulate and require renal function monitoring: Topiramate

Milnacipran - initially 25mg with careful increase if eGFR 30-60; 25-50mg if eGFR <30 or in RRT

Protryptiline - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR <30 or in RRT

Selegiline - initally 5mg with careful increase if eGFR 30-60; 5mg daily if eGFR <30 or in RRT Sertraline - no adjustment if eGFR 30-60; initially 50mg with careful increase if eGFR 15-30; 25mg and consider reducing max dose if eGFR <15 or in RRT Tianeptine - initially 12.5mg with careful increase if eGFR 30-60; 12.5-25mg if eGFR <30 or in RRT Tranylcypromine - no adjustment if eGFR 30-60; initially 30mg with careful increase if eGFR <30 or in RRT Trazadone - no adjustment if eGFR 15-60; initially 150mg with careful increase if eGFR <15 or in RRT Valproate - ascertain haematological and hepatic history and measre serum valproate levels at start of treatment; 3 monthly weight; 6 monthly FBC, LFTs, and serum valproate levels; measure blood pressure, lipid profile and fasting glucose in patients with risk factors, monitor for menstrual irregularities For patients aged 65 and over: Gabapentin and pregabalin should have reduced doses at specified levels of CrCl Gabapentin - Can cause altered mental status, myoclonus and asterixis with severe CKD/ESRD. GFR 30-59 mL/min: 200-700 mg twice daily, GFR 15-29 mL/min: 200-700 mg once per day, GFR <15 mL/min: 300 every other day, hemodialysis: 200-300 mg after each dialysis. Extended release: GFR 30-59 mL/min: 600-1,800 mg once per day, GFR < 30 mL/min to ESRD—not recommended Gabapentin - CrCl 50-79ml/min 600-1800mg daily in 3 doses; CrCl 30-49ml/min 300-900 in 2/3 doses; CrCl 15-29ml/min 600mg daily in 2/3 doses; CrCl <15ml/min 300mg daily

Medicines that may accumulate and require renal function monitoring: Gabapentin Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); >15-29 - 200-700mg/day - 200, 300, 400, 500, 700 given qd Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); >30-59 - 400-1400mg/day - 200, 300, 400, 500, 700 given bid Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); ≽60 - 900-3600mg/day - 300, 400, 600, 800, 1200 given tid Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); 15 - 100-300mg/day - 100, 125, 150, 200, 300 given qd Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); Haemodialysis (Patients on hemodialysis should receive maintenance doses based on estimates of Clcr and supplemental doses after 4 hours of hemodialysis ) - 125, 150, 200, 250, 350 [post dialysis supplemental dose] Drug - CrCl - maximum dosing recommendation (mg) Gabapentin - <15 - 300 daily In patients with renal insufficiency: Avoid: Codeine, morphine, pethidine, dextropropoxyphene and tramadol. Medicines that may accumulate and require renal function monitoring: Tramadol Recommendations for opioid prescribing in renal failure: Recommended with caution - tramadol; methadone

Tramadol if CrCl <30 - CNS adverse effects - immediate release reduce dose and extended release avoid

Duloxetine - no adjustment if eGFR 30-60; initially 40mg with careful increase if eGFR <30 or in RRT

Medicines that may accumulate and require renal function monitoring: Duloxetine Use of doluxetine is not normally recommended for patients with ESRD or for patients with a creatinine clearance <30

Mirtazapine - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR <30 or in RRT Acetaminophen - Increase dosing interval to every six hours if GFR* equals 10-50 milliliters/minute; increase dosing interval to every eight hours if GFR is less than 10 mL/minute Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Acetaminophen and derivatives

Medicines that may accumulate and require renal function monitoring: Pregabalin Pregabalin - CrCl 30-60ml/min 300mg in 1 or 2 doses; CrCl 15-30ml/min 150mg in 1 or 2 doses; CrCl <15ml/min 75mg as single dose Levetiracetam - CrCl 50-79ml/min 500-1000mg twice daily; CrCl 30-49ml/min 250-750mg twice daily; CrCl <30ml/min 250-500mh twice daily

Medicines that may accumulate and require renal function monitoring: Levetiracetam In patients with renal insufficiency: Least likely to cause harm: Fentanyl, buprenorphine and oxymorphone. In patients with renal insufficiency: Use with caution: Hydromorphone and oxycodone. Medicines that may accumulate and require renal function monitoring: Hydromorphone Recommendations for opioid prescribing in renal failure: Limited information available - buprenorphine; hydrmorphone; oxycodone; oxymorphone; tapentadol

Medicines that may accumulate and require renal function monitoring: Codeine

Recommendations for opioid prescribing in renal failure: Not recommended - codeine; hydrocodone; morphine Medicines that may accumulate and require renal function monitoring: Oxycodone Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Opioids Opioids - Reduce dose if GFR is < 60 mL/min/1.73 m2. Use with caution when GFR is < 15 mL/min/1.73 m2 Medicines that may accumulate and require renal function monitoring: Morphine Medicines that may accumulate and require renal function monitoring: Paliperidone Paliperidone - CrCl 50-80ml/min 6mg once daily; CrCl 30-50ml/min 3mg once daily/avoid injection; CrCl 10-30ml/min 3mg once daily; CrCl <10ml/min avoid use Medicines that may accumulate and require renal function monitoring: Pramipexole

Medicines that may accumulate and require renal function monitoring: Memantine

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Psycholeptics (including lithium) Lithium - measure calcium and serum lithium levels at start of treatment; 3 monthly renal function; 6 monthly thyroid function, calcium, weight and serum lithium levels

Patients on lithium therapy for bipolar disorder should have plasma creatinine cncentrations measured at least annually Desvenlafaxine - initially 25mg with careful increase if eGFR 30-60; 25g daily if GFR <30 or in RRT Medicines that may accumulate and require renal function monitoring: Desvenlafaxine Medicines that may accumulate and require renal function monitoring: Venlafaxine

Drugs requiring dosing adjustments in impaired renal function: Acamprosate calcium Medicines that may accumulate and require renal function monitoring: Acamprosate

Chlordiazepoxide - reduce doses by 33% to 50% if GFR is less than 30 mL/minute Medicines that may accumulate and require renal function monitoring: Benzidiazepines Medications requiring dose adjustments at variable GFR thresholds: Varenciline Medicines that may accumulate and require renal function monitoring: Varenicline

Clomipramine - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT Desipramine - no adjustment if eGFR 15-60; initially 25mg with carfeul increase if eGFR <15 or in RRT Imipramine - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT Lofepramine - no adjustment if eGFR 15-60; initially 140mg with careful increase if eGFR <15 or in RRT Trimipramine - no adjustment if eGFR 15-60; initially 50g with careful increase if eGFR <15 or in RRT

Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiprotazoals

Group 2 - chloroquine base/proguanil - both require dosage adjutsment if CrCl <60ml/min and because tablet is not divisible drugs must be administered seprately

Group 2 - proguanil/atovaquone - impossible to use if CrCl <60ml/min so choose therapeutic alternative

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antihistamines for systemic use Drugs requiring dosing adjustments in impaired renal function: Tiotropium bromide monohydrate Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiglaucome preparations and miotics Drug-drug interaction - adverse event in older patients with renal functon impairment Oral phosphate binders - Calcium accumulation; decreased absorption of other drugs The percentage of patients between 18-80 with CKD 3-5 and an elevated phosphate level who are prescribed a phosphate binder The percentage of patients between 18-80 with CKD 3-5 treated with phosphate binders and with a low calcium level who are prescribed a calcium-containing phosphate binder The percentage of patients between 18-80 with CKD 3-5 treated with phosphate binders and with an elevated calcium level who are prescribed a non-calcium-containing phosphate binder Patiromer - Monitor serum potassium and adjust the dose of patiromer based on the serum potassium level and the desired target range. The dose can be up-titrated based on serum potassium level at 1-week or longer intervals, in increments of 8.4 g.

CrCl <10ml/min - Acyclovir, didanosine, entecavir, meperidine, methadone, morphine, propoxyphene, zalcitabine

CrCl <30ml/min - Didanosine, emtricitabine, entecavir, gabapentin, lamivudine, memantine, paroxetine, pregabalin, telbivudine

CrCl <50ml/min - Acyclovir, adefovir, emtricitabine, entecavir, fluconazole, lamivudine, meperidine, methadone, morphine, stavudine, telbivudine, voriconazole

Patients with CKD should be prescribed preventative medication with aspirin to prevent cardiovascular events

Phenoprocoumon - Kidney insufficiency is a contraindication according to current product information Guidelines for patients with diabetic nephropathy: Start treatment in patients with sustained urinary albumin excretion of >30 mg/day. In patients with overt proteinuria treatment goal is <0.5 g/day

Nateglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 60 mg with meals if eGFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed

Repaglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 0.5 mg with meals if GFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed Repaglinide - Needs no initial dose adjustment in renal impairment (Canada). Caution advised when titrating doses in renal impairment (EU, Canada). In severe renal impairment, initiate at a dose of 0.5 mg/day and subsequently, carefully titrate doses (US)

Metformin - Avoid when GFR is <30 mL/min/1.73 m2, but consider risk-benefit if GFR is stable. Review use when GFR is <45 mL/min/1.73 m2 Hold during acute illness or prior to intravenous radiocontrast

Metformin - In CKD-3 the dosage should not exceed 1.5 g/day with eGFR > 45 mL/min and 850 mg/day with eGFR 30–45 mL/min.; In CKD-4: maximum 500 mg daily but the drug should be temporarily withheld in periods of unstable GFR; In CKD-5 Consider carefully especially in the presence of acidosis, hypoxia, dehydration

Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity.

Gliclazide - NKF-KDOQI guidelines: no dose adjustments required if CKD stages 3, 4, and 5. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; consider alternative agent if eGFR<15 mL/ min/ Glimepiride - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated Glimepiride - NKF-KDOQI guidelines: start treatment conservatively with 1 mg daily. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; maximum dose 1 mg, consider alternative agent if eGFR <15 mL/min.

Glimipramide - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated

Glyburide - Combined ADA/EASD 2012 position statement: totally avoid if any renal impairment. NKF-KDOQI guidelines: totally avoid if CKD stages 3, 4, and 5. CDA guidelines: use alternative agent if eGFR <60 mL/ min

SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) - reduced efficacy and increased toxicity in patients with moderate or severe renal impairment and contraindicated in those with eGFR <45

Canagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/1.73 m2) (US, EU, Canada). Not recommended if CrCl or eGFR <60 mL/min/1.73 m2 (EU, Canada), or eGFR <45 mL/min/1.73 m2 (US), or contraindicated if eGFR <45 mL/min/1.73 m2 (Canada). Dapagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/ 1.73 m2) (US, EU). Not recommended (US, EU) or contraindicated (Canada) if CrCl or eGFR <60 mL/min/1.73 m. Contraindicated in severe renal impairment (US, Canada). Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2 Alogliptin - 2013 AACE/ACE guidelines: decrease dose based on GFR: ≽30–\60 mL/min (12.5 mg daily); <30 mL/min (6.25 mg daily). Not in combined ADA/EASD 2012 position statement. Not in NKF-KDOQI guidelines. Alogliptin - eGFR ≽50 use at full dose (25mg/day); eGFR <50 reduce dose (12.5mg/day); eGFR <30 6.25mg/day; patients with ESRD and haemodialysis use with caution (6.25mg/day) Saxagliptin - can be used in full dose (2.5mg QDS or 5mg QDS) in mild renal insufficiency; reduce dose to 2.5mg QDS in moderatre-severe renal sufficiency and in those receiving haemodialysis

Sitagliptin - eGFR ≽50 use at full dose(100mg/day); eGFR 30-50 half dose (50mg/day); eGFR <30 quarter dose (25mg/day); patients with ESRD and haemodialysis use with caution (25mg/day)

Albiglutide - No dose adjustment in mild (eGFR 60–89 mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment (US, EU). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m2) or in dialysis due to limited data (EU). No dose adjustment in severe renal impairment (eGFR 15 to <30 mL/min/ 1.73 m2) (US).

Exenatide - Combined ADA/EASD 2012 position statement: contraindicated if GFR <30 mL/min. NKF-KDOQI guidelines: not recommended if GFR <30 mL/min/1.73 m2. 2015 AACE/ACE guidelines: contraindicated if GFR <30 mL/min. CDA guidelines: reduce dosage if eGFR 30–59 mL/min (5 lg BID); use alternative agent if eGFR <30 mL/min

Exenatide - Use with caution in moderate renal impairment (CrCl 30–50 mL/min) (US, EU, Canada). Contraindicated (Canada)/not recommended (US, EU) in severe renal impairment (CrCl <30 mL/min)/ESRD. Use with caution in renal transplantation (US, Canada)

Liraglutide - Combined ADA/EASD 2012 position statement: safety not established, although drug levels are unaffected by CKD as not renally cleared. NKF-KDOQI guidelines: not recommended if GFR <60 mL/min/1.73 m2. 2013 AACE/ACE guidelines: no restrictions on use. CDA guidelines: use alternative agent if eGFR <50 mL/ min.

Dulaglutide - No dose adjustment required in mild to moderate renal impairment (US, EU). Not recommended in severe CKD (eGFR <30 mL/min/1.73 m2) due to limited clinical data (EU) Lixisenatide - eGFR ≽50 use at full dose (1x20mcg/day); eGFR 30-50 use with caution (1x20mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use

Pioglitazone - Combined ADA/EASD 2012 position statement: no restrictions for use in CKD; be aware of risk of fluid retention. NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed.

Miglitol - Needs no dosage adjustment if CrCl >25 mL/min (EU). Contraindicated if CrCl <25 mL/min (EU). Not recommended if serum creatinine>2 mg/dL due to lack of information (US).

Oral sodium phosphate containing bowel preparations - Can cause acute kidney injury by phosphate crystal deposition and volume depletion Risk factors are CKD, > 60 years of age, female gender, HTN, diabetes, CHF, volume depletion, active colitis, and medications that may predispose to AKI (RAAS blockers, diuretics, lithium, and NSAIDs)

Calcitriol/VDRA should be reduced or stopped if (i) PTH levels fall below two times the upper limit of normal in CKD stage 5D (2C), and/or (ii) patients develop hypercalcaemia In patients with CKD stage 3–5 not on dialysis, where serum PTH is rising and remains persistently elevated despite the correction of modifiable factors, treatment with calcitriol or VDRA should be used For patients with CKD and AF the following recommendations apply: If renal function is impaired, the European Heart Rhythm Association’s practical guide recom- mends renal function to be monitored every 6 months for GFR 30–60mL/min and every 3 months for GFR<30mL/min in patients with AF receiving an NOAC Recommendations for treatment of anaemia of CKD: We suggest that Hb concentration should be monitored every 2–4 weeks in the correction phase and every 1– 3 months for stable patients in the maintenance phase.

Recommendations for treatment of anaemia of CKD: We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an op- tion, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation.

Apixaban - 5 mg bid in patients with CrCl ≽30 mL/minute; 2.5 mg bid if CrCl 15–29 mL/minute; 2.5 mg bid in the presence of 2 or more of the following characteristics: • Age $80 years • Body weight #60 kg • Serum creatinine $1.5 mg/dL (133 μmo

Apixaban - not recommended in: Pregnant women; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatment • Severe hepatic impairment

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - amiodarone - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - antiplatelets/NSAIDs - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - carbamazepine/phenytoin/phenobarbital - 3-6 months

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - HIV protease inhibitors - 3-6 months (dose adjustment with apixaban) Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - loop diuretics/thizide-like diuretics/ACEI/ARB - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - verapamil/quinidine - at least 6 months (dose adjustment with edoxaban) For patients with CKD and AF the following recommendations apply: Rivaroxaban (20 mg once a day), edoxaban (60 mg once a day) and apixaban (5 mg twice a day) do not require any dose adjustment in patients with a GFR>50mL/min

Dabigatran - 150 mg bid in patients with CrCl ≽30 mL/minute 110 mg bid may be considered in patients with the following factors: • Age ≽80 years (or 75–80 years with high risk of bleeding) • CrCl 30–50 mL/minute with a high risk of bleeding

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment

Dabigatran - CrCl ≥50 mL/min no dose adjustment is necessary; CrCl 30-50 mL/min the recommended dose is 150 mg BD (110 mg BD for patients with high risk of bleeding); CrCl < 30 ml/min contraindicated

Dabigatran - dose adjustments: 10 mg bid in patients 75–80 years with low thromboembolic risk and high risk of bleeding, or 80 years or older with CrCl 30–50 mL/min and high risk of bleeding, or receiving the strong P-gp inhibitor verapamil Dabigatran - drugs requiring caution during concomitant treatment in patients with renal impairment: Close clinical surveillance is recommended in patients with mild to moderate renal impairment when dabigatran is combined with mild to moderate P-gp inhibitors (eg, amiodarone, quinidine, verapamil, and clarithromycin) Dabigatran - increased risk of GI bleeding compared with warfarin and oter target specific oral anticoagulants in adults aged 75 and older, lack of evidence of efficacy and safety in individuals with CrCl <30ml/min Direct thrombin dabigatran and factor Xa inhibitor rivaroxaban are not recommended in patients with AF and end-stage chronic kidney disease (CKD) or on dialysis because of a lack of evidence from clinical trials regarding the balance of risks and benefits

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - dronederone - 3-6 months with dose adjustment based on renal function

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - loop diuretics/thiazide-like diuretics/ACEI/ARB - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - verapamil/quinidine - 3-6 months with dose adjustment based on renal function For patients prescribed dabigatran renal function should be monitored at least once a year if their kidney function is mildy to moderately reduced or if they are over 75 years old For patients with CKD and AF the following recommendations apply: European Medicines Agency - approved a lower dose of dabigatran 75 mg twice daily in patients with a GFR of 15–30mL/min

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - carbamazepine/phenytoin/phenobarbital - 3-6 months

Edoxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 60 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg)

Rivaroxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 20 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg)

Rivaroxaban - drugs requiring caution during concomitant treatment in patients with renal impairment: Moderate or potent inhibitors of CYP3A4 (eg, fluconazole, clarithromycin); Moderate inhibitors of both CYP3A4 and P-gp (eg, erythromycin) Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided

Rivaroxaban may be used at a reduced dose of 15mg OD for anti-coagulation management of atrial fibrillation in patients with severe renal impairment (CrCl 15-29 ml/min)

Low molecular weight heparins - Reduce dose by 50% when GFR is <30 mL/min/1.73 m2. Consider switch to conventional heparin or monitor plasma antiefactor Xa in those at high risk for bleeding Recommendations for treatment of anaemia of CKD: We recommend that adjustments to ESA doses should be considered when Hb is <105 or >115 g/L in adults, young people and children aged 2 years and older Recommendations for treatment of anaemia of CKD: We recommend that blood pressure should be moni- tored in all patients receiving ESAs and, if present, hypertension be treated by volume removal and/or anti- hypertensive drugs Recommendations for treatment of anaemia of CKD: We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the tar- get Hb level despite SC epoetin dose >300 IU/kg/ week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week Recommendations for treatment of anaemia of CKD: We suggest exerting extreme caution while prescribing ESA therapy in CKD patients with a history of stroke, or malignancy, particularly in those with active malignancy when cure is the anticipated outcome Recommendations for treatment of anaemia of CKD: We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension

Do not initiate erythropoiesis-stimulating agents in patients with chronic kidney disease (CKD) with hemoglobin levels greater than or equal to 100 g/L without symptoms of anemia Recommendations for treatment of anaemia of CKD: We recommend that serum ferritin should not exceed 800 microgram/L in patients treated with iron, and to achieve this iron management should be reviewed when the ferritin is >500 microgram/L.

Acipimox - Acipimox is eliminated almost exclusively via the kidneys. Dosage reduction in patients with renal failure is recommended. For patients with a creatinine clearance of 30 to 60 mL/min, the suggested dose is 150 mg

Guidelines for patients with diabetic nephropathy: For management of dyslipidaemia: eGFR >15 ml/min/1.73m2: advise lipid-lowering treatment for reduction of cardiovascular events; eGFR <15 ml/min/1.73m2: lipid-lowering treatment not advised

Medications to use with extreme caution in elderly patients with kdiney disease: Antiarrhythmic drugs (amiodarone, propafenone, sotalol, quinidine, and dronedarone) - Thyroid disease, pulmonary disorders, and QT interval prolongation

Moxonidine - Moxonidine should be used with caution and under close medical supervision in patients with moderate renal insufficiency (glomerular filtration rate 30 to 60 mL/min, serum creatinine 1.2 to 1.8mg/dL Guidelines recommend statin or statin/ezetimibe treatment in adults age 50 years or older with an estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 but not treated with chronic dialysis or kidney transplantation In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction

Recommendations in adults with chronic kidney disease: If LDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is bile acid sequestrant or niacin) Recommendations in adults with chronic kidney disease: If LDL 100-129 mg/dL - initiate therapeutic lifestyle changes and if fails add low dose statin (alternative is bile acid sequestrant or niacin) Recommendations in adults with chronic kidney disease: If triglycerides ≽200 mg/dL and non-HDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is fibrate or niacin)

Simvastatin/ezetimibe - GFR ≥ 60 mL/min/1.73 m2: no dosage adjustment necessary. GFR < 60 mL/min/ 1.73 m2: ezetimibe 10 mg and simvastatin 20 mg once daily in the evening (higher doses should be used with caution)

Statins - No increased toxicity for simvastatin 20 mg/day when GFR is < 30 mL/min/1.73 m2 or on dialysis. Dose reduction/increased toxicity for GFR < 30 mL/min/1.73 m2 for lovastatin, rosuvastatin, and pravastatin

Metoprolol/hydrochlorothiazide - Clcr > 30 mL/min: no dosage adjustment necessary. Clcr 61–8 mL/min: loop diuretics preferred; the use of hydrochlorothiazide may not be effective. Anuria: use is contraindicated Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

Spirinololactone - Renal impairment: mild renal failure (GFR ≥ 50 mL/min), dosing interval of 6–12 h; moderate renal failure (GFR 10–50 mL/min), dosing interval of 12 to 24 h; severe renal failure (GFR ≤ 10 mL/min), avoid the use of spinololactone If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) Furosemide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose guided by effect and indication. In case the effect is inadequate, replace furosemide by bumetanide.

Digoxin - Keep the dose down to 0.125 mg/day or lower. Since even 0.125 mg/ day or lower has a risk of digitalis toxicity in the elderly, consider discontinuing it if monitoring blood levels and electrocardiography is difficult. Has read code for chronic kidney disease stage 3B, 4 or 5 at least 3 month before audit date - prescribed digoxin at daily dose > 125 nanograms within 3 months leading up to audit date Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

Valsartan/hydrochlorothiazide - Clcr ≥ 30 mL/min: no dosage adjustment necessary, Clcr < 30 mL/min: no dosage adjustment provided in manufacturer’s labelling; safety and efficacy has not been established. Use is contraindicated in patients with anuria Do not prescribe angiotensin-converting-enzyme inhibitors in combination with angiotensin II receptor blockers for the treatment of hypertension, diabetic nephropathy or heart failure Drug-drug interaction - adverse event in older patients with renal functon impairment 2 or more renin-angiotensin-aldosterone inhibitors - Hyperkalemia, hypotension, and increase in serum creatinine Drug-drug interaction - adverse event in older patients with renal functon impairment Renin-angiotensin inhibitors and aldosterone antagonist - Hyperkalemia, gynaecomastia, and increase in serum creatinine

If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic;

AKI (i.e. estimated GFR reduced by 50 % and/or a twofold increase in serum creatinine concentration and/or urine output B0.5 mL/kg/h for 12 h) - NSAIDs, diuretics, ACE inhibitors, angiotensin receptor antagonists Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher)

In patients with existing renal insufficiency, one should take into consideration that most ACE inhibitors may further compromise renal function through accumulation of an active metabolite. Dose adjustment is not necessary for fosinopril and for most AT1 antagonists (with the exception of olmesartan)

Perindopril - eGFR 30-50ml/min if prescriber is a GP maximum dose is 2mg and if a specialised physician the dose may be higher; eGFR 10-30ml/min if prescriber is a GP maximum dose is 2mg every 48 hours and if a specialised physician the dose may be higher

RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective

When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) Clinicians should vaccinate against chronic hepatitis B virus (HBV) in all unvaccinated adults at risk for infection, including: Adults with end-stage renal disease, including those receiving predialysis care, hemodialysis, peritoneal dialysis, and home dialysis. Hepatitis B vaccine is usually given as a 3- or 4-dose series, but higher dosages may be required for immunocompromised persons and those with end-stage renal disease. These persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg level <10 mIU/mL) should be revaccinated

For adults starting tenofovir disproxil fumarate with a baseline eGFR <90 mL/min, who are on other nephrotoxic medications, or who have hypertension or diabetes, guidelines recommend that physicians check a baseline blood pressure, serum creatinine, and urine protein

Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and calcium channel blockers - Bradycardia, shock, heart block, multiorgan failure Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and digoxin - Strong increase in digoxin cardiac and neurological toxicity Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and renin-angiotensin-aldosterone inhibitor - Hyperkalemia Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole or amiodarone and warfarin - Increase in warfarin effect Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <10ml/min - Amoxicillin, amoxicillin–clavulanic acid, cefazolin, cefepime, cefoxitin, ceftazidime, cephalexin, imipenem– cilastatin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <20ml/min - Amikacin, cefixime, gentamicin, imipenem–cilastatin, levofloxacin, piperacillin– tazobactam, tobramycin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <30ml/min - Amoxicillin, ampicillin–sulbactam, cefazolin, cefepime, cefoxitin, ceftazidime, ticarcillin– clavulanic acid Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <40ml/min - Amikacin, gemifloxacin, gentamicin, imipenem, piperacillin–tazobactam, tobramycin, vancomycin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <50ml/min - Cefoxitin, ceftazidime, cephalexin, ciprofloxacin, levofloxacin, meropenem, penicillin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <60ml/min - Amikacin, cefepime, cefixime, gentamicin, ticarcillin– clavulanic acid, tobramycin, vancomycin

Afatinib dimaleate - djustments to the starting dose were not considered necessary for mild RI (CLcr = 60–89 ml/min). Closely monitor patients with moderate (CLcr = 30–59 ml/min) to severe (CLcr < 30 ml/min) RI and adjust afatinib dose if not tolerated.

Bleomycin - CrCl 90-60ml/min 10 to 20 mg/m2; CrCl 60-30ml/min 7.5 to 15 mg/m2; CrCl 30-15ml/min 7.5 to 15 mg/m2; CrCl <15ml/min +/or haemodialysis 5 to 10 mg/m2 Cabazitaxel - No dose adjustment was provided. Population PK indicated no significant difference in CL in patients with mild (CLcr = 50–80 ml/min) and moderate (CLcr = 30–50 ml/min) RI. Caution should be used in patients with severe RI or ESRD.

Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients) Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function. Crizotinib - No dose adjustment was needed for mild (CLcr = 60–90 ml/min) and moderate (CLcr = 30–60 ml/min) RI. Dose adjustment for severe RI (CLcr < 30 ml/min) was not determined (use caution).

Cytarabine - An initial dose 100 mg/m2/day for 7 to 10 days, or 200 mg/m2/day for 5 to 10 days followed by 20 mg/m2/day for 5 to 10 days.; CrCl 90-60ml/min 2 to 3 g/m2 every 12 h; CrCl 60-30ml/min 1 to 2 g/m2 every 12 h; CrCl 30-15ml/min 1 g/m2 every 12 to 24 h; CrCl <15ml/min +/or haemodialysis 1 g/m2 every 24 h

Drugs that need special attention in chronic kidney disease: Antineoplastic agents eg carboplatin, cisplatin, cyclophosphamide, etoposide, fludarabine, hydroxyurea, methotrexate

Eribulin mesylate - No dose adjustment was needed mild RI (1.4 mg/m2). Dose reduction for moderate RI (CLcr = 30–50 ml/min) to 1.1 mg/m2. No data for severe RI (CLcr < 30 ml/min) Etoposide (oral) - CrCl 90-60ml/min 80 to 300 mg/m2/day for 3 to 5 days, followed by 50 to 100 mg/m2/day; CrCl 60-15ml/min 60 to 225 mg/m2/day for 3 to 5 days, followed by 37.5 to 75 mg/m2/day; CrCl <15ml/min +/or haemodialysis 40 to 150 mg/m2/day for 3 to 5 days, followed by 25 to 50 mg/m2/day

Ifosfamide (intermittent) - CrCl 90-15ml/min dose/day: 1.5 to 3 g/m2; dose/cycle: 5 to 10 g/m2; CrCl <15ml/min +/or haemodialysis: dose/day: 1.13 to 2.25 g/m2 dose/cycle: 3.75 to 7.5 g/m2 Lenvatinib mesylate - No dose adjustment was recommended for mile or moderate RI. Dose reduction to 14 mg daily was recommended for severe RI. Patients with ESRD were not studied.

Melphalan (oral for breast cancer) - CrCl 90-60ml/min 0.15 mg/kg/day or 6 mg/m2 per os for 4 to 6 days; CrCl 60-15ml/min 0.11 mg/kg/day or 4.5 mg/m2 per os for 4 to 6 days; CrCl <15ml/min +/or haemodialysis 0.075 mg/kg/day or 3 mg/m2 per os for4to6days Melphalan (oral for ovarian cancer) - CrCl 90-60ml/min 0.2 mg/kg/day per os for 5 days; CrCl 60-15ml/min 0.15 mg/kg/day for 5 days; CrCl <15ml/min +/or haemodialysis 0.1 mg/kg/day per os for 5 days

Methotrexate (IM, IV or SC) - CrCl 90-60ml/min 30 to 50 mg/m2; CrCl 60-30ml/min 24 to 40 mg/m2; CrCl 30-15ml/min 15 to 525 mg/m2; CrCl <15ml/min +/or haemodialysis contraindicated Methotrexate (oral) - CrCl 90-60ml/min 15 to 30 mg/m2; CrCl 60-30ml/min 12 to 24 mg/m2; CrCl 30-10ml/min 7.5 to 24 mg/m2; CrCl <15ml/min +/0r haemodialysis contraindicated

Raltitrexed - 60–60 mL/min: 3 mg/m2 every 3 weeks; 65–55 mL/min: 2.25 mg/m2 every 4 weeks; 54–25 mL/min: 1.5 mg/m2 every 4 weeks; <25 mL/min and haemodialysis: contraindicated Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. Temozolomide - Pharmacokinetics appear unchanged in patients with mild-moderate renal dysfunction. Patients with severe renal failure should be monitored closely and consideration given to dose modification.

Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus azoles, macrolides, calcium channel antagonists, or grapefruit juice - Increased serum levels and toxicity of CNI (nephrotoxicity, hypertension, etc) Ibandronic acid - CrCl 30-50 50mg every second day if oral or 4mg every 4 weeks if IV; CrCl <30ml/min 50mg once each week if oral or 2mg every 4 weeks if IV; CrCl <10ml/min avoid use

Zolendronic acid - CrCl 90-60ml/min 4 mg every 3 to 4 weeks; 60–50 mL/min: 3.5 mg every 3 to 4 weeks 50–40 mL/min: 3.3 mg every 3 to 4 weeks 40–30 mL/min: 3 mg every 3 to 4 weeks; CrCl <30ml/min +/or haemodialysis not recommended

IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg.

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous)

NSAIDs - Avoid when GFR is < 30 mL/min/1.73 m2 Prolonged therapy is not recommended when GFR is <60mL/min/1.73m2 Avoid when taking RAAS-blocking agents or lithium.

Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI and a loop diuretic Bisphosphonates - Most are not recommended when GFR is < 30 mL/min/1.73 m2 Refer to bone specialist if GFR is < 30 mL/min/1.73 m2 and no evidence of CKD-MBD (calcium, phosphate, alkaline phosphatase, and intact PTH normal)

CKD stage 5 (eGFR <15) or patients on dialysis - Avoid BP. Bone biopsy may be required to distinguish from other forms of metabolic bone diseases (renal osteodystrophy) that are associated with CKD. CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. Valproate - ascertain haematological and hepatic history and measre serum valproate levels at start of treatment; 3 monthly weight; 6 monthly FBC, LFTs, and serum valproate levels; measure blood pressure, lipid profile and fasting glucose in patients with risk factors, monitor for menstrual irregularities

Gabapentin - Can cause altered mental status, myoclonus and asterixis with severe CKD/ESRD. GFR 30-59 mL/min: 200-700 mg twice daily, GFR 15-29 mL/min: 200-700 mg once per day, GFR <15 mL/min: 300 every other day, hemodialysis: 200-300 mg after each dialysis. Extended release: GFR 30-59 mL/min: 600-1,800 mg once per day, GFR < 30 mL/min to ESRD—not recommended Gabapentin - CrCl 50-79ml/min 600-1800mg daily in 3 doses; CrCl 30-49ml/min 300-900 in 2/3 doses; CrCl 15-29ml/min 600mg daily in 2/3 doses; CrCl <15ml/min 300mg daily

Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); Haemodialysis (Patients on hemodialysis should receive maintenance doses based on estimates of Clcr and supplemental doses after 4 hours of hemodialysis ) - 125, 150, 200, 250, 350 [post dialysis supplemental dose]

Acetaminophen - Increase dosing interval to every six hours if GFR* equals 10-50 milliliters/minute; increase dosing interval to every eight hours if GFR is less than 10 mL/minute

The percentage of patients between 18-80 with CKD 3-5 treated with phosphate binders and with a low calcium level who are prescribed a calcium-containing phosphate binder The percentage of patients between 18-80 with CKD 3-5 treated with phosphate binders and with an elevated calcium level who are prescribed a non-calcium-containing phosphate binder Patiromer - Monitor serum potassium and adjust the dose of patiromer based on the serum potassium level and the desired target range. The dose can be up-titrated based on serum potassium level at 1-week or longer intervals, in increments of 8.4 g. Metformin - In CKD-3 the dosage should not exceed 1.5 g/day with eGFR > 45 mL/min and 850 mg/day with eGFR 30–45 mL/min.; In CKD-4: maximum 500 mg daily but the drug should be temporarily withheld in periods of unstable GFR; In CKD-5 Consider carefully especially in the presence of acidosis, hypoxia, dehydration

Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity.

Canagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/1.73 m2) (US, EU, Canada). Not recommended if CrCl or eGFR <60 mL/min/1.73 m2 (EU, Canada), or eGFR <45 mL/min/1.73 m2 (US), or contraindicated if eGFR <45 mL/min/1.73 m2 (Canada).

Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2 Albiglutide - No dose adjustment in mild (eGFR 60–89 mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment (US, EU). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m2) or in dialysis due to limited data (EU). No dose adjustment in severe renal impairment (eGFR 15 to <30 mL/min/ 1.73 m2) (US).

Exenatide - Combined ADA/EASD 2012 position statement: contraindicated if GFR <30 mL/min. NKF-KDOQI guidelines: not recommended if GFR <30 mL/min/1.73 m2. 2015 AACE/ACE guidelines: contraindicated if GFR <30 mL/min. CDA guidelines: reduce dosage if eGFR 30–59 mL/min (5 lg BID); use alternative agent if eGFR <30 mL/min

Liraglutide - Combined ADA/EASD 2012 position statement: safety not established, although drug levels are unaffected by CKD as not renally cleared. NKF-KDOQI guidelines: not recommended if GFR <60 mL/min/1.73 m2. 2013 AACE/ACE guidelines: no restrictions on use. CDA guidelines: use alternative agent if eGFR <50 mL/ min.

Oral sodium phosphate containing bowel preparations - Can cause acute kidney injury by phosphate crystal deposition and volume depletion Risk factors are CKD, > 60 years of age, female gender, HTN, diabetes, CHF, volume depletion, active colitis, and medications that may predispose to AKI (RAAS blockers, diuretics, lithium, and NSAIDs) For patients with CKD and AF the following recommendations apply: If renal function is impaired, the European Heart Rhythm Association’s practical guide recom- mends renal function to be monitored every 6 months for GFR 30–60mL/min and every 3 months for GFR<30mL/min in patients with AF receiving an NOAC

Recommendations for treatment of anaemia of CKD: We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an op- tion, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation.

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment

Dabigatran - drugs requiring caution during concomitant treatment in patients with renal impairment: Close clinical surveillance is recommended in patients with mild to moderate renal impairment when dabigatran is combined with mild to moderate P-gp inhibitors (eg, amiodarone, quinidine, verapamil, and clarithromycin) Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided Recommendations for treatment of anaemia of CKD: We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the tar- get Hb level despite SC epoetin dose >300 IU/kg/ week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week

Recommendations for treatment of anaemia of CKD: We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic; Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher)

In patients with existing renal insufficiency, one should take into consideration that most ACE inhibitors may further compromise renal function through accumulation of an active metabolite. Dose adjustment is not necessary for fosinopril and for most AT1 antagonists (with the exception of olmesartan)

RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective

When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) Hepatitis B vaccine is usually given as a 3- or 4-dose series, but higher dosages may be required for immunocompromised persons and those with end-stage renal disease. These persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg level <10 mIU/mL) should be revaccinated

For adults starting tenofovir disproxil fumarate with a baseline eGFR <90 mL/min, who are on other nephrotoxic medications, or who have hypertension or diabetes, guidelines recommend that physicians check a baseline blood pressure, serum creatinine, and urine protein Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients)

Cytarabine - An initial dose 100 mg/m2/day for 7 to 10 days, or 200 mg/m2/day for 5 to 10 days followed by 20 mg/m2/day for 5 to 10 days.; CrCl 90-60ml/min 2 to 3 g/m2 every 12 h; CrCl 60-30ml/min 1 to 2 g/m2 every 12 h; CrCl 30-15ml/min 1 g/m2 every 12 to 24 h; CrCl <15ml/min +/or haemodialysis 1 g/m2 every 24 h Etoposide (oral) - CrCl 90-60ml/min 80 to 300 mg/m2/day for 3 to 5 days, followed by 50 to 100 mg/m2/day; CrCl 60-15ml/min 60 to 225 mg/m2/day for 3 to 5 days, followed by 37.5 to 75 mg/m2/day; CrCl <15ml/min +/or haemodialysis 40 to 150 mg/m2/day for 3 to 5 days, followed by 25 to 50 mg/m2/day

Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg.

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. Valproate - ascertain haematological and hepatic history and measre serum valproate levels at start of treatment; 3 monthly weight; 6 monthly FBC, LFTs, and serum valproate levels; measure blood pressure, lipid profile and fasting glucose in patients with risk factors, monitor for menstrual irregularities

Gabapentin - Can cause altered mental status, myoclonus and asterixis with severe CKD/ESRD. GFR 30-59 mL/min: 200-700 mg twice daily, GFR 15-29 mL/min: 200-700 mg once per day, GFR <15 mL/min: 300 every other day, hemodialysis: 200-300 mg after each dialysis. Extended release: GFR 30-59 mL/min: 600-1,800 mg once per day, GFR < 30 mL/min to ESRD—not recommended

Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); Haemodialysis (Patients on hemodialysis should receive maintenance doses based on estimates of Clcr and supplemental doses after 4 hours of hemodialysis ) - 125, 150, 200, 250, 350 [post dialysis supplemental dose]

Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity.

Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided

In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic; Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher)

RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective

When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy)

Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients) Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg.

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. Gabapentin - Can cause altered mental status, myoclonus and asterixis with severe CKD/ESRD. GFR 30-59 mL/min: 200-700 mg twice daily, GFR 15-29 mL/min: 200-700 mg once per day, GFR <15 mL/min: 300 every other day, hemodialysis: 200-300 mg after each dialysis. Extended release: GFR 30-59 mL/min: 600-1,800 mg once per day, GFR < 30 mL/min to ESRD—not recommended

Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided

Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy)

Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg.

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys.

Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy)

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous)

Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy)

Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

ATC code PSI A10A Insulin - All labels state that insulin doses should be adjusted on an individual basis (usually in the context of more intensive monitoring) in patients with renal impairment. A10A Insulin - Partly renally excreted; may need reduced dose when GFR is < 30 mL/min/1.73 m2 A10 Guidelines for patients with diabetic nephropathy: Start treatment in patients with sustained urinary albumin excretion of >30 mg/day. In patients with overt proteinuria treatment goal is <0.5 g/day A10BX Nateglinide - CKD 3-4 no dose adjustment necessary; CKD-5 therapy should be started at the lowest dose possible (60 mg/ day). To be avoided in dialysis patients A10BX Nateglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 60 mg with meals if eGFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed A10BX Repaglinide - careful dose titration recommended in advanced stages of CKD A10BX Repaglinide - CKD 3-4 no dose adjustment necessary; CKD-5 to be avoided A10BX Repaglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 0.5 mg with meals if GFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed A10BX Repaglinide - Needs no initial dose adjustment in renal impairment (Canada). Caution advised when titrating doses in renal impairment (EU, Canada). In severe renal impairment, initiate at a dose of 0.5 mg/day and subsequently, carefully titrate doses (US) A10BA Avoidance of metformin in renal impairment (SCr ≥1.5 mg/dL male and SCr ≥1.4 mg/dL female patients) A10BA Medications to use with extreme caution in elderly patients with kdiney disease: Metformin - Risk of lactic acidosis if eGFR <30 mL/min A10BA Metformin - Avoid when GFR is <30 mL/min/1.73 m2, but consider risk-benefit if GFR is stable. Review use when GFR is <45 mL/min/1.73 m2 Hold during acute illness or prior to intravenous radiocontrast A10BA Metformin - Contraindicated if CrCl <60 mL/min (EU, Canada) or abnormal CrCl (US) A10BA Metformin - CrCl 60-90ml/min 2000mg daily; CrCl 30-60ml/min 1000mg daily; CrCl <30ml/min avoid use A10BA Metformin - In CKD-3 the dosage should not exceed 1.5 g/day with eGFR > 45 mL/min and 850 mg/day with eGFR 30–45 mL/min.; In CKD-4: maximum 500 mg daily but the drug should be temporarily withheld in periods of unstable GFR; In CKD-5 Consider carefully especially in the presence of acidosis, hypoxia, dehydration A10BA Metformin - not recommended in patients with eGFR <45 and contraindicated in patients with eGFR <30 A10BA Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity. A10BA Regular monitoring of renal function is necessary (when taking metformin) A10BA Renal failure or renal dysfuntion (creatinine clearance < 60ml/ min) is considered a contraindication (to metformin) A10BB Drugs that need special attention in chronic kidney disease: Sulfonylureas A10BB Sulfonylureas - Avoid mainly renally excreted agents (eg, glyburide) Agents mainly metabolized by the liver may need reduced dose when GFR is < 30 mL/min/1.73 m2 A10BB Sulfoylureas - Avoid usage as much as possible. Consider a DPP-4 inhibitor as an alternative drug. A10BB Acetohexamide - CKD 3-5 contraindicated A10BB Chlorpropamide - CKD-3: 100 to 125 mg daily; CKD-4 avoid; CKD-5 contraindicated A10BB Glibenclamide - Clcr < 50 mL/min: not recommended A10BD Glibenclamide/metformin - Use is contraindicated in patients with serum creatinine ≥1.5 mg/dL in males, or ≥1.4 mg/dL in females or abnormal creatinine clearance A10BB Gliclazide - CKD 3-5 started at low doses and the dose titrated up every 1–4weeks A10BB Gliclazide - contraindicated in cases of severe renal insufficiency A10BB Gliclazide - NKF-KDOQI guidelines: no dose adjustments required if CKD stages 3, 4, and 5. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; consider alternative agent if eGFR<15 mL/ min/ A10BB Glimepiride - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated A10BB Glimepiride - NKF-KDOQI guidelines: start treatment conservatively with 1 mg daily. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; maximum dose 1 mg, consider alternative agent if eGFR <15 mL/min. A10BB Glimepiride - should be used with caution if eGFR <60 A10BB Medications requiring dose adjustments at variable GFR thresholds: Glimepiride A10BB Glimipramide - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated A10BB Glipizide - in renal impairment conservative dosing recommended to avoid hypoglycaemia A10BB Glyburide - Combined ADA/EASD 2012 position statement: totally avoid if any renal impairment. NKF-KDOQI guidelines: totally avoid if CKD stages 3, 4, and 5. CDA guidelines: use alternative agent if eGFR <60 mL/ min A10BB Glyburide - not recommended in CrCl <50ml/min A10BB Tolazamide - CKD 3-5 contraindicated A10BB Tolbutammide - CKD 3-4 Preferably dose titration to 250 mg one to three times/ day (especially in elderly patients); CKD-5 contraindicated A10BK SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) - reduced efficacy and increased toxicity in patients with moderate or severe renal impairment and contraindicated in those with eGFR <45 A10BK Canagliflozin - 2013 AACE/ACE guidelines: not to be used if eGFR <45 mL/min/1.73 m2 A10BK Canagliflozin - Careful monitoring in patients with GFR < 60 mL/ min; CKD-5 to be avoided A10BK Canagliflozin - for eGFR 45-60ml/min give 100mg once daily A10BK Canagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/1.73 m2) (US, EU, Canada). Not recommended if CrCl or eGFR <60 mL/min/1.73 m2 (EU, Canada), or eGFR <45 mL/min/1.73 m2 (US), or contraindicated if eGFR <45 mL/min/1.73 m2 (Canada). A10BK Dapagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/ 1.73 m2) (US, EU). Not recommended (US, EU) or contraindicated (Canada) if CrCl or eGFR <60 mL/min/1.73 m. Contraindicated in severe renal impairment (US, Canada). A10BK Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2 A10BH DPP-4 inhibitors (alogliptin, saxagliptin, sitagliptin) - require dose adjustments in with patients with moderate or severe CKD A10BH Medicines that may accumulate and require renal function monitoring: Gliptins A10BH Alogliptin - 2013 AACE/ACE guidelines: decrease dose based on GFR: ≽30–\60 mL/min (12.5 mg daily); <30 mL/min (6.25 mg daily). Not in combined ADA/EASD 2012 position statement. Not in NKF-KDOQI guidelines. A10BH Alogliptin - eGFR ≽50 use at full dose (25mg/day); eGFR <50 reduce dose (12.5mg/day); eGFR <30 6.25mg/day; patients with ESRD and haemodialysis use with caution (6.25mg/day) A10BH Saxagliptin - can be used in full dose (2.5mg QDS or 5mg QDS) in mild renal insufficiency; reduce dose to 2.5mg QDS in moderatre-severe renal sufficiency and in those receiving haemodialysis A10BH Saxagliptin - CKD 3-5 halve dose to 2.5mg once daily; administer after HD session. A10BH Saxagliptin - eGFR ≽50 use at full dose (5mg/day); eGFR <50 half dose (2.5mg/day); eGFR <30 use with caution; patients with ESRD and haemodialysis do not use A10BH Sitagliptin - CKD-3 50mg; CKD-4 25mg; CKD-5 reduce dose to 25mg and administer irrespective of HD timing A10BH Sitagliptin - eGFR ≽50 use at full dose(100mg/day); eGFR 30-50 half dose (50mg/day); eGFR <30 quarter dose (25mg/day); patients with ESRD and haemodialysis use with caution (25mg/day) A10BH Vildagliptin - eGFR ≽50 use at full dose (2x50mg/day); eGFR <50 half dose (1x50mg/day); patients with ESRD and haemodialysis use with caution (1x50mg/day) A10BH Gemigliptin - use without dose adjustment (50mg/day); patients with ESRD and haemodialysis can possibily use but no data A10BH Linagliptin - use without dose adjustment (5mg/day); patients with ESRD and haemodialysis can possibily use but no data A10BJ Albiglutide - No dose adjustment in mild (eGFR 60–89 mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment (US, EU). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m2) or in dialysis due to limited data (EU). No dose adjustment in severe renal impairment (eGFR 15 to <30 mL/min/ 1.73 m2) (US). A10BJ Contraindicated medications at variable GFR thresholds: Exenatide A10BJ Drugs requiring dosing adjustments in impaired renal function: Exenatide A10BJ Exenatide - Combined ADA/EASD 2012 position statement: contraindicated if GFR <30 mL/min. NKF-KDOQI guidelines: not recommended if GFR <30 mL/min/1.73 m2. 2015 AACE/ACE guidelines: contraindicated if GFR <30 mL/min. CDA guidelines: reduce dosage if eGFR 30–59 mL/min (5 lg BID); use alternative agent if eGFR <30 mL/min A10BJ Exenatide - eGFR ≽60 use at full dose (2x10mcg/day; eGFR 30-60 use with caution (2x10mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use A10BJ Exenatide - Use with caution in moderate renal impairment (CrCl 30–50 mL/min) (US, EU, Canada). Contraindicated (Canada)/not recommended (US, EU) in severe renal impairment (CrCl <30 mL/min)/ESRD. Use with caution in renal transplantation (US, Canada) A10BJ Contraindicated medications at variable GFR thresholds: Liraglutide A10BJ Liraglutide - Combined ADA/EASD 2012 position statement: safety not established, although drug levels are unaffected by CKD as not renally cleared. NKF-KDOQI guidelines: not recommended if GFR <60 mL/min/1.73 m2. 2013 AACE/ACE guidelines: no restrictions on use. CDA guidelines: use alternative agent if eGFR <50 mL/ min. A10BJ Liraglutide - eGFR ≽50 use at full dose (1.2-1.8mg/day); eGFR <50 do not use; patients with ESRD and haemodialysis do not use A10BJ Dulaglutide - No dose adjustment required in mild to moderate renal impairment (US, EU). Not recommended in severe CKD (eGFR <30 mL/min/1.73 m2) due to limited clinical data (EU) A10BJ Lixisenatide - eGFR ≽50 use at full dose (1x20mcg/day); eGFR 30-50 use with caution (1x20mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use A10BJ Lixisenatide - No dose adjustment in patients with GFR 50–80 mL/min. Careful use in patients with GFR 50–15 mL/min. A10BG TZDs (pioglitazone and rosiglitazone) - often avoided in non-dialysis pateints with T2Dm and CKD due to risk of fluid retention, heart failure and increased bone fracture risk A10BG Pioglitazone - Combined ADA/EASD 2012 position statement: no restrictions for use in CKD; be aware of risk of fluid retention. NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed. A10BF Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Alpha glucosidase inhibitors A10BF Acarbose - Contraindicated (EU) or not recommended (Canada) if CrCl<25 mL/ min, and not recommended if serum creatinine >2 mg/dL (US) due to lack of information A10BF Acarbose - No evidence of dose adjustment required for GFR values higher than 25 mL/min; CKD-5 to be avoided A10BF Miglitol - Needs no dosage adjustment if CrCl >25 mL/min (EU). Contraindicated if CrCl <25 mL/min (EU). Not recommended if serum creatinine>2 mg/dL due to lack of information (US). A10BG Rosiglitazone - Needs no dose adjustment in renal impairment (US, Canada). Caution recommended if CrCl <30 mL/min, due to limited data (Canada). A10BG Rosiglitazone - NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed A02A Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiacids and other dtrugs for acid related disorders A02BA Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: H2 receptor antagonists A02BA H-2 blockers in renal dysfunction; ≤1200 mg/d cimetidine, 20 mg/d famotidine, 150 mg/d nizatidine, 150 mg/d ranitidine if CrClf <50 mL/min A02BA Cimetidine if CrCl <50 - mental status change - reduce dose A02BA Ranitidine if CrCl <50 - mental status change - reduce dose A02BA Medications requiring dose adjustments at variable GFR thresholds: Famotidine A02BA Niatidine if CrCl <50 - mental status change - reduce dose A02BX Medications to use with extreme caution in elderly patients with kdiney disease: PPIs - Increased risk of fractures, infections, and cognitive decline; hypomagnesemia A03F Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Propulsives A03F Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Metoclopramide A03F Metoclopramide - GFR 10-29 reduce dose 50% A06AD Oral sodium phosphate containing bowel preparations - Can cause acute kidney injury by phosphate crystal deposition and volume depletion Risk factors are CKD, > 60 years of age, female gender, HTN, diabetes, CHF, volume depletion, active colitis, and medications that may predispose to AKI (RAAS blockers, diuretics, lithium, and NSAIDs) A06AD Sodium Phosphate should not be used as bowel preparation in patients with CKD, heart failure, cirrhosis or hypertension A07E Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Intestinal anti-inflammatory agents A11CC Calcitriol/VDRA (and calcimimetics) can be used to lower PTH in patients with CKD stage 5D where PTH is elevated or rising A11CC Calcitriol/VDRA should be reduced or stopped if (i) PTH levels fall below two times the upper limit of normal in CKD stage 5D (2C), and/or (ii) patients develop hypercalcaemia A11CC In patients with CKD stage 3–5 not on dialysis, where serum PTH is rising and remains persistently elevated despite the correction of modifiable factors, treatment with calcitriol or VDRA should be used A11CC In patients with CKD stage 5D, PTH levels should be maintained in the range of two to nine times the upper normal limit of the assay A11CC Initial drug selection for the treatment of elevated PTH should be based on serum calcium and phosphate levels and other aspects of CKD-MBD A11CA Medications to use with extreme caution in elderly patients with kdiney disease: Vitamin A - Increased serum levels of RBP4 and apoRBP4 A11G Medications to use with extreme caution in elderly patients with kdiney disease: Vitamin C - Organ accumulation of insoluble oxalate A11CC The percentage of patients ≽18 years with CKD 3-5 and elevated calcium levels who are prescribed active vitamin D A16AX Drugs requiring dosing adjustments in impaired renal function: Miglustat Insulin - All labels state that insulin doses should be adjusted on an individual basis (usually in the context of more intensive monitoring) in patients with renal impairment. Insulin - Partly renally excreted; may need reduced dose when GFR is < 30 mL/min/1.73 m2 Guidelines for patients with diabetic nephropathy: Start treatment in patients with sustained urinary albumin excretion of >30 mg/day. In patients with overt proteinuria treatment goal is <0.5 g/day Nateglinide - CKD 3-4 no dose adjustment necessary; CKD-5 therapy should be started at the lowest dose possible (60 mg/ day). To be avoided in dialysis patients Nateglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 60 mg with meals if eGFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed

Repaglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 0.5 mg with meals if GFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed Repaglinide - Needs no initial dose adjustment in renal impairment (Canada). Caution advised when titrating doses in renal impairment (EU, Canada). In severe renal impairment, initiate at a dose of 0.5 mg/day and subsequently, carefully titrate doses (US) Avoidance of metformin in renal impairment (SCr ≥1.5 mg/dL male and SCr ≥1.4 mg/dL female patients) Medications to use with extreme caution in elderly patients with kdiney disease: Metformin - Risk of lactic acidosis if eGFR <30 mL/min Metformin - Avoid when GFR is <30 mL/min/1.73 m2, but consider risk-benefit if GFR is stable. Review use when GFR is <45 mL/min/1.73 m2 Hold during acute illness or prior to intravenous radiocontrast Metformin - Contraindicated if CrCl <60 mL/min (EU, Canada) or abnormal CrCl (US) Metformin - CrCl 60-90ml/min 2000mg daily; CrCl 30-60ml/min 1000mg daily; CrCl <30ml/min avoid use Metformin - In CKD-3 the dosage should not exceed 1.5 g/day with eGFR > 45 mL/min and 850 mg/day with eGFR 30–45 mL/min.; In CKD-4: maximum 500 mg daily but the drug should be temporarily withheld in periods of unstable GFR; In CKD-5 Consider carefully especially in the presence of acidosis, hypoxia, dehydration Metformin - not recommended in patients with eGFR <45 and contraindicated in patients with eGFR <30 Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity.

Renal failure or renal dysfuntion (creatinine clearance < 60ml/ min) is considered a contraindication (to metformin)

Sulfonylureas - Avoid mainly renally excreted agents (eg, glyburide) Agents mainly metabolized by the liver may need reduced dose when GFR is < 30 mL/min/1.73 m2 Sulfoylureas - Avoid usage as much as possible. Consider a DPP-4 inhibitor as an alternative drug.

Chlorpropamide - CKD-3: 100 to 125 mg daily; CKD-4 avoid; CKD-5 contraindicated

Glibenclamide/metformin - Use is contraindicated in patients with serum creatinine ≥1.5 mg/dL in males, or ≥1.4 mg/dL in females or abnormal creatinine clearance Gliclazide - CKD 3-5 started at low doses and the dose titrated up every 1–4weeks

Gliclazide - NKF-KDOQI guidelines: no dose adjustments required if CKD stages 3, 4, and 5. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; consider alternative agent if eGFR<15 mL/ min/ Glimepiride - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated Glimepiride - NKF-KDOQI guidelines: start treatment conservatively with 1 mg daily. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; maximum dose 1 mg, consider alternative agent if eGFR <15 mL/min.

Medications requiring dose adjustments at variable GFR thresholds: Glimepiride Glimipramide - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated Glipizide - in renal impairment conservative dosing recommended to avoid hypoglycaemia Glyburide - Combined ADA/EASD 2012 position statement: totally avoid if any renal impairment. NKF-KDOQI guidelines: totally avoid if CKD stages 3, 4, and 5. CDA guidelines: use alternative agent if eGFR <60 mL/ min

Tolbutammide - CKD 3-4 Preferably dose titration to 250 mg one to three times/ day (especially in elderly patients); CKD-5 contraindicated SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) - reduced efficacy and increased toxicity in patients with moderate or severe renal impairment and contraindicated in those with eGFR <45 Canagliflozin - 2013 AACE/ACE guidelines: not to be used if eGFR <45 mL/min/1.73 m2 Canagliflozin - Careful monitoring in patients with GFR < 60 mL/ min; CKD-5 to be avoided

Canagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/1.73 m2) (US, EU, Canada). Not recommended if CrCl or eGFR <60 mL/min/1.73 m2 (EU, Canada), or eGFR <45 mL/min/1.73 m2 (US), or contraindicated if eGFR <45 mL/min/1.73 m2 (Canada). Dapagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/ 1.73 m2) (US, EU). Not recommended (US, EU) or contraindicated (Canada) if CrCl or eGFR <60 mL/min/1.73 m. Contraindicated in severe renal impairment (US, Canada). Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2 DPP-4 inhibitors (alogliptin, saxagliptin, sitagliptin) - require dose adjustments in with patients with moderate or severe CKD Medicines that may accumulate and require renal function monitoring: Gliptins Alogliptin - 2013 AACE/ACE guidelines: decrease dose based on GFR: ≽30–\60 mL/min (12.5 mg daily); <30 mL/min (6.25 mg daily). Not in combined ADA/EASD 2012 position statement. Not in NKF-KDOQI guidelines. Alogliptin - eGFR ≽50 use at full dose (25mg/day); eGFR <50 reduce dose (12.5mg/day); eGFR <30 6.25mg/day; patients with ESRD and haemodialysis use with caution (6.25mg/day) Saxagliptin - can be used in full dose (2.5mg QDS or 5mg QDS) in mild renal insufficiency; reduce dose to 2.5mg QDS in moderatre-severe renal sufficiency and in those receiving haemodialysis Saxagliptin - CKD 3-5 halve dose to 2.5mg once daily; administer after HD session. Saxagliptin - eGFR ≽50 use at full dose (5mg/day); eGFR <50 half dose (2.5mg/day); eGFR <30 use with caution; patients with ESRD and haemodialysis do not use Sitagliptin - CKD-3 50mg; CKD-4 25mg; CKD-5 reduce dose to 25mg and administer irrespective of HD timing Sitagliptin - eGFR ≽50 use at full dose(100mg/day); eGFR 30-50 half dose (50mg/day); eGFR <30 quarter dose (25mg/day); patients with ESRD and haemodialysis use with caution (25mg/day) Vildagliptin - eGFR ≽50 use at full dose (2x50mg/day); eGFR <50 half dose (1x50mg/day); patients with ESRD and haemodialysis use with caution (1x50mg/day) Gemigliptin - use without dose adjustment (50mg/day); patients with ESRD and haemodialysis can possibily use but no data Linagliptin - use without dose adjustment (5mg/day); patients with ESRD and haemodialysis can possibily use but no data Albiglutide - No dose adjustment in mild (eGFR 60–89 mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment (US, EU). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m2) or in dialysis due to limited data (EU). No dose adjustment in severe renal impairment (eGFR 15 to <30 mL/min/ 1.73 m2) (US).

Exenatide - Combined ADA/EASD 2012 position statement: contraindicated if GFR <30 mL/min. NKF-KDOQI guidelines: not recommended if GFR <30 mL/min/1.73 m2. 2015 AACE/ACE guidelines: contraindicated if GFR <30 mL/min. CDA guidelines: reduce dosage if eGFR 30–59 mL/min (5 lg BID); use alternative agent if eGFR <30 mL/min Exenatide - eGFR ≽60 use at full dose (2x10mcg/day; eGFR 30-60 use with caution (2x10mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use Exenatide - Use with caution in moderate renal impairment (CrCl 30–50 mL/min) (US, EU, Canada). Contraindicated (Canada)/not recommended (US, EU) in severe renal impairment (CrCl <30 mL/min)/ESRD. Use with caution in renal transplantation (US, Canada)

Liraglutide - Combined ADA/EASD 2012 position statement: safety not established, although drug levels are unaffected by CKD as not renally cleared. NKF-KDOQI guidelines: not recommended if GFR <60 mL/min/1.73 m2. 2013 AACE/ACE guidelines: no restrictions on use. CDA guidelines: use alternative agent if eGFR <50 mL/ min. Liraglutide - eGFR ≽50 use at full dose (1.2-1.8mg/day); eGFR <50 do not use; patients with ESRD and haemodialysis do not use Dulaglutide - No dose adjustment required in mild to moderate renal impairment (US, EU). Not recommended in severe CKD (eGFR <30 mL/min/1.73 m2) due to limited clinical data (EU) Lixisenatide - eGFR ≽50 use at full dose (1x20mcg/day); eGFR 30-50 use with caution (1x20mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use Lixisenatide - No dose adjustment in patients with GFR 50–80 mL/min. Careful use in patients with GFR 50–15 mL/min. TZDs (pioglitazone and rosiglitazone) - often avoided in non-dialysis pateints with T2Dm and CKD due to risk of fluid retention, heart failure and increased bone fracture risk Pioglitazone - Combined ADA/EASD 2012 position statement: no restrictions for use in CKD; be aware of risk of fluid retention. NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed. Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Alpha glucosidase inhibitors Acarbose - Contraindicated (EU) or not recommended (Canada) if CrCl<25 mL/ min, and not recommended if serum creatinine >2 mg/dL (US) due to lack of information Acarbose - No evidence of dose adjustment required for GFR values higher than 25 mL/min; CKD-5 to be avoided Miglitol - Needs no dosage adjustment if CrCl >25 mL/min (EU). Contraindicated if CrCl <25 mL/min (EU). Not recommended if serum creatinine>2 mg/dL due to lack of information (US). Rosiglitazone - Needs no dose adjustment in renal impairment (US, Canada). Caution recommended if CrCl <30 mL/min, due to limited data (Canada). Rosiglitazone - NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiacids and other dtrugs for acid related disorders Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: H2 receptor antagonists H-2 blockers in renal dysfunction; ≤1200 mg/d cimetidine, 20 mg/d famotidine, 150 mg/d nizatidine, 150 mg/d ranitidine if CrClf <50 mL/min

Medications requiring dose adjustments at variable GFR thresholds: Famotidine

Medications to use with extreme caution in elderly patients with kdiney disease: PPIs - Increased risk of fractures, infections, and cognitive decline; hypomagnesemia Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Propulsives Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Metoclopramide

Oral sodium phosphate containing bowel preparations - Can cause acute kidney injury by phosphate crystal deposition and volume depletion Risk factors are CKD, > 60 years of age, female gender, HTN, diabetes, CHF, volume depletion, active colitis, and medications that may predispose to AKI (RAAS blockers, diuretics, lithium, and NSAIDs) Sodium Phosphate should not be used as bowel preparation in patients with CKD, heart failure, cirrhosis or hypertension Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Intestinal anti-inflammatory agents Calcitriol/VDRA (and calcimimetics) can be used to lower PTH in patients with CKD stage 5D where PTH is elevated or rising Calcitriol/VDRA should be reduced or stopped if (i) PTH levels fall below two times the upper limit of normal in CKD stage 5D (2C), and/or (ii) patients develop hypercalcaemia In patients with CKD stage 3–5 not on dialysis, where serum PTH is rising and remains persistently elevated despite the correction of modifiable factors, treatment with calcitriol or VDRA should be used In patients with CKD stage 5D, PTH levels should be maintained in the range of two to nine times the upper normal limit of the assay Initial drug selection for the treatment of elevated PTH should be based on serum calcium and phosphate levels and other aspects of CKD-MBD Medications to use with extreme caution in elderly patients with kdiney disease: Vitamin A - Increased serum levels of RBP4 and apoRBP4 Medications to use with extreme caution in elderly patients with kdiney disease: Vitamin C - Organ accumulation of insoluble oxalate The percentage of patients ≽18 years with CKD 3-5 and elevated calcium levels who are prescribed active vitamin D Guidelines for patients with diabetic nephropathy: Start treatment in patients with sustained urinary albumin excretion of >30 mg/day. In patients with overt proteinuria treatment goal is <0.5 g/day

Nateglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 60 mg with meals if eGFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed

Repaglinide - Combined ADA/EASD 2012 position statement: no specific recommendations. NKF-KDOQI guidelines: start treatment conservatively with 0.5 mg with meals if GFR <30 mL/min/1.73 m2. CDA guidelines: no dose adjustment needed Repaglinide - Needs no initial dose adjustment in renal impairment (Canada). Caution advised when titrating doses in renal impairment (EU, Canada). In severe renal impairment, initiate at a dose of 0.5 mg/day and subsequently, carefully titrate doses (US)

Metformin - Avoid when GFR is <30 mL/min/1.73 m2, but consider risk-benefit if GFR is stable. Review use when GFR is <45 mL/min/1.73 m2 Hold during acute illness or prior to intravenous radiocontrast

Metformin - In CKD-3 the dosage should not exceed 1.5 g/day with eGFR > 45 mL/min and 850 mg/day with eGFR 30–45 mL/min.; In CKD-4: maximum 500 mg daily but the drug should be temporarily withheld in periods of unstable GFR; In CKD-5 Consider carefully especially in the presence of acidosis, hypoxia, dehydration

Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity.

Gliclazide - NKF-KDOQI guidelines: no dose adjustments required if CKD stages 3, 4, and 5. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; consider alternative agent if eGFR<15 mL/ min/ Glimepiride - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated Glimepiride - NKF-KDOQI guidelines: start treatment conservatively with 1 mg daily. CDA guidelines: consider dosage reduction if eGFR 15–29 mL/min; maximum dose 1 mg, consider alternative agent if eGFR <15 mL/min.

Glimipramide - Canadian labelling: mild-to-moderate impairment: initial: 1 mg once daily; titrate carefully based on fasting blood glucose levels, severe impairment: use is contraindicated

Glyburide - Combined ADA/EASD 2012 position statement: totally avoid if any renal impairment. NKF-KDOQI guidelines: totally avoid if CKD stages 3, 4, and 5. CDA guidelines: use alternative agent if eGFR <60 mL/ min

SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) - reduced efficacy and increased toxicity in patients with moderate or severe renal impairment and contraindicated in those with eGFR <45

Canagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/1.73 m2) (US, EU, Canada). Not recommended if CrCl or eGFR <60 mL/min/1.73 m2 (EU, Canada), or eGFR <45 mL/min/1.73 m2 (US), or contraindicated if eGFR <45 mL/min/1.73 m2 (Canada). Dapagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/ 1.73 m2) (US, EU). Not recommended (US, EU) or contraindicated (Canada) if CrCl or eGFR <60 mL/min/1.73 m. Contraindicated in severe renal impairment (US, Canada). Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2 Alogliptin - 2013 AACE/ACE guidelines: decrease dose based on GFR: ≽30–\60 mL/min (12.5 mg daily); <30 mL/min (6.25 mg daily). Not in combined ADA/EASD 2012 position statement. Not in NKF-KDOQI guidelines. Alogliptin - eGFR ≽50 use at full dose (25mg/day); eGFR <50 reduce dose (12.5mg/day); eGFR <30 6.25mg/day; patients with ESRD and haemodialysis use with caution (6.25mg/day) Saxagliptin - can be used in full dose (2.5mg QDS or 5mg QDS) in mild renal insufficiency; reduce dose to 2.5mg QDS in moderatre-severe renal sufficiency and in those receiving haemodialysis

Sitagliptin - eGFR ≽50 use at full dose(100mg/day); eGFR 30-50 half dose (50mg/day); eGFR <30 quarter dose (25mg/day); patients with ESRD and haemodialysis use with caution (25mg/day)

Albiglutide - No dose adjustment in mild (eGFR 60–89 mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment (US, EU). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m2) or in dialysis due to limited data (EU). No dose adjustment in severe renal impairment (eGFR 15 to <30 mL/min/ 1.73 m2) (US).

Exenatide - Combined ADA/EASD 2012 position statement: contraindicated if GFR <30 mL/min. NKF-KDOQI guidelines: not recommended if GFR <30 mL/min/1.73 m2. 2015 AACE/ACE guidelines: contraindicated if GFR <30 mL/min. CDA guidelines: reduce dosage if eGFR 30–59 mL/min (5 lg BID); use alternative agent if eGFR <30 mL/min

Exenatide - Use with caution in moderate renal impairment (CrCl 30–50 mL/min) (US, EU, Canada). Contraindicated (Canada)/not recommended (US, EU) in severe renal impairment (CrCl <30 mL/min)/ESRD. Use with caution in renal transplantation (US, Canada)

Liraglutide - Combined ADA/EASD 2012 position statement: safety not established, although drug levels are unaffected by CKD as not renally cleared. NKF-KDOQI guidelines: not recommended if GFR <60 mL/min/1.73 m2. 2013 AACE/ACE guidelines: no restrictions on use. CDA guidelines: use alternative agent if eGFR <50 mL/ min.

Dulaglutide - No dose adjustment required in mild to moderate renal impairment (US, EU). Not recommended in severe CKD (eGFR <30 mL/min/1.73 m2) due to limited clinical data (EU) Lixisenatide - eGFR ≽50 use at full dose (1x20mcg/day); eGFR 30-50 use with caution (1x20mcg/day); eGFR <30 do not use; patients with ESRD and haemodialysis do not use

Pioglitazone - Combined ADA/EASD 2012 position statement: no restrictions for use in CKD; be aware of risk of fluid retention. NKF-KDOQI guidelines: no restrictions for use in CKD; be aware of risk of fluid retention. CDA guidelines: no dose adjustment needed.

Miglitol - Needs no dosage adjustment if CrCl >25 mL/min (EU). Contraindicated if CrCl <25 mL/min (EU). Not recommended if serum creatinine>2 mg/dL due to lack of information (US).

Oral sodium phosphate containing bowel preparations - Can cause acute kidney injury by phosphate crystal deposition and volume depletion Risk factors are CKD, > 60 years of age, female gender, HTN, diabetes, CHF, volume depletion, active colitis, and medications that may predispose to AKI (RAAS blockers, diuretics, lithium, and NSAIDs)

Calcitriol/VDRA should be reduced or stopped if (i) PTH levels fall below two times the upper limit of normal in CKD stage 5D (2C), and/or (ii) patients develop hypercalcaemia In patients with CKD stage 3–5 not on dialysis, where serum PTH is rising and remains persistently elevated despite the correction of modifiable factors, treatment with calcitriol or VDRA should be used

Metformin - In CKD-3 the dosage should not exceed 1.5 g/day with eGFR > 45 mL/min and 850 mg/day with eGFR 30–45 mL/min.; In CKD-4: maximum 500 mg daily but the drug should be temporarily withheld in periods of unstable GFR; In CKD-5 Consider carefully especially in the presence of acidosis, hypoxia, dehydration

Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity.

Canagliflozin - Needs no dose adjustment in mild renal impairment (eGFR ≽60 mL/min/1.73 m2) (US, EU, Canada). Not recommended if CrCl or eGFR <60 mL/min/1.73 m2 (EU, Canada), or eGFR <45 mL/min/1.73 m2 (US), or contraindicated if eGFR <45 mL/min/1.73 m2 (Canada).

Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2 Albiglutide - No dose adjustment in mild (eGFR 60–89 mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment (US, EU). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m2) or in dialysis due to limited data (EU). No dose adjustment in severe renal impairment (eGFR 15 to <30 mL/min/ 1.73 m2) (US).

Exenatide - Combined ADA/EASD 2012 position statement: contraindicated if GFR <30 mL/min. NKF-KDOQI guidelines: not recommended if GFR <30 mL/min/1.73 m2. 2015 AACE/ACE guidelines: contraindicated if GFR <30 mL/min. CDA guidelines: reduce dosage if eGFR 30–59 mL/min (5 lg BID); use alternative agent if eGFR <30 mL/min

Liraglutide - Combined ADA/EASD 2012 position statement: safety not established, although drug levels are unaffected by CKD as not renally cleared. NKF-KDOQI guidelines: not recommended if GFR <60 mL/min/1.73 m2. 2013 AACE/ACE guidelines: no restrictions on use. CDA guidelines: use alternative agent if eGFR <50 mL/ min.

Oral sodium phosphate containing bowel preparations - Can cause acute kidney injury by phosphate crystal deposition and volume depletion Risk factors are CKD, > 60 years of age, female gender, HTN, diabetes, CHF, volume depletion, active colitis, and medications that may predispose to AKI (RAAS blockers, diuretics, lithium, and NSAIDs)

Recommendations for adults aged 65 and over with T2DM: It is suggested to discontinue metformin for the management of type 2 diabetes mellitus in patients with 2 or more of the following risk factors: age > 80; gastrointestinal complaints during the last year; GFR ≤60 ml/min., the benefit of metformin in this patient is uncertain and it is possibly outweighed by the risk of adverse drug reactions, depending on their severity.

Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2

Empagliflozin - Initiate with 10 mg (US, EU); if more glycemic control needed (US) and CrCl or eGFR ≽60 mL/min/1.73 m2 (EU), increase dose to 25 mg. Monitor renal function during therapy (US, EU). Adjust or maintain dose at 10 mg if CrCl or eGFR falls <60 mL/min/1.73 m2 (EU); discontinue if CrCl or eGFR <45 mL/min (EU, US). Contraindicated if eGFR <45 mL/min/1.73 m2 (US) and should not be initiated (EU) or more frequent renal function monitoring recommended (US) if CrCl or eGFR <60 mL/min/1.73 m2

ATC code PSI B01A Drugs that need special attention in chronic kidney disease: Anticoagulants B01A Evaluate renal function prior to initiation of direct thrombin or factor Xa inhibitors, and reevaluate when clinically indicated and at least annually B01AA Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Vitamin K antagonists and heparin group B02AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Tranexamic acid B01AE Drugs requiring dosing adjustments in impaired renal function: Bivalirudin B01A For patients with CKD and AF the following recommendations apply: If renal function is impaired, the European Heart Rhythm Association’s practical guide recom- mends renal function to be monitored every 6 months for GFR 30–60mL/min and every 3 months for GFR<30mL/min in patients with AF receiving an NOAC B03A Recommendations for treatment of anaemia of CKD: We suggest that Hb concentration should be monitored every 2–4 weeks in the correction phase and every 1– 3 months for stable patients in the maintenance phase. B01AB Therapeutic drug monitoring of antifactor Xa levels in patients with CKD stage 4 or 5 requring full anticoagulation is strongly recommended B01AA Warfarin - Increased risk of bleeding when GFR is < 30 mL/min/1.73 m2 B01AA With CHA2DS2-VASc score ! 2 and end-stage CKD (CrCl < 15 mL/min) or on hemodialysis, it is reasonable to prescribe warfarin for OAC B03A Recommendations for treatment of anaemia of CKD: We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an op- tion, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation. B01A With moderate-to-severe CKD and CHA2DS2-VASc scores ! 2, reduced doses of direct thrombin or factor Xa inhibitors may be considered B01AF Apixaban - 5 mg bid in patients with CrCl ≽30 mL/minute; 2.5 mg bid if CrCl 15–29 mL/minute; 2.5 mg bid in the presence of 2 or more of the following characteristics: • Age $80 years • Body weight #60 kg • Serum creatinine $1.5 mg/dL (133 μmo B01AF Apixaban - Age ≥80 years and body weight ≤60 kg or serum creatinine ≥1.5 mg/dl: reduce dose to 2.5 mg b.i.d B01AF Apixaban - Body weight ≤60 kg and age ≥80 years or serum creatinine ≥1.5 mg/dl: reduce dose to 2.5 mg b.i.d. B01AF Apixaban - CrCl <15ml/min or on dialysis use has not been studied B01AF Apixaban - CrCl 15-29 mL/min 2.5 mgBD; CrCl < 15 ml/min, or dialysis not recommended B01AF Apixaban - CrCl 30-49ml/min 5mg twice daily; CrCl 15-29ml/min 2,5mg twice daily; CrCl <15ml/min contraindicated B01AF Apixaban - not recommended in: Pregnant women; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatment • Severe hepatic impairment B01AF Apixaban if CrCl <25 - increased risk of bleeding - avoid B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - amiodarone - at least 6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - antiplatelets/NSAIDs - at least 6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - carbamazepine/phenytoin/phenobarbital - 3-6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - dronederone - 3-6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - HIV protease inhibitors - 3-6 months (dose adjustment with apixaban) B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - loop diuretics/thizide-like diuretics/ACEI/ARB - 3-6 months B01AF Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - verapamil/quinidine - at least 6 months (dose adjustment with edoxaban) B01AF For patients with CKD and AF the following recommendations apply: Rivaroxaban (20 mg once a day), edoxaban (60 mg once a day) and apixaban (5 mg twice a day) do not require any dose adjustment in patients with a GFR>50mL/min B01AF In patients with CrCl <50ml/min apixaban should be stopped 48 hours before surgery or invasive procedures B01AE Consider dose reduction if: Prescribed dabigatran and eGFR <30 B01AE Dabigatran - 150 mg bid in patients with CrCl ≽30 mL/minute 110 mg bid may be considered in patients with the following factors: • Age ≽80 years (or 75–80 years with high risk of bleeding) • CrCl 30–50 mL/minute with a high risk of bleeding B01AE Dabigatran - age <75 150mg BD; age 75-80 150mg BD (110mg BD should be considered when the risk of stroke is low and bleeding risk is high); age 80 and over 110mg BD B01AE Dabigatran - contraindicated in patients with CrCl <30ml/min B01AE Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment B01AE Dabigatran - CrCl <15ml/min use has not been studied B01AE Dabigatran - CrCl ≥50 mL/min no dose adjustment is necessary; CrCl 30-50 mL/min the recommended dose is 150 mg BD (110 mg BD for patients with high risk of bleeding); CrCl < 30 ml/min contraindicated B01AE Dabigatran - CrCl 15-30ml/min give 75mg BD B01AE Dabigatran - dose adjustments: 10 mg bid in patients 75–80 years with low thromboembolic risk and high risk of bleeding, or 80 years or older with CrCl 30–50 mL/min and high risk of bleeding, or receiving the strong P-gp inhibitor verapamil B01AE Dabigatran - drugs requiring caution during concomitant treatment in patients with renal impairment: Close clinical surveillance is recommended in patients with mild to moderate renal impairment when dabigatran is combined with mild to moderate P-gp inhibitors (eg, amiodarone, quinidine, verapamil, and clarithromycin) B01AE Dabigatran - increased risk of GI bleeding compared with warfarin and oter target specific oral anticoagulants in adults aged 75 and older, lack of evidence of efficacy and safety in individuals with CrCl <30ml/min B01AE Dabigatran - no dose adjustment is necessary according to body weight. However, close clinical follow-up is required for patients with a body weight <50 kg. B01AE Dabigatran - treatment of VTE - Avoid if CrCl <50 mL/min B01AE Dabigatran if CrCl <30 - increased risk of bleeding - avoid B01AE Dabigatran should not be used in patients with a CrCl of <30 mL/min and other NOACs should be used in reduced doses in patients with CrCl 15 – 29 mL/min B01AE Direct thrombin dabigatran and factor Xa inhibitor rivaroxaban are not recommended in patients with AF and end-stage chronic kidney disease (CKD) or on dialysis because of a lack of evidence from clinical trials regarding the balance of risks and benefits B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - amiodarone - 3-6 months B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - dronederone - 3-6 months with dose adjustment based on renal function B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - HIV protease inhibitors - 6 months B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - loop diuretics/thiazide-like diuretics/ACEI/ARB - 3-6 months B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - verapamil/quinidine - 3-6 months with dose adjustment based on renal function B01AE For patients prescribed dabigatran renal function should be monitored at least once a year if their kidney function is mildy to moderately reduced or if they are over 75 years old B01AE For patients with CKD and AF the following recommendations apply: European Medicines Agency - approved a lower dose of dabigatran 75 mg twice daily in patients with a GFR of 15–30mL/min B01AE In patients with CrCl <50ml/min dabigatran should be withdrawn at least 3 days before surgery B01AE Switching from dabigatran to warfarin: if CrCl <15 no recommendations provided B01AE Switching from dabigatran to warfarin: if CrCl >50 start warfarin 3 days before stopping dabigatran B01AE Switching from dabigatran to warfarin: if CrCl 15-30 start warfarin 1 day before stopping dabigatran B01AE Switching from dabigatran to warfarin: if CrCl 31-50 start warfarin 2 days before stopping dabigatran B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - antiplatelets/NSAIDs - at least 6 months B01AE Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - carbamazepine/phenytoin/phenobarbital - 3-6 months B01AF Edoxaban - 30 --> 15mg OD if CrC; 30-50ml/min or weight 60kg or less B01AF Edoxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 60 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg) B01AF Edoxaban - CrCl ≥50 mL/min 60 mg OD; CrCl 15-49 mL/min 30 mg OD; CrCl <15 mL/min not recommended. B01AF Edoxaban if CrCl <30 or >95 - increased risk of bleeding - avoid B01AF Edoxaban if CrCl 30-50 - increased risk of bleeding - reduce dose B01AF If CrCl <15ml/min rivaroxaban is not approved B01AF Medicines that may accumulate and require renal function monitoring: Rivaroxaban B01AF Rivaroxaban - 20 --> 15mg OD if CrCl 30-49ml/min B01AF Rivaroxaban - avoid use to treat/prevent VTE if CrCl <30ml/min B01AF Rivaroxaban - Caution in case of CrCl 15–30 ml/min Dose reduction to 15 mg/ day B01AF Rivaroxaban - CrCl >50 ml/min: 20 mg orally, QD with evening meal B01AF Rivaroxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 20 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg) B01AF Rivaroxaban - CrCl 15–50 ml/min: 15 mg orally, QD with evening meal B01AF Rivaroxaban - drugs requiring caution during concomitant treatment in patients with renal impairment: Moderate or potent inhibitors of CYP3A4 (eg, fluconazole, clarithromycin); Moderate inhibitors of both CYP3A4 and P-gp (eg, erythromycin) B01AF Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided B01AF Rivaroxaban - prevention of VTE - Avoid if CrCl <50 mL/min B01AF Rivaroxaban if CrCl <30 - increased risk of bleeding - avoid B01AF Rivaroxaban if CrCl 30-50 - increased risk of bleeding - reduce dose B01AF Rivaroxaban may be used at a reduced dose of 15mg OD for anti-coagulation management of atrial fibrillation in patients with severe renal impairment (CrCl 15-29 ml/min) B01AC Aspirin - use with caution eGFR <10ml/min B01AC Patients with eGFR <60 should be taking: Aspirin to prevent cardiovascular events B01AX Fondaparinux - GFR 30-49 reduc dse to 1.5mg daily B01AX Fondaparinux if CrCl <30 - increased risk of bleeding - avoid B01AB If CrCl <30ml/min recommend 1 mg/kg/day of enoxaparin for treatment of venous thromboembolism B01AB If CrCl <30ml/min recommend 30 mg of enoxaparin for prophylaxis of venous thromboembolism B01AB Medicines that may accumulate and require renal function monitoring: Enoxaparin B01AB For patients with renal impairment prophylatic dose of LMWH is 20 mg/24 h B01AB For patients with renal impairment treatment dose of LMWH is 1 mg/kg/24 h B01AB Low molecular weight heparins - Reduce dose by 50% when GFR is <30 mL/min/1.73 m2. Consider switch to conventional heparin or monitor plasma antiefactor Xa in those at high risk for bleeding B01A CrCl (ml/min) - preferred oral anticoagulant class <15 - VKA or NOAC (use with caution) B01A CrCl (ml/min) - preferred oral anticoagulant class ≽50 - NOAC B01A CrCl (ml/min) - preferred oral anticoagulant class 15-29 - VKA or NOAC B01A CrCl (ml/min) - preferred oral anticoagulant class 30-49 - NOAC B01A Not using of any one of the three DOACs in patients with a CrCl \30 ml/min is recommended B03XA Recommendations for treatment of anaemia of CKD: We recommend that adjustments to ESA doses should be considered when Hb is <105 or >115 g/L in adults, young people and children aged 2 years and older B03XA Recommendations for treatment of anaemia of CKD: We recommend that blood pressure should be moni- tored in all patients receiving ESAs and, if present, hypertension be treated by volume removal and/or anti- hypertensive drugs B03XA Recommendations for treatment of anaemia of CKD: We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the tar- get Hb level despite SC epoetin dose >300 IU/kg/ week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week B03XA Recommendations for treatment of anaemia of CKD: We suggest exerting extreme caution while prescribing ESA therapy in CKD patients with a history of stroke, or malignancy, particularly in those with active malignancy when cure is the anticipated outcome B03XA Recommendations for treatment of anaemia of CKD: We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension B03XA The percentage of patients ≽18 years with CKD 3-5 and Hb ≽7.5 who are prescribed an ESA B03XA Do not initiate erythropoiesis-stimulating agents in patients with chronic kidney disease (CKD) with hemoglobin levels greater than or equal to 100 g/L without symptoms of anemia B03A Recommendations for treatment of anaemia of CKD: We recommend that serum ferritin should not exceed 800 microgram/L in patients treated with iron, and to achieve this iron management should be reviewed when the ferritin is >500 microgram/L. B01AC Acetylsalicylic acid - increase dosing interval to every six hours if GFR equals 10-50 mL/minute; avoid use if GFR is less than 10 mL/minute B01AC Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Asprin and derivatives B01AC Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Aspirin Evaluate renal function prior to initiation of direct thrombin or factor Xa inhibitors, and reevaluate when clinically indicated and at least annually Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Vitamin K antagonists and heparin group Drugs requiring dosage adjustment or contraindicated in patients with CKD: Tranexamic acid

For patients with CKD and AF the following recommendations apply: If renal function is impaired, the European Heart Rhythm Association’s practical guide recom- mends renal function to be monitored every 6 months for GFR 30–60mL/min and every 3 months for GFR<30mL/min in patients with AF receiving an NOAC Recommendations for treatment of anaemia of CKD: We suggest that Hb concentration should be monitored every 2–4 weeks in the correction phase and every 1– 3 months for stable patients in the maintenance phase. Therapeutic drug monitoring of antifactor Xa levels in patients with CKD stage 4 or 5 requring full anticoagulation is strongly recommended

With CHA2DS2-VASc score ! 2 and end-stage CKD (CrCl < 15 mL/min) or on hemodialysis, it is reasonable to prescribe warfarin for OAC Recommendations for treatment of anaemia of CKD: We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an op- tion, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation. With moderate-to-severe CKD and CHA2DS2-VASc scores ! 2, reduced doses of direct thrombin or factor Xa inhibitors may be considered Apixaban - 5 mg bid in patients with CrCl ≽30 mL/minute; 2.5 mg bid if CrCl 15–29 mL/minute; 2.5 mg bid in the presence of 2 or more of the following characteristics: • Age $80 years • Body weight #60 kg • Serum creatinine $1.5 mg/dL (133 μmo Apixaban - Age ≥80 years and body weight ≤60 kg or serum creatinine ≥1.5 mg/dl: reduce dose to 2.5 mg b.i.d Apixaban - Body weight ≤60 kg and age ≥80 years or serum creatinine ≥1.5 mg/dl: reduce dose to 2.5 mg b.i.d.

Apixaban - CrCl 15-29 mL/min 2.5 mgBD; CrCl < 15 ml/min, or dialysis not recommended Apixaban - CrCl 30-49ml/min 5mg twice daily; CrCl 15-29ml/min 2,5mg twice daily; CrCl <15ml/min contraindicated Apixaban - not recommended in: Pregnant women; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatment • Severe hepatic impairment

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - amiodarone - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - antiplatelets/NSAIDs - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - carbamazepine/phenytoin/phenobarbital - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - dronederone - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - HIV protease inhibitors - 3-6 months (dose adjustment with apixaban) Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - loop diuretics/thizide-like diuretics/ACEI/ARB - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - verapamil/quinidine - at least 6 months (dose adjustment with edoxaban) For patients with CKD and AF the following recommendations apply: Rivaroxaban (20 mg once a day), edoxaban (60 mg once a day) and apixaban (5 mg twice a day) do not require any dose adjustment in patients with a GFR>50mL/min In patients with CrCl <50ml/min apixaban should be stopped 48 hours before surgery or invasive procedures

Dabigatran - 150 mg bid in patients with CrCl ≽30 mL/minute 110 mg bid may be considered in patients with the following factors: • Age ≽80 years (or 75–80 years with high risk of bleeding) • CrCl 30–50 mL/minute with a high risk of bleeding Dabigatran - age <75 150mg BD; age 75-80 150mg BD (110mg BD should be considered when the risk of stroke is low and bleeding risk is high); age 80 and over 110mg BD

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment

Dabigatran - CrCl ≥50 mL/min no dose adjustment is necessary; CrCl 30-50 mL/min the recommended dose is 150 mg BD (110 mg BD for patients with high risk of bleeding); CrCl < 30 ml/min contraindicated

Dabigatran - dose adjustments: 10 mg bid in patients 75–80 years with low thromboembolic risk and high risk of bleeding, or 80 years or older with CrCl 30–50 mL/min and high risk of bleeding, or receiving the strong P-gp inhibitor verapamil Dabigatran - drugs requiring caution during concomitant treatment in patients with renal impairment: Close clinical surveillance is recommended in patients with mild to moderate renal impairment when dabigatran is combined with mild to moderate P-gp inhibitors (eg, amiodarone, quinidine, verapamil, and clarithromycin) Dabigatran - increased risk of GI bleeding compared with warfarin and oter target specific oral anticoagulants in adults aged 75 and older, lack of evidence of efficacy and safety in individuals with CrCl <30ml/min Dabigatran - no dose adjustment is necessary according to body weight. However, close clinical follow-up is required for patients with a body weight <50 kg.

Dabigatran should not be used in patients with a CrCl of <30 mL/min and other NOACs should be used in reduced doses in patients with CrCl 15 – 29 mL/min Direct thrombin dabigatran and factor Xa inhibitor rivaroxaban are not recommended in patients with AF and end-stage chronic kidney disease (CKD) or on dialysis because of a lack of evidence from clinical trials regarding the balance of risks and benefits Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - amiodarone - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - dronederone - 3-6 months with dose adjustment based on renal function Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - HIV protease inhibitors - 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - loop diuretics/thiazide-like diuretics/ACEI/ARB - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - verapamil/quinidine - 3-6 months with dose adjustment based on renal function For patients prescribed dabigatran renal function should be monitored at least once a year if their kidney function is mildy to moderately reduced or if they are over 75 years old For patients with CKD and AF the following recommendations apply: European Medicines Agency - approved a lower dose of dabigatran 75 mg twice daily in patients with a GFR of 15–30mL/min In patients with CrCl <50ml/min dabigatran should be withdrawn at least 3 days before surgery Switching from dabigatran to warfarin: if CrCl <15 no recommendations provided Switching from dabigatran to warfarin: if CrCl >50 start warfarin 3 days before stopping dabigatran Switching from dabigatran to warfarin: if CrCl 15-30 start warfarin 1 day before stopping dabigatran Switching from dabigatran to warfarin: if CrCl 31-50 start warfarin 2 days before stopping dabigatran Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - antiplatelets/NSAIDs - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - carbamazepine/phenytoin/phenobarbital - 3-6 months

Edoxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 60 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg) Edoxaban - CrCl ≥50 mL/min 60 mg OD; CrCl 15-49 mL/min 30 mg OD; CrCl <15 mL/min not recommended.

Medicines that may accumulate and require renal function monitoring: Rivaroxaban

Rivaroxaban - Caution in case of CrCl 15–30 ml/min Dose reduction to 15 mg/ day

Rivaroxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 20 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg)

Rivaroxaban - drugs requiring caution during concomitant treatment in patients with renal impairment: Moderate or potent inhibitors of CYP3A4 (eg, fluconazole, clarithromycin); Moderate inhibitors of both CYP3A4 and P-gp (eg, erythromycin) Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided

Rivaroxaban may be used at a reduced dose of 15mg OD for anti-coagulation management of atrial fibrillation in patients with severe renal impairment (CrCl 15-29 ml/min)

Patients with eGFR <60 should be taking: Aspirin to prevent cardiovascular events

If CrCl <30ml/min recommend 1 mg/kg/day of enoxaparin for treatment of venous thromboembolism If CrCl <30ml/min recommend 30 mg of enoxaparin for prophylaxis of venous thromboembolism Medicines that may accumulate and require renal function monitoring: Enoxaparin

Low molecular weight heparins - Reduce dose by 50% when GFR is <30 mL/min/1.73 m2. Consider switch to conventional heparin or monitor plasma antiefactor Xa in those at high risk for bleeding CrCl (ml/min) - preferred oral anticoagulant class <15 - VKA or NOAC (use with caution)

Not using of any one of the three DOACs in patients with a CrCl \30 ml/min is recommended Recommendations for treatment of anaemia of CKD: We recommend that adjustments to ESA doses should be considered when Hb is <105 or >115 g/L in adults, young people and children aged 2 years and older Recommendations for treatment of anaemia of CKD: We recommend that blood pressure should be moni- tored in all patients receiving ESAs and, if present, hypertension be treated by volume removal and/or anti- hypertensive drugs Recommendations for treatment of anaemia of CKD: We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the tar- get Hb level despite SC epoetin dose >300 IU/kg/ week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week Recommendations for treatment of anaemia of CKD: We suggest exerting extreme caution while prescribing ESA therapy in CKD patients with a history of stroke, or malignancy, particularly in those with active malignancy when cure is the anticipated outcome Recommendations for treatment of anaemia of CKD: We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension The percentage of patients ≽18 years with CKD 3-5 and Hb ≽7.5 who are prescribed an ESA Do not initiate erythropoiesis-stimulating agents in patients with chronic kidney disease (CKD) with hemoglobin levels greater than or equal to 100 g/L without symptoms of anemia Recommendations for treatment of anaemia of CKD: We recommend that serum ferritin should not exceed 800 microgram/L in patients treated with iron, and to achieve this iron management should be reviewed when the ferritin is >500 microgram/L. Acetylsalicylic acid - increase dosing interval to every six hours if GFR equals 10-50 mL/minute; avoid use if GFR is less than 10 mL/minute Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Asprin and derivatives Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Aspirin For patients with CKD and AF the following recommendations apply: If renal function is impaired, the European Heart Rhythm Association’s practical guide recom- mends renal function to be monitored every 6 months for GFR 30–60mL/min and every 3 months for GFR<30mL/min in patients with AF receiving an NOAC Recommendations for treatment of anaemia of CKD: We suggest that Hb concentration should be monitored every 2–4 weeks in the correction phase and every 1– 3 months for stable patients in the maintenance phase.

Recommendations for treatment of anaemia of CKD: We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an op- tion, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation.

Apixaban - 5 mg bid in patients with CrCl ≽30 mL/minute; 2.5 mg bid if CrCl 15–29 mL/minute; 2.5 mg bid in the presence of 2 or more of the following characteristics: • Age $80 years • Body weight #60 kg • Serum creatinine $1.5 mg/dL (133 μmo

Apixaban - not recommended in: Pregnant women; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatment • Severe hepatic impairment

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - amiodarone - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - antiplatelets/NSAIDs - at least 6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - carbamazepine/phenytoin/phenobarbital - 3-6 months

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - HIV protease inhibitors - 3-6 months (dose adjustment with apixaban) Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - loop diuretics/thizide-like diuretics/ACEI/ARB - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Rivaroxaban/apixaban/edoxaban - verapamil/quinidine - at least 6 months (dose adjustment with edoxaban) For patients with CKD and AF the following recommendations apply: Rivaroxaban (20 mg once a day), edoxaban (60 mg once a day) and apixaban (5 mg twice a day) do not require any dose adjustment in patients with a GFR>50mL/min

Dabigatran - 150 mg bid in patients with CrCl ≽30 mL/minute 110 mg bid may be considered in patients with the following factors: • Age ≽80 years (or 75–80 years with high risk of bleeding) • CrCl 30–50 mL/minute with a high risk of bleeding

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment

Dabigatran - CrCl ≥50 mL/min no dose adjustment is necessary; CrCl 30-50 mL/min the recommended dose is 150 mg BD (110 mg BD for patients with high risk of bleeding); CrCl < 30 ml/min contraindicated

Dabigatran - dose adjustments: 10 mg bid in patients 75–80 years with low thromboembolic risk and high risk of bleeding, or 80 years or older with CrCl 30–50 mL/min and high risk of bleeding, or receiving the strong P-gp inhibitor verapamil Dabigatran - drugs requiring caution during concomitant treatment in patients with renal impairment: Close clinical surveillance is recommended in patients with mild to moderate renal impairment when dabigatran is combined with mild to moderate P-gp inhibitors (eg, amiodarone, quinidine, verapamil, and clarithromycin) Dabigatran - increased risk of GI bleeding compared with warfarin and oter target specific oral anticoagulants in adults aged 75 and older, lack of evidence of efficacy and safety in individuals with CrCl <30ml/min

Direct thrombin dabigatran and factor Xa inhibitor rivaroxaban are not recommended in patients with AF and end-stage chronic kidney disease (CKD) or on dialysis because of a lack of evidence from clinical trials regarding the balance of risks and benefits

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - dronederone - 3-6 months with dose adjustment based on renal function Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - loop diuretics/thiazide-like diuretics/ACEI/ARB - 3-6 months Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigatran - verapamil/quinidine - 3-6 months with dose adjustment based on renal function For patients prescribed dabigatran renal function should be monitored at least once a year if their kidney function is mildy to moderately reduced or if they are over 75 years old For patients with CKD and AF the following recommendations apply: European Medicines Agency - approved a lower dose of dabigatran 75 mg twice daily in patients with a GFR of 15–30mL/min

Drug-drug interaction risks in patients with impaired renal function - how often they should be monitored for: Dabigtran - carbamazepine/phenytoin/phenobarbital - 3-6 months

Edoxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 60 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg)

Rivaroxaban - CrCl ≥ 50 mL/min: no adjustment (i.e. 20 mg OD); If CrCl 15–29 mL/min: 2.5 mg BID; 2.5mg BID if 2 of these factors present: creatinine ≥ 1.5 mg/dL; age ≥ 80 years; weight ≤60kg)

Rivaroxaban - drugs requiring caution during concomitant treatment in patients with renal impairment: Moderate or potent inhibitors of CYP3A4 (eg, fluconazole, clarithromycin); Moderate inhibitors of both CYP3A4 and P-gp (eg, erythromycin) Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided

Rivaroxaban may be used at a reduced dose of 15mg OD for anti-coagulation management of atrial fibrillation in patients with severe renal impairment (CrCl 15-29 ml/min)

Low molecular weight heparins - Reduce dose by 50% when GFR is <30 mL/min/1.73 m2. Consider switch to conventional heparin or monitor plasma antiefactor Xa in those at high risk for bleeding

Recommendations for treatment of anaemia of CKD: We recommend that adjustments to ESA doses should be considered when Hb is <105 or >115 g/L in adults, young people and children aged 2 years and older Recommendations for treatment of anaemia of CKD: We recommend that blood pressure should be moni- tored in all patients receiving ESAs and, if present, hypertension be treated by volume removal and/or anti- hypertensive drugs Recommendations for treatment of anaemia of CKD: We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the tar- get Hb level despite SC epoetin dose >300 IU/kg/ week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week Recommendations for treatment of anaemia of CKD: We suggest exerting extreme caution while prescribing ESA therapy in CKD patients with a history of stroke, or malignancy, particularly in those with active malignancy when cure is the anticipated outcome Recommendations for treatment of anaemia of CKD: We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension

Do not initiate erythropoiesis-stimulating agents in patients with chronic kidney disease (CKD) with hemoglobin levels greater than or equal to 100 g/L without symptoms of anemia Recommendations for treatment of anaemia of CKD: We recommend that serum ferritin should not exceed 800 microgram/L in patients treated with iron, and to achieve this iron management should be reviewed when the ferritin is >500 microgram/L. For patients with CKD and AF the following recommendations apply: If renal function is impaired, the European Heart Rhythm Association’s practical guide recom- mends renal function to be monitored every 6 months for GFR 30–60mL/min and every 3 months for GFR<30mL/min in patients with AF receiving an NOAC

Recommendations for treatment of anaemia of CKD: We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an op- tion, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation.

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment

Dabigatran - drugs requiring caution during concomitant treatment in patients with renal impairment: Close clinical surveillance is recommended in patients with mild to moderate renal impairment when dabigatran is combined with mild to moderate P-gp inhibitors (eg, amiodarone, quinidine, verapamil, and clarithromycin) Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided Recommendations for treatment of anaemia of CKD: We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the tar- get Hb level despite SC epoetin dose >300 IU/kg/ week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week

Recommendations for treatment of anaemia of CKD: We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided

Dabigatran - contraindicatons: Active clinically significant bleeding; Hepatic impairment or liver disease expected to have any impact on survival; Lesion or condition causing significant risk of major bleeding; Hypersensitivity to the active substance or excipients Concomitant treatment with any other anticoagulant agent; a CrCl ,30 mL/min; Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole, and dronedarone (strong P-gp inhibitors); Prosthetic heart valves requiring anticoagulant treatment Rivaroxaban - not recommended in: Children ,18 years old; Patients with: • CrCl ,15 mL/min • Prosthetic heart valves requiring anticoagulant treatmentc • Increased bleeding risk (eg, genetic bleeding disorders, uncontrolled hypertension).; Patients receiving concomitant systemic treatment with azole- antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (eg, ritonavir; Patients receiving dronedarone – coadministration with rivaroxaban should be avoided

ATC code PSI C01B CrCl <10ml/min - Flecainide, milrinone, procainamide, quinidine, sotalol C01B CrCl <30ml/min - Disopyramide, enoxaparin sodium, milrinone, sotalol, tirofiban C01B CrCl <40ml/min - Disopyramide, dofetilide, milrinone C01B CrCl <50ml/min - Eptifibatide, milrinone, procainamide C01BA Drugs that need special attention in chronic kidney disease: Procainamide C10AD Acipimox - Acipimox is eliminated almost exclusively via the kidneys. Dosage reduction in patients with renal failure is recommended. For patients with a creatinine clearance of 30 to 60 mL/min, the suggested dose is 150 mg C02DB Cadralazine - GFR < 40 max 10 mg daily, GFR > 40 max 15 mg daily C03DA Contraindicated medications at variable GFR thresholds: Eplerenone C01B CrCl <20ml/min - Dofetilide, milrinone C01B CrCl <60ml/min - Dofetilide, sotalol C02A Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiadrenegic agents, centrally acting C02C Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiadrenegic agents, peripherally acting C10AX Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Other lipid modifying agents C01C Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Adrenergics for systemic use C01B Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiarrhythmics (class Ia and Ic) C04 Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Peipheral vasodilators C02AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Methyldopa C01BD Drugs requiring dosing adjustments in impaired renal function: Dofetilide C02CA Drugs that need special attention in chronic kidney disease: Alpha adrenergic blockes eg methyldopa, doxazosin, prazosin, reserpine C03EA Epitizide - eGFR <30 contraindicated C10AB Gemfibrozil - Severe impairment: use is contraindicated C10 Guidelines for patients with diabetic nephropathy: For management of dyslipidaemia: eGFR >15 ml/min/1.73m2: advise lipid-lowering treatment for reduction of cardiovascular events; eGFR <15 ml/min/1.73m2: lipid-lowering treatment not advised C02CA Medications to use with extreme caution in elderly patients with kdiney disease: alpha-Adrenergic inhibitors - Bradycardia and orthostatic hypotension C01B Medications to use with extreme caution in elderly patients with kdiney disease: Antiarrhythmic drugs (amiodarone, propafenone, sotalol, quinidine, and dronedarone) - Thyroid disease, pulmonary disorders, and QT interval prolongation C08CA Medications to use with extreme caution in elderly patients with kdiney disease: Nifedipine (immediate release) - Risk of hypotension and cerebral or myocardial ischemia C02AC Moxonidine - Moxonidine should be used with caution and under close medical supervision in patients with moderate renal insufficiency (glomerular filtration rate 30 to 60 mL/min, serum creatinine 1.2 to 1.8mg/dL C03DB Triamterene - eGFR <30 contraindicated C03DB Triamterene - eGFR 30-50 dose 50%, monitor potassium C03DB Triamterene if CrCl <30 - increased potassium and decreased sodium - avoid C10AB Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Fibrates C10AB Fenofibrate - Associated with AKI C10AB Fenofibrate - CrCl 20-60ml/min 96mg once daily; CrCl 10-20ml/min 48mg once daily; CrCl <10 avoid use C10AB Fenofibrate - Not recommended in severely impaired renal function C10AB Medicines that may accumulate and require renal function monitoring: Fenofibrate C10 Recommendations in adults with chronic kidney disease: If triglycerides ≽500 mg/dL - initiate therapeutic lifestyle changes and if fails add fibrate or niacin C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Lovastatin - <15 - decrease to 50% C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Lovastatin - 15-59 - decrease to 50% C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Pravastatin - 15-59 - Start at 10 mg/day for GFR <60 ml/min/1.73 m2 C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Rosuvastatin - <15 - 5-10mg /day C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Rosuvastatin - 15-59 - 5-10mg /day C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Simvastatin - <15 - start at 5mg/day C10AA Drug - GFR (ml/min) - dose adjustments (mg/day) Simvastatin - Reduce by 50% in patients with GFR b30 ml/min/1.73 m C10AA Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Statin C10AA Drugs requiring dosing adjustments in impaired renal function: Rosuvastatin calcium C10AA Fluvastatin - caution when exceed doses >40mg/day C10AA For patients aged 65 and over: If CrCl <30ml/min dose of simvastatin >10mg/day should be carefully considered and if deemed necessary, implemented cautiously C10AA Guidelines recommend statin or statin/ezetimibe treatment in adults age 50 years or older with an estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 but not treated with chronic dialysis or kidney transplantation C10AA In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction C10AA In CKD patients lifestyle and/or statin therapy are recommended to reduce levels of LDL-C to <100mg/dL and non-HDL-LDL-C to <130mg/dL C10AA Lovastatin - Renal impairment, severe (CrCl ≤ 30 mL/min): doses ≥20 mg/day should be undertaken with caution if deemed necessary; Aronoff no adjustmen C10AA Pitavastatin - in severe renal impairment (GFR 15-29ml/min not receiving dialysis) initally 1mg orally daly with max 2mg daily C10AA Pravastatin - if significant kidney impairment 10mg/day intially C10AA Recommendations in adults with chronic kidney disease: If LDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is bile acid sequestrant or niacin) C10AA Recommendations in adults with chronic kidney disease: If LDL 100-129 mg/dL - initiate therapeutic lifestyle changes and if fails add low dose statin (alternative is bile acid sequestrant or niacin) C10AA Recommendations in adults with chronic kidney disease: If triglycerides ≽200 mg/dL and non-HDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is fibrate or niacin) C10AA Rosuvastatin - Clcr <30 mL/min/1.73 m2: initial: 5 mg/day; do not exceed 10 mg once daily C10AA Rosuvastatin - GFR 25ml/min avoid C10AA Simvastatin - GFR 10-29 reduce dose 50-75% C10AA Simvastatin - if severe kidney impairment 5mg/day initially C10BA Simvastatin/ezetimibe - GFR ≥ 60 mL/min/1.73 m2: no dosage adjustment necessary. GFR < 60 mL/min/ 1.73 m2: ezetimibe 10 mg and simvastatin 20 mg once daily in the evening (higher doses should be used with caution) C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Atorvastatin - 20 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Fluvastatin - 80 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Pitavastatin - 2 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Pravastatin - 40 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Rosuvastatin - 10 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Simvastatin - 40 C10AA Statin - recommended dose in patients with eGFR 45-59 (mg/day) Simvastatin/ezetimibe - 20/10 C10AA Statin therapy or combination therapy is recommended in patients with CKD2-4 and treatment to LDL-C levels of <70mg/dL C10AA Statins - No increased toxicity for simvastatin 20 mg/day when GFR is < 30 mL/min/1.73 m2 or on dialysis. Dose reduction/increased toxicity for GFR < 30 mL/min/1.73 m2 for lovastatin, rosuvastatin, and pravastatin C07AB Atenolol - GFR >35 no change; GFR 15-35 maximum 50mg/day; GFR <15 maximum 25mg/day C07AB Atenolol - GFR 10-29 reduce dose 50-75% C07AB Atenolol - GFR 32ml/min recommended maximum dose 50mg/day C07AB Bisoprolol - 2.5 mg initially 10 mg maximum C07AB Bisoprolol - eGFR 10-30ml/min starting dose 50% of normal dose and if necessary increase to a maximum of 10mg per day C07AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Atenolol C07AB Medicines that may accumulate and require renal function monitoring: Atenolol C07AB Medicines that may accumulate and require renal function monitoring: Bisoprolol C07BB Metoprolol/hydrochlorothiazide - Clcr > 30 mL/min: no dosage adjustment necessary. Clcr 61–8 mL/min: loop diuretics preferred; the use of hydrochlorothiazide may not be effective. Anuria: use is contraindicated C07A Beta blockers - Reduce dose by 50% when GFR is < 30 mL/min/1.73 m2 C07B Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Beta blocking agents and thiazides or other diuretics C07A Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Beta blocking agents C07AA Sotalol - eGFR 10-30 max dose 80mg/day C07AA Sotalol - eGFR 30-50 max dose 160mg/day C03 Caution warranted if combining diuretics and duloxetine, due to increased risk of orthostatic hypotension C03 Diuretic - Coprescription of thiazide and loop diuretic (without valid indication); Overdosing due to lack of monitoring of fluid balance, renal function, electrolytes, etc. C03 Drug-drug interaction - adverse event in older patients with renal functon impairment Thiazides and loop diuretics - Hyponatremia and hypokalemia C02L Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antihypertensives and diuretics in combination C03E Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Diuretics and potassium sparing agents in combination C03 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Low-ceiling diuretics and thiazides C03C Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: High ceilin diuretics C03 Drugs that need special attention in chronic kidney disease: Diuretics C03AA Hydrochlorothiazide - Clcr < 10 mL/min: avoid use. Usually ineffective with GFR < 30 mL/min. Effective at lower GFR in combination with a loop diuretic C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - AT1 antagonists C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - eplerenone C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - potassium C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - potassium sparing diuretic C03D Hypokalaemia - Use of a non-potassium sparing diuretic; No use of a potassium supplement; No electrolyte test in the 6 months prior to admission C03D Medications to use with extreme caution in elderly patients with kdiney disease: Potassium-sparing diuretics - Hyperkalemia C09 Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic C03 Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - AT1 antagonists + NSAID C03CA Furosemide - eGFR 10-30 dose higher C03CA Furosemide - in chronic renal failure initially 80-120mg orally daily with a maximum of 1500mg orally daily C03DA Contraindicated medications at variable GFR thresholds: Spironolactone C03DA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Spironolactone C03DA Medications to use with extreme caution in elderly patients with kdiney disease: Spironolactone and triamterene - Hyperkalemia; cautious if eGFR <30 mL/min C03DA Reduce spironolactone if >25-mg daily in elderly patients with congestive heart failure or with creatinine clearance less than 30 mL/min C03DA Spironolactone - eGFR 10-50 monitor potassium C03DB Amiloride - eGFR <30 contraindicated C03DB Amiloride - eGFR 30-50 monitor potassium C03DB Amiloride if CrCL <30 - increased potassium and decreased sodium - avoid C03D Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Potassium sparing agents C03AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Chlorothiazide C03AA For patients aged 65 and over: Thiazides likely to be ineffective at CrCl <30ml/min C03AA Hydrochlorothiazide - eGFR <30 contraindicated C03AA Hydrochlorothiazide - eGFR 10-30ml/min avoid C03AA Hydrochlorothiazide - eGFR 30-50 initial dose 12.5mg C03DA Spirinolactone - eGFR 10-50ml/min monitor serum potassium levels regularly C03DA Spirinolactone >25mg/day - Risk of hyperkalemia C03DA Spirinolactone if CrCl <30 - increased potassium - avoid C03AA Bendroflumethiazde with potassium chloride - GFR 10-29 avoid C03CA Bumetanide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose to maximum of 10mg per day C03DA Spirinololactone - Renal impairment: mild renal failure (GFR ≥ 50 mL/min), dosing interval of 6–12 h; moderate renal failure (GFR 10–50 mL/min), dosing interval of 12 to 24 h; severe renal failure (GFR ≤ 10 mL/min), avoid the use of spinololactone C03D If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) C03CA Furosemide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose guided by effect and indication. In case the effect is inadequate, replace furosemide by bumetanide. C01AA Digoxin - eGFR 10-50 intial dose 50% C01AA Digoxin - Keep the dose down to 0.125 mg/day or lower. Since even 0.125 mg/ day or lower has a risk of digitalis toxicity in the elderly, consider discontinuing it if monitoring blood levels and electrocardiography is difficult. C01AA Digoxin - Overdosing due to lack of GFR/digoxin level monitoring C01AA Digoxin >125 mcg/day if low GFR C01AA Digoxin toxicity - Use of digoxin; No BUN or serum creatinine test in the 6 months prior to admission; No digoxin level test in the 6 months prior to admission C01AA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Digoxin C01AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Digoxin C01AA Has read code for chronic kidney disease stage 3B, 4 or 5 at least 3 month before audit date - prescribed digoxin at daily dose > 125 nanograms within 3 months leading up to audit date C03D Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years) C01AA Potential hazard - at risk patient group; Prescribed digoxin at a daily dose of >125 - patients with a diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 C01AA The percentage of patients ≽18 years with eGFR <50ml/min who are prescribed digoxin >0.125mg/day C01AA When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year C09DA Candesartan/hydrochlorothiazide - Contraindicated with severe renal impairment (Clcr < 30 mL/min) C09CA Drug - CrCl - maximum dosing recommendation (mg) Olmesartan - <30 - avoid use C09CA Drug - CrCl - maximum dosing recommendation (mg) Valsartan - <30 - 80 once daily C09CA Eprosartan - in moderate-severe impairment no initial starting dosage adjustment is necessary hoewever carefully monitor the patient, maximum dose 600mg daily C03D Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - valsartan C09B Lisinopril–irbesartan - hyperkalaemia, renal deterioration C09DA Losartan with hydrochlorothiazide - GFR 10-29 reduce dose of hydrocholorthiazde C09DA Losartan/hydrochlorothiazide - Clcr ≤ 30 mL/min: use of combination formulation is not recommended C09DA Telmisartan/hydrochlorothiazide - Clcr ≤ 30 mL/min: not recommended C09DA Valsartan/hydrochlorothiazide - Clcr ≥ 30 mL/min: no dosage adjustment necessary, Clcr < 30 mL/min: no dosage adjustment provided in manufacturer’s labelling; safety and efficacy has not been established. Use is contraindicated in patients with anuria C09D Do not prescribe angiotensin-converting-enzyme inhibitors in combination with angiotensin II receptor blockers for the treatment of hypertension, diabetic nephropathy or heart failure C09D Drug-drug interaction - adverse event in older patients with renal functon impairment 2 or more renin-angiotensin-aldosterone inhibitors - Hyperkalemia, hypotension, and increase in serum creatinine C09D Drug-drug interaction - adverse event in older patients with renal functon impairment Renin-angiotensin inhibitors and aldosterone antagonist - Hyperkalemia, gynaecomastia, and increase in serum creatinine C09D Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Angiotensin II antagonists and diuretics C03DA Aldosterone antagonists - Monitor electrolytes and renal function as deemed necessary. Limit to low-dose usage in patients with high potassium level or renal impairment. C09CA Drugs that need special attention in chronic kidney disease: ARBs C09CA Medicines that may accumulate and require renal function monitoring: ARBs C09 If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic; C09D ACE inhibitor - ARB - kidney failure/hypotension C09D ACE inhibitor/ARB/diuretic - Coprescription of potassium sparing diuretic (without valid indication) C09AA ACEI in diabetics with nephropathy C09 AKI (i.e. estimated GFR reduced by 50 % and/or a twofold increase in serum creatinine concentration and/or urine output B0.5 mL/kg/h for 12 h) - NSAIDs, diuretics, ACE inhibitors, angiotensin receptor antagonists C09AA Alacepril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09AA Altiopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09B Attention: higher risk of hyperkalaemia with concomitant use of higher doses of ACEIs (captopril ‡75 mg/day; enalapril, lisinopril ‡10 mg/day) C09B Avoidance of (ACEI or ARB) with K-sparing diuretic in patients with CrClf <50 mL/min C09AA Benazepril- mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose C09AA Captopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose to be administered in 2 daily doses C09AA Cilazapril - CrCl >40 maximum 5mg; CrCl 10-40 maximum 2.5mg; GFR <10 maximum 0.25-0.5mg once or twice weekly per response C09AA Cilazepril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09 CKD patients on ACEi/ARBs should have close and indefinite monitoring C09AA Delapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09 Diabetes - use of ACEI/ARB if micro-albuminuria C09 Diabetes and proteinuria/microalbuminuria and eGFR <50ml/min - ACEI or ARB C09 Discontinue ACE-Is/ARBs if there is confirmed progressive and continuous loss of kidney function after all other causes have been ruled out C09AA Drug - CrCl - maximum dosing recommendation (mg) Perindopril - <15 - 2.5/2 on day of dialysis C09AA Drug - CrCl - maximum dosing recommendation (mg) Perindopril - 15-30 - 2.5/2 alternate days C09AA Drug - CrCl - maximum dosing recommendation (mg) Perindopril - 30-60 - 2.5/2 once daily C09AA Drug-drug interaction - adverse event in older patients with renal functon impairment ACEis and lithium - Acute kidney injury in 1.5/100 persons per year. C09AA Drugs contraindicated in patients with impaired kidney function and aged 65 and over: ACE inhibitors, plain and combinations C09AA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Captopril C09AA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Enalapril C09AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Captopril C09AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Perindopril C09AA Enalapril - eGFR 10-30 initial dose 2.5mg C09AA Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher) C09AA Enalapril - maximum 40mg daily C09AA Enalapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09 For patients aged 65 and over: ACEIs and ARBs should be used with caution in reduced kidney function (<30ml/min) C09AA Fosinopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 100% C09 Guidelines for patients with diabetic nephropathy: To reduce BP and albuminuria start RAAS blockade with ACEi or AT1 receptor blockade; aim for maximal dosage C09BA Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - ACEI C09BA Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - ACEI + loop diuretic C09 Hyperkalaemia - Use of an ACEI or ARB; No electrolyte or potassium test in the 6 months prior to admission C09AA Hypertensive patients with chronic renal failure should receive, unless contraindicated, an ACE-I C09AA In patients with existing renal insufficiency, one should take into consideration that most ACE inhibitors may further compromise renal function through accumulation of an active metabolite. Dose adjustment is not necessary for fosinopril and for most AT1 antagonists (with the exception of olmesartan) C09 K in the past 6 months for ACEI or ARB with K-sparing diuretic in patients with CrClf < 50 mL/min C09AA Lisinopril - Maximum of 40 mg daily C09AA Lisinopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09AA Moexipril - CrCl ≤ 40: maximum 15 mg/day C09 Patients with CKD should be prescribed preventative medication with ACEIs or ARBs to slow the progression of renal dysfunction C09 Patients with CKD stages 3 or 4 should be prescribed an ACEI/ARB C09 Patients with eGFR <60 should be taking: ACEI/ARB to slow progression of renal disfunction C09AA Pentopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure no data C09AA Perindopril - CrCl > 30 max 8 mg/day, CrCl < 30 mL/min, not recommended C09AA Perindopril - CrCl 30-60ml/min 2.5/2mg once daily; CrCl 15-30ml/min 2.5/2mg alternate days; CrCl <15ml/min 2.5/2mg on day of dialysis C09AA Perindopril - eGFR 30-50ml/min if prescriber is a GP maximum dose is 2mg and if a specialised physician the dose may be higher; eGFR 10-30ml/min if prescriber is a GP maximum dose is 2mg every 48 hours and if a specialised physician the dose may be higher C09AA Perindopril - GFR 48ml/min recommended maximum dose 2mg/day C09AA Perindopril - mild renal failure 150-00% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09BA Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - ACEI C03 Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - acetylsalicylic acid C09AA Quinapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09 RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective C09AA Ramipril - GFR 10-29 maximal dose 5mg daily C09AA Ramipril - GFR 30-49 maximal dose 5mg daily C09AA Ramipril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose C09AA Ramipril - starting dose 1.25mg orally daily, titrate to effect with maximum 5mg daily C09 SCr in the past 6 months for ACEI or ARB with K-sparing diuretic in patients with CrClf <50 mL/min C09 The percentage of patients ≽18 years with CKD 3-5 and a prescription of RAS blockers wo are prescribed at least 2 RAS blockers simultaneously C09 Triple blockade with ACE inhibitors and ARBs [with mineralocorticoid receptor antagonists] should be avoided, as should the use of other potassium sparing diuretics C09 When initiating ACE-I/ARB/combination, do not stop drug unless creatinine rises >30% C09 When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). C09AA Zofenopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose CrCl <30ml/min - Disopyramide, enoxaparin sodium, milrinone, sotalol, tirofiban

Acipimox - Acipimox is eliminated almost exclusively via the kidneys. Dosage reduction in patients with renal failure is recommended. For patients with a creatinine clearance of 30 to 60 mL/min, the suggested dose is 150 mg

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiadrenegic agents, centrally acting Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiadrenegic agents, peripherally acting Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Other lipid modifying agents Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Adrenergics for systemic use Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiarrhythmics (class Ia and Ic) Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Peipheral vasodilators Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Methyldopa

Drugs that need special attention in chronic kidney disease: Alpha adrenergic blockes eg methyldopa, doxazosin, prazosin, reserpine

Guidelines for patients with diabetic nephropathy: For management of dyslipidaemia: eGFR >15 ml/min/1.73m2: advise lipid-lowering treatment for reduction of cardiovascular events; eGFR <15 ml/min/1.73m2: lipid-lowering treatment not advised Medications to use with extreme caution in elderly patients with kdiney disease: alpha-Adrenergic inhibitors - Bradycardia and orthostatic hypotension Medications to use with extreme caution in elderly patients with kdiney disease: Antiarrhythmic drugs (amiodarone, propafenone, sotalol, quinidine, and dronedarone) - Thyroid disease, pulmonary disorders, and QT interval prolongation Medications to use with extreme caution in elderly patients with kdiney disease: Nifedipine (immediate release) - Risk of hypotension and cerebral or myocardial ischemia Moxonidine - Moxonidine should be used with caution and under close medical supervision in patients with moderate renal insufficiency (glomerular filtration rate 30 to 60 mL/min, serum creatinine 1.2 to 1.8mg/dL

Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Fibrates

Fenofibrate - CrCl 20-60ml/min 96mg once daily; CrCl 10-20ml/min 48mg once daily; CrCl <10 avoid use

Medicines that may accumulate and require renal function monitoring: Fenofibrate Recommendations in adults with chronic kidney disease: If triglycerides ≽500 mg/dL - initiate therapeutic lifestyle changes and if fails add fibrate or niacin Drug - GFR (ml/min) - dose adjustments (mg/day) Lovastatin - <15 - decrease to 50% Drug - GFR (ml/min) - dose adjustments (mg/day) Lovastatin - 15-59 - decrease to 50% Drug - GFR (ml/min) - dose adjustments (mg/day) Pravastatin - 15-59 - Start at 10 mg/day for GFR <60 ml/min/1.73 m2 Drug - GFR (ml/min) - dose adjustments (mg/day) Rosuvastatin - <15 - 5-10mg /day Drug - GFR (ml/min) - dose adjustments (mg/day) Rosuvastatin - 15-59 - 5-10mg /day Drug - GFR (ml/min) - dose adjustments (mg/day) Simvastatin - <15 - start at 5mg/day Drug - GFR (ml/min) - dose adjustments (mg/day) Simvastatin - Reduce by 50% in patients with GFR b30 ml/min/1.73 m Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Statin Drugs requiring dosing adjustments in impaired renal function: Rosuvastatin calcium

For patients aged 65 and over: If CrCl <30ml/min dose of simvastatin >10mg/day should be carefully considered and if deemed necessary, implemented cautiously Guidelines recommend statin or statin/ezetimibe treatment in adults age 50 years or older with an estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 but not treated with chronic dialysis or kidney transplantation In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction In CKD patients lifestyle and/or statin therapy are recommended to reduce levels of LDL-C to <100mg/dL and non-HDL-LDL-C to <130mg/dL Lovastatin - Renal impairment, severe (CrCl ≤ 30 mL/min): doses ≥20 mg/day should be undertaken with caution if deemed necessary; Aronoff no adjustmen Pitavastatin - in severe renal impairment (GFR 15-29ml/min not receiving dialysis) initally 1mg orally daly with max 2mg daily

Recommendations in adults with chronic kidney disease: If LDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is bile acid sequestrant or niacin) Recommendations in adults with chronic kidney disease: If LDL 100-129 mg/dL - initiate therapeutic lifestyle changes and if fails add low dose statin (alternative is bile acid sequestrant or niacin) Recommendations in adults with chronic kidney disease: If triglycerides ≽200 mg/dL and non-HDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is fibrate or niacin) Rosuvastatin - Clcr <30 mL/min/1.73 m2: initial: 5 mg/day; do not exceed 10 mg once daily

Simvastatin/ezetimibe - GFR ≥ 60 mL/min/1.73 m2: no dosage adjustment necessary. GFR < 60 mL/min/ 1.73 m2: ezetimibe 10 mg and simvastatin 20 mg once daily in the evening (higher doses should be used with caution) Statin - recommended dose in patients with eGFR 45-59 (mg/day) Atorvastatin - 20 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Fluvastatin - 80 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Pitavastatin - 2 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Pravastatin - 40 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Rosuvastatin - 10 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Simvastatin - 40 Statin - recommended dose in patients with eGFR 45-59 (mg/day) Simvastatin/ezetimibe - 20/10 Statin therapy or combination therapy is recommended in patients with CKD2-4 and treatment to LDL-C levels of <70mg/dL Statins - No increased toxicity for simvastatin 20 mg/day when GFR is < 30 mL/min/1.73 m2 or on dialysis. Dose reduction/increased toxicity for GFR < 30 mL/min/1.73 m2 for lovastatin, rosuvastatin, and pravastatin Atenolol - GFR >35 no change; GFR 15-35 maximum 50mg/day; GFR <15 maximum 25mg/day

Bisoprolol - eGFR 10-30ml/min starting dose 50% of normal dose and if necessary increase to a maximum of 10mg per day Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Atenolol Medicines that may accumulate and require renal function monitoring: Atenolol Medicines that may accumulate and require renal function monitoring: Bisoprolol Metoprolol/hydrochlorothiazide - Clcr > 30 mL/min: no dosage adjustment necessary. Clcr 61–8 mL/min: loop diuretics preferred; the use of hydrochlorothiazide may not be effective. Anuria: use is contraindicated

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Beta blocking agents and thiazides or other diuretics Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Beta blocking agents

Caution warranted if combining diuretics and duloxetine, due to increased risk of orthostatic hypotension Diuretic - Coprescription of thiazide and loop diuretic (without valid indication); Overdosing due to lack of monitoring of fluid balance, renal function, electrolytes, etc. Drug-drug interaction - adverse event in older patients with renal functon impairment Thiazides and loop diuretics - Hyponatremia and hypokalemia Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antihypertensives and diuretics in combination Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Diuretics and potassium sparing agents in combination Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Low-ceiling diuretics and thiazides Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: High ceilin diuretics

Hydrochlorothiazide - Clcr < 10 mL/min: avoid use. Usually ineffective with GFR < 30 mL/min. Effective at lower GFR in combination with a loop diuretic Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - AT1 antagonists Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - eplerenone Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - potassium Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - potassium sparing diuretic Hypokalaemia - Use of a non-potassium sparing diuretic; No use of a potassium supplement; No electrolyte test in the 6 months prior to admission Medications to use with extreme caution in elderly patients with kdiney disease: Potassium-sparing diuretics - Hyperkalemia Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - AT1 antagonists + NSAID

Furosemide - in chronic renal failure initially 80-120mg orally daily with a maximum of 1500mg orally daily

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Spironolactone Medications to use with extreme caution in elderly patients with kdiney disease: Spironolactone and triamterene - Hyperkalemia; cautious if eGFR <30 mL/min Reduce spironolactone if >25-mg daily in elderly patients with congestive heart failure or with creatinine clearance less than 30 mL/min

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Potassium sparing agents Drugs requiring dosage adjustment or contraindicated in patients with CKD: Chlorothiazide For patients aged 65 and over: Thiazides likely to be ineffective at CrCl <30ml/min

Bumetanide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose to maximum of 10mg per day Spirinololactone - Renal impairment: mild renal failure (GFR ≥ 50 mL/min), dosing interval of 6–12 h; moderate renal failure (GFR 10–50 mL/min), dosing interval of 12 to 24 h; severe renal failure (GFR ≤ 10 mL/min), avoid the use of spinololactone If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) Furosemide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose guided by effect and indication. In case the effect is inadequate, replace furosemide by bumetanide.

Digoxin - Keep the dose down to 0.125 mg/day or lower. Since even 0.125 mg/ day or lower has a risk of digitalis toxicity in the elderly, consider discontinuing it if monitoring blood levels and electrocardiography is difficult.

Digoxin toxicity - Use of digoxin; No BUN or serum creatinine test in the 6 months prior to admission; No digoxin level test in the 6 months prior to admission Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Digoxin Drugs requiring dosage adjustment or contraindicated in patients with CKD: Digoxin Has read code for chronic kidney disease stage 3B, 4 or 5 at least 3 month before audit date - prescribed digoxin at daily dose > 125 nanograms within 3 months leading up to audit date Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years) Potential hazard - at risk patient group; Prescribed digoxin at a daily dose of >125 - patients with a diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 The percentage of patients ≽18 years with eGFR <50ml/min who are prescribed digoxin >0.125mg/day When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year Candesartan/hydrochlorothiazide - Contraindicated with severe renal impairment (Clcr < 30 mL/min) Drug - CrCl - maximum dosing recommendation (mg) Olmesartan - <30 - avoid use Drug - CrCl - maximum dosing recommendation (mg) Valsartan - <30 - 80 once daily Eprosartan - in moderate-severe impairment no initial starting dosage adjustment is necessary hoewever carefully monitor the patient, maximum dose 600mg daily Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - valsartan

Losartan with hydrochlorothiazide - GFR 10-29 reduce dose of hydrocholorthiazde Losartan/hydrochlorothiazide - Clcr ≤ 30 mL/min: use of combination formulation is not recommended

Valsartan/hydrochlorothiazide - Clcr ≥ 30 mL/min: no dosage adjustment necessary, Clcr < 30 mL/min: no dosage adjustment provided in manufacturer’s labelling; safety and efficacy has not been established. Use is contraindicated in patients with anuria Do not prescribe angiotensin-converting-enzyme inhibitors in combination with angiotensin II receptor blockers for the treatment of hypertension, diabetic nephropathy or heart failure Drug-drug interaction - adverse event in older patients with renal functon impairment 2 or more renin-angiotensin-aldosterone inhibitors - Hyperkalemia, hypotension, and increase in serum creatinine Drug-drug interaction - adverse event in older patients with renal functon impairment Renin-angiotensin inhibitors and aldosterone antagonist - Hyperkalemia, gynaecomastia, and increase in serum creatinine Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Angiotensin II antagonists and diuretics Aldosterone antagonists - Monitor electrolytes and renal function as deemed necessary. Limit to low-dose usage in patients with high potassium level or renal impairment.

If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic;

ACE inhibitor/ARB/diuretic - Coprescription of potassium sparing diuretic (without valid indication)

AKI (i.e. estimated GFR reduced by 50 % and/or a twofold increase in serum creatinine concentration and/or urine output B0.5 mL/kg/h for 12 h) - NSAIDs, diuretics, ACE inhibitors, angiotensin receptor antagonists Alacepril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose Altiopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose Attention: higher risk of hyperkalaemia with concomitant use of higher doses of ACEIs (captopril ‡75 mg/day; enalapril, lisinopril ‡10 mg/day) Avoidance of (ACEI or ARB) with K-sparing diuretic in patients with CrClf <50 mL/min Benazepril- mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose Captopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose to be administered in 2 daily doses Cilazapril - CrCl >40 maximum 5mg; CrCl 10-40 maximum 2.5mg; GFR <10 maximum 0.25-0.5mg once or twice weekly per response Cilazepril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose

Delapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose

Diabetes and proteinuria/microalbuminuria and eGFR <50ml/min - ACEI or ARB Discontinue ACE-Is/ARBs if there is confirmed progressive and continuous loss of kidney function after all other causes have been ruled out Drug - CrCl - maximum dosing recommendation (mg) Perindopril - <15 - 2.5/2 on day of dialysis Drug - CrCl - maximum dosing recommendation (mg) Perindopril - 15-30 - 2.5/2 alternate days Drug - CrCl - maximum dosing recommendation (mg) Perindopril - 30-60 - 2.5/2 once daily Drug-drug interaction - adverse event in older patients with renal functon impairment ACEis and lithium - Acute kidney injury in 1.5/100 persons per year. Drugs contraindicated in patients with impaired kidney function and aged 65 and over: ACE inhibitors, plain and combinations Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Captopril Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Enalapril Drugs requiring dosage adjustment or contraindicated in patients with CKD: Captopril Drugs requiring dosage adjustment or contraindicated in patients with CKD: Perindopril

Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher)

Enalapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose For patients aged 65 and over: ACEIs and ARBs should be used with caution in reduced kidney function (<30ml/min) Fosinopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 100% Guidelines for patients with diabetic nephropathy: To reduce BP and albuminuria start RAAS blockade with ACEi or AT1 receptor blockade; aim for maximal dosage Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - ACEI Hyperkalaemia - potassium sparing diuretic/potassium/co-trimoxazole/amiodarone - ACEI + loop diuretic Hyperkalaemia - Use of an ACEI or ARB; No electrolyte or potassium test in the 6 months prior to admission Hypertensive patients with chronic renal failure should receive, unless contraindicated, an ACE-I In patients with existing renal insufficiency, one should take into consideration that most ACE inhibitors may further compromise renal function through accumulation of an active metabolite. Dose adjustment is not necessary for fosinopril and for most AT1 antagonists (with the exception of olmesartan) K in the past 6 months for ACEI or ARB with K-sparing diuretic in patients with CrClf < 50 mL/min

Lisinopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose

Patients with CKD should be prescribed preventative medication with ACEIs or ARBs to slow the progression of renal dysfunction

Patients with eGFR <60 should be taking: ACEI/ARB to slow progression of renal disfunction Pentopril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure no data

Perindopril - CrCl 30-60ml/min 2.5/2mg once daily; CrCl 15-30ml/min 2.5/2mg alternate days; CrCl <15ml/min 2.5/2mg on day of dialysis Perindopril - eGFR 30-50ml/min if prescriber is a GP maximum dose is 2mg and if a specialised physician the dose may be higher; eGFR 10-30ml/min if prescriber is a GP maximum dose is 2mg every 48 hours and if a specialised physician the dose may be higher

Perindopril - mild renal failure 150-00% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - ACEI Potential adverse events - drug-drug interactions in patients aged 60 and over: Renal impairment - loop/thiazide/potassium sparing diuretics - acetylsalicylic acid Quinapril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective

Ramipril - mild renal failure 100% dose; moderature renal failure 50% full dose; severe renal failure 25% full dose Ramipril - starting dose 1.25mg orally daily, titrate to effect with maximum 5mg daily SCr in the past 6 months for ACEI or ARB with K-sparing diuretic in patients with CrClf <50 mL/min The percentage of patients ≽18 years with CKD 3-5 and a prescription of RAS blockers wo are prescribed at least 2 RAS blockers simultaneously Triple blockade with ACE inhibitors and ARBs [with mineralocorticoid receptor antagonists] should be avoided, as should the use of other potassium sparing diuretics When initiating ACE-I/ARB/combination, do not stop drug unless creatinine rises >30% When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus). Zofenopril - mild renal failure 100% dose; moderature renal failure 100%; severe renal failure 50% full dose Acipimox - Acipimox is eliminated almost exclusively via the kidneys. Dosage reduction in patients with renal failure is recommended. For patients with a creatinine clearance of 30 to 60 mL/min, the suggested dose is 150 mg

Guidelines for patients with diabetic nephropathy: For management of dyslipidaemia: eGFR >15 ml/min/1.73m2: advise lipid-lowering treatment for reduction of cardiovascular events; eGFR <15 ml/min/1.73m2: lipid-lowering treatment not advised

Medications to use with extreme caution in elderly patients with kdiney disease: Antiarrhythmic drugs (amiodarone, propafenone, sotalol, quinidine, and dronedarone) - Thyroid disease, pulmonary disorders, and QT interval prolongation

Moxonidine - Moxonidine should be used with caution and under close medical supervision in patients with moderate renal insufficiency (glomerular filtration rate 30 to 60 mL/min, serum creatinine 1.2 to 1.8mg/dL

Guidelines recommend statin or statin/ezetimibe treatment in adults age 50 years or older with an estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 but not treated with chronic dialysis or kidney transplantation In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction

Recommendations in adults with chronic kidney disease: If LDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is bile acid sequestrant or niacin) Recommendations in adults with chronic kidney disease: If LDL 100-129 mg/dL - initiate therapeutic lifestyle changes and if fails add low dose statin (alternative is bile acid sequestrant or niacin) Recommendations in adults with chronic kidney disease: If triglycerides ≽200 mg/dL and non-HDL ≽130 mg/dL - initiate therapeutic lifestyle changes and low dose statin and if fails add max dose statin (alternative is fibrate or niacin)

Simvastatin/ezetimibe - GFR ≥ 60 mL/min/1.73 m2: no dosage adjustment necessary. GFR < 60 mL/min/ 1.73 m2: ezetimibe 10 mg and simvastatin 20 mg once daily in the evening (higher doses should be used with caution)

Statins - No increased toxicity for simvastatin 20 mg/day when GFR is < 30 mL/min/1.73 m2 or on dialysis. Dose reduction/increased toxicity for GFR < 30 mL/min/1.73 m2 for lovastatin, rosuvastatin, and pravastatin

Metoprolol/hydrochlorothiazide - Clcr > 30 mL/min: no dosage adjustment necessary. Clcr 61–8 mL/min: loop diuretics preferred; the use of hydrochlorothiazide may not be effective. Anuria: use is contraindicated Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

Spirinololactone - Renal impairment: mild renal failure (GFR ≥ 50 mL/min), dosing interval of 6–12 h; moderate renal failure (GFR 10–50 mL/min), dosing interval of 12 to 24 h; severe renal failure (GFR ≤ 10 mL/min), avoid the use of spinololactone If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic)) Furosemide - eGFR 10-30ml/min starting dose as in normal renal function and if necessary increase the dose guided by effect and indication. In case the effect is inadequate, replace furosemide by bumetanide.

Digoxin - Keep the dose down to 0.125 mg/day or lower. Since even 0.125 mg/ day or lower has a risk of digitalis toxicity in the elderly, consider discontinuing it if monitoring blood levels and electrocardiography is difficult.

Has read code for chronic kidney disease stage 3B, 4 or 5 at least 3 month before audit date - prescribed digoxin at daily dose > 125 nanograms within 3 months leading up to audit date Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year Valsartan/hydrochlorothiazide - Clcr ≥ 30 mL/min: no dosage adjustment necessary, Clcr < 30 mL/min: no dosage adjustment provided in manufacturer’s labelling; safety and efficacy has not been established. Use is contraindicated in patients with anuria Do not prescribe angiotensin-converting-enzyme inhibitors in combination with angiotensin II receptor blockers for the treatment of hypertension, diabetic nephropathy or heart failure Drug-drug interaction - adverse event in older patients with renal functon impairment 2 or more renin-angiotensin-aldosterone inhibitors - Hyperkalemia, hypotension, and increase in serum creatinine Drug-drug interaction - adverse event in older patients with renal functon impairment Renin-angiotensin inhibitors and aldosterone antagonist - Hyperkalemia, gynaecomastia, and increase in serum creatinine

If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic;

AKI (i.e. estimated GFR reduced by 50 % and/or a twofold increase in serum creatinine concentration and/or urine output B0.5 mL/kg/h for 12 h) - NSAIDs, diuretics, ACE inhibitors, angiotensin receptor antagonists

Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher) In patients with existing renal insufficiency, one should take into consideration that most ACE inhibitors may further compromise renal function through accumulation of an active metabolite. Dose adjustment is not necessary for fosinopril and for most AT1 antagonists (with the exception of olmesartan)

Perindopril - eGFR 30-50ml/min if prescriber is a GP maximum dose is 2mg and if a specialised physician the dose may be higher; eGFR 10-30ml/min if prescriber is a GP maximum dose is 2mg every 48 hours and if a specialised physician the dose may be higher

RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective

When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus).

In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic))

Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic;

Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher) In patients with existing renal insufficiency, one should take into consideration that most ACE inhibitors may further compromise renal function through accumulation of an active metabolite. Dose adjustment is not necessary for fosinopril and for most AT1 antagonists (with the exception of olmesartan)

RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective

When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus).

In adults ages 18 to 49 years with CKD but not treated with maintenance dialysis or kidney transplantation, the guidelines suggest statin treatment in patients with one or more of the following conditions: known coronary disease (myocardial infarction or coro- nary revascularization), diabetes mellitus, prior ischemic stroke, and a greater than 10% estimated 10-year incidence of coronary death or nonfatal myocardial infarction Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic))

Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year If a RASI or renin inhibitor is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; there is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic;

Enalapril - eGFR 30-50ml/min starting dose is 5mg once daily and if necessary increase the dose guided by clinical effect (if prescriber is a GP maximum dose is 10mg and if a specialised physician the dose may be higher); eGFR 10-30ml/min starting dose is 2.5mg once daily and if necessary increase dose guided by clinical effect (if prescriber is a GP maximum dose is 5mg and if a specialised physician the dose may be higher) RAAS antagonists - Caution in patients with suspected renal artery stenosis. Start lower dose with GFR <45ml/min. Assess GFR and serum potassium 1 week after starting or escalating dose. Consider temporarily holding during illness, intravenous contrast administration, bowel preparation before colonoscopy, or before major surgery. Do not routinely discontinue when GFR is < 30 mL/min/1.73 m2 as these agents remain nephroprotective

When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus).

Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic))

Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus).

Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

If a potassium-losing diuretic is started, potassium and creatinine levels are checked beforehand if: the patient is at least 70 years of age; one of the following situations applies (the potassium-losing diuretic is combined with a potassium-sparing diuretic; there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia or coronary heart disease); the potassium-losing diuretic is combined with digoxin in the absence of a potassium-sparing agent (RASI, renin inhibitor or potassium-sparing diuretic))

Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

When prescribing a RASI, one should carefully weigh the expected benefits against the increased risk of renal insufficiency, and monitor creatinine level in any of the following situations: pre-existing renal insufficiency or renal artery stenosis (cave: generalized atherosclerosis); reduced effective circulating volume (cave: heart failure, intercurrent diseases, inadequate fluid intake or aggressive diuresis with a loop diuretic); sepsis; simultaneous use of an NSAID (including COX-2 selective inhibitor) or calcineurin inhibitor (ciclosporin, tacrolimus).

Potassium and creatinine levels are checked again within 1–2 weeks after the start of the RASI or renin inhibitor and then at least every 6 months and following every dose increase in any of the following situations: There is an increased risk of hyperkalaemia or an increased risk from hyperkalaemia (e.g. heart failure, cardiac conduction disorder, diabetes, renal insufficiency, simultaneous use of a potassium-sparing diuretic; simultaneous use of a thiazide diuretic and loop diuretic, age ≽70 years; Within 1–2 weeks after the addition of a potassium-sparing diuretic to a RASI or renin inhibitor, and after every dose increase of such a potassium-sparing diuretic

Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

Potassium and creatinine levels are checked again within 1–2 weeks after the start of a potassium-losing diuretic and then every year and following every dose increase in any of the following situations; f the patient is ≽80 years of age; if the patient is ≽70 years of age and uses a combination of a potassium-losing diuretic and a potassium-sparing diuretic; if the patient is ≽70 years of age and simultaneously uses a potassium-losing diuretic and digoxin in the absence of a potassium- sparing agent (RASI, renin inhibitor or potassium-sparing diuretic); if the patient is ‡70 years of age and there is an increased risk of hypokalaemia or an increased risk from hypokalaemia (e.g. pre-existent hypokalaemia, cardiac arrhythmia, coronary heart disease or age ≽70 years)

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

When digoxin and/or sotalol are given to elderly users, risk factors for the development of bradycardia should be carefully considered: renal function should be checked before the start of treatment, before each dose increase, and subsequently at least once a year; combinations with other cardiovascular agents that can enhance their effects (such as verapamil and diltiazem) should only be given on strict indication; sotalol should only be combined with another b-blocker on strict indication; he risk of drug-drug interactions between digoxin and potentiating non-cardiovascular drugs (macrolides, itraconazole, ketaconazole) should be carefully controlled; when digoxin is added to a potassium-losing diuretic without the addition of a potassium-sparing agent (RASI, potassium-sparing diuretic), the potassium level should be checked before the start of therapy, before each increase in dose, and subsequently at least once a year

ATC code PSI G04BD Drugs requiring dosing adjustments in impaired renal function: Solifenacin succinate G04BE Drugs requiring dosing adjustments in impaired renal function: Tadalafil G04BD Drugs requiring dosing adjustments in impaired renal function: Trospium chloride G04BX Medications requiring dose adjustments at variable GFR thresholds: Phenazopyrdine G04BE Medicines that may accumulate and require renal function monitoring: Sildenafil G04BD Medicines that may accumulate and require renal function monitoring: Solifenacin G04BE Medicines that may accumulate and require renal function monitoring: Tadalafil G04BD Medicines that may accumulate and require renal function monitoring: Tolterodine G04BE Medicines that may accumulate and require renal function monitoring: Vardenafil G04BD Solifenacin - CrCl <30ml/min 5mg once daily G04BD Tolterodine - CrCl <30ml/min 1mg once daily G04BD Tolterodine tartate - GFR 10-29 reduce dose 50% G04BD Trospium chloride - GFR 30-49 reduce dose 25% G03 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Sex hormones Drugs requiring dosing adjustments in impaired renal function: Solifenacin succinate

Drugs requiring dosing adjustments in impaired renal function: Trospium chloride Medications requiring dose adjustments at variable GFR thresholds: Phenazopyrdine Medicines that may accumulate and require renal function monitoring: Sildenafil Medicines that may accumulate and require renal function monitoring: Solifenacin Medicines that may accumulate and require renal function monitoring: Tadalafil Medicines that may accumulate and require renal function monitoring: Tolterodine Medicines that may accumulate and require renal function monitoring: Vardenafil

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Sex hormones ATC code PSI H01CB Drugs requiring dosing adjustments in impaired renal function: Lanreotide H02AB When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) H05AA Teriparatide - CrCl <30ml/min avoid use H05AA Medicines that may accumulate and require renal function monitoring: Teriparatide When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy)

Medicines that may accumulate and require renal function monitoring: Teriparatide When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) When a glucocorticoid therapy with ≽7.5 mg prednisone equivalents per day is started, the blood glucose level should be checked (unless treatment consists of a single injection). When there is no evidence that the patient has diabetes, the glucose level is checked before therapy is started and 3–7 days after its start. When a risk factor is present (e.g. a renal disease or a high corticosteroid dose of ‡15 mg prednisone equivalents per day) one or more additional checks should be considered. When the patient is known to have diabetes or develops hyperglycaemia during corticosteroid use, it is advisable to check the glucose level more frequently (every 1–2 weeks at the beginning of therapy) ATC code PSI J01XE Drugs that need special attention in chronic kidney disease: Nitrofurantoin J01XE Nitrofurantoin - Long-term use associated with pulmonary side-effects, renal impairment, liver damage J01XE Contraindicated medications at variable GFR thresholds: Nitrofurantoin J01XE Patient with a creatinine clearance <60 mL/min is not receiving nitrofurantoin for UTI J01XE Potentially dangerous or contraindicated in patients with eGFR <50:Nitrofurantoin J01XE For patients aged 65 and over: Nitrofurantoin likely to be ineffective at CrCl <45ml/min J01XE Medications to use with extreme caution in elderly patients with kdiney disease: Nitrofurantoin - Pulmonary toxicity; do not use if eGFR <30 mL/min J01XE Nitrofurantoin - potential for pulmonary toxicity, hepatotoxicity and peripheral neuropathy - avoid in individuals with creatinine clearance <30ml/min J01MB Chronic renal failure - nalidixic acid J01XX Methenamine - GFR 10-29 avoid J01XX Patient with a creatinine clearance <50 mL/min is not receiving methenamine (hexamine) for UTI prophylaxis J01A Tetracyclines - Reduce dose when GFR is < 45 mL/min/1.73 m2; can exacerbate uremia J01EA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): TMP/SMX J01EA Trimethoprim - Reduce dose by 50% when GFR is < 30 mL/min/1.73 m2. Risk factors for hyperkalemia include high doses, the elderly, CKD, orwith ACE-Is or NSAIDs J01CA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Amoxicillin J01CR Medications requiring dose adjustments at variable GFR thresholds: Amoxicillin/clavulanata J01CA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Ampicillin/sulbactam J01CA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Penicillin G J01CA Drugs that need special attention in chronic kidney disease: Penicillins J01CA Medications requiring dose adjustments at variable GFR thresholds: Piperacillin/tazobactam J01XA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Vancomycin J01XA Vancomycin - GFR 10-29 150-500mg daily J01GB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Gentamicin J01G Medications to use with extreme caution in elderly patients with kdiney disease: Aminoglycosides - Nephrotoxicity; otovestibular toxicity J01FA Macrolides - Reduce dose by 50% when GFR is < 30 mL/min/1.73 m2 J01FA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Clarithyromycin J01FA Drugs requiring dosage adjustment in renal impairment: Erythromycin J01XX Drugs requiring dosage adjustment in renal impairment: Fosfomycin J01GB Drugs requiring dosage adjustment in renal impairment: Tobramycin J01FA Drugs requiring dosing adjustments in impaired renal function: Telithromycin J01GB Nephrotoxic Medications: Kanamycin sulfate J01MA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ciprofloxacin J01MA Medications requiring dose adjustments at variable GFR thresholds: Gemifloxacin J01MA Medications requiring dose adjustments at variable GFR thresholds: Levofloxacin J01MA Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Norfloxacin J01DB Drugs that need special attention in chronic kidney disease: Cephalosporins J01DD Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Cefotaxime J01DD Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ceftazidime J01DB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Cephalexin J01DC Drugs requiring dosage adjustment or contraindicated in patients with CKD: Cefuroxime J01DB Drugs requiring dosing adjustments in impaired renal function: Cefditorn pivoxil J01M Medications to use with extreme caution in elderly patients with kdiney disease: Quinolones - Tendinitis; acute kidney injury J01MA Fluroquinolones - Reduce dose by 50% when GFR is < 15 mL/min/1.73 m2 J01GB Drugs requiring dosage adjustment in renal impairment: Amikacin J01CR Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Augmentin J01XB Nephrotoxic Medications: Colistimethate sodium J01XD Medications requiring dose adjustments at variable GFR thresholds: Metronidazole J05AF Drugs requiring dosing adjustments in impaired renal function: Emtricitabine J01DH Drugs requiring dosing adjustments in impaired renal function: Ertapenem J04AK Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ethambutol J04AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Rifampin J04AC Drugs requiring dosage adjustment in renal impairment: Isoniazid J07 Clinicians should vaccinate against chronic hepatitis B virus (HBV) in all unvaccinated adults at risk for infection, including: Adults with end-stage renal disease, including those receiving predialysis care, hemodialysis, peritoneal dialysis, and home dialysis. J07 Hepatitis B vaccine is usually given as a 3- or 4-dose series, but higher dosages may be required for immunocompromised persons and those with end-stage renal disease. These persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg level <10 mIU/mL) should be revaccinated J07 Vaccination guidelines for kidney transplant recipients: Influenza - annially J05AF CrCl - dosing recommendation for tenofovir CrCl ≽50 - tenofovir disoproxil fumarate 300mg every 24 hours J05AF CrCl - dosing recommendation for tenofovir CrCl 10-29 - tenofovir disoproxil fumarate 300mg every 72-96 hours J05AF CrCl - dosing recommendation for tenofovir CrCl 30-49 - tenofovir disoproxil fumarate 300mg every 48 hours J05AF CrCl - dosing recommendation for tenofovir Haemodialysis patients - tenofovir disoproxil fumarate 300mg every 7 days or after approximately 12 hours of haemodialyis J05AF For adults starting tenofovir disproxil fumarate with a baseline eGFR <90 mL/min, who are on other nephrotoxic medications, or who have hypertension or diabetes, guidelines recommend that physicians check a baseline blood pressure, serum creatinine, and urine protein J05AF For adults taking tenofovir disproxil fumarate monitor kidney function with biannual serum creatinine, serum phosphorous, and urinalysis for proteinuria and glycosuria J05AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Acyclovir J05AB Drug - CrCl at which dosage reduction recommended Acyclovir - creatinine clearance <25 mL/min J05AB Drug - CrCl at which dosage reduction recommended Famciclovir - creatinine clearance <60 mL/min J05AB Drug - CrCl at which dosage reduction recommended Valacyclovir - creatinine clearance <50 mL/min J05AB Valganciclovir - GFR 10-29 50% of standard dose vevery 48 hours J05AF For patients with eGFR 30-50 E/C/F/TAF (single pill antiretroviral regimen) has been approved J05AR Ledipasvir/sofosbuvir - Contraindicated in patients with GFR < 30 mL/min J05AR Velpatasvir/sofosbuvir - Contraindicated in patients with GFR < 30 mL/min J05AP Sofosbuvir - Contraindicated in patients with GFR < 30 mL/min J05AF Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Lamivudine J05AF Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Stavudine J05AF Drugs requiring dosing adjustments in impaired renal function: Telbivudine J05AF Drugs requiring dosing adjustments in impaired renal function: Adefovir dipivoxil J05AF Drugs requiring dosing adjustments in impaired renal function: Entecavir J05AH Drugs requiring dosing adjustments in impaired renal function: Oseltamivir phosphate J02AC Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Fluconazole J02AC Antifungals - Reduce maintenance dose of fluconazole by 50% when GFR is < 45 mL/min/1.73 m2 J02AC Drugs requiring dosing adjustments in impaired renal function: Voriconazole J01XB Nephrotoxic Medications: Polymyxin B sulfate J02AA Nephrotoxic Medications: Amphotericin B J02AA Drugs that need special attention in chronic kidney disease: Amphoteracin B J01FA Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and calcium channel blockers - Bradycardia, shock, heart block, multiorgan failure J01FA Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and digoxin - Strong increase in digoxin cardiac and neurological toxicity J01FA Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and statins - Myopathy J01EE Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and phenytoin- Phenytoin intoxication J01EE Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and renin-angiotensin-aldosterone inhibitor - Hyperkalemia J01EE Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole or amiodarone and warfarin - Increase in warfarin effect J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <10ml/min - Amoxicillin, amoxicillin–clavulanic acid, cefazolin, cefepime, cefoxitin, ceftazidime, cephalexin, imipenem– cilastatin J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <20ml/min - Amikacin, cefixime, gentamicin, imipenem–cilastatin, levofloxacin, piperacillin– tazobactam, tobramycin J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <30ml/min - Amoxicillin, ampicillin–sulbactam, cefazolin, cefepime, cefoxitin, ceftazidime, ticarcillin– clavulanic acid J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <40ml/min - Amikacin, gemifloxacin, gentamicin, imipenem, piperacillin–tazobactam, tobramycin, vancomycin J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <50ml/min - Cefoxitin, ceftazidime, cephalexin, ciprofloxacin, levofloxacin, meropenem, penicillin J01 Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <60ml/min - Amikacin, cefepime, cefixime, gentamicin, ticarcillin– clavulanic acid, tobramycin, vancomycin J Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antibacterials and antivirals for systemic use Nitrofurantoin - Long-term use associated with pulmonary side-effects, renal impairment, liver damage

Patient with a creatinine clearance <60 mL/min is not receiving nitrofurantoin for UTI Potentially dangerous or contraindicated in patients with eGFR <50:Nitrofurantoin For patients aged 65 and over: Nitrofurantoin likely to be ineffective at CrCl <45ml/min Medications to use with extreme caution in elderly patients with kdiney disease: Nitrofurantoin - Pulmonary toxicity; do not use if eGFR <30 mL/min Nitrofurantoin - potential for pulmonary toxicity, hepatotoxicity and peripheral neuropathy - avoid in individuals with creatinine clearance <30ml/min

Patient with a creatinine clearance <50 mL/min is not receiving methenamine (hexamine) for UTI prophylaxis Tetracyclines - Reduce dose when GFR is < 45 mL/min/1.73 m2; can exacerbate uremia Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): TMP/SMX Trimethoprim - Reduce dose by 50% when GFR is < 30 mL/min/1.73 m2. Risk factors for hyperkalemia include high doses, the elderly, CKD, orwith ACE-Is or NSAIDs Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Amoxicillin Medications requiring dose adjustments at variable GFR thresholds: Amoxicillin/clavulanata Drugs requiring dosage adjustment or contraindicated in patients with CKD: Ampicillin/sulbactam Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Penicillin G

Medications requiring dose adjustments at variable GFR thresholds: Piperacillin/tazobactam Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Vancomycin

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Gentamicin Medications to use with extreme caution in elderly patients with kdiney disease: Aminoglycosides - Nephrotoxicity; otovestibular toxicity

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Clarithyromycin

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ciprofloxacin Medications requiring dose adjustments at variable GFR thresholds: Gemifloxacin Medications requiring dose adjustments at variable GFR thresholds: Levofloxacin Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Norfloxacin

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Cefotaxime Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ceftazidime Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Cephalexin Drugs requiring dosage adjustment or contraindicated in patients with CKD: Cefuroxime Drugs requiring dosing adjustments in impaired renal function: Cefditorn pivoxil Medications to use with extreme caution in elderly patients with kdiney disease: Quinolones - Tendinitis; acute kidney injury

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Augmentin

Medications requiring dose adjustments at variable GFR thresholds: Metronidazole Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Ethambutol Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Rifampin

Clinicians should vaccinate against chronic hepatitis B virus (HBV) in all unvaccinated adults at risk for infection, including: Adults with end-stage renal disease, including those receiving predialysis care, hemodialysis, peritoneal dialysis, and home dialysis. Hepatitis B vaccine is usually given as a 3- or 4-dose series, but higher dosages may be required for immunocompromised persons and those with end-stage renal disease. These persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg level <10 mIU/mL) should be revaccinated

CrCl - dosing recommendation for tenofovir CrCl ≽50 - tenofovir disoproxil fumarate 300mg every 24 hours CrCl - dosing recommendation for tenofovir CrCl 10-29 - tenofovir disoproxil fumarate 300mg every 72-96 hours CrCl - dosing recommendation for tenofovir CrCl 30-49 - tenofovir disoproxil fumarate 300mg every 48 hours CrCl - dosing recommendation for tenofovir Haemodialysis patients - tenofovir disoproxil fumarate 300mg every 7 days or after approximately 12 hours of haemodialyis For adults starting tenofovir disproxil fumarate with a baseline eGFR <90 mL/min, who are on other nephrotoxic medications, or who have hypertension or diabetes, guidelines recommend that physicians check a baseline blood pressure, serum creatinine, and urine protein For adults taking tenofovir disproxil fumarate monitor kidney function with biannual serum creatinine, serum phosphorous, and urinalysis for proteinuria and glycosuria Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Acyclovir Drug - CrCl at which dosage reduction recommended Acyclovir - creatinine clearance <25 mL/min Drug - CrCl at which dosage reduction recommended Famciclovir - creatinine clearance <60 mL/min Drug - CrCl at which dosage reduction recommended Valacyclovir - creatinine clearance <50 mL/min

For patients with eGFR 30-50 E/C/F/TAF (single pill antiretroviral regimen) has been approved

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Lamivudine Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Stavudine

Drugs requiring dosing adjustments in impaired renal function: Adefovir dipivoxil

Drugs requiring dosing adjustments in impaired renal function: Oseltamivir phosphate Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Fluconazole Antifungals - Reduce maintenance dose of fluconazole by 50% when GFR is < 45 mL/min/1.73 m2

Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and calcium channel blockers - Bradycardia, shock, heart block, multiorgan failure Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and digoxin - Strong increase in digoxin cardiac and neurological toxicity Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and statins - Myopathy Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and phenytoin- Phenytoin intoxication Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and renin-angiotensin-aldosterone inhibitor - Hyperkalemia Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole or amiodarone and warfarin - Increase in warfarin effect Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <10ml/min - Amoxicillin, amoxicillin–clavulanic acid, cefazolin, cefepime, cefoxitin, ceftazidime, cephalexin, imipenem– cilastatin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <20ml/min - Amikacin, cefixime, gentamicin, imipenem–cilastatin, levofloxacin, piperacillin– tazobactam, tobramycin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <30ml/min - Amoxicillin, ampicillin–sulbactam, cefazolin, cefepime, cefoxitin, ceftazidime, ticarcillin– clavulanic acid Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <40ml/min - Amikacin, gemifloxacin, gentamicin, imipenem, piperacillin–tazobactam, tobramycin, vancomycin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <50ml/min - Cefoxitin, ceftazidime, cephalexin, ciprofloxacin, levofloxacin, meropenem, penicillin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <60ml/min - Amikacin, cefepime, cefixime, gentamicin, ticarcillin– clavulanic acid, tobramycin, vancomycin Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antibacterials and antivirals for systemic use

Clinicians should vaccinate against chronic hepatitis B virus (HBV) in all unvaccinated adults at risk for infection, including: Adults with end-stage renal disease, including those receiving predialysis care, hemodialysis, peritoneal dialysis, and home dialysis. Hepatitis B vaccine is usually given as a 3- or 4-dose series, but higher dosages may be required for immunocompromised persons and those with end-stage renal disease. These persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg level <10 mIU/mL) should be revaccinated

For adults starting tenofovir disproxil fumarate with a baseline eGFR <90 mL/min, who are on other nephrotoxic medications, or who have hypertension or diabetes, guidelines recommend that physicians check a baseline blood pressure, serum creatinine, and urine protein

Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and calcium channel blockers - Bradycardia, shock, heart block, multiorgan failure Drug-drug interaction - adverse event in older patients with renal functon impairment Clarithromycin and digoxin - Strong increase in digoxin cardiac and neurological toxicity

Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole and renin-angiotensin-aldosterone inhibitor - Hyperkalemia Drug-drug interaction - adverse event in older patients with renal functon impairment Trimethoprim-sulfamethoxazole or amiodarone and warfarin - Increase in warfarin effect Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <10ml/min - Amoxicillin, amoxicillin–clavulanic acid, cefazolin, cefepime, cefoxitin, ceftazidime, cephalexin, imipenem– cilastatin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <20ml/min - Amikacin, cefixime, gentamicin, imipenem–cilastatin, levofloxacin, piperacillin– tazobactam, tobramycin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <30ml/min - Amoxicillin, ampicillin–sulbactam, cefazolin, cefepime, cefoxitin, ceftazidime, ticarcillin– clavulanic acid Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <40ml/min - Amikacin, gemifloxacin, gentamicin, imipenem, piperacillin–tazobactam, tobramycin, vancomycin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <50ml/min - Cefoxitin, ceftazidime, cephalexin, ciprofloxacin, levofloxacin, meropenem, penicillin Dosage adjustment required: (CrCl - drugs requiring dosage adjustment); CrCl <60ml/min - Amikacin, cefepime, cefixime, gentamicin, ticarcillin– clavulanic acid, tobramycin, vancomycin

Hepatitis B vaccine is usually given as a 3- or 4-dose series, but higher dosages may be required for immunocompromised persons and those with end-stage renal disease. These persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg level <10 mIU/mL) should be revaccinated

For adults starting tenofovir disproxil fumarate with a baseline eGFR <90 mL/min, who are on other nephrotoxic medications, or who have hypertension or diabetes, guidelines recommend that physicians check a baseline blood pressure, serum creatinine, and urine protein ATC code PSI L01XE Afatinib dimaleate - djustments to the starting dose were not considered necessary for mild RI (CLcr = 60–89 ml/min). Closely monitor patients with moderate (CLcr = 30–59 ml/min) to severe (CLcr < 30 ml/min) RI and adjust afatinib dose if not tolerated. L01XE Axitinib - No dose adjustment was needed for mild to severe RI (CLcr ≥ 15 ml/min). Use caution for end-stage renal disease (CLcr < 15 ml/min). L01DC Bleomycin - CrCl <30 - do not adminster L01DC Bleomycin - CrCl 90-60ml/min 10 to 20 mg/m2; CrCl 60-30ml/min 7.5 to 15 mg/m2; CrCl 30-15ml/min 7.5 to 15 mg/m2; CrCl <15ml/min +/or haemodialysis 5 to 10 mg/m2 L01CD Cabazitaxel - No dose adjustment was provided. Population PK indicated no significant difference in CL in patients with mild (CLcr = 50–80 ml/min) and moderate (CLcr = 30–50 ml/min) RI. Caution should be used in patients with severe RI or ESRD. L01BC Capecitabine - CrCl <30 - do not administer L01BC Capecitabine - CrCl 90-60ml/min 1250 mg/m2 every 12 h; CrCl 60-30ml/min 950 mg/m2 every 12 h; CrCl <30ml/min +/or haemodilysis contraindicated L01XA Carboplatin - Adjust according to patient using a formula such as the Calvert formula. L01XA Carboplatin - CrCl <10 - 25% of full dose L01XA Carboplatin - CrCl >50 - 100% full dose L01XA Carboplatin - CrCl 10-50 - 50% of full dose L01XA Cisplatin - CrCl <30 - do not use; use an alternative drug L01XA Cisplatin - CrCl <60ml/min contraindicated L01XA Cisplatin - CrCl 31-45 - 25% of full dose L01XA Cisplatin - CrCl 46-60 - 50% of full dose L01XA Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients) L04AD Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function. L01XE Crizotinib - No dose adjustment was needed for mild (CLcr = 60–90 ml/min) and moderate (CLcr = 30–60 ml/min) RI. Dose adjustment for severe RI (CLcr < 30 ml/min) was not determined (use caution). L01AA Cyclophosphamide - CrCl <10 - 50% of full dose L04AD Cyclosporin - perindopril - hyprkalaemia/kidney failure L01BC Cytarabine - An initial dose 100 mg/m2/day for 7 to 10 days, or 200 mg/m2/day for 5 to 10 days followed by 20 mg/m2/day for 5 to 10 days.; CrCl 90-60ml/min 2 to 3 g/m2 every 12 h; CrCl 60-30ml/min 1 to 2 g/m2 every 12 h; CrCl 30-15ml/min 1 g/m2 every 12 to 24 h; CrCl <15ml/min +/or haemodialysis 1 g/m2 every 24 h L01BC Cytarabine - CrCl <40 - if dose >0.75g/m2/dose decrease to <200mg/m2/dose L01BC Cytarabine - CrCl 40-60 - if dose >2g/m2/dose decrease to 1g/m2/dose; if dose 0.75-1g/m2/dose decrease to 0.5g/m2/dose L01AX Dacarbazine - CrCl <10 - omit L01AX Dacarbazine - CrCl 10-30 - 50% of full dose L01AX Dacarbazine - CrCl 30-60 - 75% of full dose L01DB Daunorubicin - SCr >3mg/dL - 50% of full dose L01DB Doxorubicin - CrCl <10 - 75% of full dose L04AC Drugs requiring dosing adjustments in impaired renal function: Anakinra L03AB Drugs requiring dosing adjustments in impaired renal function: Peginterferon alfa-2a L03AB Drugs requiring dosing adjustments in impaired renal function: Peginterferon alfa-2b L01BA Drugs requiring dosing adjustments in impaired renal function: Pemetrexed disodium L01 Drugs that need special attention in chronic kidney disease: Antineoplastic agents eg carboplatin, cisplatin, cyclophosphamide, etoposide, fludarabine, hydroxyurea, methotrexate L01DB Epirubicin - SCr >5mg/dL - lower doses should be considered L01XX Eribulin mesylate - No dose adjustment was needed mild RI (1.4 mg/m2). Dose reduction for moderate RI (CLcr = 30–50 ml/min) to 1.1 mg/m2. No data for severe RI (CLcr < 30 ml/min) L01CB Etoposide - CrCl <10 - 50% of full dose L01CB Etoposide - CrCl 10-50 - 75% of full dose L01CB Etoposide - CrCl 15-50ml/min require dose to be reduced; CrCl <15ml/min contraindicated L01CB Etoposide - SCr >1.4mg/dL - 70% of full dose L01CB Etoposide (oral) - CrCl 90-60ml/min 80 to 300 mg/m2/day for 3 to 5 days, followed by 50 to 100 mg/m2/day; CrCl 60-15ml/min 60 to 225 mg/m2/day for 3 to 5 days, followed by 37.5 to 75 mg/m2/day; CrCl <15ml/min +/or haemodialysis 40 to 150 mg/m2/day for 3 to 5 days, followed by 25 to 50 mg/m2/day L01BB Fludarabine - CrCl <10 - omit L01BB Fludarabine - CrCl 10-30 - 50% of full dose L01BB Fludarabine - CrCl 30-60 - 75% of full dose L01DB Idarubicin - SCr ≽2.5mg/dL - dose reduction is recommended L01XX Idelalisib - No dose adjustment was necessary for CLcr ≥ 15 ml/min L01AA Ifosfamide - CrCl <10 - omit L01AA Ifosfamide - CrCl 10-30 - 50% of full dose L01AA Ifosfamide - CrCl 30-60 - 75% of full dose L01AA Ifosfamide - should not be used in patients with impaired renal function L01AA Ifosfamide (continuous) - CrCl 90-15ml/min dose/day 5 to 8 g/m2; CrCl <15ml/min +/or haemodialysis dose/day: 3.75 to 6 g/m2 L01AA Ifosfamide (intermittent) - CrCl 90-15ml/min dose/day: 1.5 to 3 g/m2; dose/cycle: 5 to 10 g/m2; CrCl <15ml/min +/or haemodialysis: dose/day: 1.13 to 2.25 g/m2 dose/cycle: 3.75 to 7.5 g/m2 L01XE Lenvatinib mesylate - No dose adjustment was recommended for mile or moderate RI. Dose reduction to 14 mg daily was recommended for severe RI. Patients with ESRD were not studied. L01AX Medications to use with extreme caution in elderly patients with kdiney disease: Azathioprine - Bone marrow suppression and leukopenia L01AA Melphalan - CrCl <10 - 50% of full dose L01AA Melphalan - CrCl 10-50 - 75% of full dose L01AA Melphalan (oral for breast cancer) - CrCl 90-60ml/min 0.15 mg/kg/day or 6 mg/m2 per os for 4 to 6 days; CrCl 60-15ml/min 0.11 mg/kg/day or 4.5 mg/m2 per os for 4 to 6 days; CrCl <15ml/min +/or haemodialysis 0.075 mg/kg/day or 3 mg/m2 per os for4to6days L01AA Melphalan (oral for ovarian cancer) - CrCl 90-60ml/min 0.2 mg/kg/day per os for 5 days; CrCl 60-15ml/min 0.15 mg/kg/day for 5 days; CrCl <15ml/min +/or haemodialysis 0.1 mg/kg/day per os for 5 days L01BA Methotrexate - CrCl <30 - omit L01BA Methotrexate - CrCl 30-60 - 50% of full dose L01BA Methotrexate (IM, IV or SC) - CrCl 90-60ml/min 30 to 50 mg/m2; CrCl 60-30ml/min 24 to 40 mg/m2; CrCl 30-15ml/min 15 to 525 mg/m2; CrCl <15ml/min +/or haemodialysis contraindicated L01BA Methotrexate (oral) - CrCl 90-60ml/min 15 to 30 mg/m2; CrCl 60-30ml/min 12 to 24 mg/m2; CrCl 30-10ml/min 7.5 to 24 mg/m2; CrCl <15ml/min +/0r haemodialysis contraindicated L01DC Mitomycin C - CrCl <10 - omit L01DC Mitomycin C - CrCl 10-30 - 50% of full dose L01DC Mitomycin C - CrCl 30-60 - 75% of full dose L01XX Olaparib - No dose adjustment was required for mild RI (CLcr = 50–80 ml/min). Patients should be monitored. L01XA Oxaliplatin - CrCl 90-15ml/min 85 or 100 mg/m2 every 2 weeks, or 130 mg/m2 every 3 weeks; CrCl <15ml/min +/or haemodialysis contraindicated L01XX Pentostatin - CrCl <30 - consider to use alternative drugs if possible L01XX Pentostatin - CrCl 30-45 - 60% of full dose L01XX Pentostatin - CrCl 45-60 - 70% of full dose L04AX Pomalidomide - No dose established for RI. Safety, efficacy, and PK were not evaluated in RI. Avoid POMALYST in patients with serum creatinine>3.0mg/dl. L01XB Procarbazine - SCr >2mg/dL - dose reduction should be considered L01BA Raltitrexed - 60–60 mL/min: 3 mg/m2 every 3 weeks; 65–55 mL/min: 2.25 mg/m2 every 4 weeks; 54–25 mL/min: 1.5 mg/m2 every 4 weeks; <25 mL/min and haemodialysis: contraindicated L01XE Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. L01AX Temozolomide - Pharmacokinetics appear unchanged in patients with mild-moderate renal dysfunction. Patients with severe renal failure should be monitored closely and consideration given to dose modification. L01XX Topotecan - CrCl <10 - omit L01XX Topotecan - CrCl 10-30 - 50% of full dose L01XX Topotecan - CrCl 30-60 - 75% of full dose L01XX Topotecan - CrCl 90-60ml/min 1.5 mg/m2/day; 60–40 mL/min: 1.5 mg/m2/day; 39–20 mL/min: <20 mL/min and haemodialysis: not available L01XE Vandetinib - Dose reduced to 200 mg for moderate (CLcr = 30–50 ml/min) and severe (CLcr < 30 ml/min) RI. L04AD Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus azoles, macrolides, calcium channel antagonists, or grapefruit juice - Increased serum levels and toxicity of CNI (nephrotoxicity, hypertension, etc) L04AD Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus rifampicin or anticonvulsant - Decreased serum levels of CNI Afatinib dimaleate - djustments to the starting dose were not considered necessary for mild RI (CLcr = 60–89 ml/min). Closely monitor patients with moderate (CLcr = 30–59 ml/min) to severe (CLcr < 30 ml/min) RI and adjust afatinib dose if not tolerated. Axitinib - No dose adjustment was needed for mild to severe RI (CLcr ≥ 15 ml/min). Use caution for end-stage renal disease (CLcr < 15 ml/min).

Bleomycin - CrCl 90-60ml/min 10 to 20 mg/m2; CrCl 60-30ml/min 7.5 to 15 mg/m2; CrCl 30-15ml/min 7.5 to 15 mg/m2; CrCl <15ml/min +/or haemodialysis 5 to 10 mg/m2 Cabazitaxel - No dose adjustment was provided. Population PK indicated no significant difference in CL in patients with mild (CLcr = 50–80 ml/min) and moderate (CLcr = 30–50 ml/min) RI. Caution should be used in patients with severe RI or ESRD.

Capecitabine - CrCl 90-60ml/min 1250 mg/m2 every 12 h; CrCl 60-30ml/min 950 mg/m2 every 12 h; CrCl <30ml/min +/or haemodilysis contraindicated Carboplatin - Adjust according to patient using a formula such as the Calvert formula.

Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients) Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function. Crizotinib - No dose adjustment was needed for mild (CLcr = 60–90 ml/min) and moderate (CLcr = 30–60 ml/min) RI. Dose adjustment for severe RI (CLcr < 30 ml/min) was not determined (use caution).

Cytarabine - An initial dose 100 mg/m2/day for 7 to 10 days, or 200 mg/m2/day for 5 to 10 days followed by 20 mg/m2/day for 5 to 10 days.; CrCl 90-60ml/min 2 to 3 g/m2 every 12 h; CrCl 60-30ml/min 1 to 2 g/m2 every 12 h; CrCl 30-15ml/min 1 g/m2 every 12 to 24 h; CrCl <15ml/min +/or haemodialysis 1 g/m2 every 24 h

Cytarabine - CrCl 40-60 - if dose >2g/m2/dose decrease to 1g/m2/dose; if dose 0.75-1g/m2/dose decrease to 0.5g/m2/dose

Drugs requiring dosing adjustments in impaired renal function: Peginterferon alfa-2a Drugs requiring dosing adjustments in impaired renal function: Peginterferon alfa-2b Drugs requiring dosing adjustments in impaired renal function: Pemetrexed disodium Drugs that need special attention in chronic kidney disease: Antineoplastic agents eg carboplatin, cisplatin, cyclophosphamide, etoposide, fludarabine, hydroxyurea, methotrexate

Eribulin mesylate - No dose adjustment was needed mild RI (1.4 mg/m2). Dose reduction for moderate RI (CLcr = 30–50 ml/min) to 1.1 mg/m2. No data for severe RI (CLcr < 30 ml/min)

Etoposide - CrCl 15-50ml/min require dose to be reduced; CrCl <15ml/min contraindicated

Etoposide (oral) - CrCl 90-60ml/min 80 to 300 mg/m2/day for 3 to 5 days, followed by 50 to 100 mg/m2/day; CrCl 60-15ml/min 60 to 225 mg/m2/day for 3 to 5 days, followed by 37.5 to 75 mg/m2/day; CrCl <15ml/min +/or haemodialysis 40 to 150 mg/m2/day for 3 to 5 days, followed by 25 to 50 mg/m2/day Ifosfamide (continuous) - CrCl 90-15ml/min dose/day 5 to 8 g/m2; CrCl <15ml/min +/or haemodialysis dose/day: 3.75 to 6 g/m2 Ifosfamide (intermittent) - CrCl 90-15ml/min dose/day: 1.5 to 3 g/m2; dose/cycle: 5 to 10 g/m2; CrCl <15ml/min +/or haemodialysis: dose/day: 1.13 to 2.25 g/m2 dose/cycle: 3.75 to 7.5 g/m2 Lenvatinib mesylate - No dose adjustment was recommended for mile or moderate RI. Dose reduction to 14 mg daily was recommended for severe RI. Patients with ESRD were not studied. Medications to use with extreme caution in elderly patients with kdiney disease: Azathioprine - Bone marrow suppression and leukopenia

Melphalan (oral for breast cancer) - CrCl 90-60ml/min 0.15 mg/kg/day or 6 mg/m2 per os for 4 to 6 days; CrCl 60-15ml/min 0.11 mg/kg/day or 4.5 mg/m2 per os for 4 to 6 days; CrCl <15ml/min +/or haemodialysis 0.075 mg/kg/day or 3 mg/m2 per os for4to6days Melphalan (oral for ovarian cancer) - CrCl 90-60ml/min 0.2 mg/kg/day per os for 5 days; CrCl 60-15ml/min 0.15 mg/kg/day for 5 days; CrCl <15ml/min +/or haemodialysis 0.1 mg/kg/day per os for 5 days

Methotrexate (IM, IV or SC) - CrCl 90-60ml/min 30 to 50 mg/m2; CrCl 60-30ml/min 24 to 40 mg/m2; CrCl 30-15ml/min 15 to 525 mg/m2; CrCl <15ml/min +/or haemodialysis contraindicated Methotrexate (oral) - CrCl 90-60ml/min 15 to 30 mg/m2; CrCl 60-30ml/min 12 to 24 mg/m2; CrCl 30-10ml/min 7.5 to 24 mg/m2; CrCl <15ml/min +/0r haemodialysis contraindicated

Olaparib - No dose adjustment was required for mild RI (CLcr = 50–80 ml/min). Patients should be monitored. Oxaliplatin - CrCl 90-15ml/min 85 or 100 mg/m2 every 2 weeks, or 130 mg/m2 every 3 weeks; CrCl <15ml/min +/or haemodialysis contraindicated

Pomalidomide - No dose established for RI. Safety, efficacy, and PK were not evaluated in RI. Avoid POMALYST in patients with serum creatinine>3.0mg/dl.

Raltitrexed - 60–60 mL/min: 3 mg/m2 every 3 weeks; 65–55 mL/min: 2.25 mg/m2 every 4 weeks; 54–25 mL/min: 1.5 mg/m2 every 4 weeks; <25 mL/min and haemodialysis: contraindicated Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. Temozolomide - Pharmacokinetics appear unchanged in patients with mild-moderate renal dysfunction. Patients with severe renal failure should be monitored closely and consideration given to dose modification.

Topotecan - CrCl 90-60ml/min 1.5 mg/m2/day; 60–40 mL/min: 1.5 mg/m2/day; 39–20 mL/min: <20 mL/min and haemodialysis: not available Vandetinib - Dose reduced to 200 mg for moderate (CLcr = 30–50 ml/min) and severe (CLcr < 30 ml/min) RI. Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus azoles, macrolides, calcium channel antagonists, or grapefruit juice - Increased serum levels and toxicity of CNI (nephrotoxicity, hypertension, etc) Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus rifampicin or anticonvulsant - Decreased serum levels of CNI Afatinib dimaleate - djustments to the starting dose were not considered necessary for mild RI (CLcr = 60–89 ml/min). Closely monitor patients with moderate (CLcr = 30–59 ml/min) to severe (CLcr < 30 ml/min) RI and adjust afatinib dose if not tolerated.

Bleomycin - CrCl 90-60ml/min 10 to 20 mg/m2; CrCl 60-30ml/min 7.5 to 15 mg/m2; CrCl 30-15ml/min 7.5 to 15 mg/m2; CrCl <15ml/min +/or haemodialysis 5 to 10 mg/m2 Cabazitaxel - No dose adjustment was provided. Population PK indicated no significant difference in CL in patients with mild (CLcr = 50–80 ml/min) and moderate (CLcr = 30–50 ml/min) RI. Caution should be used in patients with severe RI or ESRD.

Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients) Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function. Crizotinib - No dose adjustment was needed for mild (CLcr = 60–90 ml/min) and moderate (CLcr = 30–60 ml/min) RI. Dose adjustment for severe RI (CLcr < 30 ml/min) was not determined (use caution).

Cytarabine - An initial dose 100 mg/m2/day for 7 to 10 days, or 200 mg/m2/day for 5 to 10 days followed by 20 mg/m2/day for 5 to 10 days.; CrCl 90-60ml/min 2 to 3 g/m2 every 12 h; CrCl 60-30ml/min 1 to 2 g/m2 every 12 h; CrCl 30-15ml/min 1 g/m2 every 12 to 24 h; CrCl <15ml/min +/or haemodialysis 1 g/m2 every 24 h

Drugs that need special attention in chronic kidney disease: Antineoplastic agents eg carboplatin, cisplatin, cyclophosphamide, etoposide, fludarabine, hydroxyurea, methotrexate

Eribulin mesylate - No dose adjustment was needed mild RI (1.4 mg/m2). Dose reduction for moderate RI (CLcr = 30–50 ml/min) to 1.1 mg/m2. No data for severe RI (CLcr < 30 ml/min)

Etoposide (oral) - CrCl 90-60ml/min 80 to 300 mg/m2/day for 3 to 5 days, followed by 50 to 100 mg/m2/day; CrCl 60-15ml/min 60 to 225 mg/m2/day for 3 to 5 days, followed by 37.5 to 75 mg/m2/day; CrCl <15ml/min +/or haemodialysis 40 to 150 mg/m2/day for 3 to 5 days, followed by 25 to 50 mg/m2/day Ifosfamide (intermittent) - CrCl 90-15ml/min dose/day: 1.5 to 3 g/m2; dose/cycle: 5 to 10 g/m2; CrCl <15ml/min +/or haemodialysis: dose/day: 1.13 to 2.25 g/m2 dose/cycle: 3.75 to 7.5 g/m2 Lenvatinib mesylate - No dose adjustment was recommended for mile or moderate RI. Dose reduction to 14 mg daily was recommended for severe RI. Patients with ESRD were not studied.

Melphalan (oral for breast cancer) - CrCl 90-60ml/min 0.15 mg/kg/day or 6 mg/m2 per os for 4 to 6 days; CrCl 60-15ml/min 0.11 mg/kg/day or 4.5 mg/m2 per os for 4 to 6 days; CrCl <15ml/min +/or haemodialysis 0.075 mg/kg/day or 3 mg/m2 per os for4to6days Melphalan (oral for ovarian cancer) - CrCl 90-60ml/min 0.2 mg/kg/day per os for 5 days; CrCl 60-15ml/min 0.15 mg/kg/day for 5 days; CrCl <15ml/min +/or haemodialysis 0.1 mg/kg/day per os for 5 days

Methotrexate (IM, IV or SC) - CrCl 90-60ml/min 30 to 50 mg/m2; CrCl 60-30ml/min 24 to 40 mg/m2; CrCl 30-15ml/min 15 to 525 mg/m2; CrCl <15ml/min +/or haemodialysis contraindicated Methotrexate (oral) - CrCl 90-60ml/min 15 to 30 mg/m2; CrCl 60-30ml/min 12 to 24 mg/m2; CrCl 30-10ml/min 7.5 to 24 mg/m2; CrCl <15ml/min +/0r haemodialysis contraindicated

Raltitrexed - 60–60 mL/min: 3 mg/m2 every 3 weeks; 65–55 mL/min: 2.25 mg/m2 every 4 weeks; 54–25 mL/min: 1.5 mg/m2 every 4 weeks; <25 mL/min and haemodialysis: contraindicated Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. Temozolomide - Pharmacokinetics appear unchanged in patients with mild-moderate renal dysfunction. Patients with severe renal failure should be monitored closely and consideration given to dose modification.

Drug-drug interaction - adverse event in older patients with renal functon impairment CNI plus azoles, macrolides, calcium channel antagonists, or grapefruit juice - Increased serum levels and toxicity of CNI (nephrotoxicity, hypertension, etc) Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients)

Cytarabine - An initial dose 100 mg/m2/day for 7 to 10 days, or 200 mg/m2/day for 5 to 10 days followed by 20 mg/m2/day for 5 to 10 days.; CrCl 90-60ml/min 2 to 3 g/m2 every 12 h; CrCl 60-30ml/min 1 to 2 g/m2 every 12 h; CrCl 30-15ml/min 1 g/m2 every 12 to 24 h; CrCl <15ml/min +/or haemodialysis 1 g/m2 every 24 h

Etoposide (oral) - CrCl 90-60ml/min 80 to 300 mg/m2/day for 3 to 5 days, followed by 50 to 100 mg/m2/day; CrCl 60-15ml/min 60 to 225 mg/m2/day for 3 to 5 days, followed by 37.5 to 75 mg/m2/day; CrCl <15ml/min +/or haemodialysis 40 to 150 mg/m2/day for 3 to 5 days, followed by 25 to 50 mg/m2/day Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. Cisplatin - CrCl 90-60ml/min 50 to 120 mg/m2 every 3 to 6 weeks; CrCl 60-15ml/min Not recommended, however if unavoidable an appropriate dose should be used: 25 to 60 mg/m2 every 3 to 6 weeks; CrCl <15ml/min +/or haemodialysis Not recommended, however if unavoidable an appropriate dose should be used: 25 mg/m2 (evidence in haemodialysis patients) Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l.

Ruxolitinib phosphate - 10 mg (from 20 mg) twice daily for moderate (CLcr = 30–59 ml) and severe (CLcr = 15–29 ml/min) RI and platelet count 100–150 × 109/l; 15 mg for patients with ESRD and platelet 100–200 × 109/l on dialysis days; 20 mg for patients with ESRD and platelet > 200 × 109/l on dialysis days. Additional dose modifications should be made with careful safety and efficacy monitoring. Avoid in patients with ESRD (CLcr < 15 ml/min) not on dialysis and in patients with moderate or severe RI and platelet count < 100 × 109/l. ATC code PSI M04 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antigout preparations M01CC Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Other (including gold salt and penicillamine) M01AE Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Propionic acid derivatives M05BA Alendronate - if GFR <35ml/min not recommended M05BA Drug - CrCl - maximum dosing recommendation (mg) Alendronate - <35 - avoid use M05BA Ibandronate - CrCl 90-15ml/min 6 mg every 3 to 4 weeks; CrCl <15ml/min +/or haemodialysis 2 mg every 3 to 4 weeks M05BA Ibandronic acid - CrCl <30ml/min not recommended M05BA Ibandronic acid - CrCl 30-50 50mg every second day if oral or 4mg every 4 weeks if IV; CrCl <30ml/min 50mg once each week if oral or 2mg every 4 weeks if IV; CrCl <10ml/min avoid use M05BA Zoledronic acid - CrCl <40ml/min not recommended M05BA Zoledronic acid - GFR 40-49 3.3mg M05BA Zolendronic acid - CrCl <30ml/min avoid use M05BA Zolendronic acid - CrCl 30-60ml/min graded dose reduction M05BA Zolendronic acid - CrCl 90-60ml/min 4 mg every 3 to 4 weeks; 60–50 mL/min: 3.5 mg every 3 to 4 weeks 50–40 mL/min: 3.3 mg every 3 to 4 weeks 40–30 mL/min: 3 mg every 3 to 4 weeks; CrCl <30ml/min +/or haemodialysis not recommended M05BA Clodronate - CrCl 50-80ml/min 1600mg daily; CrCl 30-50 1200mg daily; CrCl 10-30ml/min 800mg daily; CrCl <10ml/min avoid use M04AA Allopurinol in renal dysfunction: ≤200 mg/d if CrClf 20 to 60 mL/min, 100 mg/d if CrCl ≤20 mL/min M04AA Allopurinol without baseline urea, electrolytes, creatinine and eGFR M04AA Drugs requiring dosage adjustment or contraindicated in patients with CKD: Allopurinol M04AA Drugs that need special attention in chronic kidney disease: Allopurinol M04AA IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg. M04AA Medicines that may accumulate and require renal function monitoring: Allopurinol M04AA Patients with creatinine clearance < 60 ml/min, initial allopurinol dose to be < 300 mg/day M04AA Potentially dangerous or contraindicated in patients with eGFR <50: Allopurinol exceeding recommended standard dose M04AC Colchicine if CrCl <30 - GI, neuromuscular, bone marro toxicity - reduce dose M04AC Drugs requiring dosage adjustment or contraindicated in patients with CKD: Colchicine M04AC Medicines that may accumulate and require renal function monitoring: Colchicine M01A Avoid NSAID use in individuals with hypertension, heart failure, or chronic kidney disease of all causes, including diabetes M01A Avoidance of NSAID or Cox 2 Inhibitor in CHF, HTN or renal dysfunction: pts with dx of CHF, HTN or CrCl £20 ml/min M01A Drugs that need special attention in chronic kidney disease: NSAIDs M01A For patients aged 65 and over: NSAIDs should be used with caution in reduced kidney function (<30ml/min) M01A If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) M01A Medications to use with extreme caution in elderly patients with kdiney disease: NSAIDs, nondihydropyridine CCBs, antidiabetic glitazones - Fluid retention M01A NSAID - methotrexate - reduce renal clearing of methotrexate M01A NSAID prescribed in patients aged 65 and over with estimated glomerular filtration rate <60 M01A NSAIDs - Avoid when GFR is < 30 mL/min/1.73 m2 Prolonged therapy is not recommended when GFR is <60mL/min/1.73m2 Avoid when taking RAAS-blocking agents or lithium. M01A NSAIDS - with chronic kidney disease (eGFR<50ml/min) - risk of renal impairment M01A Patient with risk factors for impaired renal function (l) is not taking an NSAID M01A Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 M01A Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI M01A Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI and a loop diuretic M01A Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiinflammatory and antirheumatic products (non steroids) M01AB Diclofenac - GFR 39-57ml/min recommended maximum dose 75mg/day M01AB Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Diclofenac M01AB Nephrotoxic Medications: Diclofenac sodium M01AE Nephrotoxic Medications: Ibuprofen M01AB Nephrotoxic Medications: Indomethacin M01AE Nephrotoxic Medications: Naproxen M01AC Drugs requiring dosing adjustments in impaired renal function: Meloxicam M01AH Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Coxibs M01AC Nephrotoxic Medications: Piroxicam M01AB Ketorolac - increased risk of GI bleeding, peptic ulcer and AKI M01AG Mefenamic acid–lisinopril - hypertension, nephrotoxicity M01AB Nephrotoxic Medications: Sulindac M05BA Risedronate dosium - CrCl <30ml/min contraindicated M05BA Bisphosphonates - Most are not recommended when GFR is < 30 mL/min/1.73 m2 Refer to bone specialist if GFR is < 30 mL/min/1.73 m2 and no evidence of CKD-MBD (calcium, phosphate, alkaline phosphatase, and intact PTH normal) M05BA Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Bisphosphonates M05BA Medicines that may accumulate and require renal function monitoring: Bisphosphonates M05BA Disodium etidronate - in mild renal impairment reduce dose M05BA Drug - CrCl - maximum dosing recommendation (mg) Tiludronate - <30 - avoid use M05BA Pamidronate - CrCl 90-30ml/min 90mg every 4weeks; CrCl <30ml/min +/or haemodialysis not recommended M05BA CKD stage 3a (eGFR 45-59) - Dose of BP is the same as in non-renal patients, but ensure that patient is vitamin D replete. M05BA CKD stage 5 (eGFR <15) or patients on dialysis - Avoid BP. Bone biopsy may be required to distinguish from other forms of metabolic bone diseases (renal osteodystrophy) that are associated with CKD. M05BA CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. M05BX Drug - CrCl - maximum dosing recommendation (mg) Strontium - <30 - avoid use M05BX Medicines that may accumulate and require renal function monitoring: Strontium ranelate M04AB Contraindicated medications at variable GFR thresholds: Probenecid M04AB Probenecid if CrCl <30 - loss of effectiveness - avoid M03BX Baclofen - GFR 30-49 reduce dose 75% M03BX Medicines that may accumulate and require renal function monitoring: Baclofen Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antigout preparations Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Other (including gold salt and penicillamine) Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Propionic acid derivatives

Drug - CrCl - maximum dosing recommendation (mg) Alendronate - <35 - avoid use Ibandronate - CrCl 90-15ml/min 6 mg every 3 to 4 weeks; CrCl <15ml/min +/or haemodialysis 2 mg every 3 to 4 weeks

Ibandronic acid - CrCl 30-50 50mg every second day if oral or 4mg every 4 weeks if IV; CrCl <30ml/min 50mg once each week if oral or 2mg every 4 weeks if IV; CrCl <10ml/min avoid use

Zolendronic acid - CrCl 90-60ml/min 4 mg every 3 to 4 weeks; 60–50 mL/min: 3.5 mg every 3 to 4 weeks 50–40 mL/min: 3.3 mg every 3 to 4 weeks 40–30 mL/min: 3 mg every 3 to 4 weeks; CrCl <30ml/min +/or haemodialysis not recommended Clodronate - CrCl 50-80ml/min 1600mg daily; CrCl 30-50 1200mg daily; CrCl 10-30ml/min 800mg daily; CrCl <10ml/min avoid use Allopurinol in renal dysfunction: ≤200 mg/d if CrClf 20 to 60 mL/min, 100 mg/d if CrCl ≤20 mL/min

Drugs requiring dosage adjustment or contraindicated in patients with CKD: Allopurinol

IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg. Medicines that may accumulate and require renal function monitoring: Allopurinol Patients with creatinine clearance < 60 ml/min, initial allopurinol dose to be < 300 mg/day Potentially dangerous or contraindicated in patients with eGFR <50: Allopurinol exceeding recommended standard dose

Drugs requiring dosage adjustment or contraindicated in patients with CKD: Colchicine Medicines that may accumulate and require renal function monitoring: Colchicine Avoid NSAID use in individuals with hypertension, heart failure, or chronic kidney disease of all causes, including diabetes Avoidance of NSAID or Cox 2 Inhibitor in CHF, HTN or renal dysfunction: pts with dx of CHF, HTN or CrCl £20 ml/min

For patients aged 65 and over: NSAIDs should be used with caution in reduced kidney function (<30ml/min) If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) Medications to use with extreme caution in elderly patients with kdiney disease: NSAIDs, nondihydropyridine CCBs, antidiabetic glitazones - Fluid retention

NSAID prescribed in patients aged 65 and over with estimated glomerular filtration rate <60 NSAIDs - Avoid when GFR is < 30 mL/min/1.73 m2 Prolonged therapy is not recommended when GFR is <60mL/min/1.73m2 Avoid when taking RAAS-blocking agents or lithium. NSAIDS - with chronic kidney disease (eGFR<50ml/min) - risk of renal impairment

Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI and a loop diuretic Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Antiinflammatory and antirheumatic products (non steroids)

Drugs requiring dosage adjustment in renal impairment (CrCl ≼50ml/min): Diclofenac Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Coxibs

Bisphosphonates - Most are not recommended when GFR is < 30 mL/min/1.73 m2 Refer to bone specialist if GFR is < 30 mL/min/1.73 m2 and no evidence of CKD-MBD (calcium, phosphate, alkaline phosphatase, and intact PTH normal) Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Bisphosphonates Medicines that may accumulate and require renal function monitoring: Bisphosphonates

Drug - CrCl - maximum dosing recommendation (mg) Tiludronate - <30 - avoid use Pamidronate - CrCl 90-30ml/min 90mg every 4weeks; CrCl <30ml/min +/or haemodialysis not recommended CKD stage 3a (eGFR 45-59) - Dose of BP is the same as in non-renal patients, but ensure that patient is vitamin D replete. CKD stage 5 (eGFR <15) or patients on dialysis - Avoid BP. Bone biopsy may be required to distinguish from other forms of metabolic bone diseases (renal osteodystrophy) that are associated with CKD. CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. Drug - CrCl - maximum dosing recommendation (mg) Strontium - <30 - avoid use Medicines that may accumulate and require renal function monitoring: Strontium ranelate

Medicines that may accumulate and require renal function monitoring: Baclofen Ibandronic acid - CrCl 30-50 50mg every second day if oral or 4mg every 4 weeks if IV; CrCl <30ml/min 50mg once each week if oral or 2mg every 4 weeks if IV; CrCl <10ml/min avoid use

Zolendronic acid - CrCl 90-60ml/min 4 mg every 3 to 4 weeks; 60–50 mL/min: 3.5 mg every 3 to 4 weeks 50–40 mL/min: 3.3 mg every 3 to 4 weeks 40–30 mL/min: 3 mg every 3 to 4 weeks; CrCl <30ml/min +/or haemodialysis not recommended

IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg.

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous)

NSAIDs - Avoid when GFR is < 30 mL/min/1.73 m2 Prolonged therapy is not recommended when GFR is <60mL/min/1.73m2 Avoid when taking RAAS-blocking agents or lithium.

Potential hazard - at risk patient group; Prescribed an NSAID - patients with diagnosis of CKD (3b, 4 or 5) or with latest eGFR <45 who have been prescribed an ACEI and a loop diuretic Bisphosphonates - Most are not recommended when GFR is < 30 mL/min/1.73 m2 Refer to bone specialist if GFR is < 30 mL/min/1.73 m2 and no evidence of CKD-MBD (calcium, phosphate, alkaline phosphatase, and intact PTH normal)

CKD stage 5 (eGFR <15) or patients on dialysis - Avoid BP. Bone biopsy may be required to distinguish from other forms of metabolic bone diseases (renal osteodystrophy) that are associated with CKD. CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg.

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg.

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. IF a gout patient is receiving an initial prescription for allopurinol AND has significant renal impairment (defined as a serum creatinine 2 mg/dl or measured/estimated creatinine clearance 50 ml/min) THEN the initial daily allopurinol dose should be less than 300 mg per day BECAUSE the risk of allopurinol-related toxicity is increased in the presence of significant renal impairment in gout patients given a daily allopurinol dose equal to or exceeding 300 mg.

If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous) CKD stage 4 (eGFR 15-29) - There are no prospective safety data on use of BP. BP are especially not appropriate for CKD patients with already low bone turnover. Bone biopsy may be required in some patients. If osteoporosis is the cause of fracture (and not renal osteodystrophy), one expert opinion suggests trying risedronate in half the usual dose (2.5 mg daily or 35 mg every 2 weeks) for up to 3 years [102]. This recommendation is based on post hoc data (see text) and also the fact that 50% of the absorbed drug is excreted by kidneys. If it is in any way possible, the prescribing of NSAIDs (including selective COX-2 inhibitors) should not only be avoided in cardiovascular risk patients, including patients with heart failure and hypertension, but also in the following risk situations: a history of renal disease; educed effective circulating volume (not only in patients with heart failure, but also, for instance, in patients with hepatic cirrhosis, chronic renal insufficiency and dehydration); simultaneous use of drugs that may also compromise renal function, such as a RASI and/or a diuretic (the combination of these two drugs with an NSAID seems particularly hazardous)

ATC code PSI N06AA Amitriptylinoxide - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR 15-30; 15-150mg daily if eGFR <15 or in RRT N05CC Chloral hydrate - avoid use if GFR is less than 50 mL/minute N05BA Clorazepate - reduce doses by 33% to 50% if GFR is less than 30 mL/minute N06AA Dibenzepine - no adjustment if eGFR 30-60; initially 240mg with careful increase if eGFR <30 or in RRT N06AA Dosulepine - no adjustment if eGFR 30-60; initially 75mg with careful increase if eGFR <30 or in RRT N02CA Drug - CrCl - maximum dosing recommendation (mg) Methysergide - <50 - avoid use N06 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Psychoanaleptics N03 Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiepileptics N04B Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Dopaminergic agents N02CC Drugs requiring dosing adjustments in impaired renal function: Almotriptan malate N03AF Drugs requiring dosing adjustments in impaired renal function: Oxacarbazepine N02A Drugs that need special attention in chronic kidney disease: Narcotic analgesics N03AB Drugs that need special attention in chronic kidney disease: Phenytoin N06AB Escitalopram - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT N06AA Maprotiline - no adjustment if eGFR 30-60; initially 50mg with careful increase if eGFR <30 or in RRT N05AL Medicines that may accumulate and require renal function monitoring: Amisulpride N06AX Medicines that may accumulate and require renal function monitoring: Buproprion N06DA Medicines that may accumulate and require renal function monitoring: Galantamine N02CA Medicines that may accumulate and require renal function monitoring: Methysergide N06AX Medicines that may accumulate and require renal function monitoring: Reboxetine N03AX Medicines that may accumulate and require renal function monitoring: Topiramate N05BC Meprobamate - double the dosing interval if GFR is 10-50 mL/minute N02BB Metamizol - GFR 29-30ml/min avoid high doses N06AX Mianserin - initially 30mg with careful increase if eGFR <60 or in RRT N06AX Milnacipran - initially 25mg with careful increase if eGFR 30-60; 25-50mg if eGFR <30 or in RRT N06AX Nefazodone - initially 100mg with careful increase if eGFR <60 or in RRT N06AB Paroxetine - initially 10mg with careful increase if eGFR <60 or in RRT N05BE Patients with anuria a 25 to 50% dosage reduction of buspirone indicated N02AC Propoxyphene - avoid use if GFR is less than 10 mL/minute N06AA Protryptiline - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR <30 or in RRT N06AX Reboxetine - 4-6mg daily if eGFR <60 or in RRT N04BD Selegiline - initally 5mg with careful increase if eGFR 30-60; 5mg daily if eGFR <30 or in RRT N06AB Sertraline - no adjustment if eGFR 30-60; initially 50mg with careful increase if eGFR 15-30; 25mg and consider reducing max dose if eGFR <15 or in RRT N06AX Tianeptine - initially 12.5mg with careful increase if eGFR 30-60; 12.5-25mg if eGFR <30 or in RRT N06AF Tranylcypromine - no adjustment if eGFR 30-60; initially 30mg with careful increase if eGFR <30 or in RRT N06AX Trazadone - no adjustment if eGFR 15-60; initially 150mg with careful increase if eGFR <15 or in RRT N03AG Valproate - ascertain haematological and hepatic history and measre serum valproate levels at start of treatment; 3 monthly weight; 6 monthly FBC, LFTs, and serum valproate levels; measure blood pressure, lipid profile and fasting glucose in patients with risk factors, monitor for menstrual irregularities N03AX For patients aged 65 and over: Gabapentin and pregabalin should have reduced doses at specified levels of CrCl N03AX Gabapentin - Can cause altered mental status, myoclonus and asterixis with severe CKD/ESRD. GFR 30-59 mL/min: 200-700 mg twice daily, GFR 15-29 mL/min: 200-700 mg once per day, GFR <15 mL/min: 300 every other day, hemodialysis: 200-300 mg after each dialysis. Extended release: GFR 30-59 mL/min: 600-1,800 mg once per day, GFR < 30 mL/min to ESRD—not recommended N03AX Gabapentin - CrCl 50-79ml/min 600-1800mg daily in 3 doses; CrCl 30-49ml/min 300-900 in 2/3 doses; CrCl 15-29ml/min 600mg daily in 2/3 doses; CrCl <15ml/min 300mg daily N03AX Gabapentin if CrCl <60 - CNS adverse effects - reduce dose N03AX Medicines that may accumulate and require renal function monitoring: Gabapentin N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); >15-29 - 200-700mg/day - 200, 300, 400, 500, 700 given qd N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); >30-59 - 400-1400mg/day - 200, 300, 400, 500, 700 given bid N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); ≽60 - 900-3600mg/day - 300, 400, 600, 800, 1200 given tid N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); 15 - 100-300mg/day - 100, 125, 150, 200, 300 given qd N03AX Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); Haemodialysis (Patients on hemodialysis should receive maintenance doses based on estimates of Clcr and supplemental doses after 4 hours of hemodialysis ) - 125, 150, 200, 250, 350 [post dialysis supplemental dose] N03AX Drug - CrCl - maximum dosing recommendation (mg) Gabapentin - <15 - 300 daily N02A In patients with renal insufficiency: Avoid: Codeine, morphine, pethidine, dextropropoxyphene and tramadol. N02AX Medicines that may accumulate and require renal function monitoring: Tramadol N02AX Recommendations for opioid prescribing in renal failure: Recommended with caution - tramadol; methadone N02AX Tramadol - GFR 30-49 reduce dose 25% N02AX Tramadol if CrCl <30 - CNS adverse effects - immediate release reduce dose and extended release avoid N06AX Duloxetine - CrCl <30ml/min 30mg once daily N06AX Duloxetine - no adjustment if eGFR 30-60; initially 40mg with careful increase if eGFR <30 or in RRT N06AX Duloxetine if CrCl <30 - increased GI adverse effects - avoid N06AX Medicines that may accumulate and require renal function monitoring: Duloxetine N06AX Use of doluxetine is not normally recommended for patients with ESRD or for patients with a creatinine clearance <30 N06AX Mirtazapine - GFR 10-29 reduce dose 50% N06AX Mirtazapine - GFR 30-49 reduce dose 25% N06AX Mirtazapine - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR <30 or in RRT N02BE Acetaminophen - Increase dosing interval to every six hours if GFR* equals 10-50 milliliters/minute; increase dosing interval to every eight hours if GFR is less than 10 mL/minute N02BE Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Acetaminophen and derivatives N02BE Paracetamol - GFR 25-59ml/min recommended maximum dose 2500mg/day N03AX Medicines that may accumulate and require renal function monitoring: Pregabalin N03AX Pregabalin - CrCl 30-60ml/min 300mg in 1 or 2 doses; CrCl 15-30ml/min 150mg in 1 or 2 doses; CrCl <15ml/min 75mg as single dose N03AX Levetiracetam - CrCl 50-79ml/min 500-1000mg twice daily; CrCl 30-49ml/min 250-750mg twice daily; CrCl <30ml/min 250-500mh twice daily N03AX Levetiracetam if CrCl < or equal to 80 - CNS adverse effects - reduce dose N03AX Medicines that may accumulate and require renal function monitoring: Levetiracetam N02A In patients with renal insufficiency: Least likely to cause harm: Fentanyl, buprenorphine and oxymorphone. N02A In patients with renal insufficiency: Use with caution: Hydromorphone and oxycodone. N02AA Medicines that may accumulate and require renal function monitoring: Hydromorphone N02A Recommendations for opioid prescribing in renal failure: Limited information available - buprenorphine; hydrmorphone; oxycodone; oxymorphone; tapentadol N02AA Codeine - GFR 30-49 reduce dose 50% N02AA Medicines that may accumulate and require renal function monitoring: Codeine N02AA Paracetamol with codeine - GFR 10-29 avoid use of codeine N02A Recommendations for opioid prescribing in renal failure: Not recommended - codeine; hydrocodone; morphine N02AA Medicines that may accumulate and require renal function monitoring: Oxycodone N02A Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Opioids N02A Opioids - Reduce dose if GFR is < 60 mL/min/1.73 m2. Use with caution when GFR is < 15 mL/min/1.73 m2 N04BC Drugs requiring dosing adjustments in impaired renal function: Apomorphine N02AA Medicines that may accumulate and require renal function monitoring: Morphine N05AX Medicines that may accumulate and require renal function monitoring: Paliperidone N05AX Paliperidone - CrCl 50-80ml/min 6mg once daily; CrCl 30-50ml/min 3mg once daily/avoid injection; CrCl 10-30ml/min 3mg once daily; CrCl <10ml/min avoid use N04BC Medicines that may accumulate and require renal function monitoring: Pramipexole N04BC Pramipexole - CrCl 20-50ml/min 2.25mg once daily; CrCl <20 1.5mg once daily N06DX Medicines that may accumulate and require renal function monitoring: Memantine N06DX Memantine - CrCl 5-29ml/min 10mg once daily N05 Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Psycholeptics (including lithium) N05AN Lithium - measure calcium and serum lithium levels at start of treatment; 3 monthly renal function; 6 monthly thyroid function, calcium, weight and serum lithium levels N05AN Medicines that may accumulate and require renal function monitoring: Lithium N05AN Nephrotoxic Medications: Lithium N05AN Patients on lithium therapy for bipolar disorder should have plasma creatinine cncentrations measured at least annually N06AX Desvenlafaxine - initially 25mg with careful increase if eGFR 30-60; 25g daily if GFR <30 or in RRT N06AX Medicines that may accumulate and require renal function monitoring: Desvenlafaxine N06AX Medicines that may accumulate and require renal function monitoring: Venlafaxine N06AX Venlafaxine - no adjustment if eGFR 30-60; 37.5-112.5mg if eGFR <30 N07BB Drugs requiring dosing adjustments in impaired renal function: Acamprosate calcium N07BB Medicines that may accumulate and require renal function monitoring: Acamprosate N05BA Diazepam - reduce doses by 33% to 50% if GFR is less than 30 mL/minute N05CD Flurazepam - reduce doses by 33% to 50% if GFR is less than 30 mL/minute N05BA Chlordiazepoxide - reduce doses by 33% to 50% if GFR is less than 30 mL/minute N05BA Medicines that may accumulate and require renal function monitoring: Benzidiazepines N07BA Medications requiring dose adjustments at variable GFR thresholds: Varenciline N07BA Medicines that may accumulate and require renal function monitoring: Varenicline N07BA Varenicline - CrCl <30ml/min 1mg daily N06AA Clomipramine - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT N06AA Desipramine - no adjustment if eGFR 15-60; initially 25mg with carfeul increase if eGFR <15 or in RRT N06AA Imipramine - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT N06AA Lofepramine - no adjustment if eGFR 15-60; initially 140mg with careful increase if eGFR <15 or in RRT N06AA Trimipramine - no adjustment if eGFR 15-60; initially 50g with careful increase if eGFR <15 or in RRT N06AX Bupropion - CrCl ≼50ml/min 150mg once daily N06AX Buproprion - 150mg daily if eGFR <60 or in RRT Amitriptylinoxide - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR 15-30; 15-150mg daily if eGFR <15 or in RRT

Dibenzepine - no adjustment if eGFR 30-60; initially 240mg with careful increase if eGFR <30 or in RRT Dosulepine - no adjustment if eGFR 30-60; initially 75mg with careful increase if eGFR <30 or in RRT Drug - CrCl - maximum dosing recommendation (mg) Methysergide - <50 - avoid use Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Psychoanaleptics Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Antiepileptics Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Dopaminergic agents Drugs requiring dosing adjustments in impaired renal function: Almotriptan malate Drugs requiring dosing adjustments in impaired renal function: Oxacarbazepine Drugs that need special attention in chronic kidney disease: Narcotic analgesics

Escitalopram - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT Maprotiline - no adjustment if eGFR 30-60; initially 50mg with careful increase if eGFR <30 or in RRT Medicines that may accumulate and require renal function monitoring: Amisulpride Medicines that may accumulate and require renal function monitoring: Buproprion Medicines that may accumulate and require renal function monitoring: Galantamine Medicines that may accumulate and require renal function monitoring: Methysergide Medicines that may accumulate and require renal function monitoring: Reboxetine Medicines that may accumulate and require renal function monitoring: Topiramate

Milnacipran - initially 25mg with careful increase if eGFR 30-60; 25-50mg if eGFR <30 or in RRT

Protryptiline - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR <30 or in RRT

Selegiline - initally 5mg with careful increase if eGFR 30-60; 5mg daily if eGFR <30 or in RRT Sertraline - no adjustment if eGFR 30-60; initially 50mg with careful increase if eGFR 15-30; 25mg and consider reducing max dose if eGFR <15 or in RRT Tianeptine - initially 12.5mg with careful increase if eGFR 30-60; 12.5-25mg if eGFR <30 or in RRT Tranylcypromine - no adjustment if eGFR 30-60; initially 30mg with careful increase if eGFR <30 or in RRT Trazadone - no adjustment if eGFR 15-60; initially 150mg with careful increase if eGFR <15 or in RRT Valproate - ascertain haematological and hepatic history and measre serum valproate levels at start of treatment; 3 monthly weight; 6 monthly FBC, LFTs, and serum valproate levels; measure blood pressure, lipid profile and fasting glucose in patients with risk factors, monitor for menstrual irregularities For patients aged 65 and over: Gabapentin and pregabalin should have reduced doses at specified levels of CrCl Gabapentin - Can cause altered mental status, myoclonus and asterixis with severe CKD/ESRD. GFR 30-59 mL/min: 200-700 mg twice daily, GFR 15-29 mL/min: 200-700 mg once per day, GFR <15 mL/min: 300 every other day, hemodialysis: 200-300 mg after each dialysis. Extended release: GFR 30-59 mL/min: 600-1,800 mg once per day, GFR < 30 mL/min to ESRD—not recommended Gabapentin - CrCl 50-79ml/min 600-1800mg daily in 3 doses; CrCl 30-49ml/min 300-900 in 2/3 doses; CrCl 15-29ml/min 600mg daily in 2/3 doses; CrCl <15ml/min 300mg daily

Medicines that may accumulate and require renal function monitoring: Gabapentin Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); >15-29 - 200-700mg/day - 200, 300, 400, 500, 700 given qd Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); >30-59 - 400-1400mg/day - 200, 300, 400, 500, 700 given bid Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); ≽60 - 900-3600mg/day - 300, 400, 600, 800, 1200 given tid Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); 15 - 100-300mg/day - 100, 125, 150, 200, 300 given qd Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); Haemodialysis (Patients on hemodialysis should receive maintenance doses based on estimates of Clcr and supplemental doses after 4 hours of hemodialysis ) - 125, 150, 200, 250, 350 [post dialysis supplemental dose] Drug - CrCl - maximum dosing recommendation (mg) Gabapentin - <15 - 300 daily In patients with renal insufficiency: Avoid: Codeine, morphine, pethidine, dextropropoxyphene and tramadol. Medicines that may accumulate and require renal function monitoring: Tramadol Recommendations for opioid prescribing in renal failure: Recommended with caution - tramadol; methadone

Tramadol if CrCl <30 - CNS adverse effects - immediate release reduce dose and extended release avoid

Duloxetine - no adjustment if eGFR 30-60; initially 40mg with careful increase if eGFR <30 or in RRT

Medicines that may accumulate and require renal function monitoring: Duloxetine Use of doluxetine is not normally recommended for patients with ESRD or for patients with a creatinine clearance <30

Mirtazapine - no adjustment if eGFR 30-60; initially 15mg with careful increase if eGFR <30 or in RRT Acetaminophen - Increase dosing interval to every six hours if GFR* equals 10-50 milliliters/minute; increase dosing interval to every eight hours if GFR is less than 10 mL/minute Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Acetaminophen and derivatives

Medicines that may accumulate and require renal function monitoring: Pregabalin Pregabalin - CrCl 30-60ml/min 300mg in 1 or 2 doses; CrCl 15-30ml/min 150mg in 1 or 2 doses; CrCl <15ml/min 75mg as single dose Levetiracetam - CrCl 50-79ml/min 500-1000mg twice daily; CrCl 30-49ml/min 250-750mg twice daily; CrCl <30ml/min 250-500mh twice daily

Medicines that may accumulate and require renal function monitoring: Levetiracetam In patients with renal insufficiency: Least likely to cause harm: Fentanyl, buprenorphine and oxymorphone. In patients with renal insufficiency: Use with caution: Hydromorphone and oxycodone. Medicines that may accumulate and require renal function monitoring: Hydromorphone Recommendations for opioid prescribing in renal failure: Limited information available - buprenorphine; hydrmorphone; oxycodone; oxymorphone; tapentadol

Medicines that may accumulate and require renal function monitoring: Codeine

Recommendations for opioid prescribing in renal failure: Not recommended - codeine; hydrocodone; morphine Medicines that may accumulate and require renal function monitoring: Oxycodone Drugs requiring dosage adjustment in patients with impaired kidney function and aged 65 and over: Opioids Opioids - Reduce dose if GFR is < 60 mL/min/1.73 m2. Use with caution when GFR is < 15 mL/min/1.73 m2

Medicines that may accumulate and require renal function monitoring: Morphine Medicines that may accumulate and require renal function monitoring: Paliperidone Paliperidone - CrCl 50-80ml/min 6mg once daily; CrCl 30-50ml/min 3mg once daily/avoid injection; CrCl 10-30ml/min 3mg once daily; CrCl <10ml/min avoid use Medicines that may accumulate and require renal function monitoring: Pramipexole

Medicines that may accumulate and require renal function monitoring: Memantine

Drugs contraindicated in patients with impaired kidney function and aged 65 and over: Psycholeptics (including lithium) Lithium - measure calcium and serum lithium levels at start of treatment; 3 monthly renal function; 6 monthly thyroid function, calcium, weight and serum lithium levels

Patients on lithium therapy for bipolar disorder should have plasma creatinine cncentrations measured at least annually Desvenlafaxine - initially 25mg with careful increase if eGFR 30-60; 25g daily if GFR <30 or in RRT Medicines that may accumulate and require renal function monitoring: Desvenlafaxine Medicines that may accumulate and require renal function monitoring: Venlafaxine

Drugs requiring dosing adjustments in impaired renal function: Acamprosate calcium Medicines that may accumulate and require renal function monitoring: Acamprosate

Chlordiazepoxide - reduce doses by 33% to 50% if GFR is less than 30 mL/minute Medicines that may accumulate and require renal function monitoring: Benzidiazepines Medications requiring dose adjustments at variable GFR thresholds: Varenciline Medicines that may accumulate and require renal function monitoring: Varenicline

Clomipramine - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT Desipramine - no adjustment if eGFR 15-60; initially 25mg with carfeul increase if eGFR <15 or in RRT Imipramine - no adjustment if eGFR 30-60; initially 10mg with careful increase if eGFR <30 or in RRT Lofepramine - no adjustment if eGFR 15-60; initially 140mg with careful increase if eGFR <15 or in RRT Trimipramine - no adjustment if eGFR 15-60; initially 50g with careful increase if eGFR <15 or in RRT Valproate - ascertain haematological and hepatic history and measre serum valproate levels at start of treatment; 3 monthly weight; 6 monthly FBC, LFTs, and serum valproate levels; measure blood pressure, lipid profile and fasting glucose in patients with risk factors, monitor for menstrual irregularities

Gabapentin - Can cause altered mental status, myoclonus and asterixis with severe CKD/ESRD. GFR 30-59 mL/min: 200-700 mg twice daily, GFR 15-29 mL/min: 200-700 mg once per day, GFR <15 mL/min: 300 every other day, hemodialysis: 200-300 mg after each dialysis. Extended release: GFR 30-59 mL/min: 600-1,800 mg once per day, GFR < 30 mL/min to ESRD—not recommended Gabapentin - CrCl 50-79ml/min 600-1800mg daily in 3 doses; CrCl 30-49ml/min 300-900 in 2/3 doses; CrCl 15-29ml/min 600mg daily in 2/3 doses; CrCl <15ml/min 300mg daily

Recommendations for gabapentin dose adjustment (CrCl ml/min - dose mg/day - dosage regimen); Haemodialysis (Patients on hemodialysis should receive maintenance doses based on estimates of Clcr and supplemental doses after 4 hours of hemodialysis ) - 125, 150, 200, 250, 350 [post dialysis supplemental dose] Acetaminophen - Increase dosing interval to every six hours if GFR* equals 10-50 milliliters/minute; increase dosing interval to every eight hours if GFR is less than 10 mL/minute