Histamine H2 Receptor Antagonist
Action And Clinical Pharmacology: Cimetidine inhibits competitively the action of histamine at the histamine H2 receptor and it is not an anticholinergic agent. It inhibits both daytime and nocturnal basal gastric acid secretion. Similarly, gastric acid secretion stimulated by food, histamine, pentagastrin, insulin and caffeine is inhibited by cimetidine.
After oral administration, cimetidine is absorbed rapidly. The plasma half-life is about 2 hours. The drug is excreted primarily in the urine.
The level and duration of inhibition of both basal and stimulated gastric acid secretion has been shown to be dose-related. An 80% or higher inhibition for 24 hours can be obtained with a dosage regimen of 300 mg 4 times daily given with meals and before retiring. A reduction of total pepsin output determined by a decrease in the volume of gastric juice takes place following the administration of 300 mg cimetidine. No effect was detected on the rate of gastric emptying or lower esophageal sphincter pressure.
Indications And Clinical Uses: For conditions where the inhibition of gastric acid secretion is expected to be beneficial, such as: duodenal ulcer, nonmalignant gastric ulcer, gastroesophageal reflux disease, pathological hypersecretion associated with Zollinger-Ellison Syndrome, systemic mastocytosis and multiple endocrine adenomas.
Contra-Indications: None known. Precautions
Precautions: Pregnancy and Lactation: There has been no experience with cimetidine use in pregnant women. Reproduction studies in rats, mice and rabbits have revealed no impairment of fertility or fetal damage connected with cimetidine. The drug crosses the placental barrier and is secreted in the milk of animals. Cimetidine should be used in pregnant or lactating patients or women of childbearing potential only when the anticipated benefits outweigh the potential risks.
Children: Clinical experience is limited. Therefore, cimetidine cannot be recommended for children unless anticipated benefits outweigh potential risks. In a few cases, oral divided doses of 20 to 40 mg/kg daily have been administered.
Use in impaired renal function: Because cimetidine is excreted by the kidney, a reduced dosage should be administered to patients with an impaired renal function (see Dosage).
Drug Interactions: Cimetidine may interact with other drugs by several mechanisms: inhibition of the hepatic microsomal oxidative system (the most important in this connection), reduction of the hepatic blood flow, reduction of the gastric pH.
Potentially clinically significant interactions have been reported with: benzodiazepines (diazepam, chlordiazepoxide), warfarin, theophylline, phenytoin, beta adrenergic blocking agents (propranolol), lidocaine, carbamazepine, digitoxin. The most important clinical consequences of these interactions involve the inhibition of usual drug metabolism with subsequent higher steady-state blood concentrations and an increased incidence of side effects. Drugs with a narrow therapeutic index (phenytoin, warfarin, theophylline) are more likely to produce such problems.
Proper dose adjustment, especially when changes are made in dosage regimens should be implemented whenever the administration of cimetidine is necessary in conjunction with these drugs.
Adverse Reactions: CNS: The most common symptoms reported have been confusion or delirium with dizziness, drowsiness, slurred speech, flushing and sweating. The occurrence of cimetidine-induced confusional states seems to be rare. The reported cimetidine CNS effects occurred either after high dosage, in elderly patients, in the presence of renal impairment, or in the presence of a previous psychiatric history.
Gastrointestinal: Mild and transient diarrhea, some increases in serum transaminase not requiring cimetidine discontinuance may occur.
Perforation of duodenal, esophageal and gastric ulcers has been reported following abrupt discontinuance of the drug. There is no firm evidence, however, that recurrences of ulcer disease occur sooner or more severely in patients withdrawn from cimetidine than in patients withdrawn from other forms of treatment.
Gastritis and duodenitis during cimetidine therapy have been described.
Rare cases of hepatitis and pancreatitis reacting favorably to cimetidine withdrawal have been reported.
Endocrine: Gynecomastia with and without elevated prolactin levels has been reported. Galactorrhea with elevated prolactin levels has also been reported in females only.
Decreased libido and impotence during cimetidine treatment has been described.
Hematology: Decreased white blood cell counts including agranulocytosis have been reported, including a few cases of recurrence on rechallenge. These patients generally presented other concomitant pathology and received other drugs known to produce neutropenia. Thrombocytopenia and a few cases of aplastic anemia have also been reported.
Renal: Small increases in plasma creatinine, which did not progress when treatment was continued and disappeared on its withdrawal, have been reported. Rare cases of interstitial nephritis have been reported.
Skin: Rash, giant urticaria, Stevens-Johnson syndrome and psoriasis secondary to cimetidine have been reported.
Miscellaneous: Fever and muscular pain have been reported.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: A 25-year-old man after taking 12 g of cimetidine presented disorientation and nonsensical speech. He recovered fully after 24 hours.
A 35-year-old man after taking one hundred and twenty 200 mg cimetidine together with 400 mg oxazepam was unconscious for 6 hours and responded favorably to forced diuresis.
Dosage And Administration: Experience with cimetidine in children is limited and it has not been evaluated in clinical studies (see Precautions).
In clinical studies, cimetidine has been used in doses up to 2 400 mg/day in divided doses.
Acute Duodenal Ulcer: The daily oral dosage for adults is 800 mg before retiring, or 400 mg twice a day at breakfast and before retiring or 300 mg 4 times daily with meals and before retiring. While symptoms may disappear frequently during the first or second week of treatment, cimetidine administration should be continued for at least 4 weeks or until endoscopic healing is obtained. Concomitant antacids might be needed in some patients until symptoms disappear.
For patients known to be at risk of frequent recurrences of duodenal ulcer and for those patients who, in the judgment of the attending physician, might benefit from a longer-term reduction of gastric acid secretion, consideration should be given to a maintenance treatment.
It has been shown that in duodenal ulcer patients, following cimetidine-induced ulcer healing, a daily maintenance regimen of 400 mg at bedtime for 6 to 12 months reduces the incidence of recurrences. These patients should be reassessed periodically.
Nonmalignant Gastric Ulcer and Gastroesophageal Reflux Disease: The recommended adult oral dosage for these conditions is 300 mg, 4 times daily, with meals and at bedtime. Frequently patients may become asymptomatic during the first week or two, but treatment should be continued for at least 4 weeks or until endoscopic healing is documented.
Impaired Renal Function: Use of cimetidine in patients with severely impaired renal function has been very limited. Based on this experience, the recommended dosage in such patients is 300 mg every 12 hours. If the patient’s condition requires it, the frequency of dosing may be increased to every 8 hours or, with caution, even further. Accumulation may occur in severe renal failure and the lowest frequency of dosing compatible with an adequate therapeutic response should be used. Hemodialysis removes circulating cimetidine and therefore the timing of dosage should be adjusted to the dialysis schedule.
Pathological Hypersecretory Conditions (e.g. Zollinger-Ellison Syndrome): Recommended adult oral dosage: 300 mg, 4 times a day, with meals and at bedtime. Some patients may require more frequent 300 mg doses to control symptoms. Dosage should be individually adjusted, without exceeding 2 400 mg daily. When necessary, 600 mg 4 times daily or 800 mg 3 times daily with meals and at bedtime.
Special Cases: In patients in whom control of gastric acid secretion is desirable, the recommended oral dosage is 300 mg, 4 times daily, with meals and at bedtime.
Availability And Storage: 300 mg: Each round, blue, biconvex, film-coated tablet, one side engraved “300” and “FWH” on the other side, contains: cimetidine 300 mg. Nonmedicinal ingredients: alumina, cellulose, cornstarch, FD&C Blue No. 2, FD&C Red No. 3, glycerin, magnesium stearate, povidone, propylene glycol, sodium starch glycolate and titanium dioxide. Energy: 0.4 kJ (0.1 kcal). Sodium:
400 mg: Each round, peach-colored, biconvex, film-coated tablet, one side engraved “400” and “FWH” on the other side, contains: cimetidine 400 mg. Nonmedicinal ingredients: alumina, cellulose, FD&C Yellow No. 6, magnesium stearate, polyethylene glycol, povidone, sodium starch glycolate, cornstarch and titanium dioxide. Energy: 0.8 kJ (0.2 kcal). Sodium:
600 mg: Each ellipsoid, blue, biconvex tablet, bisected on one side, the other side engraved FWH 600, contains: cimetidine 600 mg. Nonmedicinal ingredients: alumina, cellulose, cornstarch, FD&C Blue No. 2, FD&C Red No. 3, glycerin, magnesium stearate, povidone, sodium starch glycolate and titanium dioxide. Energy: 1.2 kJ (0.3 kcal). Sodium:
800 mg: Each ellipsoid, peach-colored, biconvex tablet, bisected on one side, the other side engraved FWH 800, contains: cimetidine 800 mg. Nonmedicinal ingredients: alumina, cellulose, cornstarch, FD&C Yellow No. 6, magnesium stearate, polyethylene glycol, povidone, sodium starch glycolate and titanium dioxide. Energy: 2.9 kJ (0.7 kcal). Sodium:
PEPTOL® Carter Horner Cimetidine Histamine H2 Receptor Antagonist