ANTABUSE

Posology Adults and elderly patients only:

It is recommended that treatment with Disulfiram should be initiated only in a hospital or specialised clinic and by physicians experienced in its use. The patient should have adequate social and family support to avoid ingestion of alcohol.

Suitable patients should not have ingested alcohol for at least 24 hours and must be warned that a Disulfiram-alcohol reaction is potentially dangerous. On the first day of treatment, the patient should be given no more than 4 tablets of Disulfiram in one dose (800 mg).

The next day the patient should take 3 tablets followed on the third day by 2 tablets and on the fourth and fifth days by 1 tablet. Subsequently, daily dosing should continue at 1 or half a tablet daily for as long as advised by the physician but no longer than six months without review.

In the routine management of the alcoholic it is not recommended to carry out an alcohol challenge test. If the clinician feels an alcohol challenge test is essential for the success of the therapy, full information of the procedure and risks of this test can be obtained from the company.

As severe reactions can occur any alcohol challenge should be carried out in specialised units by physicians acquainted with the procedure. Full resuscitation facilities must be immediately available.

Paediatric population:

There is no relevant use of disulfram in the paediatric population.

8. The intensity of the Disulfiram-alcohol reaction may be increased by amitriptyline. Chlorpromazine while decreasing certain components of the Disulfiram-alcohol reaction may increase the overall intensity of the reaction. Disulfiram inhibits the metabolism of certain benzodiazepines such as chlordiazepoxide and diazepam enhancing their sedative effect.

The interaction is not indicated for oxazepam. Benzodiazepines may reduce the disulfiram-alcohol reaction. Disulfiram inhibits the metabolism of many drugs which are converted in the liver (such as phenytoin, theophylline and warfarin) and thereby enhances efficacy.

Dose adjustment may be necessary. Animal studies have indicated similar inhibition of metabolism of pethidine, morphine and amphetamines. A few case reports of increase in confusion and changes in affective behaviour have been noted with the concurrent administration of metronidazole, isoniazid or paraldehyde.

Potentiation of organic brain syndrome and choreoatphetosis following pimozide have occurred very rarely. Disulfiram inhibits the oxidation and renal excretion of rifampicin. 6 Fertility, Pregnancy and lactation Pregnancy The use of Disulfiram in the first trimester of pregnancy is not advised.

The risk/benefit ratio in assessing adverse effects of alcoholism in pregnancy should be taken into account when considering the use of Disulfiram in pregnant patients. There have been rare reports of congenital abnormalities in infants whose mothers have received Disulfiram in conjunction with other medicines.

Breast-feeding Should not be used. No information is available on whether Disulfiram is excreted in breast milk. Its use during breast feeding is not advised especially where there is a possibility of interaction with medicines that the baby may be taking.

7 Effects on ability to drive and use machines Disulfiram may cause side effects such as drowsiness or fatigue. Patients should make sure they are not affected before driving or operating machinery. 8 Undesirable effects The following terms and frequencies are applied: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (frequency not known).

Caution should be exercised in the presence of: • renal failure • reduced hepatic function • respiratory disease • diabetes mellitus • hypothyroidism • cerebral damage • epilepsy Alcohol must not be consumed during treatment and for up to 14 days after discontinuation, as disulfiram prevents the metabolism of ethanol, causing acetaldehyde to accumulate in the body.

8). Before initiating treatment it is advised that appropriate examinations should be carried out to establish the suitability of the patient for treatment. Patients must be warned of the unpredictable and potentially severe nature of a Disulfiram- alcohol reaction as, in rare cases deaths have been reported following the drinking of alcohol by patients receiving Disulfiram.

Certain foods, liquid medicines, remedies, tonics, toiletries, perfumes and aerosol sprays may contain sufficient alcohol to elicit a Disulfiram-alcohol reaction and patients should be made aware of this. Caution should also be exercised with low alcohol and “non-alcohol” or “alcohol-free” beers and wines, which may provoke a reaction when consumed in sufficient quantities.

All personnel involved in the administration of Disulfiram to the patient know that Disulfiram should not be given during a drinking episode. Disulfiram treatment may cause drug-induced liver injury. 8). Liver function should be monitored before initiation of treatment and periodically thereafter; caution should be taken in patients with known reduced hepatic function.

Please consider drug discontinuation if symptoms or signs of liver injury associated with jaundice occur. Excipient(s) Lactose Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sodium This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

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