CIMETIDINE TABLETS BP 200 MG, ZABCID 200 MG TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 200mg cimetidine

BP.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

4.   CLINICAL PARTICULARS

4.1.   Therapeutic indications

4.2 Posology and method of administration

4.3 Contraindications

4.4 Special warnings and precautions for use

4.5 Interaction with other medicinal products and other forms of interaction

4.6 Fertility, Pregnancy and lactation

Although tests in animals and clinical evidence have not revealed any hazards from the administration of cimetidine during pregnancy or lactation, both animal and human studies have shown that it does cross the placental barrier and is excreted in breast milk. The use of this preparation during pregnancy and lactation should be avoided unless considered essential by the physician.

4.7 Effects on ability to drive and use machines

Patients should take care when driving, operating machinery or carrying out other activities which require full alertness if they feel dizzy, very tired and/or confused.

4.8 Undesirable effects

Adverse experiences with cimetidine are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to

<1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Uncommon: Leukopenia

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

Tachycardia

Rare: Sinus bradycardia Very rare: Heart block

Common: Diarrhoea

Very rare: Pancreatitis. Pancreatitis cleared on withdrawal of the drug.

Uncommon: Hepatitis

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.

Common: Myalgia

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

Common: Tiredness

Very rare: Fever. Fever cleared on withdrawal of the drug.

4.9 Overdose

Acute overdosage of up to 20g has been reported several times with no significant ill-effects. Induction of vomiting and/or gastric lavage may be employed together with symptomatic and supportive therapy.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Cimetidine, one of the H2 blockers, is a reversible, competitive antagonist of the actions of histamine on H2 receptors. It is highly selective in its action and is virtually without effect on H1 receptors or, indeed, on receptors for other autacoids or drugs. The most prominent of the effects of histamine that are mediated by H2 receptors is stimulation of gastric acid secretion and they interfere remarkably little with physiological functions other than gastric secretion.

Cimetidine inhibits gastric acid secretion elicited by histamine or other H2 agonists in a dose-dependent, competitive manner; the degree of inhibition parallels the plasma concentration of the drug over a wide range. In addition, the H2 blockers inhibit gastric secretion elicited by muscarinic agonists or by gastrin, although this effect is not always complete. This breadth of inhibitory effect is not due to non specific actions at the receptors for these other secretagogues. Rather, this effect, which is non-competitive and indirect, appears to indicate either that these 2 classes of secretagogues utilise histamine as the final common mediator or, more probably, that ongoing histaminergic stimulation of the parietal cell is important for amplification of the stimuli provided by acetyl choline or gastrin when they act on their own discrete receptors. Receptors for all 3 secretagogues are present on the parietal cell. The ability of H2 blockers to suppress responses to all 3 physiological secretagogues makes them potent inhibitors of all phases of gastric acid secretion. Thus, these drugs will inhibit basal (fasting) secretion and nocturnal secretion and also that stimulated by food, sham feeding, fundic distension, insulin, or caffeine. The H2 blockers reduce both the volume of gastric juice secreted and its hydrogen ion concentration. Output of pepsin, which is secreted by the chief cells of the gastric glands (mainly under cholinergic control), generally falls in parallel with the reduction in volume of the gastric juice. Secretion of intrinsic factor is also reduced, but it is normally secreted in great excess, and absorption of vitamin B12 is usually adequate even during long-term therapy with H2 blockers.

Concentrations of gastrin in plasma are not significantly altered under fasting conditions; however, the normal prandial elevation of gastrin concentration may be augmented, apparently as a consequence of a reduction in the negative feedback that is normally provided by acid.

5.2 Pharmacokinetic properties

Cimetidine is rapidly and virtually completely absorbed. Absorption is little impaired by food or by antacids. Peak concentrations in plasma are attained in about 1 to 2 hours. Hepatic first-class metabolism results in a bioavailability of about 60% for cimetidine. The elimination half-life is about 2 to 3 hours. Cimetidine is eliminated primarily by the kidneys, and 60% or more may appear in the urine unchanged; much of the rest as oxidation products. Small amounts are recovered in the stool.

5.3 Preclinical safety data

None stated.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose, povidone 30, sodium starch glycollate, sodium lauryl sulphate, colloidal silicon dioxide and magnesium stearate.

Film coating: hydroxypropyl methylcellulose (E464), polyethylene glycol, and colours: quinoline yellow aluminium lake (E104), indigo carmine aluminium lake (E132), titanium dioxide (E171) and iron oxide yellow (E172).

6.2 Incompati­bilities

None known.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Store below 25°C. Protect from light.

6.5 Nature and contents of container

1) Polypropylene tubes with low density polyethylene caps. High density polyethylene film may be used as packing material.

Pack sizes: 100, 250, 500 and 1,000 tablets.

2) Blister packs consisting of clear PVC and hard temper aluminium foil, contained in a carton.

Pack sizes: 12, 24, 48, 60 and 120 tablets.

6.6 Special precautions for disposal Not applicable.

7 MARKETING AUTHORISATION HOLDER

Ennogen Pharma Limited

Unit G4,

Riverside Industrial Estate,

Riverside Way, Dartford

DA1 5BS UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 40147/0013