H2-receptor antagonist (antiulcer)
Cimetidine is a medicine that reduces stomach acid, used to treat stomach and duodenal ulcers, gastro-oesophageal reflux disease and conditions in which the stomach produces too much acid. It is also available over the counter in low doses for occasional heartburn.
Also known as: Cimetidina, Tagamet
Warfarin + cimetidine: cimetidine increases the anticoagulant effect of warfarin — QUADRO 2 records the increased anticoagulant effect as a documented cimetidine interaction.
Cimetidine is a non-selective CYP450 inhibitor (including CYP2C9, the main enzyme metabolising active S-warfarin), so it reduces warfarin clearance and raises INR in a clinically relevant way. QUADRO 2 of Annex 7 lists cimetidine among the drugs that increase the effect of oral anticoagulants. The effect is dose-dependent and usually appears within the first days of starting cimetidine. Patients with previously stable INR are the most exposed to bleeding, especially the elderly and those on multiple drugs. If an H2 blocker is needed, prefer famotidine or a proton pump inhibitor (no relevant CYP2C9 interaction); if cimetidine is kept, intensify INR monitoring and adjust the warfarin dose.
Warfarin + cimetidine: cimetidine inhibits warfarin metabolism and increases INR — bleeding risk; monitor INR when starting, adjusting or stopping cimetidine.
Cimetidine inhibits the hepatic microsomal enzymes (CYP2C9 and others) that metabolise warfarin, increasing its levels and the anticoagulant effect (QUADRO 2, Cimetidine: "Warfarin: increased anticoagulant effect").
Monitor INR after starting/stopping cimetidine.
INR above target or bleeding after starting cimetidine.
Prefer a non-inhibiting H2 antagonist (famotidine) or a PPI; if cimetidine is unavoidable, reduce the warfarin dose and adjust by INR.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Cimetidine)
Acenocoumarol + cimetidine: cimetidine inhibits coumarin metabolism and increases INR — bleeding risk; monitor when starting, adjusting or stopping.
QUADRO 2 (Warfarin) lists cimetidine among drugs that increase the anticoagulant effect with bleeding risk. Cimetidine inhibits the CYP enzymes (including CYP2C9 and CYP3A4) responsible for coumarin metabolism, raising concentrations and anticoagulant effect.
Monitor INR in the first days after starting or stopping cimetidine.
Elevated INR or bleeding after starting cimetidine.
Consider an alternative H2 antagonist (e.g. famotidine) that does not inhibit CYP; if cimetidine is kept, watch INR and reduce the anticoagulant dose if needed.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, Table 2 (Oral anticoagulants: Acenocoumarol — see Warfarin; Cimetidine)
Cimetidine has no clinically significant food interaction; absorption is not relevantly affected by food.
May be taken with or without food; usual dosing is after meals and at bedtime.
DailyMed/FDA (NIH/NLM) — approved Cimetidine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c0a509-026f-44e0-9975-a94a8de51d43
FDA label (DOSAGE AND ADMINISTRATION): in severe renal impairment, the recommended dose is 300 mg every 12 hours; the frequency may be increased to every 8 hours with caution; in severe renal failure accumulation may occur and the lowest frequency compatible with an adequate response should be used.
Reduce dose in severe renal impairment; haemodialysis removes the drug — time the dose to the end of dialysis.
DailyMed/FDA (NIH/NLM) — Cimetidine, DOSAGE AND ADMINISTRATION: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c0a509-026f-44e0-9975-a94a8de51d43
FDA label (Pregnancy, Category B): reproduction studies in rats, rabbits and mice at up to 40× the normal human dose with no evidence of impaired fertility or fetal harm; no adequate and well-controlled studies in pregnant women — use only if clearly needed.
Category B: use only if clearly needed (no adequate studies in pregnant women).
The label does not detail excretion in breast milk; cimetidine is excreted in human milk (literature data).
Not applicable (no specific contraception requirements in the label).
DailyMed/FDA (NIH/NLM) — approved Cimetidine label, Pregnancy section: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c0a509-026f-44e0-9975-a94a8de51d43
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Antiulcer: H2-receptor antagonist — reduces basal and stimulated gastric acid secretion, including nocturnal and post-meal secretion (FDA label).
Competitive blockade of histamine H2 receptors on gastric parietal cells; dose-dependent inhibition of cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2D6, CYP3A4) — the basis of pharmacokinetic interactions.
Rapid oral absorption; peak plasma levels 45-90 minutes after oral administration (FDA label Pharmacokinetics).
Extensively metabolised (the sulfoxide is the main metabolite); renal excretion of the drug and metabolites (48% of a single oral dose recovered in urine within 24 h).
Half-life of approximately 2 hours; concentrations remain above those required for 80% inhibition of basal gastric acid secretion for 4-5 hours after 300 mg.
