Antabuse, Disulfiram®

• Disulfiram®

• Antabuse is designed to act as a deterrent to alcohol consumption in patients as an aid in the overall management of chronic alcoholism.
• Disulfiram is a sulfhydryl (-SH, thiol) group reagent and inhibits enzymes concerned with oxidation of active (-SH group) sites on enzyme protein molecules. The pharmacological action of disulfiram is based on its inhibition of enzymes involved in ethanol catabolism.

• Tablets 250 mg

• Alcoholism
• Only alcoholic patients who are motivated to abstain from drinking and who are undergoing supportive psychotherapeutic treatment ancillary to a total program of rehabilitation should be selected for Antabuse administration.
• The disulfiram-alcohol reaction provokes a number of unpleasant symptoms:
  • intense flushing of the face,
  • a feeling of difficulty in breathing,
  • palpitations, a throbbing headache,
  • nausea and vomiting
• Ingestion of large amounts of alcohol may cause the blood pressure to fall, with fainting and the risk of collapse.
• In patients receiving maintenance treatment with Antabuse, the ingestion of alcohol may bring about a typical reaction as quickly as within five to ten minutes.

• Disulfiram produces irreversible inhibition of the enzyme responsible for oxidation of the ethanol metabolite acetaldehyde. The accumulation of acetaldehyde contributes to the reaction occurring after alcohol ingestion in disulfiram treated patients.
• Blockage of the enzyme leads to accumulation of acetaldehyde, which is an important factor for the clinical disulfiramalcohol reaction.

• Absorption of disulfiram from the gastrointestinal tract is rapid but incomplete and approximately 20% is excreted in the faeces

Initial Dosage Schedule

• 500 mg daily is given in a single dose for one to two weeks

Maintenance Regimen

• The average maintenance dose is 250 mg daily (range, 125 to 500 mg)

• Concomitant ingestion of antacids containing divalent cations may reduce absorption.
• Large doses of ferrous salts similarly block absorption.
• Disulfiram blocks the oxidation and renal excretion of rifampicin.
• Disulfiram may retard the metabolism of certain drugs and thus prolong the duration of action or increase the possibility of clinical toxicity of drugs given concomitantly. The drugs include phenytoin and its congeners, and isoniazid. Isoniazid. The adverse reactions associated with concurrent use of isoniazid include ataxia and changes in mental state.
• Phenytoin:
  • Concurrent use with phenytoin may increase serum levels of phenytoin and possibly lead to phenytoin intoxication.
  • Phenytoin serum levels should be carried out and dosage adjustments of phenytoin may have to be made during concurrent therapy with Antabuse tablets. There is evidence that phenobarbitone is not affected by disulfiram.
• Benzodiazepines:
  • The effects of chlordiazepoxide and diazepam, but not oxazepam are increased and prolonged by the concurrent use of disulfiram.
• Anticoagulants:
  • Since disulfiram may prolong prothrombin time, it may be necessary to adjust dosage of oral anticoagulants, e.g. warfarin, in patients receiving these drugs.
• Metronidazole. Acute psychotic reaction and confusion can result.
• Paraldehyde. Concurrent use, theoretically may cause a modified disulfiram-ethanol reaction, and is not recommended.
• Miscellaneous. The toxicity of certain centrally acting drugs has been increased by disulfiram in rats. These drugs include morphine, pethidine, amphetamine and barbiturates.

• Hypersensitivity to this drug or to other thiuram derivatives used in pesticides and rubber vulcanisation
• Severe myocardial disease or ischaemic heart disease
• pregnancy
• advanced hepatic and renal disease
• suicidal risk or psychotic states
• serious organic brain damage.
• Antabuse should not be administered to patients receiving paraldehyde or metronidazole (see Interactions).
• Antabuse should never be administered to a patient who is taking alcohol or is in a state of alcoholic intoxication.
• Antabuse should never be administered to patients without their consent and full explanation, and the doctor should caution the relatives accordingly.
• The patient should be fully informed of the disulfiram-ethanol reaction and cautioned against the possible consequences of taking alcohol either surreptitiously or unwittingly.

Use in pregnancy (Category B2):

• The safe use of this drug in pregnancy has not been established and Antabuse should not be used.
• Therefore, the administration of Antabuse in women of childbearing potential requires that the benefits of the drug be weighed against the possible hazards.

Use in lactation:

• The safe use of this drug during lactation has not been established and use during lactation requires that benefits be weighed against the possible hazards to the infant.

• Do not administer Antabuse until the patient has abstained from alcohol for at least 24 hours.
• Patients who stop taking Antabuse should be advised to wait at least one week before taking alcohol and that reactions with alcohol may occur for up to three weeks after ingesting disulfiram.

Management of the disulfiram-ethanol reaction.

• In the event of an aldehyde reaction as a consequence of a disulfiram treated patient receiving alcohol, supportive measures should be undertaken.
• Generous amounts of ascorbic acid (1 g) should be administered intravenously.
• It is possible that serotonin, histamine, and various catecholamines which are released play some part in the reaction, and the administration of intravenous or intramuscular antihistamines have been used in treatment. In uncomplicated reactions, chlorpromazine 5 to 100 mg intramuscularly has been found to be useful.
• Maintenance care of a patient with an aldehyde reaction includes routine nursing care, intensive supportive therapy, and standard cardiorespiratory resuscitation measures, involving the treatment of hypotension, circulatory failure, correction of hypoxia, and fluid and electrolyte imbalance to restore haemodynamic equilibrium, all of which are determined by monitoring examinations.
• The foot of the bed should be elevated raising the patient’s feet by about 20 to 25 cm.
• Other measures include an adequate patent airway, adequate ventilation with oxygen, if necessary, the correction of arterial pCO2 and pO2, pH, and the intravenous infusion of standard bicarbonate, if there is obvious acidaemia.
• An infusion of plasma to counteract shock and fluid therapy should be administered according to monitoring of central venous pressure.

• Under all circumstances, patients receiving Antabuse must not take alcohol or alcohol containing preparations, e.g. certain cough syrups, sauces, vinegar, tonics, foods prepared with wine, and even should avoid the use of aftershave lotions and back rubs containing alcohol.