Non-ARV Drug Dosing: Renal Insufficiency

Selected Non-ARV Drugs Requiring Dosage Adjustment in Renal Insufficiency
Therapeutic class
< and drugs
CLCRT threshold for adjustmenta,b Additional informationc
ANTIBACTERIALSd
Fluoroquinolones
Ciprofloxacin ≤ 60 mL/min  
Levofloxacin ≤ 50 mL/min  
Ofloxacin ≤ 50 mL/min  
Cephalosporins
Cefpodoxime ≤ 40 mL/min  
Ceftazidime ≤ 50 mL/min  
Cefepime ≤ 50 mL/min  
Penicillins
Amoxicillin/clavulanate ≤ 30 mL/min  
Benzylpenicillin (parenteral) ≤ 60 mL/min  
Piperacillin/tazobactam ≤ 40 mL/min  
Aminoglycosides
Amikacin ≤ 70 mL/min Dose dependent oto- and nephrotoxicity. Avoid in renal insufficiency if alternatives otherwise perform TDM
Gentamicin ≤ 70 mL/min
Tobramycin ≤ 70 mL/min
Miscellaneous
Nitrofurantoin    
Trimethoprim-sulfamethoxazole ≤ 30 mL/min  
Vancomycin ≤ 50 mL/min Dose dependent nephrotoxicity. TDM recommended
Antimycotics
Fluconazole ≤ 50 mL/min No adjustment in single dose therapy
Antivirals
Ribavirin ≤ 50 mL/min  
Valaciclovir variable Dose adjustment depends on indication and person characteristics (< 30, < 50 or < 75 mL/min)
Antimycobacterials
Ethambutol ≤ 30 mL/min  
Antithrombotics
Apixaban < 50 mL/min Dose adjustment depends on indication and person characteristics. It may be required for CLCRT < 50 mL/min. Avoid if CLCRT < 15 mL/min
Dabigatran ≤ 50 mL/min Contraindicated if CLCRT < 30 mL/min
Edoxaban ≤ 50 mL/min Avoid if CLCRT < 15 mL/min
Enoxaparin < 30 mL/min Dose adjustment depends on indication and person characteristics.
Rivaroxaban < 50 mL/min Dose adjustment depends on indication and person characteristics. It may be required for CLCRT < 50 mL/min. No dose adjustment if recommended dose is 10 mg qd
Avoid if CLCRT < 15 mL/min
BETA BLOCKERS
Atenolol ≤ 35 mL/min  
Sotalol ≤ 60 mL/min  
ACE INHIBITORS
Enalapril ≤ 80 mL/min Dose adjustment for starting dose
Lisinopril ≤ 80 mL/min Dose adjustment for starting dose
Perindopril < 60 mL/min  
Ramipril < 60 mL/min  
CARDIOTONIC AGENT
Digoxin ≤ 100 mL/min Dose adjustment for maintenance and loading dose. Avoid in renal insufficiency if alternatives
ANTIDIABETICS
Biguanide
Metformin < 60 mL/min Contraindicated if CLCRT < 30 mL/min
GLP1-agonist
Exenatide ≤ 50 mL/min Avoid if CLCRT < 30 mL/min
DPP4-inhibitors
Alogliptin ≤ 50 mL/min  
Saxagliptin < 45 mL/min  
Sitagliptin < 45 mL/min  
Vildagliptin < 50 mL/min  
SGLT2-inhibitors
Canagliflozin < 60 mL/min Should not be initiated if CLCRT < 60 mL/min. Dose adjustment if CLCRT falls below 60 mL/min during treatment, and stop if CLCRT < 45 mL/min (lack of efficacy)
Dapagliflozin - Should not be initiated if CLCRT < 60 mL/min. Stop if CLCRT < 45 mL/min (lack of efficacy)
Empagliflozin < 60 mL/min Should not be initiated if CLCRT < 60 mL/min. Dose adjustment if CLCRT falls below 60 mL/min during treatment, and stop if CLCRT < 45 mL/min (lack of efficacy)
GOUT MEDICATION
Allopurinol ≤ 50 mL/min  
Colchicine ≤ 50 mL/min Dose dependent toxicity. Routine monitoring of colchicine adverse reactions recommended
ANTIPARKINSON DRUG
Pramipexole ≤ 50 mL/min Dose adjustment depends on indication
ANALGESICS
NSAIDs - Avoid chronic use in persons with any stage of renal insufficiency
Morphine - Risk of respiratory depression in persons with renal insufficiency due to accumulation of 6-morphine-glucuronide (highly active metabolite). Avoid if alternatives; or titration to adequate pain control with close monitoring for signs of overdose
Oxycodone < 50 mL/min Initial dosage: reduced dose at initiation and further titration to adequate pain control and close monitoring for signs of overdose
Tramadol < 30 mL/min Increase dosing interval to 8-12 hours. Maximum daily dose 200 mg
ANTIEPILEPTICS
Gabapentin < 80 mL/min  
Levetiracetam < 80 mL/min  
Pregabalin < 60 mL/min  
PSYCHOLEPTIC
Lithium < 90 mL/min Reduced dose and slow titration. TDM recommended. Avoid if CLCRT < 30 mL/min
DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (DMARDs)
Methotrexate (low dose) < 60 mL/min Dose dependent toxicity. Contraindicated if CLCRT < 30 mL/min

Legend

  1. Renal function estimated for dosage adjustment mostly based on Cockcroft formula (CLCRT: creatinine clearance)
  2. For persons with creatinine clearance < 15 mL/min or persons on dialysis, a nephrologist should be consulted
  3. The drug package insert should be consulted for specific dose adjustments
  4. No dose adjustment on antibacterial loading dose

[1], [8], [9]