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Non-ARV Drug Dosing: Renal Insufficiency
Selected Non-ARV Drugs Requiring Dosage Adjustment in Renal Insufficiency
|
Therapeutic class |
CLCRT threshold for adjustmenta,b | Additional informationc |
| ANTIBACTERIALSd | ||
| Fluoroquinolones | ||
| Ciprofloxacin | ≤ 60 mL/min | |
| Delafloxacin | < 30 mL/min | iv dosage: 200 mg every 12 hours; oral dosage: 450 mg every 12 hours |
| 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 | ||
| Solriamfetol | <60 mL/min | ≥30-60 mL/min: initial dose 37.5 mg daily, may increase to max 75 mg daily after at least 7 days based upon efficacy and tolerability <30 mL/min: max 37.5 mg daily <15 mL/min: not recommended |
| 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 | ||
| Nirmatrelvir/r | <60 mL/min |
≥30-60 mL/min: nirmatrelvir/r 150 /100 mg BID <30 mL/min incl. Hemodialysis*e |
| 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 | ||
| Eslicarbazepine | 30-60 mL/min | Start with a dose of 200 mg qd or 400 mg every other day for 2 weeks followed by 400 mg qd Not recommended in case of severe renal impairment |
| 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
- Renal function estimated for dosage adjustment mostly based on Cockcroft formula (CLCRT: creatinine clearance)
- For persons with creatinine clearance < 15 mL/min or persons on dialysis, a nephrologist should be consulted
- The drug package insert should be consulted for specific dose adjustments
- No dose adjustment on antibacterial loading dose
- The product label does not recommend nirmatrelvir/ritonavir for patients with eGFR <30 mL/min. However, on the basis of clinical, modelling and patient data, an adjusted dose given at a lower frequency has been proposed for use in people with eGFR <30 mL/min and those on dialysis. The adjusted dose of nirmatrelvir/ritonavir was found to be safe and well tolerated in a small sample of 134 maintenance dialysis patients (Hiremath S et al. Clin J Am Soc Nephrol 2023).
* Hiremath S et al. Prescribing nirmatrelvir/ritonavir for COVID-19 in advanced CKD. Clin J Am Soc Nephrol 2022