Antabus^® (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group hf. (Iceland)

Manufactured By

Kemwell Biopharma, Pvt. Ltd. (India)

ATC Code

N07BB01 (Disulfiram)

Active Substance

Disulfiram (Rec.INN registered by WHO)

Dosage Forms

	Antabus®	Effervescent tablets 200 mg: 100 pcs.
		Effervescent tablets 400 mg: 50 pcs.

Dosage Form, Packaging, and Composition

Effervescent tablets white or almost white, round, flat, with beveled edges, with a score and marking “CD” on one side of the score and “C” on the other side of the score.

Excipients: corn starch, povidone, tartaric acid, sodium bicarbonate, talc, colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose.

100 pcs. – polyethylene containers (1) – cardboard packs.

Effervescent tablets white or almost white, round, flat, with beveled edges, with a cross-shaped score dividing the tablet into four parts, and marking “CJ” on one side.

Excipients: corn starch, povidone, tartaric acid, sodium bicarbonate, talc, colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose.

50 pcs. – polyethylene containers (1) – cardboard packs.

Clinical-Pharmacological Group

Drug for the treatment of alcohol dependence

Pharmacotherapeutic Group

Remedy for the treatment of alcoholism

Pharmacological Action

The drug’s action is based on the blockade of acetaldehyde dehydrogenase, which is involved in the metabolism of ethyl alcohol. This leads to an increase in the concentration of the metabolite of ethyl alcohol – acetaldehyde, which causes negative sensations (flushing of the face, nausea, vomiting, tachycardia, decreased blood pressure, etc.), which make alcohol consumption extremely unpleasant after taking Antabus^®. This leads to a conditioned reflex aversion to the taste and smell of alcoholic beverages.

Pharmacokinetics

After oral administration, the absorption of disulfiram from the gastrointestinal tract is from 70% to 90%; it is rapidly metabolized, being reduced to diethyldithiocarbamate, which is itself excreted as a glucuronide conjugate or converted to diethylamine and carbon sulfide, part of which (4-53%) is excreted through the lungs.

Indications

• Treatment and prevention of relapses of chronic alcoholism.

ICD codes

Dosage Regimen

The effervescent tablet is dissolved in an amount of water sufficient for complete dissolution of the drug (half a glass).

Treatment is prescribed after a thorough examination of the patient and warning about the consequences and complications. The drug is taken orally at 200-500 mg 1-2 times/day according to an individual scheme.

After 7-10 days, a Disulfiram-alcohol test is performed (20-30 ml of vodka after taking 500 mg of the drug); if the reaction is weak, the dose of alcohol is increased by 10-20 ml (maximum dose of vodka 100-120 ml). The test is repeated after 1-2 days in a hospital and after 3-5 days on an outpatient basis with correction of alcohol and/or drug doses as necessary. Subsequently, a maintenance dose of 150-200 mg/day can be used for 1-3 years.

Adverse Reactions

Due to the properties of disulfiram

Metallic taste in the mouth, unpleasant odor in patients with colostomy (associated with carbon sulfide), rare cases of hepatitis, sometimes occurring in patients with nickel eczema who do not suffer from alcoholism; polyneuritis of the lower extremities, optic neuritis; memory loss, confusion, asthenia, headaches; skin allergic manifestations.

Associated with the Disulfiram-ethyl alcohol combination

Cases have been described of respiratory failure; cardiovascular collapse, heart rhythm disturbances, angina, sometimes myocardial infarction, as well as neurological disorders; cerebral edema.

Complications with long-term use: rarely – psychoses resembling alcoholic ones, hepatitis, gastritis; in persons suffering from cardiovascular diseases, thrombosis of cerebral vessels is possible, therefore, if complaints of paresthesia in the extremities and face occur, the drug should be immediately discontinued; exacerbation of polyneuritis.

When taking alcohol doses exceeding 50-80 ml of vodka against the background of disulfiram intake, severe disorders of the cardiovascular and respiratory systems, edema, and convulsions may develop. In this case, detoxification therapy is urgently carried out, analeptics are administered, and symptomatic treatment is performed.

Contraindications

Absolute:

• Severe diseases of the cardiovascular system, hearing organs (auditory nerve neuritis) and eyes (glaucoma, optic neuritis);
• Bronchial asthma, pulmonary emphysema;
• Pulmonary tuberculosis;
• Severe hepatic insufficiency;
• Diseases of the hematopoietic organs;
• Diabetes mellitus;
• Thyrotoxicosis;
• Epilepsy and convulsive syndrome of any genesis;
• Mental illnesses;
• Exacerbation of peptic ulcer;
• Kidney diseases;
• Malignant tumors;
• Polyneuritis of any etiology;
• Pregnancy and lactation period;
• Increased individual sensitivity to the drug;

Relative:

• Cardiovascular diseases in the compensation stage;
• Elderly age (over 60 years);
• Gastric and duodenal ulcer in remission;
• Residual effects after cerebrovascular accident;
• Previously experienced disulfiram (Antabus) psychoses.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

The drug is contraindicated in severe hepatic insufficiency.

Use in Renal Impairment

The drug is contraindicated in kidney disease.

Pediatric Use

The drug is not intended for use in children.

Geriatric Use

The drug is contraindicated in elderly patients (over 60 years).

Special Precautions

Patients should be warned about the danger of an intolerance reaction to alcoholic beverages. In case of simultaneous prescription with oral anticoagulants, more frequent monitoring of prothrombin levels and adjustment of anticoagulant doses is necessary, which is associated with an increased risk of bleeding.

Disulfiram should be used with caution in patients with renal insufficiency or hypothyroidism, especially if there is a risk of possible combination with alcohol.

Overdose

The Disulfiram-ethanol combination can cause depression of consciousness up to coma, cardiovascular collapse, and neurological complications.

Treatment is symptomatic.

Drug Interactions

Ascorbic acid reduces the reaction to ethanol.

Contraindicated combinations

Alcohol. Intolerance reaction (flushing, erythema, vomiting, tachycardia). Avoid consumption of alcoholic beverages and medicines containing alcohol.

Undesirable combinations

Isoniazid. Behavioral and coordination disorders.

Nitro-5-imidazoles (metronidazole, ornidazole, secnidazole, tinidazole). Delirious disorders, confusion.

Phenytoin. Significant and rapid increase in plasma phenytoin levels with toxic symptoms (suppression of its metabolism).

If the combinations cannot be avoided, clinical monitoring and monitoring of drug concentrations in plasma should be carried out during and after treatment with disulfiram.

Combinations requiring caution

Warfarin (and other oral anticoagulants). Increased effect of oral anticoagulants and risk of bleeding (reduced breakdown of warfarin in the liver). More frequent monitoring of warfarin concentration and adjustment of the dose of anticoagulants is recommended for 8 days after discontinuation of Antabus^®.

Theophylline. Disulfiram inhibits the metabolism of theophylline. As a result, the dose of theophylline should be adjusted (reduced dosage) depending on clinical symptoms and plasma drug concentration.

Benzodiazepines. Disulfiram may potentiate the sedative effect of benzodiazepines by inhibiting their oxidative metabolism (especially chlordiazepoxide and diazepam). The dosage of the benzodiazepine should be adjusted according to clinical manifestations.

Tricyclic antidepressants. Possible intensification of the alcohol intolerance reaction, especially if patients consume alcoholic beverages while taking disulfiram.

Storage Conditions

At a temperature not exceeding 30°C (86°F). Keep out of reach of children.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.