09. Drugs Requiring Adjustment in Renal Failure

Antihyperglycemics

  • Prescribing guidelines recommend against metformin in individuals with CKD or severe AKI due to rare risk of lactic acidosis. However, follow-up studies suggest safety in mild to moderate kidney CKD (eGFR >30) with proper dose adjustment (max 1000mg daily GFR 30-45). Though holding metformin on admission is not studied, practice is to hold metformin in favor of insulin sliding scale. Consider restarting home metformin a few days before discharge if renal function stable.
  • Glipizide preferred to other oral sulfonylureas (e.g., glyburide has renally cleared active metabolite that can precipitate hypoglycemia).
  • Adjust insulin as it is partially renally cleared and could build up in renal failure.

Antihypertensives

  • Diuretics: avoid HCTZ when Cr >2.5 or GFR <30, loop diuretics preferred in this situation. Eplerenone and aldactone are often discontinued to avoid hyperkalemia.
  • ACEI/ARBs: although these medications have the potential to decrease GFR (esp. in CHF or those using NSAIDs and/or diuretics), the beneficial effects (slowing progression of CKD, arrest of proteinuria and decreased BP) often outweigh detrimental effects. Can be used safely when started at reduced dose and increased gradually.
  • Beta blockers: atenolol and nadolol are cleared renally and need dose adjustments. Metoprolol, propranolol and labetalol do not need dose adjustment (liver clearance).
  • Clonidine, calcium channel blockers and alpha blockers do not require dose adjustment.

Antimicrobials

Consult pharmacist for dosing:

  • Imipenem/cilastin metabolites increase in CKD causing seizures. Consider meropenem.
  • Cefepime (and high dose PCN) can lead to neuromuscular toxicity, myoclonus, altered mental status, seizure and coma.
  • Nitrofurantoin: metabolites can accumulate, causing peripheral neuropathy.
  • Avoid aminoglycosides when possible, monitor levels closely if essential.

Pain Medications

  • Morphine, codeine, meperidine and propoxyphene are metabolized and cleared via the kidney. Beware oversedation and respiratory depression.
  • Hydromorphone (Dilaudid) and oxycodone are hepatically cleared and preferred. Methadone and fentanyl are OK in renal failure.
  • Choosing Wisely: avoid NSAID use.

Other Common Medications Requiring Renal Dose Adjustment

  • Allopurinol.
  • H2 blockers (PPIs do not need dose adjustment).
  • Statins in patients with GFR <30 (no adjustment for atorvastatin).
  • Digoxin: reduced clearance in CKD and ESRD, not dialyzable.
  • Gabapentin.
  • Chemotherapeutic agents.
  • Lithium.

 

Inzucchi S, Lipska KJ. Metformin in Type 2 Diabetes and Kidney Disease: A systematic review. JAMA. 2014;312(24):2668-2675.

Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician 2007;75:1498-1496.

Perazella MA, Parikh C. Pharmacology. Am J Kidney Dis 2005;46:1129-1139.

UpToDate, Drug Prescribing in Renal Failure: Dosing Guidelines. American College of Physicians, Sanford Guide for Antibiotics