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).