Are there any interactions between famotidine (H2 receptor antagonist) and metronidazole (antibiotic) in a patient with acid reflux or peptic ulcer disease?

No Clinically Significant Interaction Between Famotidine and Metronidazole

There are no known drug interactions between famotidine and metronidazole, and these medications can be safely used together. 1, 2

Pharmacokinetic and Metabolic Profile

Famotidine Metabolism

• Famotidine is primarily eliminated unchanged through renal excretion (70% after intravenous administration), with minimal hepatic metabolism 2
• Famotidine does not bind to the cytochrome P-450 system and therefore has extremely low potential for drug-drug interactions 1
• Unlike cimetidine, famotidine does not alter hepatic metabolism of other drugs 3, 4
• Famotidine has low plasma protein binding (15-22%), further reducing interaction potential 2

Metronidazole Metabolism

• Metronidazole is metabolized hepatically but does not share metabolic pathways with famotidine 5
• The combination of metronidazole with famotidine has been studied in clinical trials without safety concerns 5

Clinical Evidence Supporting Safety

Direct Combination Studies

• A randomized controlled trial specifically evaluated triple therapy (bismuth, tetracycline, metronidazole) combined with either famotidine 40 mg nightly or omeprazole for H. pylori eradication 5
• The famotidine plus metronidazole combination was well-tolerated with mild and infrequent side effects comparable to the omeprazole group 5
• Compliance exceeded 95% in patients taking both medications together 5

H2 Receptor Antagonist Safety Profile

• Among H2 receptor antagonists, only cimetidine has significant cytochrome P-450 interactions (inhibiting CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) 1
• Ranitidine interacts only weakly with cytochrome P-450 1
• Famotidine and nizatidine do not bind to the cytochrome P-450 system at all 1

Practical Clinical Considerations

Dosing Recommendations

• Standard famotidine dosing (20-40 mg daily) can be used without adjustment when combined with metronidazole 3, 5
• No timing separation between doses is required 5

Monitoring

• No specific laboratory monitoring is needed for this drug combination beyond what is indicated for each medication individually 2
• Routine assessment for therapeutic efficacy and adverse effects of each drug should proceed as usual 3

Common Pitfall to Avoid

• Do not confuse famotidine with cimetidine—cimetidine has extensive drug interactions through cytochrome P-450 inhibition, while famotidine does not 1, 2