Pharmacology · H2 receptor antagonists (H2 blockers)

Famotidine !

The H2 blocker of choice now that ranitidine is gone: it lowers stomach acid with few interactions. Its dose is reduced when the kidneys are weak.

Updated 2026-11-01

Class: H2 receptor antagonists (H2 blockers)
Receptor: Histamine H2 receptor
ATC code: A02BA03

Histamine H2 receptorFamotidine

Cryo-EM structure of the human H2 receptor in its inactive state with famotidine in the histamine pocket (antibody fragments were added to help imaging).

Target in 3D: Histamine H2 receptor. PDB structure 7UL3 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Famotidine competes with histamine at the H2 receptor of the gastric parietal cell. With the receptor blocked, Gs is not activated, cAMP does not rise and the proton pump receives less stimulus. Both the acidity and the volume of gastric juice fall; basal and nocturnal secretion are inhibited most, and secretion after food or gastrin is also reduced.

Famotidine occupies the histamine site of the parietal cell's H2 receptor
Gs and cAMP stay off, so the pump gets less stimulus
Basal and night-time acid fall most
Ulcers and oesophagitis heal in a less acid stomach

Pharmacokinetics

Absorption: Incompletely absorbed: oral bioavailability is about 40–45%; also given IV.
Distribution: Only 15–20% bound to plasma proteins.
Metabolism: Little first-pass metabolism; the only known metabolite is the S-oxide.
Elimination: Mostly by the kidney (65–70%), with some tubular secretion; levels rise several-fold in moderate to severe kidney impairment.
Half-life: About 2.5–3.5 hours.
Onset and duration: Acid falls within an hour of an oral dose; the effect lasts about 10–12 hours.

Indications

Active duodenal and gastric ulcer, and lowering the risk of duodenal ulcer recurrence. Peptic ulcer disease →
Symptomatic reflux and erosive oesophagitis. Gastro-oesophageal reflux disease (GERD) →
Zollinger–Ellison syndrome and other hypersecretory states. Zollinger-Ellison syndrome (gastrinoma) →

Adverse effects

Common

Headache
Dizziness
Constipation

Contraindications

Serious hypersensitivity to famotidine or another H2 receptor antagonist

Key interactions

Drugs that need gastric acid to be absorbed (dasatinib, atazanavir, ketoconazole, itraconazole, rilpivirine): Less absorption and loss of effect; some combinations are not recommended.
Tizanidine: Famotidine weakly inhibits CYP1A2 and may raise tizanidine levels (low blood pressure, slow pulse, drowsiness).

What is monitored

Kidney function (creatinine clearance) to adjust the dose
Mental status in older adults and in kidney impairment
Persistent or relapsing symptoms, which call for a search for gastric cancer

Administration and safety

Oral forms can be given with or without food
The IV form is given in hospital when the patient cannot take it by mouth
A good symptom response does not rule out gastric cancer in adults; alarm symptoms are evaluated

Nursing care

Review creatinine before starting and in older adults, because the dose depends on kidney function
Watch for new confusion or agitation, mainly in older or kidney patients
Check the medication list for acid-dependent drugs such as some antiretrovirals and antifungals
Teach the patient to report black stools, vomiting blood or weight loss

Pregnancy and breastfeeding

Data in pregnant women are not enough to set a risk; animal studies showed no harm, and it is used when needed.

Test yourself

Think of the answer, then tap the question to see it.

Why must the famotidine dose be lowered in moderate to severe kidney impairment?

Most of it is eliminated unchanged by the kidney; exposure rises and with it the risk of confusion, seizures and QT prolongation.

What advantage does famotidine have over cimetidine regarding interactions?

It barely inhibits cytochrome P450 enzymes, so it does not raise warfarin, phenytoin or theophylline levels.

Which H2 blocker was withdrawn in Colombia in 2020, and which replaced it?

Ranitidine, withdrawn in the US and in Colombia in 2020 because of the NDMA impurity, although it is still on the WHO Model List of Essential Medicines; famotidine and cimetidine are the alternatives.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - FAMOTIDINE tablet (DailyMed (U.S. National Library of Medicine), 2026); Medications for the Treatment of Gastric Acidity - Gastroenterology - MSD Manual Professional Edition (MSD Manual Professional Edition, 2025); Alerta sanitaria sobre retiro del mercado Ranitidina | Invima (Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA), 2020); RCSB PDB - 7UL3: CryoEM Structure of Inactive H2R Bound to Famotidine, Nb6M, and NabFab (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.