Histamine H2 Receptor Antagonists

Histamine H2 receptor antagonists competitively block H2 receptors on parietal cells, reducing basal and nocturnal acid secretion by about 70 percent, with less effect on meal-stimulated secretion. They are weaker than proton pump inhibitors and lose effect within 3 to 14 days of continuous use through tachyphylaxis.

Pharmacokinetics. Oral bioavailability 40 to 60 percent. Renal elimination dominates, so accumulation occurs in kidney impairment. Cimetidine also inhibits several CYP enzymes.

• Famotidine 20 mg twice daily or 40 mg at night; intravenous 20 mg every 12 hours.
• Cimetidine 400 mg twice daily or 800 mg at night.
• Nizatidine 150 mg twice daily or 300 mg at night.
• Ranitidine 150 mg twice daily or 300 mg at night. It was withdrawn from many markets after nitrosamine contamination; availability varies.

Differences. Famotidine has the fewest interactions and is preferred. Cimetidine inhibits CYP1A2, CYP2D6 and CYP3A4 and has antiandrogen effects.

• Mild reflux or dyspepsia: on-demand or short courses when a proton pump inhibitor is unavailable or declined.
• Nocturnal acid breakthrough on a proton pump inhibitor: famotidine 20 to 40 mg at night, effective for only a few weeks.
• Duodenal ulcer: second-line to a proton pump inhibitor, 4 to 8 weeks.
• Stress ulcer prophylaxis: famotidine 20 mg intravenously every 12 hours when a proton pump inhibitor is unsuitable.
• Adjunct in allergic reactions: famotidine 20 mg intravenously with an H1 antihistamine in anaphylaxis after adrenaline, and in chronic urticaria.

Selection. Proton pump inhibitors are better for oesophagitis, bleeding and H. pylori eradication.

Contraindications. Hypersensitivity to the class.

Adverse effects. Headache, dizziness, constipation or diarrhoea. Confusion, delirium and hallucinations in older adults and kidney impairment. Rare thrombocytopenia and bradycardia after rapid intravenous injection. Cimetidine causes gynaecomastia and impotence.

Interactions.

• Cimetidine raises levels of warfarin, phenytoin, theophylline, lidocaine, carbamazepine and ciclosporin.
• Reduced absorption of ketoconazole, itraconazole, atazanavir and rilpivirine.

Special groups.

• Kidney impairment: with creatinine clearance under 50 mL/min halve the dose or double the interval; reduce further in severe impairment.
• Liver impairment: no adjustment.
• Pregnancy: famotidine is acceptable when needed.
• Breastfeeding: famotidine preferred; cimetidine less so.
• Children: famotidine about 0.5 mg/kg twice daily, maximum 20 mg a dose.
• Older adults: use the lowest dose; watch for confusion.

Monitoring. Renal function and mental state in older adults; INR when cimetidine is given with warfarin.

Referral and escalation. Alarm features (dysphagia, weight loss, bleeding, anaemia, persistent vomiting) need endoscopy rather than continued acid suppression.