Cimetidine

Mechanism of Action:

Cimetidine is a histamine H2-antagonist and inhibits actions of histamine mediated by H2-receptors such as gastric acid secretion and pepsin output.

Drug Label Information | Brands:

Brands of Cimetidine

Cemet®, Cosmos Ltd
Labcimet®,Lab and Allied
Medicit® , Medisel
Tagamet®, GSK
Ulcidin®,West Coast
Ulmet® , Universal Corporation Limited

Pharmacokinetics:

Cimetidine is readily absorbed from the gastro-intestinal tract and peak plasma concentrations are obtained about an hour after administration on an empty stomach; a second peak may be seen after about 3 hours. Food delays the rate and may slightly decrease the extent of absorption, with the peak plasma concentration occurring after about 2 hours. The bioavailability of Cimetidine after oral administration is about 60 to 70%. Cimetidine is widely distributed and has a volume of distribution of about 1 litre per kg and is weakly bound, about 20%, to plasma proteins. The elimination haIf-Iife from plasma is about 2 hours and is increased in renal impairment. Cimetidine is partially metabolised in the liver to sulfoxide and to hydroxymethylcimetidine. About 50% of an oral dose, and 75% of an intravenous dose, is excreted unchanged in the urine in 24 hours. Cimetidine crosses the placental barrier and is distributed into breast milk.

USES:

it is used in conditions where inhibition of gastric acid secretion may be beneficial as in peptic ulcer disease, including stress ulceration, gastro-oesophageal reflux disease, selected cases of persistent dyspepsia, pathological hypersecretory states such as the Zollinger-Ellison syndrome, stress ulceration, acid aspiration syndrome, dyspepsia and pancreatic insufficiency.

Cimetidine may also be used to reduce malabsorption and fluid loss in patients with short bowel syndrome and to reduce the degradation of enzyme supplements given to patients with pancreatic insufficiency.

DOSAGE AND ADMINISTRATION:

For management of benign gastric and duodenal ulcers: A single daily dose of 800mg by mouth at bedtime given initially for at least 4 weeks in the case of duodenal, and at least 6 weeks in the case of gastric ulcers. A maintenance dose of 400mg may be given once at bedtime.

Gastro-oesaphageal reflux disease: 400mg by mouth four times daily (with meals and at bedtime) or 800mg twice daily for 4 to 12 weeks.

Zollinger-Ellison Syndrome: 300 or 400mg by mouth four times daily. Sometimes higher doses may be necessary.

Stress ulceration: 200mg to 400mg by mouth or by nasogastric administration.

Acid aspiration syndrome: 400mg by mouth may be given 90 to 120 minutes before the induction of anaesthesia or at the start of the labour.

Dyspepsia: 800mg daily in divided doses for non-ulcer dyspepsia, 100mg at night for the prophylaxis of nocturnal heartburn.

Pancreatic insufficiency: 800 to 1600mg daily by mouth in four divided
doses, 60 to 90 minutes before meals. For the patients with impaired renal function, it is recommended that the dose is adjusted according to the patient’s Creatinine Clearance.

CONTRA-INDICATIONS AND WARNINGS:

Precautions:

Before giving Cimetidine or other histamine H2 -antagonists to patients with gastric ulcers the possibility of malignancy should be considered since Cimetidine may mask symptoms and delay diagnosis. It should be gIven In reduced dosage to patients with renal impairment.

Adverse Effects:

Adverse reactions to Cimetidine and other histamine H2-antagonists are generally infrequent. The most common adverse-effects reported have been diarrhoea and other gastrointestinal disturbances, dizziness, tiredness, headache, and rashes. Reversible confusional states, especially in the elderly or in seriously ill patients such as those with renal failure, have occasionally occurred. Other adverse effects that have been reported rarely are hypersensitivity reactions and fever, arthralgia and myalgia, blood disorders including agranulocytosis and thrombocytopenia, acute pancreatitis, hallucinations and depression, and cardiovascular disorders including bradycardia and heart block.

Overdosage:

No serious toxic effects were noted In reports of overdosage‘ In patients who took Cimetidine 5.2 to 20gm (including one patient who took about 12gm daily for 5 days).

Interactions:

Cimetidine and other H2-antagonists can reduce the absorption of drugs such as ketoconazole, and possibly itraconazole whose absorption is dependent on an acid gastric pH. Cimetidine may inhibit the hepatic metabolism of many drugs by binding to cytochrome P450 isoenzymes, notably CYP1A2, CYPZC9, CYP2D6, and CYP3A4.