cimetidine
Tagamet, Tagamet HB

Available forms
Available by prescription only
Injection: 300 mg/2 ml, 300 mg/50 ml normal saline solution (premixed)
Liquid: 300 mg/5 ml
Tablets: 200 mg, 300 mg, 400 mg, 800 mg
Tablets: 200 mg

Indications and dosages
 Duodenal ulcer (short-term treatment). Adults: 800 mg P.O. h.s. for maximum of 8 weeks. Or, 400 mg P.O. b.i.d. or 300 mg P.O. q.i.d. with meals and h.s. When healing occurs, stop treatment or give h.s. dose only to control nocturnal hypersecretion.
Parenteral: 300 mg diluted to 20 ml with normal saline solution or other compatible I.V. solution by I.V. push over 5 minutes q 6 hours. Or, 300 mg diluted in 50 ml D₅W or other compatible I.V. solution by I.V. infusion over 15 to 20 minutes q 6 to 8 hours. Or, 300 mg I.M. q 6 to 8 hours (no dilution needed). To increase dose, give more frequently to maximum daily dose of 2,400 mg.
 Duodenal ulcer prophylaxis. Adults: 400 mg P.O. h.s.
 Active benign gastric ulcer. Adults: 800 mg P.O. h.s., or 300 mg P.O. q.i.d. with meals and h.s. for up to 8 weeks.
 Pathologic hypersecretory conditions (such as Zollinger-Ellison syndrome, systemic mastocytosis, and multiple endocrine adenomas), short-bowel syndrome ◇. Adults: 300 mg P.O. q.i.d. with meals and h.s.; adjust to patient needs. Maximum daily dose is 2,400 mg.
Parenteral: 300 mg diluted to 20 ml with normal saline solution or other compatible I.V. solution by I.V. push over 5 minutes q 6 to 8 hours. Or, 300 mg diluted in 50 ml D₅W or other compatible I.V. solution by I.V. infusion over 15 to 20 minutes q 6 to 8 hours. To increase dosage, give 300-mg doses more frequently to maximum daily dose of 2,400 mg.
 Symptomatic relief of gastroesophageal reflux. Adults: 800 mg P.O. b.i.d. or 400 mg q.i.d., before meals and h.s.
 Active upper GI bleeding, peptic esophagitis, stress ulcer ◇. Adults: 1 to 2 g I.V. or P.O. daily, in four divided doses.
 Continuous infusion for patients unable to tolerate oral medication. Adults: 37.5 mg/hour (900 mg daily) by continuous I.V. infusion. Use an infusion pump if total volume is below 250 ml daily.
 Heartburn, acid indigestion, sour stomach. Adults: 200 mg P.O. up to a maximum of b.i.d. (400 mg).
≡ Dosage adjustment. For patients with renal failure, recommended dosage is 300 mg P.O. or I.V. q 8 to 12 hours at end of dialysis. Dosage may be decreased further if hepatic failure is also present.

Pharmacodynamics
Antiulcer action: Cimetidine competitively inhibits histamine’s action at H₂ receptors in gastric parietal cells, inhibiting basal and nocturnal gastric acid secretion (such as from stimulation by food, caffeine, insulin, histamine, betazole, or pentagastrin). Cimetidine also may enhance gastromucosal defense and healing.
A 300-mg oral or parenteral dose inhibits about 80% of gastric acid secretion for 4 to 5 hours.

Pharmacokinetics
Absorption: About 60% to 75% of oral dose is absorbed. Absorption rate (but not extent) may be affected by food.
Distribution: Distributed to many body tissues. About 15% to 20% of drug is protein-bound. Cimetidine crosses the placental barrier and appears in breast milk.
Metabolism: About 30% to 40% of dose is metabolized in the liver. Drug has a half-life of 2 hours in patients with normal renal function; half-life increases with decreasing renal function.
Excretion: Excreted primarily in urine (48% of oral dose, 75% of parenteral dose); 10% of oral dose is excreted in feces. Some drug appears in breast milk.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in elderly or debilitated patients.

Interactions
Drug-drug. Benzodiazepines, beta blockers (such as propranolol), carmustine, disulfiram, hormonal contraceptives, isoniazid, lidocaine, metronidazole, phenytoin, procainamide, quinidine, triamterene, tricyclic antidepressants, warfarin, xanthines: Decreases metabolism of these drugs, increasing risk of toxicity and possibly necessitating dosage reduction. Monitor patient closely.
Digoxin: May reduce serum digoxin level. Monitor patient closely.
Ferrous salts, indomethacin, ketoconazole, tetracyclines: May affect absorption of these drugs by altering gastric pH. Avoid use together.
Flecainide: May increase serum flecainide level. Avoid use together.
Drug-herb. Guarana: May increase serum caffeine level or prolong half-life. Monitor patient closely.
Pennyroyal: May change rate at which toxic metabolites of pennyroyal form. Discourage use together.
Yerba maté: May decrease yerba maté methylxanthine clearance and cause toxicity. Discourage use together.
Drug-lifestyle. Alcohol use, smoking: May increase gastric acid secretion and worsen disease. Discourage alcohol use and smoking.

Adverse reactions
CNS: confusion, dizziness, headache, peripheral neuropathy, somnolence, hallucinations.
GI: mild and transient diarrhea.
GU: impotence.
Hematologic: neutropenia.
Musculoskeletal: muscle pain, arthralgia.
Other: hypersensitivity reactions, mild gynecomastia if used for longer than 1 month.

Effects on lab test results
• May increase creatinine, prolactin, alkaline phosphatase, AST, and ALT levels.
• May decrease neutrophil count.

Overdose and treatment
Effects of overdose include respiratory failure and tachycardia. Overdose is rare; intake of up to 10 g has caused no adverse effects.
 Support respiration and maintain a patent airway. Induce emesis or use gastric lavage; follow with activated charcoal to prevent further absorption. Treat tachycardia with propranolol if necessary. Hemodialysis removes drug.

Special considerations
• Ask patient about use of other drugs before starting treatment with cimetidine.
 ALERT For I.V. use, cimetidine must be diluted before administration. Don’t dilute drug with sterile water for injection; use normal saline solution or D₅W to a total volume of 20 ml.
• For I.M. administration, drug may be given undiluted. Injection may be painful.
• After administration of the liquid via nasogastric tube, flush tube to clear it and ensure passage of drug to stomach.
• Because hemodialysis removes drug, schedule dose after dialysis session.
• Cimetidine may antagonize pentagastrin’s effect during gastric acid secretion tests; it may cause false-negative results in skin tests using allergen extracts.
• FD&C blue dye #2 used in Tagamet tablets may impair interpretation of Hemoccult and Gastroccult tests on gastric content aspirate. Be sure to wait at least 15 minutes after tablet administration before drawing the sample, and follow test manufacturer’s instructions closely.
Breast-feeding patients
• Drug appears in breast milk. Avoid use in breast-feeding women.
Geriatric patients
• Use with caution in elderly patients because of the risk of adverse reactions affecting the CNS.

Patient education
• Instruct patient to take drug as directed and to continue taking it even after pain subsides, to allow for adequate healing.
• Urge patient to avoid smoking and alcohol use because they may increase gastric acid secretion and worsen disease.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use