CIMETIDINE HYDROCHLORIDE
Clinical safety rating: safe
Inhibits CYP450 enzymes increasing levels of many drugs (eg warfarin phenytoin) Mental confusion and dizziness are more common in elderly or severely ill patients.
Competitive antagonist of histamine at H2-receptors on gastric parietal cells, reducing basal and stimulated gastric acid secretion.
| Metabolism | Hepatic metabolism via CYP1A2, CYP2C19, CYP2D6, and CYP3A4; also undergoes renal tubular secretion. |
| Excretion | Renal (60-70% unchanged), biliary/fecal (30-40% as metabolites) |
| Half-life | 2-3 hours; prolonged in renal impairment (creatinine clearance <30 mL/min: up to 4-5 hours); clinical context: short half-life necessitates twice-daily dosing for chronic therapy |
| Protein binding | 15-20%; primarily to albumin |
| Volume of Distribution | 1.0-2.4 L/kg; clinical meaning: extensive distribution into tissues, including gastric mucosa and central nervous system |
| Bioavailability | Oral: 60-70% (increased to ~80% with hepatic impairment); IM: 90-100% |
| Onset of Action | Oral: 30-45 minutes; IM: 10-15 minutes; IV: 5-10 minutes; onset defined as reduction in gastric acid secretion |
| Duration of Action | 4-6 hours (single dose); clinical note: duration sufficient for twice-daily dosing in acid suppression due to sustained H2-receptor blockade |
300 mg orally or IV/IM every 6 hours or 400 mg orally at bedtime; maximum 2400 mg/day.
| Dosage form | SOLUTION |
| Renal impairment | CrCl <30 mL/min: 300 mg every 12 hours; CrCl 30-50 mL/min: 300 mg every 8 hours. |
| Liver impairment | No specific adjustment, but caution in severe hepatic impairment; consider reducing dose. |
| Pediatric use | Neonates: 5-10 mg/kg orally every 12 hours; Infants/Children: 10-20 mg/kg/day divided every 6-12 hours; maximum 800 mg/day. |
| Geriatric use | Reduce dose or increase dosing interval due to age-related renal impairment; dosing similar to renal adjustment. |
| 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.
| FDA category | Animal |
| Breastfeeding | Cimetidine is excreted into human breast milk with an M/P ratio of approximately 1.6 to 5.1. Milk concentrations are similar to or slightly higher than maternal plasma concentrations. A nursing infant would receive less than 10% of the maternal dose (weight-adjusted). No adverse effects in infants have been reported. Consider alternative agents with more safety data. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | GERD |
| Serious Effects |
Hypersensitivity to cimetidine or any component of the formulation.
| Precautions | May cause confusion, delirium, hallucinations, especially in elderly or renally impaired; monitor renal function; adjust dose in renal impairment; potential for drug interactions via CYP450 inhibition; may mask symptoms of gastric malignancy; long-term use associated with vitamin B12 deficiency; may increase risk of Clostridioides difficile infection; use with caution in immunosuppressed patients. |
Loading safety data…
| Cimetidine crosses the placenta. Available data from human studies do not indicate an increased risk of major congenital anomalies or adverse fetal outcomes with use during pregnancy; however, clinical experience is limited. In the first trimester, no known teratogenic effect. In second and third trimesters, no consistent fetal harm reported; however, cimetidine can inhibit cytochrome P450 and theoretically affect fetal steroid metabolism. Use only if clearly needed. |
| Fetal Monitoring | Monitor maternal liver function, renal function, and CBC if long-term therapy. No specific fetal monitoring required. For high-dose or prolonged use, consider monitoring for potential maternal vitamin B12 deficiency (cimetidine can reduce B12 absorption). |
| Fertility Effects | Cimetidine is a known antiandrogen at high doses, potentially causing decreased sperm count, reduced sperm motility, and gynecomastia in males due to prolactin elevation and androgen receptor blockade. In females, cimetidine can inhibit estradiol metabolism but clinical effect on fertility is uncertain. Reversible upon discontinuation. |