Pharmacology · H2 receptor antagonists (H2 blockers)
Cimetidine !
The first H2 blocker. It lowers stomach acid but inhibits liver enzymes and has antiandrogen effects, so it causes more interactions than famotidine.
Updated 2026-11-01
No structure of cimetidine in the H2 receptor exists; the figure shows famotidine, another H2 blocker, in the same histamine pocket of the human receptor.
Mechanism of action
Cimetidine competes with histamine at the H2 receptor of the parietal cell and lowers basal, nocturnal and food-stimulated acid secretion. Separately, its imidazole ring binds cytochrome P450 enzymes in the liver and slows the metabolism of many drugs. It also blocks androgen receptors weakly, which explains gynaecomastia with prolonged use, and competes with creatinine for tubular secretion.
- Cimetidine blocks histamine at the parietal cell's H2 receptor
- Less cAMP signal: basal and nocturnal acid fall
- Its imidazole ring also inhibits liver CYP enzymes
- Other drugs build up; weak antiandrogen effects appear
Pharmacokinetics
- Absorption
- Rapidly absorbed by mouth; peak levels in 45–90 minutes.
- Metabolism
- Partly in the liver; the sulfoxide is the main metabolite.
- Elimination
- Mainly in the urine, about half as unchanged drug.
- Half-life
- About 2 hours.
Indications
- Active duodenal ulcer and benign gastric ulcer, and maintenance after a duodenal ulcer heals. Peptic ulcer disease →
- Erosive oesophagitis from reflux. Gastro-oesophageal reflux disease (GERD) →
- Zollinger–Ellison syndrome, systemic mastocytosis and other hypersecretory states. Zollinger-Ellison syndrome (gastrinoma) →
Adverse effects
Common
- Headache, dizziness and drowsiness
- Diarrhoea
- Small rise in serum creatinine without real kidney damage
- Gynaecomastia with prolonged use
Contraindications
- Hypersensitivity to cimetidine
Key interactions
- Warfarin
- Slower warfarin metabolism; the INR (prothrombin time) rises and is monitored closely.
- Phenytoin, theophylline and lidocaine
- Higher levels with clinical toxicity reported.
- Propranolol, nifedipine, diazepam, chlordiazepoxide, tricyclic antidepressants, metronidazole
- Slower elimination and higher blood levels.
- Ketoconazole and other acid-dependent drugs
- Less absorption when gastric pH rises.
- Antacids taken at the same time
- They may reduce cimetidine absorption; the label does not recommend giving them together.
What is monitored
- INR in patients on warfarin, and levels of phenytoin or theophylline
- Mental status in older adults and in liver or kidney disease
- Breast changes or sexual problems with long courses
Administration and safety
- IV doses are not given as a rapid bolus, which has caused arrhythmias and hypotension
- Separated in time from antacids
- A response to treatment does not rule out gastric cancer
Nursing care
- Review the medication list for warfarin, phenytoin, theophylline and other drugs with a narrow margin
- Watch for confusion in older or very ill patients
- Explain that a slight rise in creatinine can be due to the drug and not to kidney damage
- Teach the patient to report breast swelling or tenderness
Pregnancy and breastfeeding
Animal studies showed no harm and there are no well-controlled studies in women; it is used in pregnancy only if clearly needed.
Test yourself
Think of the answer, then tap the question to see it.
Which feature of cimetidine's structure explains its many drug interactions?
Its imidazole ring binds and inhibits hepatic cytochrome P450 enzymes.
A man on long-term cimetidine for Zollinger–Ellison syndrome develops breast enlargement. What is the cause?
Cimetidine's weak antiandrogen effect.
Why can cimetidine raise serum creatinine without damaging the kidney?
It competes with creatinine for tubular secretion in the kidney.
Related drugs
Related conditions
← Back to the class: H2 receptor antagonists (H2 blockers)
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 - CIMETIDINE tablet, film coated (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); Cimetidine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.