Hypersensitivity to cimetidine.
Dosage should be reduced in patients with impaired renal function according to creatinine clearance. The following dosages are suggested: creatinine clearance of 0-15ml per minute, 200mg twice a day; 15 to 30ml per minute, 200mg three times a day; 30 to 50ml per minute, 200mg four times a day; over 50ml per minute, normal dosage. Cimetidine is removed by haemodialysis, but not to any significant extent by peritoneal dialysis.
Clinical trials of over six years' continuous treatment and more than 15 years' widespread use have not revealed unexpected adverse reactions related to long-term therapy
The safety of prolonged use is not fully established and care should be taken to observe periodically patients given prolonged treatment.
Care should be taken that patients with a history of peptic ulcer, particularly the elderly, being treated with cimetidine and a non-steroidal anti-inflammatory agent are observed regularly.
Before initiating therapy with this preparation for any gastric ulceration, malignancy should be excluded by endoscopy and biopsy, if possible, because Tagamet tablets 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.
Due to possible interaction with coumarins, close monitoring of prothrombin time is recommended when cimetidine is concurrently used.
Co-administration of therapeutic agents with a narrow therapeutic index, such as phenytoin or theophylline, may require dosage adjustment when starting or stopping concomitantly administered cimetidine (see Section 4.5).
Cimetidine can prolong the elimination of drugs metabolised by oxidation in the liver.
Although pharmacological interactions between cimetidine and a number of drugs have been demonstrated e.g. diazepam and propranolol, only those with oral anticoagulants, phenytoin, theophylline and intravenous lidocaine appear, to date, to be of clinical significance. Close monitoring of patients on cimetidine receiving oral anticoagulants or phenytoin is recommended and a reduction in the dosage of these drugs may be necessary.
In patients on drug treatment or with illnesses that could cause falls in blood cell count, the possibility that H2-receptor antagonism could potentiate this effect should be borne in mind.
Cimetidine has the potential to affect the absorption, metabolism or renal excretion of other drugs which is particularly important when drugs with a narrow therapeutic index are administered concurrently. The altered pharmacokinetics may necessitate dosage adjustment of the affected drug or discontinuation of treatment (see Section 4.4).
Interactions may occur by several mechanisms including:
Although tests in animals and clinical evidence have not revealed any hazards from the administration of Tagamet during pregnancy or lactation, both animal and human studies have shown that it does cross the placental barrier and is excreted in milk. The use of this preparation during pregnancy and lactation should be avoided unless considered essential.
Adverse experiences with cimetidine are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10000, <1/1000), very rare (<1/10000).
Rare: Thrombocytopenia, aplastic anaemia
Very rare: Pancytopenia, agranulocytosis
Very rare: Anaphylaxis. Anaphylaxis is usually cleared on withdrawal of the drug.
Uncommon: Depression, confusional states, hallucinations. Confusional states, reversible within a few days of withdrawing cimetidine, have been reported, usually in elderly or ill patients.
Common: Headache, dizziness
Rare: Sinus bradycardia
Very rare: Heart block
Very rare: Pancreatitis. Pancreatitis cleared on withdrawal of the drug.
Rare: Increased serum transaminase levels. Hepatitis and increased serum transaminase levels cleared on withdrawal of the drug.
Common: Skin rashes
Very rare: Reversible alopecia and hypersensitivity vasculitis. Hypersensitivity vasculitis usually cleared on withdrawal of the drug.
Very rare: Arthralgia
Uncommon: Increases in plasma creatinine
Rare: Interstitial nephritis. Interstitial nephritis cleared on withdrawal of the drug. 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.
Uncommon: 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.
Very rare: Galactorrhoea
Very rare: Fever. Fever cleared on withdrawal of the drug.