Pepcid - Drug Monograph

Introduction

Pepcid (famotidine) is a histamine-2 (H₂) receptor antagonist that reduces gastric acid secretion. First approved by the FDA in 1986, it has become a widely used medication for managing various acid-related gastrointestinal disorders. Famotidine is available in both prescription and over-the-counter formulations, offering flexibility in clinical management.

Mechanism of Action

Famotidine competitively inhibits histamine at H₂ receptors of parietal cells in the gastric mucosa. This action reduces basal and nocturnal gastric acid secretion, as well as acid secretion stimulated by food, histamine, pentagastrin, caffeine, and insulin. Unlike proton pump inhibitors, famotidine does not affect the H⁺/K⁺ ATPase enzyme system directly.

Indications

• Active duodenal ulcer
• Gastric ulcer
• Gastroesophageal reflux disease (GERD)
• Erosive esophagitis
• Pathological hypersecretory conditions (Zollinger-Ellison syndrome, multiple endocrine adenomas)
• Heartburn, acid indigestion, and sour stomach (OTC formulations)

• Stress ulcer prophylaxis in critically ill patients
• Prevention of NSAID-induced ulcers
• Adjunctive treatment in urticaria

Dosage and Administration

• Active 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 6 weeks
• Erosive esophagitis: 20-40 mg twice daily for up to 12 weeks
• Hypersecretory conditions: 20-160 mg every 6 hours (max 640 mg/day)
• OTC use: 10-20 mg for heartburn relief

• Renal impairment: CrCl <50 mL/min requires dose reduction (e.g., 20 mg at bedtime or 10 mg twice daily)
• Hepatic impairment: No specific adjustment needed
• Elderly: Consider renal function when dosing
• Pediatrics: 0.5-1 mg/kg/day divided every 12 hours (max 40 mg/day)

Pharmacokinetics

• Absorption: Rapid but incomplete (40-45% bioavailability); not significantly affected by food
• Distribution: Volume of distribution: 1.1-1.4 L/kg; Protein binding: 15-20%
• Metabolism: Minimal hepatic metabolism (cytochrome P450 system not involved)
• Elimination: Half-life: 2.5-3.5 hours; primarily renal excretion (65-70% unchanged in urine)
• Onset/Duration: Onset within 1 hour; duration 10-12 hours

Contraindications

• Hypersensitivity to famotidine or other H₂ receptor antagonists
• History of acute porphyria
• Concomitant use with certain HIV medications (atazanavir, rilpivirine)

Warnings and Precautions

• Cross-sensitivity: Possible with other H₂ antagonists
• GI malignancy: Symptoms may mask gastric malignancy
• Renal impairment: Increased risk of CNS adverse effects; dose adjustment required
• QT prolongation: Reported with intravenous administration in critically ill patients
• Vitamin B12 deficiency: Long-term use may reduce vitamin B12 absorption
• Bone fractures: Some observational studies suggest increased risk with long-term, high-dose use
• Pregnancy: Category B - Use only if clearly needed
• Lactation: Excreted in breast milk; use with caution

Drug Interactions

• Atazanavir: Reduced absorption and decreased efficacy (avoid combination)
• Rilpivirine: Decreased absorption and antiviral efficacy (contraindicated)
• Ketoconazole/Itraconazole: Reduced absorption of these antifungals
• Warfarin: Potential increased anticoagulant effect (monitor INR)
• Sucralfate: Reduced famotidine absorption (administer 2 hours apart)

Adverse Effects

• Headache (4.7%)
• Dizziness (1.3%)
• Constipation (1.2%)
• Diarrhea (1.7%)

• Fatigue
• Dry mouth
• Rash
• Elevated liver enzymes

• Thrombocytopenia
• Agranulocytosis
• Hepatitis
• Pancreatitis
• Bradycardia
• AV block
• CNS effects (confusion, hallucinations, especially in elderly or renal impairment)
• Anaphylaxis

Monitoring Parameters

• Efficacy: Symptom improvement, ulcer healing (endoscopy if indicated)
• Safety: Renal function (serum creatinine), CBC with prolonged therapy
• Adverse effects: Mental status changes (especially in elderly), cardiac monitoring with IV use in critically ill patients
• Long-term use: Vitamin B12 levels, bone density assessment consideration

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 any severe or persistent side effects, especially confusion or irregular heartbeat
• Inform healthcare providers of all medications being taken
• Avoid alcohol and smoking, which can worsen acid-related conditions
• Tablets may be crushed and mixed with water if swallowing difficulty occurs
• Store at room temperature away from moisture

References

1. Pepcid [package insert]. Whitehouse Station, NJ: Merck & Co.; 2021. 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. Sigterman KE, van Pinxteren B, Bonis PA, et al. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2013;(5):CD002095. 4. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10(6):528-534. 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. FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. U.S. Food and Drug Administration; 2010. 7. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine-2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.