Cimetidine

Class: Histamine H2-Antagonists

Brands: Tagamet

Medically reviewed by Drugs.com. Last updated on Nov 23, 2020.

Introduction

Histamine H2 receptor antagonist.

Uses for Cimetidine

Duodenal Ulcer

Short-term treatment of active duodenal ulcer (endoscopically or radiographically confirmed).

Maintainence of healing and reduction in recurrence of duodenal ulcer.

Pathologic GI Hypersecretory Conditions

Long-term treatment of Zollinger-Ellison syndrome, multiple endocrine adenomas, systemic

mastocytosis.

Gastric Ulcer

Short-term treatment of active benign gastric ulcer.

Gastroesophageal Reflux (GERD)

Short-term treatment of erosive esophagitis (endoscopically diagnosed) in patients with GERD.

Treatment of symptomatic GERD†.

Self-medication as initial therapy to achieve acid suppression, control symptoms, and prevent
complications of less severe symptomatic GERD†.

Upper GI Bleeding

Prevention of upper GI bleeding resulting from stress-related mucosal damage (erosive esophagitis,
stress ulcers) in critically ill patients.

Treatment of upper GI bleeding† secondary to hepatic failure, esophagitis, duodenal or gastric ulcers
when hemorrhage is not caused by major blood vessel erosion.

Heartburn (pyrosis), Acid Indigestion (hyperchlorhydria), or Sour Stomach

Short-term self-medication for relief of heartburn symptoms in adults and adolescents≥12 years of age.

Short-term self-medication for prevention of heartburn symptoms associated with acid indigestion
(hyperchlorhydria) and sour stomach brought on by ingestion of certain foods and beverages in adults
and children ≥12 years of age.

Cimetidine Dosage and Administration

Administration

Administer orally,

Oral Administration

Administer with or without food; administration with food may delay and slightly decrease absorption,
but achieves maximum antisecretory effect when stomach is no longer protected by food buffering
effect. Administer oral tablets with water.

Antacids may be given as necessary for pain relief, but not at the same time.

For duodenal ulcer treatment, administration once daily at bedtime is the regimen of choice because of
a high healing rate, maximal pain relief, decreased drug interaction potential, and maximal compliance.

For gastric ulcer treatment, administration once daily at bedtime is the regimen of choice because of
convenience and decreased drug interaction potential.
For gastroesophageal reflux, once-daily dosing is not considered appropriate.

Dosage of cimetidine hydrochloride expressed in terms of cimetidine.

Pediatric Patients

20–40 mg/kg daily in divided doses has been used in a limited number of children when potential
benefits are thought to outweigh the possible risks.

Heartburn, Acid Indigestion, or Sour Stomach

Heartburn Relief (Self-medication)

Oral

Adolescents ≥12 years of age: 200 mg once or twice daily, or as directed by a clinician.

Prevention of Heartburn (Self-medication)

Oral

Adolescents ≥12 years of age: 200 mg once or twice daily or as directed by a clinician; administer
immediately (or up to 30 minutes) before ingestion of causative food or beverage.

Adults

Duodenal Ulcer

Treatment of Active Duodenal Ulcer

Oral

Dosage of choice: 800 mg once daily at bedtime.

Patients with ulcer >1 cm in diameter who are heavy smokers (i.e., ≥1 pack daily) when rapid healing
(e.g., within 4 weeks) is considered important: 1.6 g daily at bedtime.
Administer for 4–6 weeks unless healing is confirmed earlier. If not healed or symptoms continue after 4
weeks, additional 2–4 weeks of full dosage therapy may be beneficial. More than 6–8 weeks at full
dosage is rarely needed.

Healing of active duodenal ulcers may occur in 2 weeks in some, and occurs within 4 weeks in most
patients.

Other regimens (no apparent rationale for these other than familiarity of use) that have been used: 300
mg 4 times daily with meals and at bedtime; 200 mg 3 times daily and 400 mg at bedtime; 400 mg twice
daily in the morning and at bedtime.

Maintenance of Healing of Duodenal Ulcer

Oral

400 mg daily at bedtime. Efficacy not increased by higher dosages or more frequent administration.

Pathologic GI Hypersecretory Conditions

Zollinger-Ellison Syndrome

Oral

300 mg 4 times daily with meals and at bedtime.

Higher doses administered more frequently may be necessary; adjust dosage according to response and
tolerance but in general, do not exceed 2400 mg daily.

Continue as long as necessary.

Gastric Ulcer

Oral

Preferred regimen: 800 mg once daily at bedtime.

Alternative regimen: 300 mg 4 times daily, with meals and at bedtime.

Monitor to ensure rapid progress to complete healing.

Studies limited to 6 weeks, efficacy for >8 weeks not established.

GERD

Once daily (at bedtime) not considered appropriate therapy.

Treatment of Symptomatic GERD†

Oral

300 mg 4 times daily has been used.

Treatment of Erosive Esophagitis

Oral

800 mg twice daily or 400 mg 4 times daily (e.g., before meals and at bedtime) for up to 12 weeks.

Upper GI Bleeding

Treatment of Upper GI Bleeding†

Oral

1–2 g daily in 4 divided doses has been used.

IV

1–2 g daily in 4 divided doses has been used.

Heartburn, Acid Indigestion, or Sour Stomach

Heartburn (Self-medication)

Oral

200 mg once or twice daily, or as directed by clinician.

Maximum 400 mg in 24 hours, but not continuously for >2 weeks except under clinician supervision.

Prevention of Heartburn (Self-medication)

Oral

200 mg once or twice daily or as directed by a clinician; administer immediately (or up to 30 minutes)
before ingestion of causative food or beverage.

Maximum 400 mg in 24 hours, but not continuously for >2 weeks except under clinician supervision.

Prescribing Limits

Pediatric Patients

Heartburn, Acid Indigestion, or Sour Stomach

Heartburn (Self-Medication)

Oral

Adolescents ≥12 years of age: Maximum 400 mg in 24 hours, but not continuously for >2 weeks except
under clinician supervision.

Prevention of Heartburn (Self-medication)

Oral

Adolescents ≥12 years of age: Maximum 400 mg in 24 hours, but not continuously for >2 weeks except
under clinician supervision.
Adults

Short-term Treatment of Erosive Esophagitis

Oral

Safety and efficacy beyond 12 weeks of administration have not been established.

Heartburn, Acid Indigestion, or Sour Stomach

Heartburn Relief (Self-medication)

Oral

Maximum 400 mg in 24 hours, but not continuously for >2 weeks except under clinician supervision.

Prevention of Heartburn (Self-medication)

Oral

Maximum 400 mg in 24 hours, but not continuously for >2 weeks except under clinician supervision.

Duodenal Ulcer

Intermittent Direct IV Injecton

Maximum 2.4 g daily.

Intermittent IV Infusion

Maximum 2.4 g daily.

Gastric Ulcer

Short-term treatment of Active Benign Gastric Ulcer

Oral
Cautions for Cimetidine

Contraindications known hypersensitivity to cimetidine or any ingredient in the formulation.

Warnings/Precautions

General Precautions

Cardiovascular Effects

Rapid IV administration associated rarely with hypotension, cardiac arrhythmias; avoid.

Gastric Malignancy

Response to cimetidine does not preclude presence of gastric malignancy.

CNS Effects

Reversible confusional states reported, especially in geriatric (i.e., ≥50 years) and severely ill (e.g.,
hepatic or renal disease, organic brain syndrome) patients. Usually occurs within 2–3 days after initiating
cimetidine and resolves within 3–4 days after discontinuance.

Respiratory Effects

Administration of H2-receptor antagonists has been associated with an increased risk for developing
certain infections (e.g., community-acquired pneumonia).

Specific Populations

Pregnancy Category B.

Pregnant women should consult a clinician before using for self-medication.

Lactation Distributed into milk. Generally, do not nurse during therapy with cimetidine.

Nursing women should consult a clinician before using for self-medication.

Pediatric Use

Safety and efficacy not established in children <16 years of age; do not use unless potential benefits
outweigh risks.

Safety and efficacy for self-medication not established in children <12 years of age; do not use unless
directed by a clinician.

Renal Impairment

Dosage adjustments necessary in patients with severe renal impairment. (See Renal Impairment under
Dosage and Administration.)

Hepatic Impairment

Further dosage adjustments may be necessary in presence of severe renal impairment. (See Hepatic
Impairment under Dosage and Administration.)

Immunocompromised Patients

Increased possibility of Strongyloides stercoralis hyperinfection with decreased gastric acidity.

Common Adverse Effects

Headache, dizziness, somnolence, diarrhea.

With ≥1 month of therapy: gynecomastia.

With IM therapy: transient pain at injection site.

Interactions for Cimetidine

Inhibits hepatic microsomal enzyme systems, decreases hepatic metabolism of some drugs. If necessary,
adjust dosage of hepatically metabolized drugs when cimetidine therapy is initiated or discontinued.

Specific Drugs

Drug Interaction comments

Possible increased blood alcohol concentrations, psychomotor impairment

Alcohol
Potential for psychomotor impairment controversial, but use caution during performance of hazardous
tasks requiring mental alertness, physical coordination

Antacids

Decreased cimetidine absorption

Administer 1 hour before or after cimetidine in the fasting state, or 1 hour after cimetidine is taken with
food.

Benzodiazepines

Potential for delayed elimination, increased blood concentrations of certain benzodiazepines (e.g.,
diazepam, chlordiazepoxide, triazolam)

Adjust dosage if needed

Calcium-channel blockers (e.g., nifedipine)

Potential for delayed elimination, increased blood concentrations of nifedipine

Adjust dosage if needed

Ketoconazole

Absorption of ketoconazole may be affected by altered gastric pH

Administer ≥2 hours before cimetidine

Lidocaine

Potential for delayed elimination, increased blood concentrations of lidocaine

Adverse effects reported, adjust dosage if needed

Metronidazole
Potential for delayed elimination, increased blood concentrations of metronidazole

Adjust dosage if needed

Myelosuppressive drugs (e.g., alkylating agents [e.g., carmustine], antimetabolites) and/or therapies
(radiation)

May potentiate myelosuppression

Phenytoin

Potential for delayed elimination, increased blood concentrations of phenytoin

Adverse effects reported, adjust dosage if needed

Propranolol

Potential for delayed elimination, increased blood concentrations of propranolol

Adjust dosage if needed

Theophylline

Potential for delayed elimination, increased blood concentrations of theophylline

Adverse effects reported, adjust dosage if needed

Triamterene

Potential for delayed elimination, increased blood concentrations of triamterene

Consider potential of clinically important interaction

Tricyclic Antidepressants

Potential for delayed elimination, increased blood concentrations of certain tricyclic antidepressants

Adjust dosage if needed

Warfarin

Potential for delayed elimination, increased blood concentrations of warfarin

Monitor PT, adjust dosage if needed

Cimetidine drug interactions (more detail)

Cimetidine Pharmacokinetics

Absorption

Bioavailability

Oral: 60–70%.

Onset

≥70% decrease in basal acid secretion within 45 minutes after single 300- or 400-mg IV dose in healthy
males.

Duration

Dosage Regimen

Effect On Acid Secretion

Comments
Oral: 800 mg at bedtime in duodenal ulcer patients

Mean hourly nocturnal secretion decreased by 85% over 8 hours.

No effect on daytime acid secretion

Oral: 1600 mg at bedtime in duodenal ulcer patients

Mean hourly nocturnal secretion decreased by 100% over 8 hours, 35% decrease for additional 5 hours.

Moderate (<60%) 24-hour suppression

Oral: 400 mg twice daily in duodenal ulcer pateints

Nocturnal secretion decreased by 47–83% over 6–8 hours

Moderate (<60%) 24-hour suppression

Oral: 300 mg 4 times daily in duodenal ulcer patients

Nocturnal secretion decreased by 54% over 9 hours

Moderate (<60%) 24-hour suppression

Oral: Single 300-mg dose within 1 hour after meal in duodenal ulcer patients

Food-stimulated secretion decreased by 50% for 1 hour, then 75% for 2 hours.

Oral: 300-mg dose at breakfast in duodenal ulcer patients

Continued suppression for 4 hours, with partial suppression after lunch

Effect enhanced and maintained by additional 300-mg dose with lunch

Oral: 300-mg dose with food

Mean gastric pH 3.5–4 at 1 hour, 5.5–6.1 at 4 hours

Oral: Single dose 300 mg with food

Mean gastric pH: 3.5, 3.1, 3.8, 6.1 at hour 1, 2, 3, 4, respectively

Placebo mean gastric pH: 2.6, 1.6, 1.9, 2.2 at hour 1, 2, 3, 4, respectively

Oral: 300–400 mg in fasting state in duodenal ulcer patients

Anacidity for up to 8 hours

Oral: 300 mg in duodenal ulcer patients

Basal gastric acid output decreased by 90% for 4 hours

Meal-stimulated acid secretion by 66% for 3 hours

Food

Delays, slightly decreases absorption. However, administration with meals achieves maximum blood
concentrations and antisecretory effect when stomach is no longer protected by food buffering effect.
Distribution

Extent

Widely distributed throughout the body.

Distributed into human milk.

Crosses the placenta in animals.

Plasma Protein Binding

15–20%.

Elimination

Metabolism

Metabolized to sulfoxide (major metabolite) and 5-hydroxymethyl derivatives in liver. More extensively
metabolized after oral than parenteral administration.

Elimination Route

Excreted principally in urine. Single oral dose: 48% (unchanged) excreted in urine over 24 hours. IV or
IM: about 75% (unchanged) excreted in urine within 24 hours. Single IV dose of radiolabeled cimetidine:
80–90% (50–73% unchanged, remainder as metabolites) excreted in urine over 24 hours. About 10%
excreted in feces.

Half-life 2 hours.

After IV administration in children 4.1–15 years of age: Apparent biphasic decline of plasma cimetidine
and cimetidine sulfoxide concentrations with half-lives of 1.4 and 2.6 hours, respectively.

Special Populations

2.9 hours in patients with Clcr 20–50 mL/minute. 3.7 hours in patients with Clcr <20 mL/minute. 5 hours
in anephric patients.