44. Drug dosage in renal failure Appendix: Drug dosing in renal failure Abbreviations used: ACE: angiotensin-converting enzyme AV: atrioventricular BUN: blood urea nitrogen CCr: Creatinine clearance CAPD: continuous ambulatory peritoneal dialysis CHF: congestive heart failure CMV: cytomegalovirus CNS: central nervous system CRRT: continuous renal replacement therapy CSA/FK: cyclosporine A and tacrolimus CVD: cardiovascular disease CVVH: Continuous venovenous hemofiltration DVT: deep vein thrombosis ESRD: end-stage renal disease GI: gastrointestinal GFR: glomerular filtration rate HBV: hepatitis B virus HD: hemodialysis HDL: high-density lipoprotein HIT: heparin-induced thrombocytopenia HSV: herpes simplex virus INR: international normalized ratio IV: intravenous MI: myocardial infarction MMF: mycophenolate mofetil NA: not applicable NC: No data: no change required NSAIDs: nonsteroidal anti-inflammatory drugs TB: tuberculosis TDM: therapeutic drug monitoring VD: volume of distribution VZV: varicella zoster virus. 919 920 Table 2 . Antibacterial agents % of drug Dosage adjustment for renal failure with GFR Method of dosage adjustment Drug Normal dosage excreted (ml/min): Comments renally >50 10−50 <10 HD CAPD CVVH Aminoglycosides Group toxicity: all agents in this group are nephrotoxic and ototoxic; ototoxicity is worse when the patient is hyperbilirubinemic; measure serum levels for efficacy and toxicity; peritoneal absorption increases with presence of inflammation. V increases with edema, obesity, and ascites D Streptomycin 7.5 mg/kg q. 12 hr 60% q. 24 hr q. 24−72 hr q. 72−96 hr May be less nephrotoxic than other Half normal 20−40 mg/L/ Dose for GFR (1.0 g q. 24 hr members of class dose after day 10−50 ml/min; for TB) dialysis measure levels Kanamycin 7.5 mg/kg q. 8 hr 50%−90% 60%−90% q. 30%−70% q. 20%−30% q. Avoid once-daily dosing in patients Half full 15−20 mg/L/ Dose for GFR 12 hr; 12−18 hr; 100% 24−48 hr; 100% with CCr < 30−40 ml/min or in patients dose after day 10−50 ml/min; 100% q. 12− q. 24−48 hr q. 48−72 hr with acute renal failure or an uncertain dialysis measure levels 24 hr level of kidney function Gentamicin 1.7 mg/kg q. 8 hr 95% 60%−90% q. 30%−70% q. 20%−30% q. Concurrent penicillin treatment may Half full 3−4 mg/L/day Dose for GFR 8−12 hr; 100% 12−18 hr; 100% 24−48 hr; 100% result in subtherapeutic aminoglycoside dose after 10−50 ml/min; q. 12−24 hr q. 24-48 hr q. 48−72 hr levels dialysis measure levels Peak, 6−8; trough, < 2 Tobramycin 1.7 mg/kg q. 8 hr 95% 60%−90% q. 30−70% q. 20−30% q. Concurrent penicillin treatment may Half full 3−4 mg/L/day Dose for GFR 8−12 hr; 100% 12−18 hr; 100% 24−48 hr; 100% result in subtherapeutic aminoglycoside dose after 10−50 ml/min, BENNETT & OLYAEI q. 12−24 hr q. 24-48 hr q. 48−72 hr levels dialysis measure levels Peak, 6−8; trough, < 2 Netilmicin 2 mg/kg q. 8 hr 95% 50%−90% q. 20−60% q 12 10−20% q. May be less ototoxic than other mem- Half full 3−4 mg/L/day Dose for GFR 8−12 hr; 100% hr; 100% q 24−48 hr; 100% bers of class dose after 10−50 ml/min; q. 12−24 hr 24−48 hr q 48−72 hr Peak, 6−8; trough, < 2 dialysis measure levels Amikacin 7.5 mg/kg q. 12 hr 95% 60%−90% q. 30−70% q. 20−30% q. Monitor levels Half full 15−20 mg/L/ Dose for GFR 12 hr: 100% q. 12−18 hr; 100% 24−48 hr; 100% Peak, 20−30; trough, <5 dose after day 10−50 ml/min; 12−24 hr q. 24−48 hr q. 48−72 hr dialysis measure levels Cephalosporins (oral) Group toxicity: Adverse effects: coagulation abnormalities, transitory elevation of BUN, rash, and serum sicknesslike syndrome Cefaclor 250−500 mg 70% 100% 100% 50% Group toxicity 250 mg after 250 mg q. 8− No data q. 8 hr dialysis 12 hr Cefadroxil 500 mg to 1 g q. 80% 100% 100% 50% Group toxicity 0.5−1.0 g 0.5 g/day No data 12 hr after dialysis Cefixime 200−400 mg q. 85% 100% 100% 50% Group toxicity 300 mg after 200 mg/day Not recom- 12 hr dialysis mended Cefpodoxime 200 mg q. 12 hr 30% 100% 100% 100% Group toxicity 200 mg after Dose for No data dialysis GFR<10 ml/min Ceftibuten 400 mg q. 24 hr 70% 100% 100% 50% Group toxicity 300 mg after No data: Dose Dose for GFR dialysis for GFR <10 10−50 ml/min ml/min Cefuroxime 250−500 mg 90% 100% 100% 100% Malabsorbed in presence of H2 blockers; Dose after Dose for No data axetil q. 8 hr absorbed better with food dialysis GFR<10 ml/min Cephalexin 250−500 mg 95% 100% 100% 100% Rare allergic interstitial nephritis; ab- Dose after Dose for No data q. 8 hr sorbed well when given intraperitone- dialysis GFR<10 ml/min ally; may cause bleeding from impaired prothrombin biosynthesis % of drug Dosage adjustment for renal failure with GFR Method of dosage adjustment Drug Normal dosage excreted (ml/min): Comments renally >50 10−50 <10 HD CAPD CVVH Cephradine 250−500 mg 100% 100% 100% 50% Rare allergic interstitial nephritis; ab- Dose after Dose for No darta q. 8 hr sorbed well when given intraperitone- dialysis GFR<10 ml/min ally; may cause bleeding from impaired prothrombin biosynthesis Cephalosporins (IV) Group toxicity: may cause coagulation abnormalities, transitory elevation of BUN, rash, and serum sicknesslike syndrome Cefamandole 1−2 g IV q. 6−8 hr 100% q. 6 hr q. 8 hr q. 12 hr Group toxicity 0.5−1.0 g 0.5−1.0 g q. Dose for GFR after dialysis 12 hr 10−50 ml/min Cefazolin 1−2 g IV q. 8 hr 80% q. 8 hr q. 12 hr q. 12−24 hr Group toxicity 0.5−1.0 g 0.5 g q. 12 hr Dose for GFR after dialysis 10−50 ml/min Cefepime 1−2 g IV q. 8 hr 85% q. 8−12 hr q. 12 hr q. 24 hr Group toxicity 1 g after Dose for GFR < Not recom- dialysis 10 ml/min mended Cefmetazole 1−2 g IV q. 8 hr 85% q. 8 hr q. 12 hr q. 24 hr Group toxicity Dose after Dose for GFR Dose for GFR dialysis <10 ml/min 10−50 ml/min Cefoperazone 1−2 g IV q. 12 hr 20% No renal adjustment required. Displaced from protein by bilirubin; may 1 g after NC NC prolong prothrombin time; reduce dose dialysis failure 44. Drugdosageinrenal by 50% in patients with jaundice Cefotaxime 1−2 g IV q. 6−8 hr 60% q. 8 hr q. 12 hr q. 12−24 hr Group toxicity 1 g after 1 g/day 1 g q. 12 hr dialysis Cefotetan 1−2 g IV q. 12 hr 75% q. 12 hr q. 12−24 hr q. 24 hr Group toxicity 1 g after 1 g/day 750 mg q. 12 hr dialysis Cefoxitin 1−2 g IV q. 6 hr 80% q. 6 hr q. 8−12 hr q. 12 hr May produce false increase in serum 1 g after 1 g/day Dose for GFR creatinine level by interference with dialysis 10−50 ml/min assay Ceftazidime 1−2 g IV q. 8 hr 70% q. 8 hr q. 12 hr q. 24 hr Group toxicity 1 g after 0.5 g/day Dose for GFR dialysis 10−50 ml/min Ceftriaxone 1−2 g IV q. 24 hr 50% No renal adjust- Dose after di- 750 mg q. 12 hr Dose for ment required alysis GFR 10−50 ml/min Cefuroxime 0.75−1.5 g IV q. 90% q. 8 hr q. 8−12 hr q. 12−24 hr Absorbed well when given intraperito- Dose after Dose for GFR 1.0 g q. 12 hr sodium 8 hr neally; may cause rare allergic interstitial dialysis <10 nephritis; may cause bleeding from impaired prothrombin biosynthesis Clindamycin 150−450 mg q. 10% No renal adjustment required Increase CSA/FK level NC NC NC 8 hr Imipenem- 250−500 mg IV 50% 500 mg q. 8 hr 250−500 q. 250 mg q. 12 hr Causes seizures in ESRD; nonrenal clear- Dose after Dose for GFR Dose for GFR cilastatin q. 6 hr 8−12 hr ance in acute renal failure is less than dialysis <10 ml/min 10−5 ml/min in chronic renal failure; administer with cilastin to prevent nephrotoxicity of renal metabolite Macrolides Azithromycin 250−500 mg q. 6% No renal adjustment required No drug-drug interaction with CSA/KF NC NC NC 24 hr Clarithromycin 500 mg q. 12 hr 20% No renal adjustment required NC NC NC 921 Dirithromycin 500 mg q. 24 hr No renal adjustment required Nonenzymatically hydrolyzed to active NC NC Dose for GFR compound erythromycylamine. 10−50 ml/min 922 % of drug Dosage adjustment for renal failure with GFR Method of dosage adjustment Drug Normal dosage excreted (ml/min): Comments renally >50 10−50 <10 HD CAPD CVVH Erythromycin 250−500 mg q. 15% No renal adjustment required Increase CSA/FK levels; avoid in NC NC NC 8 hr transplant patients Meropenem 1 g IV q. 8 hr 65% 1 g q. 8 hr 0.5−1g q. 12 hr 0.5−1 g q.