Is Pepcid (famotidine) nephrotoxic?

Pepcid (Famotidine) Is Not Nephrotoxic But Requires Dose Adjustment in Renal Impairment

Pepcid (famotidine) is not considered nephrotoxic, but it requires dose adjustment in patients with moderate to severe renal impairment due to reduced clearance. 1

Pharmacokinetics and Renal Handling

• Famotidine is primarily eliminated through the kidneys (approximately 70% excreted unchanged in urine), with both glomerular filtration and tubular secretion as elimination mechanisms 2, 3
• The drug has a normal elimination half-life of 2-4 hours in patients with normal renal function 3
• In patients with renal impairment, the elimination half-life increases significantly:
  • Normal renal function: 2.59 hours
  • Moderate renal failure (CrCl 30-60 ml/min): 4.72 hours
  • Severe renal failure (CrCl <30 ml/min): 12.07 hours 2

Safety in Renal Function

• Unlike many other medications that can directly damage kidney structures, famotidine does not cause direct nephrotoxicity 1
• The FDA label for famotidine does not list nephrotoxicity as an adverse effect, which distinguishes it from known nephrotoxic drugs 1
• This contrasts with medications like aminoglycosides (streptomycin, amikacin, kanamycin) which are documented to cause direct nephrotoxicity 4

Dose Adjustment Requirements

• Dose adjustment is required in patients with moderate to severe renal impairment:
  • No dose adjustment needed for mild renal impairment (CrCl ≥60 ml/min)
  • For moderate renal impairment (CrCl 30-60 ml/min): reduce dose by 50%
  • For severe renal impairment (CrCl <30 ml/min): reduce dose by 75% 2, 1
• These adjustments are necessary due to reduced drug clearance rather than nephrotoxicity concerns 3

Central Nervous System Considerations

• The primary concern with famotidine in renal impairment is the risk of CNS adverse effects rather than nephrotoxicity
• CNS adverse reactions (confusion, delirium, hallucinations, disorientation, agitation, seizures, lethargy) have been reported in elderly patients and those with moderate to severe renal impairment 1
• These CNS effects occur due to higher blood levels of famotidine in patients with impaired renal function 1

Comparison to Known Nephrotoxic Drugs

• Unlike documented nephrotoxic agents such as aminoglycosides which can cause direct kidney damage, famotidine does not have this property 4
• For example, streptomycin causes nephrotoxicity in about 2% of patients requiring discontinuation 4
• Amikacin and kanamycin cause renal impairment in 8.7% of patients, with higher rates in those with pre-existing renal issues 4
• Capreomycin causes significant renal toxicity requiring discontinuation in 20-25% of patients 4

Clinical Implications

• Famotidine is generally considered safe from a renal perspective and can be used in patients with kidney disease with appropriate dose adjustments 1, 5
• Monitoring of renal function is prudent but not due to nephrotoxicity concerns - rather to guide appropriate dosing 1
• In elderly patients, use the lowest effective dose and monitor renal function due to age-related decline in kidney function 1

Hemodialysis Considerations

• Famotidine is not significantly removed by hemodialysis, peritoneal dialysis, or hemofiltration 6, 3
• This differs from known nephrotoxic drugs like aminoglycosides, which require specific timing around dialysis sessions 4

In summary, while famotidine requires careful dosing in renal impairment, it does not cause direct kidney damage and is not considered nephrotoxic in the way that many other medications are.