INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo APO-CIMETIDINE 200 mg tablet
APO-CIMETIDINE 400 mg tablet
APO-CIMETIDINE 800 mg tablet

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

APO-CIMETIDINE 200 mg tablet
APO-CIMETIDINE 400 mg tablet
APO-CIMETIDINE 800 mg tablet

COMPOSITION:
Each film coated tablet contains 200, 400 or 800 mg of
Cimetidine.

PHARMACOLOGICAL CLASSIFICATION:
A 11.4.3 Medicines Acting on the Gastrointestinal Tract. Antacids: Other.

PHARMACOLOGICAL ACTION:
Cimetidine is a specific competitive histamine H2-receptor antagonist which effectively inhibits gastric acid secretion.

INDICATIONS:
APO-CIMETIDINE is indicated in conditions where the inhibition of gastric acid secretion is likely to be beneficial, such as:
Duodenal ulcer
Prophylaxis of recurrent duodenal ulcer
Non-malignant gastric ulcer
Gastro-oesophageal reflux disease
Management of upper gastro-intestinal haemorrhage in patients at high risk from haemorrhage due to hepatic failure and treatment with immuno-suppressive agents, following kidney transplant.
Control of gastric hypersecretion and peptic ulceration in the Zollinger-Ellison syndrome.

CONTRA-INDICATIONS:
Hypersensitivity to cimetidine
Safety in pregnancy and lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE:
Cimetidine is used in divided doses of up to a maximum of 2400 mg/day in adults.
Clinical experience in children is limited. Therefore, cimetidine therapy cannot be recommended in children unless anticipated benefits outweigh the potential risks. In very limited experience, 20 to 40 mg/kg/day has been administered in doses by mouth. There is no evidence of clinical use in babies and cimetidine should therefore not be given to infants under one year of age.

Active Ulcer
Active duodenal, benign gastric and stomal ulceration:
The usual dose is 200 mg three times a day with meals and 400 mg at bedtime.
400 mg twice a day and at bedtime has also been shown to be effective. The preferred dose is 200 mg three times a day with meals and 400 mg at bedtime. If there is inadequate symptomatic improvement or other evidence of continuing ulceration this dose may be increased to 400 mg four times a day taken with meals and at bedtime. The treatment should be continued for at least four weeks even if symptomatic relief is achieved in a short time.

Duodenal Ulcer
The efficacy of a single bedtime dose of 800 mg has been shown to be comparable to that of a daily dose of 800 mg divided in two doses (400 mg in the morning and 400 mg at bedtime).

Maintenance Treatment
Prophylaxis of Recurrent Ulcer:
In patients with a history of recurrent duodenal ulceration, relapse after healing is prevented during treatment at reduced dosage for a period of up to one year. It is recommended after healing to continue treatment at reduced dosage for as long as the doctor deems necessary to prevent a relapse.
A maintenance dose of 400 mg at bedtime has been shown to confer protection against recurrence after duodenal ulceration, during this period of 1 year while on maintenance treatment; some patients may require 400 mg twice a day.

Upper Gastro-Intestinal Haemorrhage
Patients with hepatic failure who are at risk from haemorrhage can be treated with the usual dose of 200 mg three times a day and 400 mg at bedtime. It may be necessary to increase the dose to 400 mg four times a day. Patients who have had renal transplants : Please refer to dosages in renal impairment.

Hypersecretory Conditions such as Zollinger-Ellison Syndrome
The usual dose is 200 mg three times a day and 400 mg at bedtime. It may be necessary to Increase the dose to 400 mg four times a day. Dosages should be adjusted to individual needs and should continue as long as clinically indicated.

Gastro-oesophageal Reflux Disease
400 mg four times daily with meals and at bedtime for a period of up to 12 weeks.
Since cimetidine may not always give immediate symptomatic relief, antacids should be made available to the patients as needed for the relief of pain.

Dosage Adjustments for Patients with Impaired Renal Function
In patients with impaired renal function, the dosage should be reduced according to creatinine clearance levels.
CREATININE CLEARANCE         DOSAGE
0 - 15 mL per minute         200 mg twice daily
15 - 30 mL per minute         200 mg three times daily
30 - 50 mL per minute         200 mg four times daily
Over 50 mL per minute         normal dosage

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
SIDE-EFFECTS
Diarrhoea,
tiredness,
dizziness,
headache
and rashes
have been reported in patients during treatment with cimetidine.
Cases of reversible confusional states, slurred speech, hallucinations, delirium and coma have occurred in the elderly or severely ill patients, such as those with renal insufficiency.
There have been reports that a few male patients, receiving relatively high doses of cimetidine have developed gynaecomastia and impotence. The condition remained unchanged or normalised on continued treatment.
Other reported side-effects include hypersensitivity reactions and fever, arthralgia and myalgia, blood disorders including agranulocytosis or neutropenia and thrombocytopenia, interstitial nephritis, pancreatitis, hepatotoxicity and cardiovascular disorders.

SPECIAL PRECAUTIONS
Patients with impaired renal function : See dosage and directions for use.
Gastric ulcers should be checked and malignancy excluded, since cimetidine may mask symptoms and delay diagnosis.
The level of cimetidine in the circulation is reduced by dialysis, therefore cimetidine should be administered following dialysis.
There have been reports that glucose handling is impaired on long term use of cimetidine hence caution should be observed in the treatment of elderly and diabetic patients with cimetidine.

DRUG INTERACTIONS
Anticholinergic agents should not be administered concurrently with cimetidine for maintenance treatment because of the possibility of interactions.
Cimetidine, apparently through an effect on certain microsomal enzyme systems has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, chlordiazepoxide, diazepam, lignocaine, nifedipine and theophylline; thereby delaying elimination and increasing blood levels.
Since clinically significant interactions have been reported with the warfarin anticoagulants dose monitoring of prothrombin time is recommended, and adjustment of the anticoagulant dose may be necessary when cimetidine is administered concomitantly.
Interaction with phenytoin, theophylline, lignocaine and calcium channel blockers has also been reported to produce adverse clinical effects.
Increased plasma levels of nifedipine have been reported during concomitant cimetidine administration. For concomitant administration of these two medicines, cautious titration of nifedipine is advised.
Doses of all of the above mentioned medicines and other similarly metabolised medicines may require adjustments on starting or stopping concomitantly administered cimetidine to maintain safe optimum therapeutic blood levels.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdosage
See side-effects and special precautions.
Treatment
Treatment is symptomatic and supportive.

IDENTIFICATION:
APO-CIMETIDINE 200 mg is a pale green, round, biconvex, film coated tablet, engraved APO - 200
APO-CIMETIDINE 400 mg is a pale green, oblong, biconvex, film coated tablet, engraved APO - 400
APO-CIMETIDINE 800 mg is a pale green, oblong, biconvex, film coated tablet, engraved APO - 800

PRESENTATION:
APO-CIMETIDINE 200 mg tablets are packaged in white, high density polyethylene bottles of 100, 120, 500 and 1000. APO-CIMETIDINE 400 mg tablets are packaged in white, high density polyethylene bottles of 60, 100 and 500. APO-CIMETIDINE 800 mg tablets are packaged in white, high density polyethylene bottles of 100 and 500.

STORAGE INSTRUCTIONS:
APO-CIMETIDINE tablets, 200, 400 and 800 mg, should be stored at room temperature (below 25°C), in tight, light resistant containers.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
200 mg : 30/11.4.3/0046
400 mg : 30/11.4.3/0047
800 mg : 30/11.4.3/0059

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Apotex S.A.
PHARMACEUTICAL INNOVATION
Apotex S.A. (Pty) Ltd
Cnr Fleming and Watt Streets
Meadowdale Ext. 1

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
13 November 1995

                P300046/47/59/3
7681-1

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