CIMETIDINE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Histamine H2-receptor antagonist that competitively inhibits the action of histamine on parietal cells of the stomach, reducing gastric acid secretion (basal and stimulated).

What the body does with it

Metabolism	Primarily hepatic metabolism via CYP1A2, CYP2C19, CYP2D6, and CYP3A4; forms cimetidine sulfoxide and other metabolites.
Excretion	Renal (70% unchanged via tubular secretion), hepatic metabolism (30%), minimal fecal excretion. Clearance is primarily renal, requiring dose adjustment in renal impairment.
Half-life	Terminal elimination half-life ~2 hours (prolonged to >5 hours in renal impairment, ~20 hours in anephric patients).
Protein binding	~20% bound to plasma proteins (mainly albumin). Low binding minimizes displacement interactions.
Volume of Distribution	1.2–1.8 L/kg, indicating extensive tissue distribution (e.g., crosses placenta and blood-brain barrier in low amounts).
Bioavailability	Oral: 60–80% (first-pass metabolism). IM: 90–100%. IV: 100%.
Onset of Action	Oral: ~45 minutes (peak effect at 1–2 hours); IV: immediate (within minutes); IM: 15–30 minutes.
Duration of Action	Oral: 4–6 hours (single dose); continuous IV infusion provides sustained effect. Note: Rapid IV administration may cause transient hypotension.

Classification & Brands

Dosing & administration

300 mg IV/IM every 6 hours or 300-600 mg orally every 6 hours; maximum 2400 mg/day.

Dosage form	TABLET
Renal impairment	GFR 10-50 mL/min: 50% dose or 300 mg every 12 hours; GFR <10 mL/min: 25% dose or 300 mg every 24 hours.
Liver impairment	No specific Child-Pugh guidelines; use caution and consider dose reduction in severe impairment.
Pediatric use	Neonates: 10-20 mg/kg/day IM/IV divided every 6-12 hours; Infants/Children: 20-40 mg/kg/day orally divided every 6 hours; maximum 300 mg/dose.
Geriatric use	In elderly with normal renal function, use lowest effective dose; reduce dose if renal impairment present.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Inhibits CYP450 enzymes increasing levels of many drugs (eg warfarin phenytoin) Mental confusion and dizziness are more common in elderly or severely ill patients.

Breastfeeding	Cimetidine is excreted into breast milk with a milk-to-plasma ratio of approximately 4.6 to 12.0. After a single 400 mg oral dose, peak milk concentration ~6 mcg/mL; estimated infant dose ~6% of maternal weight-adjusted dose. Theoretical risk of gastric pH alteration and H2 blockade in infant. Use with caution; alternative agents (e.g., famotidine) preferred due to lower excretion.
Teratogenic Risk	AU TGA pregnancy category B1. No evidence of teratogenicity in animal studies. Limited human data: no increased risk of major malformations based on observational studies. First trimester: no documented teratogenic effects. Second/third trimester: potential risk of transient neonatal liver enzyme elevation and mild CNS depression if used near term. Avoid in pregnancy unless clearly needed.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	GERD
Serious Effects

Absolute Contraindications

["Hypersensitivity to cimetidine or any H2-receptor antagonist"]

Clinical Precautions

Precautions

["Confusion and other CNS effects (especially in elderly or renally impaired)","Gynecomastia and impotence with prolonged high doses","Increased serum creatinine (reversible)","Drug interactions via CYP450 inhibition (warfarin, theophylline, phenytoin, etc.)","Use in pregnancy: Only if clearly needed (category B)","Lactation: Excreted in breast milk; caution"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…