Bio Cimetidine Tablets

BIO CIMETIDINE is indicated in:

• The treatment of duodenal and benign gastric ulceration and peptic oesophagitis, recurrent ulceration, stomal ulceration and other conditions where reduction of gastric acid secretion has been shown to be beneficial.
• Maintenance therapy for periods of up to one year in those patients with recurrence of duodenal ulceration after short-term therapy.
• The management of those patients who are at high risk from haemorrhage of the upper- intestinal tract due to hepatic failure and treatment with immunosuppressive medicines, following kidney transplant.
• Management of pathological hypersecretion such as Zollinger-Ellison syndrome, systemic mastocytosis, multiple endocrine adenomas.
• Erosive gastro-oesophageal reflux disease (GORD).

Posology

Duodenal and gastric ulcers

A single dose of 800 mg daily taken at bedtime, for 4 weeks in the case of duodenal ulcer and 6 weeks for a gastric ulcer. Where appropriate, a maintenance dose of 400 mg at bedtime or 200 mg twice daily should be taken for a period up to a year.

Oesophageal reflux

A dose of 400 mg four times daily (with meals and at bedtime) for 4 u2013 8 weeks is recommended.

Zollinger-Ellison syndrome

A dose of 400 mg four times daily (with meals and at bedtime) for 4 u2013 8 weeks is recommended. This dose can be increased to a maximum of 2,4 g per day, if necessary.

Maintenance treatment: Prophylaxis of recurrent ulcer

400 mg at bedtime or increase to 400 mg twice a day, if necessary for up to one year.

Special populations

The dose of BIO CIMETIDINE should be reduced in patients with impaired renal function (see section 4.4).

Paediatric population

Safety and/or efficacy of BIO CIMETIDINE in children have not been established.

Method of administration

BIO CIMETIDINE may be given by mouth or the nasogastric route, and the total daily dose should not exceed 2,4 g. When BIO CIMETIDINE is given orally, the daytime doses should be taken with meals.

• Patients with a known hypersensitivity to cimetidine or to any of the excipients (see section 6.1).
• Pregnancy and breastfeeding.

The dosage of BIO CIMETIDINE should be reduced in patients with impaired renal function according to creatinine clearance. Suggested doses according to creatinine clearance are creatinine clearance of 0 u2013 15 L per minute, 200 mg twice daily; 15 u2013 30 mL per minute, 200 mg three times daily; 30 u2013 50 mL per minute, 200 mg four times daily; over 50 mL per minute, normal dosage.

Before giving BIO CIMETIDINE to patients with gastric ulcer, the possibility of malignancy should be excluded by endoscopy and biopsy, if possible, because BIO CIMETIDINE can relieve the symptoms and help the superficial healing of the gastric cancer. The consequences of potential delay in diagnosis should be borne in mind especially in middle aged patients or over, with new or recently changed dyspeptic symptoms.

Care should be taken that patients with a history of peptic ulcer, particularly the elderly, being treated with BIO CIMETIDINE and a non-steroidal anti-inflammatory drug (NSAID) are observed regularly.

Due to possible interaction with coumarins (e.g. warfarin), close monitoring of prothrombin time is recommended when BIO CIMETIDINE is concurrently used (see section 4.5).

Co-administration of medicines with a narrow therapeutic index, such as phenytoin or theophylline, may require dosage adjustment when starting or stopping concomitantly administered BIO CIMETIDINE (see section 4.5).

BIO CIMETIDINE contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially sodium free.

BIO CIMETIDINE can prolong the elimination of medicines metabolised by oxidation in the liver. Close monitoring of patients on BIO CIMETIDINE receiving oral anticoagulants (e.g. warfarin) or phenytoin is recommended and a reduction in the dosage of these medicines may be necessary.

In patients on treatment or with illnesses that could cause falls in blood cell count, the possibility that H 2 -receptor antagonism could potentiate this effect should be borne in mind.

BIO CIMETIDINE has the potential to affect absorption, metabolism or renal excretion of other medicines which is particularly important when medicines with a narrow therapeutic index are administered concurrently. The altered pharmacokinetics may necessitate dosage adjustment of the affected medicine or discontinuation of treatment (see section 4.4).

Interactions may occur by several mechanisms including:

• BIO CIMETIDINE inhibits the activity of cytochrome P450 in the liver, thereby slowing the hepatic metabolism of many medicines. Inhibition of certain cytochrome P450 enzymes (including CYP1A2, CYP2C9, CYP2D6 and CYP3A3/A4, and CYP2C18) may result in increased plasma levels of certain medicines, including warfarin-type coumarin anticoagulants (e.g. warfarin), tricyclic antidepressants (e.g. amitriptyline), class I antiarrhythmics (e.g. lidocaine (lignocaine)), calcium channel blockers (e.g. nifedipine, diltiazem), oral sulfonylureas (e.g. glipizide), phenytoin, suxamethonium, theophylline and metoprolol.
• Competition for renal tubular secretion: This may result in increased plasma levels of certain medicines including procainamide, metformin, ciclosporin and tacrolimus.
• Alteration of gastric pH: The bioavailability of certain medicines may be affected. This can result in either an increase in absorption (e.g. atazanavir) or a decrease in absorption (e.g. some azole antifungals such as ketoconazole, itraconazole or posaconazole).
• Unknown mechanisms: BIO CIMETIDINE may potentiate the myelosuppressive effects (e.g. neutropenia, agranulocytosis) of chemotherapeutic medicines such as carmustine, fluorouracil, epirubicin, or therapies such as radiation. Isolated cases of clinically relevant interactions have been documented with narcotic analgesics (e.g. morphine).

Safety and efficacy in pregnancy and breastfeeding have not been established. Although tests in animals and clinical evidence have not revealed any hazards from the administration of cimetidine, as contained in BIO CIMETIDINE, during pregnancy or breastfeeding, both animal and human studies have shown that it does cross the placental barrier and is excreted in breast milk. BIO CIMETIDINE should not be used during pregnancy and breastfeeding.

Confusion, headache and dizziness have been reported with BIO CIMETIDINE (see section 4.8). Patients should not drive or use machines until it has been established that BIO CIMETIDINE does not affect their ability to do so safely.

Blood and lymphatic system disorders

Less frequent: Leucopenia, thrombocytopenia, aplastic anaemia, pancytopenia and agranulocytosis or neutropenia.

Immune system disorders

Less frequent: Hypersensitivity reactions, anaphylaxis. Anaphylaxis is usually cleared on withdrawal of the medicine.

Psychiatric disorders

Less frequent: Depression, confusion, hallucinations. Confusional states, reversible within a few days of withdrawing cimetidine as contained in BIO CIMETIDINE, have been reported, usually in elderly or ill patients (such as those with renal failure).

Nervous system disorders

Frequent: Headache, dizziness.

Cardiac disorders

Less frequent: Tachycardia, sinus bradycardia and heart block.

Gastrointestinal disorders

Frequent: Diarrhoea.

Less frequent: Pancreatitis. Pancreatitis cleared on withdrawal of the medicine.

Hepatobiliary disorders

Less frequent: Hepatitis, increased serum transaminase levels, hepatotoxicity. Hepatitis and increased serum transaminase levels cleared on withdrawal of the medicine.

Skin and subcutaneous tissue disorders

Frequent: Skin rashes.

Less frequent: Reversible alopecia and hypersensitivity vasculitis. Hypersensitivity vasculitis usually cleared on withdrawal of the medicine.

Musculoskeletal and connective tissue disorders

Frequent: Myalgia.

Less frequent: Arthralgia.

Renal and urinary disorders

Less frequent: Increases in plasma creatinine and interstitial nephritis. Interstitial nephritis cleared on withdrawal of the medicine. Small increases in plasma creatinine have been reported, unassociated with changes in glomerular filtration rate. The increases do not progress with continued therapy and disappear at the end of therapy.

Reproductive system and breast disorders

Less frequent: Gynaecomastia and reversible impotence. Gynaecomastia is usually reversible upon discontinuation of cimetidine therapy. Reversible impotence has been reported particularly in patients receiving high doses (e.g. in Zollinger-Ellison syndrome). However, at regular dosage, the incidence is similar to that in the general population. Galactorrhoea.

General disorders and administrative site conditions

Frequent: Tiredness.

Less frequent: Fever. Fever cleared on withdrawal of the medicine.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of BIO CIMETIDINE is important. It allows continued monitoring of the benefit/risk balance of BIO CIMETIDINE. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the 6.04 Adverse Drug Reactions Reporting Form , found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

Symptoms of overdose

Acute overdosage of up to 20 grams has been reported several times with no significant ill effects.

Management

Treatment of overdosage should consist of emesis, if ingestion occurred not more than four hours before, followed by symptomatic and supportive measures only.