Schedule H

Oral

Formulation Type Strengths Available

Tablets 250 mg, 500 mg

Note: Disulfiram is available as single-agent tablets only. No fixed-dose combinations are marketed in India.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Alcohol Dependence (Aversive/Deterrent Therapy)

Prerequisites before initiation:

• Patient must have abstained from alcohol for minimum 12–24 hours

• No signs of acute alcohol intoxication or withdrawal

• Written informed consent obtained

• Patient and family educated about disulfiram-ethanol reaction

• Baseline hepatic function confirmed

Parameter Dosing

Starting dose 500 mg once daily in the morning for 1–2 weeks

Titration Reduce to maintenance dose after initial period based on tolerance

Usual maintenance dose 250 mg once daily

Maximum dose 500 mg/day

Clinical Notes:

• Best administered in the morning to avoid insomnia

• Supervised administration (by family member or healthcare worker) significantly improves outcomes

• Duration of therapy: Typically 3–6 months; some patients benefit from 12 months or longer

• Disulfiram effect persists for up to 1–2 weeks after last dose — counsel patient accordingly

• Should be used as part of comprehensive de-addiction programme including psychosocial interventions

Secondary Indications — Adults (Off-label)

Not applicable. No established off-label indications in Indian practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable. Disulfiram is NOT approved for use in children and adolescents.

Secondary Indications — Paediatric (Off-label)

Not applicable.

Clear Statement: Use in patients below 18 years of age is NOT RECOMMENDED. Safety and efficacy have not been established in the paediatric population. Alcohol use disorders in adolescents should be managed with psychosocial interventions under specialist supervision.

Mild to moderate impairment No dose adjustment required

Uraemia Avoid use due to elevated neurotoxicity risk

Haemodialysis Limited data; use with caution under specialist supervision

Note: Alcoholic liver disease is common in target population. Baseline LFTs must be obtained before initiation, and therapy should not be started if transaminases are >3 times upper limit of normal.

• Current alcohol intoxication or alcohol ingestion within past 12–24 hours

• Severe hepatic disease or hepatic failure

• Severe myocardial disease or coronary artery disease

• History of psychosis or severe psychiatric illness (unless under close specialist supervision)

• Known hypersensitivity to disulfiram or thiuram derivatives (used in rubber industry)

• Pregnancy

• Concurrent use of alcohol or alcohol-containing preparations (medications, tonics, mouthwashes)

• Concurrent use of metronidazole or paraldehyde

• History of seizures or epilepsy — may lower seizure threshold

• Diabetes mellitus — risk of hypoglycaemia; may also interfere with glucose metabolism

• Mild to moderate hepatic dysfunction — requires close LFT monitoring

• Pre-existing cardiovascular disease — disulfiram-ethanol reaction can be life-threatening

• Chronic kidney disease — increased risk of neurotoxicity

• History of depression or suicidal ideation — may worsen; psychiatric monitoring required

• Hypothyroidism

• Cerebrovascular disease

• Respiratory disease

• Peripheral neuropathy

• Occupations requiring mental alertness (drivers, machine operators, pilots) — risk of drowsiness and impaired cognition

• Patients with poor motivation or unreliable for follow-up — supervised administration essential

Parameter Details

Risk category Contraindicated — evidence of teratogenicity in animal studies; potential for fetal harm

Preferred alternatives Non-pharmacological interventions: psychosocial therapy, motivational interviewing, cognitive behavioural therapy

When it may be used Should NOT be used in pregnancy under any circumstances

Monitoring If inadvertent exposure occurs in early pregnancy, specialist obstetric and genetic counselling indicated

Parameter Details

Compatibility NOT recommended during breastfeeding

Drug levels in milk Unknown; potential for accumulation

Preferred alternatives Non-pharmacological interventions; delay disulfiram initiation until breastfeeding completed

Monitoring in infant If inadvertent exposure: feeding difficulties, sedation, irritability, poor weight gain

Parameter Recommendation

Starting dose 125–250 mg once daily

Titration Very slow; assess tolerance over 1–2 weeks before any increase

Extra risks Increased sensitivity to CNS effects (confusion, drowsiness, cognitive impairment), hepatotoxicity, cardiac complications during disulfiram-ethanol reaction

Special considerations More likely to have occult cardiovascular disease; ECG recommended before initiation; LFT monitoring more frequent; lower threshold for discontinuation if adverse effects emerge

Interacting Drug Effect Recommendation

Alcohol (including alcohol-containing medications, mouthwashes, tonics, cough syrups) Severe disulfiram-ethanol reaction: flushing, nausea, vomiting, hypotension, tachycardia, chest pain, respiratory distress; potentially fatal Absolutely contraindicated; counsel patient extensively

Metronidazole Disulfiram-like reaction; acute psychosis and confusion reported Avoid combination

Isoniazid Increased risk of CNS toxicity — psychosis, ataxia, behavioural changes Avoid if possible; if essential, close neuropsychiatric monitoring

Warfarin Disulfiram inhibits warfarin metabolism — increased anticoagulant effect, bleeding risk Monitor INR closely; reduce warfarin dose as needed

Ritonavir and other Protease Inhibitors Alcohol content in liquid formulations; may also increase disulfiram levels Avoid alcohol-containing formulations; monitor for neurotoxicity

Paraldehyde Risk of severe reaction (chemically related to acetaldehyde) Contraindicated

Interacting Drug Effect Recommendation

Phenytoin Disulfiram inhibits phenytoin metabolism — increased phenytoin levels, toxicity risk Monitor serum phenytoin levels; reduce dose if needed

Theophylline Disulfiram inhibits theophylline metabolism — increased levels Monitor serum theophylline levels; adjust dose accordingly

Benzodiazepines (especially diazepam, chlordiazepoxide) Enhanced CNS depression; disulfiram inhibits metabolism of some benzodiazepines Use with caution; monitor for excessive sedation; consider lorazepam or oxazepam (glucuronidated, not affected)

Tricyclic Antidepressants Enhanced CNS effects; potential for confusion Monitor closely; use lower doses of TCAs

Antipsychotics Enhanced sedation; possible extrapyramidal effects Use with caution; monitor mental status

Caffeine Disulfiram may reduce caffeine clearance Minor; be aware if patient reports jitteriness or insomnia

Oral Hypoglycaemics Altered glucose control; may enhance hypoglycaemia Monitor blood glucose more frequently

• Drowsiness, fatigue, lethargy

• Metallic or garlic-like taste in mouth

• Headache

• Mild gastrointestinal upset (nausea, vomiting)

• Skin eruptions (acneiform rash)

• Sexual dysfunction (impotence, decreased libido)

• Body odour

• Mild transaminase elevation

• Hepatotoxicity / Fulminant Hepatic Failure — can be fatal; requires immediate discontinuation and hospitalisation; presents with jaundice, abdominal pain, dark urine, markedly elevated transaminases

• Psychosis / Acute Confusional States — especially in predisposed individuals; requires discontinuation

• Peripheral Neuropathy — dose-related; usually reversible on discontinuation

• Optic Neuritis — rare; may cause visual impairment

• Severe Disulfiram-Ethanol Reaction — cardiovascular collapse, arrhythmias, myocardial infarction, respiratory depression, seizures, death; requires emergency management

Signs of Disulfiram-Ethanol Reaction:

• Flushing of face and body

• Throbbing headache

• Nausea, vomiting

• Chest pain, palpitations

• Hypotension, syncope

• Respiratory distress

• Confusion

Phase Parameters to Monitor

Baseline Liver function tests (AST, ALT, bilirubin, ALP), renal function, ECG (if cardiac history or elderly), complete psychiatric evaluation, confirmation of alcohol abstinence (breathalyser/blood alcohol), written informed consent

After initiation / dose change LFTs at 2 weeks, 4 weeks, then monthly for first 3 months; clinical assessment for CNS effects, adherence

Long-term LFTs monthly for first 6 months, then every 3 months; periodic mental status evaluation; alcohol abstinence verification; assessment for neuropathy (symptoms, examination); ongoing psychosocial support engagement

Note: "Antabuse" (original brand) is NOT commonly available in India. Generic disulfiram tablets are widely accessible.

Note: Disulfiram is NOT included in NLEM India 2022; prices are not NPPA-controlled. Available in both private pharmacies and some government de-addiction centres.

• Ensure 12–24 hour alcohol-free period before initiation — starting disulfiram in a patient with recent alcohol intake can precipitate severe reaction.

• Supervised administration is key to success — have a reliable family member or healthcare worker administer the daily dose; unsupervised therapy has poor adherence and outcomes.

• Educate thoroughly about hidden alcohol sources — alcohol is present in many cough syrups, tonics, aftershaves, mouthwashes, sauces, vinegars, and some medications; provide comprehensive list to patient.

• Reaction persists 1–2 weeks after stopping — patients must be warned that disulfiram effect continues for up to 14 days after last dose; drinking during this period can still cause reaction.

• LFTs are non-negotiable — hepatotoxicity can be severe and fatal; never skip baseline LFTs; discontinue immediately if transaminases rise >3 times ULN or if clinical hepatitis develops.

• Not a standalone treatment — disulfiram works best as part of comprehensive de-addiction programme including psychotherapy, counselling, and family involvement.

Disulfiram; alcohol dependence; alcohol deterrent; aversive therapy; aldehyde dehydrogenase inhibitor; hepatotoxicity; disulfiram-ethanol reaction; supervised therapy; psychiatric-caution; pregnancy-contraindicated; Schedule H; Psychiatry

RxIndia v1.0 — 11 Jun 2025

• CDSCO approved product inserts

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine — Psychiatry and Toxicology chapters

• AIIMS De-addiction Centre Protocols

• Government of India Guidelines for Treatment of Substance Use Disorders

• ICMR Technical Report on Alcohol Use Treatment

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine, 21st edition