Famotidine

Famotidine is a competitive, reversible histamine H2 receptor antagonist that reduces basal, nocturnal and stimulated gastric acid secretion. It is the most potent widely available H2 receptor antagonist, has no meaningful cytochrome P450 inhibition and is renally cleared, so dose reduction in kidney impairment is essential.

Classification. H2 receptor antagonist; gastric antisecretory agent.

Mechanism. Blocks histamine at basolateral H2 receptors on parietal cells, reducing cyclic AMP-driven pump activity. Effect is strongest on nocturnal and basal secretion and weaker on meal-stimulated secretion, where gastrin and acetylcholine still drive acid output.

Pharmacodynamics. Onset within 1 hour; duration 10 to 12 hours. Tolerance develops within days of continuous dosing, particularly with IV use, which limits long-term efficacy compared with PPIs.

Pharmacokinetics. Oral bioavailability 40 to 45%; protein binding 15 to 20%; half-life 2.5 to 3.5 hours, rising to over 20 hours in anuria.

Elimination. About 65 to 70% of a dose is excreted unchanged by the kidney through filtration and tubular secretion; minor hepatic metabolism.

Adult oral doses unless stated. Doses assume creatinine clearance (CrCl) over 60 mL/min.

Duodenal ulcer. 40 mg at night or 20 mg twice daily for 4 to 8 weeks. Maintenance 20 mg at night.

Benign gastric ulcer. 40 mg at night for 4 to 8 weeks.

GORD.

• Symptomatic reflux: 20 mg twice daily for up to 6 weeks.

• Erosive oesophagitis: 40 mg twice daily for up to 12 weeks. A PPI is more effective and is preferred.

• Maintenance: 20 mg twice daily.

Episodic heartburn and dyspepsia. 10 to 20 mg as needed, up to twice daily; maximum 40 mg daily, for no more than 2 weeks without review.

Zollinger-Ellison syndrome. Start 20 mg every 6 hours and titrate to acid output; doses up to 160 mg every 6 hours have been used. A PPI is preferred.

Nocturnal acid breakthrough on twice daily PPI. 20 to 40 mg at bedtime, used intermittently because tolerance develops within a week.

Prevention of acid aspiration. 40 mg orally the evening before and 40 mg 2 hours before surgery, or 20 mg IV 1 hour before induction.

Parenteral use. 20 mg IV every 12 hours, switching to oral when possible.

Adjunct in refractory urticaria and allergic reactions. 20 mg orally or IV twice daily, added to an H1 antihistamine. It has no place as a substitute for adrenaline in anaphylaxis.

Paediatric dosing.

• Age under 3 months, GORD: 0.5 mg/kg orally once daily for up to 8 weeks.

• Age 3 to 12 months, GORD: 0.5 mg/kg orally twice daily for up to 8 weeks.

• Age 1 to 16 years, GORD: 0.5 mg/kg orally twice daily, maximum 40 mg each dose.

• Age 1 to 16 years, peptic ulcer: 0.5 mg/kg at bedtime or divided twice daily, maximum 40 mg daily.

Contraindications. Hypersensitivity to famotidine or other H2 receptor antagonists.

Before starting. Endoscopy first for alarm features: new dyspepsia over age 55, weight loss, dysphagia, bleeding, iron deficiency anaemia, persistent vomiting or a mass.

Common adverse effects. Headache, dizziness, constipation and diarrhoea.

Serious adverse effects.

• CNS effects: confusion, delirium, hallucinations and seizures, mainly in older adults and with unadjusted doses in kidney impairment.

• QT prolongation, reported with renal impairment and unadjusted dosing.

• Rare thrombocytopenia, agranulocytosis, cholestatic hepatitis, interstitial nephritis and severe cutaneous reactions.

• Bradycardia and hypotension with rapid IV injection.

Major interactions.

• No clinically relevant CYP inhibition, unlike cimetidine.

• Reduced absorption of drugs needing gastric acid: ketoconazole, itraconazole capsules, dasatinib and oral iron. Avoid with dasatinib.

• Atazanavir: give famotidine at least 12 hours apart and boost atazanavir; follow dose limits for the H2 receptor antagonist.

• Rilpivirine: give famotidine at least 12 hours before or 4 hours after rilpivirine.

• Tizanidine: famotidine may raise levels; avoid or monitor for hypotension and sedation.

• QT prolonging drugs: additive risk when famotidine is not dose adjusted in kidney impairment.

Special groups.

• Pregnancy: human data are reassuring; acceptable when an H2 receptor antagonist is needed.

• Breastfeeding: low milk transfer; famotidine is the H2 receptor antagonist of choice during breastfeeding.

• Children: weight-based dosing; infants under 3 months need once daily dosing because of immature renal clearance.

• Older adults: reduced renal function raises the risk of delirium; calculate CrCl before dosing and use the lowest dose.

• Liver impairment: no dose adjustment.

• Regional: ranitidine was withdrawn worldwide in 2020 over N-nitrosodimethylamine contamination, leaving famotidine as the main H2 receptor antagonist.

Kidney impairment (oral dosing).

For IV dosing at CrCl under 50 mL/min, give 20 mg once daily. On haemodialysis, give the dose after dialysis.

Formulations. Tablets 10 mg, 20 mg and 40 mg; oral suspension 40 mg in 5 mL; injection 10 mg/mL. IV availability varies by market.

Oral administration. May be taken with or without food. For episodic heartburn, take 15 to 60 minutes before the trigger meal.

IV administration.

• Bolus: dilute 20 mg to 5 to 10 mL with sodium chloride 0.9% and inject over at least 2 minutes.

• Infusion: dilute 20 mg in 100 mL glucose 5% or sodium chloride 0.9% and infuse over 15 to 30 minutes.

• Rapid injection causes hypotension and bradycardia.

Baseline. Creatinine and calculated CrCl in older adults and anyone with suspected kidney disease.

Monitoring.

• Mental state in older adults and in kidney impairment; stop if confusion develops.

• ECG when used with other QT prolonging drugs or in significant kidney impairment.

• Review response at 4 to 8 weeks; switch to a PPI if healing fails.

• Stop at least 24 hours (some laboratories advise 48 hours) before H. pylori breath testing.

Therapeutic drug monitoring. Not applicable.

Stopping. No taper needed. Stop for delirium, cytopenia, rising liver enzymes or rash.

Referral and escalation. Endoscopy for alarm features or failure to respond. Urgent review if CNS toxicity occurs in kidney impairment; famotidine is partly removed by haemodialysis.