Famotidine - Drug Monograph

Introduction

Famotidine is a competitive histamine H₂-receptor antagonist that inhibits gastric acid secretion. First approved by the FDA in 1986, it remains a widely used medication for managing acid-related gastrointestinal disorders. Famotidine is available in both prescription and over-the-counter formulations under various brand names, including Pepcid.

Mechanism of Action

Famotidine competitively inhibits histamine at H₂ receptors of gastric parietal cells, resulting in reduced gastric acid secretion, decreased hydrogen ion concentration, and reduced pepsin production. Unlike proton pump inhibitors, famotidine does not require acid activation and provides more rapid onset of action, though with shorter duration of acid suppression.

Indications

• Treatment and maintenance of active duodenal ulcers
• Treatment of active benign gastric ulcers
• Management of gastroesophageal reflux disease (GERD)
• Treatment of pathological hypersecretory conditions (Zollinger-Ellison syndrome)
• Prophylaxis of stress ulceration in hospitalized patients
• Relief of heartburn, acid indigestion, and sour stomach (OTC indication)

Dosage and Administration

• Duodenal ulcer: 40 mg once daily at bedtime or 20 mg twice daily for 4-8 weeks
• Gastric ulcer: 40 mg once daily at bedtime
• GERD: 20 mg twice daily for up to 6 weeks
• Hypersecretory conditions: 20 mg every 6 hours, titrated based on response
• OTC use: 10-20 mg as needed for heartburn relief

• CrCl <30 mL/min: Reduce dose to 20 mg daily or extend dosing interval to 36-48 hours

• May be administered with or without food
• Tablets should be swallowed whole with water
• Oral suspension should be shaken well before use

Pharmacokinetics

• Absorption: Rapid but incomplete (40-45% bioavailability); not significantly affected by food
• Distribution: Protein binding: 15-20%; Volume of distribution: 1.1-1.4 L/kg
• Metabolism: Minimal hepatic metabolism (30-35%); primarily renal elimination unchanged
• Elimination: Half-life: 2.5-3.5 hours; prolonged in renal impairment
• Excretion: Primarily renal (65-70% unchanged in urine)

Contraindications

• Hypersensitivity to famotidine or other H₂ antagonists
• History of acute porphyria (may precipitate attacks)

Warnings and Precautions

• Cross-sensitivity: Possible with other H₂ antagonists
• Gastric malignancy: Symptoms may mask underlying malignancy
• Renal impairment: Requires dosage adjustment
• Hepatic impairment: Use with caution in severe liver disease
• Elderly: Increased risk of adverse CNS effects
• QT prolongation: Cases reported with high intravenous doses
• Blood dyscrasias: Thrombocytopenia reported rarely

Drug Interactions

• Ketoconazole/Itraconazole: Reduced absorption due to increased gastric pH
• Atazanavir: Reduced bioavailability (requires separation by several hours)
• Warfarin: Potential increased anticoagulant effect (monitor INR)
• Probenecid: May reduce renal clearance of famotidine
• Sucralfate: May reduce famotidine absorption (administer 2 hours apart)

Adverse Effects

• Headache
• Dizziness
• Constipation
• Diarrhea

• Dry mouth
• Fatigue
• Nausea/vomiting
• Abdominal discomfort

• Confusion (especially in elderly)
• Hepatitis, elevated liver enzymes
• Agranulocytosis, thrombocytopenia
• Bradycardia, AV block
• Anaphylaxis, Stevens-Johnson syndrome
• Gynecomastia (with long-term use)
• Vitamin B12 deficiency (with prolonged therapy)

Monitoring Parameters

• Efficacy: Symptom improvement, ulcer healing (endoscopy if indicated)
• Safety: Renal function (baseline and periodically)
• Adverse effects: Mental status changes (especially elderly)
• Long-term therapy: Vitamin B12 levels (if >2 years continuous use)
• Drug interactions: INR monitoring with concurrent warfarin use

Patient Education

• Take as directed; do not exceed recommended dosage
• OTC formulations should not be used for more than 14 days without medical consultation
• Report persistent symptoms, black stools, vomiting blood, or unexplained weight loss
• Be aware that antacids may be used concomitantly but should be separated by at least 1 hour
• Inform healthcare providers of all medications being taken
• Store at room temperature away from moisture
• Report any signs of infection (fever, sore throat) or unusual bruising/bleeding

References

1. FDA Prescribing Information: Pepcid (famotidine) 2. Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology. 2000;118(2 Suppl 1):S9-S31. 3. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10(6):528-534. 4. Thomson AB, Sauve MD, Kassam N, et al. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. 2010;16(19):2323-2330. 5. McQuaid KR, Laine L. A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures. Gastrointest Endosc. 2008;67(6):910-923. 6. Lexicomp Online, Lexi-Drugs. Famotidine. Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2023. 7. Micromedex Solutions. Famotidine. Truven Health Analytics, Inc.; 2023.