Cimetidine Information
Cimetidine () Description
Cimetidine () is a histamine H-receptor antagonist. Chemically it is "-cyano--methyl-'-[2-[[(5-methyl-1-imidazol-4-yl)methyl]thio]-ethyl]-guanidine. Its structural formula is:
CHNS M.W. 252.34
Cimetidine () contains an imidazole ring, and is chemically related to histamine.
Cimetidine () has a bitter taste and characteristic odor.
Cimetidine () is soluble in alcohol, slightly soluble in water, very slightly soluble in chloroform and insoluble in ether.
Each film-coated tablet, for oral administration, contains 300 mg, 400 mg or 800 mg of Cimetidine () . In addition, each tablet contains the following inactive ingredients: corn starch, hydroxypropyl cellulose, hypromellose, magnesium stearate, polyethylene glycol, povidone, sodium starch glycolate, and titanium dioxide.
Cimetidine () Clinical Pharmacology
Cimetidine () competitively inhibits the action of histamine at the histamine H-receptors of the parietal cells and thus is a histamine H-receptor antagonist.
Cimetidine () is not an anticholinergic agent. Studies have shown that Cimetidine () inhibits both daytime and nocturnal basal gastric acid secretion. Cimetidine () also inhibits gastric acid secretion stimulated by food, histamine, pentagastrin, caffeine and insulin.
Cimetidine () Indications And Usage
Cimetidine () tablets are indicated in:
Cimetidine () Contraindications
Cimetidine () is contraindicated for patients known to have hypersensitivity to the product.
Cimetidine () Precautions
Rare instances of cardiac arrythmias and hypotension have been reported following the rapid administration of Cimetidine () hydrochloride injection by intravenous bolus.
Symptomatic response to treatment with Cimetidine () does not preclude the presence of a gastric malignancy. There have been rare reports of transient healing of gastric ulcers despite subsequently documented malignancy.
Reversible confusional states (see ) have been observed on occasion, predominantly, but not exclusively, in severely ill patients. Advancing age (50 or more years) and preexisting liver and/or renal disease appear to be contributing factors. In some patients these confusional states have been mild and have not required discontinuation of Cimetidine () . In cases where discontinuation was judged necessary, the condition usually cleared within 3 to 4 days of drug withdrawal.
Cimetidine () , apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.
Clinically significant effects have been reported with the warfarin anticoagulants; therefore, close monitoring of prothrombin time is recommended, and adjustment of the anticoagulant dose may be necessary when Cimetidine () is administered concomitantly. Interaction with phenytoin, lidocaine and theophylline has also been reported to produce adverse clinical effects.
However, a crossover study in healthy subjects receiving either 300 mg four times daily or 800 mg at bedtime of Cimetidine () concomitantly with a 300 mg twice daily dosage of theophylline (Theo-Dur®) demonstrated less alteration in steady-state theophylline peak serum levels with the 800 mg at bedtime regimen, particularly in subjects aged 54 years and older. Data beyond ten days are not available. (Note: All patients receiving theophylline should be monitored appropriately, regardless of concomitant drug therapy.)
Dosage of the drugs mentioned above and other similarly metabolized drugs, particularly those of low therapeutic ratio or in patients with renal and/or hepatic impairment, may require adjustment when starting or stopping the concomitant administration of Cimetidine () to maintain optimum therapeutic blood levels.
Alteration of pH may affect the absorption of certain drugs (e.g., ketoconazole). If these products are needed, they should be given at least 2 hours before Cimetidine () administration.
Additional clinical experience may reveal other drugs affected by the concomitant administration of Cimetidine () .
In a 24-month toxicity study conducted in rats, at dose levels of 150, 378 and 950 mg/kg/day (approximately 8 to 48 times the recommended human dose), there was a small increase in the incidence of benign Leydig cell tumors in each dose group; when the combined drug-treated groups and control groups were compared, this increase reached statistical significance. In a subsequent 24-month study, there were no differences between the rats receiving 150 mg/kg/day and the untreated controls. However, a statistically significant increase in benign Leydig cell tumor incidence was seen in the rats that received 378 and 950 mg/kg/day. These tumors were common in control groups as well as treated groups and the difference became apparent only in aged rats.
Cimetidine () has demonstrated a weak antiandrogenic effect. In animal studies this was manifested as reduced prostate and seminal vesicle weights. However, there was no impairment of mating performance or fertility, nor any harm to the fetus in these animals at doses 8 to 48 times the full therapeutic dose of Cimetidine () , as compared with controls. The cases of gynecomastia seen in patients treated for one month or longer may be related to this effect.
In human studies, Cimetidine () has been shown to have no effect on spermatogenesis, sperm count, motility, morphology or fertilizing capacity.
Cimetidine () Adverse Reactions
Adverse effects reported in patients taking Cimetidine () are described below by body system. Incidence figures of 1 in 100 and greater are generally derived from controlled clinical studies.
Headaches, ranging from mild to severe, have been reported in 3.5% of 924 patients taking 1600 mg/day, 2.1% of 2,225 patients taking 800 mg/day and 2.3% of 1,897 patients taking placebo. Dizziness and somnolence (usually mild) have been reported in approximately 1 in 100 patients on either 1600 mg/day or 800 mg/day.
Reversible confusional states, e.g., mental confusion, agitation, psychosis, depression, anxiety, hallucinations, disorientation, have been reported predominantly, but not exclusively, in severely ill patients. They have usually developed within 2 to 3 days of initiation of treatment with Cimetidine () and have cleared within 3 to 4 days of discontinuation of the drug.
Gynecomastia has been reported in patients treated for one month or longer. In patients being treated for pathological hypersecretory states, this occurred in about 4% of cases while in all others the incidence was 0.3% to 1% in various studies. No evidence of induced endocrine dysfunction was found, and the condition remained unchanged or returned toward normal with continuing treatment with Cimetidine () .
Reversible impotence has been reported in patients with pathological hypersecretory disorders, e.g., Zollinger-Ellison Syndrome, receiving Cimetidine () , particularly in high doses, for at least 12 months (range 12 to 79 months, mean 38 months). However, in large-scale surveillance studies at regular dosage, the incidence has not exceeded that commonly reported in the general population.
Dose-related increases in serum transaminase have been reported. In most cases they did not progress with continued therapy and returned to normal at the end of therapy. There have been rare reports of cholestatic or mixed cholestatic-hepatocellular effects. These were usually reversible. Because of the predominance of cholestatic features, severe parenchymal injury is considered highly unlikely. However, as in the occasional liver injury with other H-receptor antagonists, in exceedingly rare circumstances fatal outcomes have been reported.
There has been reported a single case of biopsy-proven periportal hepatic fibrosis in a patient receiving Cimetidine () .
Rare cases of pancreatitis, which cleared on withdrawal of the drug, have been reported.
Cimetidine () Overdosage
Studies in animals indicate that toxic doses are associated with respiratory failure and tachycardia that may be controlled by assisted respiration and the administration of a beta-blocker.
Reported acute ingestions orally of up to 20 grams have been associated with transient adverse effects similar to those encountered in normal clinical experience. The usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.
There have been reports of severe CNS symptoms, including unresponsiveness, following ingestion of between 20 and 40 grams of Cimetidine () , and extremely rare reports following concomitant use of multiple CNS-active medications and ingestion of Cimetidine () at doses less than 20 grams. An elderly, terminally ill dehydrated patient with organic brain syndrome receiving concomitant antipsychotic agents and 4800 mg of Cimetidine () intravenously over a 24-hour period experienced mental deterioration with reversal on discontinuation.
There have been two deaths in adults who were reported to have ingested over 40 grams orally on a single occasion of Cimetidine () .
Cimetidine () How Supplied
Cimetidine () Tablets USP 300 mg are available as white to off-white, round, unscored, film-coated tablets, debossed "300" on one side and "7117" on the other side, packaged in bottles of 100, 500 and 1000 tablets.
Cimetidine () Tablets USP 400 mg are available as white to off-white, capsule-shaped, scored, film-coated tablets, debossed "400" on one side and "7171" on the other side, packaged in bottles of 60, 100 and 500 tablets.
Cimetidine () Tablets USP 800 mg are available as white to off-white, oval-shaped, scored, film-coated tablets, debossed "800" on one side and "7711" on the other side, packaged in bottles of 30, 100 and 500 tablets.
PHARMACIST: Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
*Theo-Dur is a registered trademark of Key Pharmaceuticals, Inc.
Iss. 3/2009
Manufactured in Ireland By:
IVAX PHARMACEUTICALS IRELAND
Waterford, Ireland
Manufactured For:
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Cimetidine () Principal Display Panel
NDC 0172-7117-60
Cimetidine ()
Tablets USP
300 mg
Rx only
100 TABLETS
Cimetidine () Principal Display Panel
NDC 0172-7171-60
Cimetidine ()
Tablets USP
400 mg
Rx only
100 TABLETS
Cimetidine () Principal Display Panel
NDC 0172-7711
Cimetidine ()
Tablets USP
800 mg
Rx only
100 TABLETS
