Famotidine: Clinical Overview
Indications
Famotidine is FDA-approved for peptic ulcer disease (duodenal and gastric ulcers), gastroesophageal reflux disease (GERD), erosive esophagitis, and pathological hypersecretory conditions including Zollinger-Ellison syndrome. 1, 2
- Treatment of active duodenal and gastric ulcers 1
- Maintenance therapy for prevention of duodenal ulcer recurrence 1
- GERD and erosive esophagitis 3, 1
- Zollinger-Ellison syndrome and other hypersecretory conditions 1, 2
- Stress ulcer prophylaxis in critically ill patients (low-dose ≤40 mg daily preferred) 4
- Perioperative gastric acid reduction when oral administration not feasible 4
- Preferred over PPIs in patients on dual antiplatelet therapy (clopidogrel) as it does not interfere with antiplatelet activity 5, 6
Dosing Regimens
Prescription Dosing
For GERD/heartburn: Start with famotidine 20 mg twice daily, providing approximately 6 hours of acid suppression per dose. 6
- Peptic ulcer disease (active): 40 mg once daily at bedtime OR 20 mg twice daily 1
- GERD/erosive esophagitis: 20 mg twice daily initially; if inadequate response at 4 weeks, increase to 40 mg twice daily or switch to PPI 6, 3
- Maintenance therapy (ulcer prevention): 20 mg once daily at bedtime 1
- Zollinger-Ellison syndrome: Individualized dosing, mean 330 mg/day in divided doses; doses up to 800 mg daily have been tolerated 1, 2
- Perioperative acid suppression (IM): 20 mg intramuscularly, providing approximately 6 hours of effect 4
- Infusion reaction management (IV): 20 mg IV for moderate hypersensitivity reactions 5
- Premedication for patisiran infusion: 20 mg as part of premedication protocol 5
OTC Dosing
- Heartburn relief/prevention: 10-20 mg once or twice daily 1
- Maximum OTC duration: Should not exceed 2 weeks without physician consultation 6
Renal Dose Adjustments
Famotidine elimination half-life is prolonged nonlinearly in renal insufficiency, requiring dose reduction. 7, 8
- CrCl <50 mL/min: Reduce dose by 50% OR increase dosing interval to every 36-48 hours 7
- Famotidine is 70% eliminated unchanged in urine via both glomerular filtration and tubular secretion 7
- Hemodialysis, peritoneal dialysis, and hemofiltration do NOT significantly remove famotidine 7
- Elderly patients often require dose reduction due to age-related decline in renal function 7
Important Clinical Limitations
Critical Efficacy Consideration
PPIs are superior to H2-receptor antagonists like famotidine for healing esophagitis and symptom relief (Grade A recommendation from American Gastroenterological Association). 6
- PPIs heal erosive esophagitis in 69-71% of patients at 12 weeks versus 54-60% with H2 blockers 6
- If no response after 8 weeks on famotidine, consider treatment failure and perform endoscopy with prolonged wireless pH monitoring off medication 6
Tachyphylaxis
Tachyphylaxis can develop within 6 weeks of initiating H2-receptor antagonist therapy, requiring periodic assessment of continued need. 4
Pharmacokinetics
- Oral bioavailability: 40-50% due to incomplete absorption 7, 8
- Peak plasma concentration: 1-3 hours after oral administration 7, 8
- Onset of antisecretory effect: Within 1 hour orally 8
- Duration of action: 10-12 hours orally 8
- Elimination half-life: 2.8 hours in healthy subjects 8
- Protein binding: Low (15-22%) 7
- Volume of distribution: 1.0-1.3 L/kg 7
Side Effects and Tolerability
Famotidine has an excellent tolerability profile with minimal adverse effects in an estimated 18.8 million patients treated worldwide since 1985. 2
- Generally well tolerated with no clinically significant adverse effects in most patients 1, 2
- Free of antiandrogenic effects (unlike cimetidine) 1
- Well tolerated in patients with cardiovascular, renal, or hepatic dysfunction 2
- No notable binding to cytochrome P-450 or gastric alcohol dehydrogenase 2
Contraindications
- Hypersensitivity to famotidine or other H2-receptor antagonists 2
- No other absolute contraindications identified in clinical use 2
Drug Interactions
Famotidine has minimal drug interaction potential and does not affect hepatic oxidative drug metabolism. 7, 2
- Does NOT interfere with clopidogrel antiplatelet activity (major advantage over PPIs in patients on dual antiplatelet therapy) 5, 6
- Potent antacids reduce oral absorption by 20-30% when coadministered 7
- No clinically important interactions with other drugs described to date 8, 2
Pregnancy Considerations
- Pregnancy category information not explicitly provided in the evidence reviewed
- Safety profile suggests generally well tolerated, but specific pregnancy data requires consultation of FDA labeling 2
Special Populations
Elderly Patients
- Dose reduction often necessary due to decreased renal function 7
- Increased risk of side effects; consult Beers Criteria for potentially inappropriate medication use 5
Hepatic Dysfunction
- Liver cirrhosis does not affect famotidine disposition unless severe renal insufficiency coexists 7
Critically Ill Patients
- For stress ulcer prophylaxis: Use low-dose famotidine (≤40 mg daily); enteral route preferred when GI tract functional 4