Schedule H

Oral

Formulation Type Strengths Available

Tablets 50 mg

Note: Extended-release intramuscular depot formulation (Vivitrol) is NOT AVAILABLE in India. Only oral tablets are available for clinical use.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Opioid Dependence — Relapse Prevention (Abstinence Maintenance)

Prerequisites before initiation:

• Patient must be completely detoxified from opioids

• Minimum 7–10 days since last short-acting opioid use (e.g., heroin, morphine)

• Minimum 10–14 days since last long-acting opioid use (e.g., methadone, buprenorphine)

• Urine drug screen negative for opioids

• Patient should be warned about precipitated withdrawal risk

Naltrexone Challenge Test (Optional but Recommended):

• Administer naloxone 0.4–0.8 mg IM or SC

• Observe for 30–60 minutes for withdrawal signs

• If no withdrawal signs, proceed with naltrexone initiation

Parameter Dosing

Starting dose 25 mg orally once daily; observe for 1–2 hours for any withdrawal symptoms

Titration If no adverse reaction, increase to 50 mg once daily from day 2

Usual maintenance dose 50 mg once daily

Maximum dose 50 mg/day (standard); up to 100–150 mg/day in supervised alternate-day regimens under specialist care

Alternate Dosing Schedules (Supervised Settings Only):

Schedule Dosing

Daily 50 mg once daily

Thrice weekly 100 mg on Monday, 100 mg on Wednesday, 150 mg on Friday

Alternate day 100 mg every other day

Clinical Notes:

• NOT for treatment of opioid withdrawal — use only after detoxification is complete

• Duration: Typically 6–12 months; longer in high-risk patients

• Concurrent psychosocial support is essential for efficacy

• Supervised administration improves adherence and outcomes

1. Alcohol Dependence — Relapse Prevention

Parameter Dosing

Starting dose 25 mg once daily for 3–4 days

Titration Increase to 50 mg once daily after initial period if tolerated

Usual maintenance dose 50 mg once daily

Maximum dose 50 mg/day (standard); up to 100 mg/day under specialist supervision in selected cases

Clinical Notes:

• May be started while patient is still drinking (unlike disulfiram), but abstinence improves outcomes

• Best efficacy when combined with psychosocial interventions (motivational enhancement therapy, cognitive behavioural therapy)

• Duration: Typically 3–6 months; may be extended to 12 months in patients at high relapse risk

• Contraindicated in patients currently using opioids or opioid-containing medications

• Does NOT cause disulfiram-like reaction with alcohol

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes Evidence Basis

Impulse Control Disorders (e.g., pathological gambling, kleptomania) 50–100 mg once daily Variable; typically 12 weeks trial OFF-LABEL; Specialist psychiatrist only Limited RCTs; not standard practice in India

Self-Injurious Behaviour (e.g., in borderline personality disorder) 25–50 mg once daily Variable OFF-LABEL; Specialist only Small RCTs; case series

Binge Eating Disorder 50 mg once daily 12–24 weeks OFF-LABEL; Specialist only Limited evidence

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable. Naltrexone is NOT approved for routine use in children and adolescents below 18 years of age.

Secondary Indications — Paediatric (Off-label)

Indication Age Group Dose Notes

Opioid Dependence (Relapse Prevention) 16–18 years Starting dose: 25 mg once daily OFF-LABEL; Specialist only

Titration: Increase to 50 mg once daily if tolerated

Maximum: 50 mg/day

Alcohol Use Disorder 16–18 years Same as above OFF-LABEL; Specialist only

Safety Monitoring in Adolescents:

• Confirm complete opioid detoxification before initiation

• Baseline and periodic liver function tests (higher vigilance for hepatotoxicity)

• Psychiatric monitoring including suicidal ideation screening

• Assess medication adherence closely

Clear Statement: Use in patients below 16 years of age is NOT RECOMMENDED. Any use in adolescents (16–18 years) requires specialist de-addiction psychiatrist supervision with enhanced hepatotoxicity monitoring.

Note: Naltrexone and its active metabolite 6-beta-naltrexol are primarily renally excreted. Accumulation may occur in severe renal impairment.

Active hepatitis or transaminases >5× ULN Contraindicated

Transaminases 3–5× ULN Avoid initiation; if on therapy, discontinue and reassess

Important: Naltrexone carries a dose-dependent hepatotoxicity risk. Baseline LFTs are mandatory before initiation. Alcoholic liver disease is common in target population — assess hepatic reserve carefully.

• Current opioid use (including prescription opioid analgesics, opioid agonist therapy such as methadone or buprenorphine)

• Positive urine opioid screen (risk of precipitated withdrawal)

• Acute opioid withdrawal syndrome

• Acute hepatitis or hepatic failure

• Severe hepatic impairment (transaminases >5× ULN or bilirubin elevation)

• Known hypersensitivity to naltrexone or any excipient

• Anticipated need for opioid analgesia (e.g., scheduled surgery)

• History of liver disease (including alcoholic liver disease) — even if current LFTs are normal

• Moderate hepatic impairment — requires dose adjustment and close monitoring

• History of depression, suicidal ideation, or psychiatric illness — may worsen; monitor closely

• Patients at risk of opioid overdose if they attempt to override blockade with high-dose opioids (loss of tolerance during naltrexone therapy increases overdose risk upon relapse)

• Concurrent use with hepatotoxic medications (e.g., Isoniazid, Rifampicin, Methotrexate)

• Chronic pain conditions requiring opioid analgesia — need for pain management planning

• Renal impairment — monitor for accumulation

• Thrombocytopenia (rare association reported)

Parameter Details

Risk category Limited human data; animal studies suggest possible adverse effects at high doses; use only if clearly needed

Preferred alternatives Non-pharmacological interventions first-line; for opioid dependence in pregnancy, buprenorphine or methadone maintenance is preferred over antagonist therapy

When it may be used Only if maternal benefit clearly outweighs fetal risk; specialist psychiatry and obstetric supervision mandatory

Monitoring Fetal growth parameters; maternal mood and LFTs

Note: Antagonist therapy (naltrexone) is generally avoided in pregnant women with opioid dependence — opioid agonist maintenance (buprenorphine, methadone) is preferred to prevent relapse and fetal withdrawal.

Parameter Details

Compatibility Probably compatible; limited data but low expected infant exposure

Drug levels in milk Low (based on limited studies)

Preferred alternatives Non-pharmacological interventions if feasible; if medication needed, naltrexone may be considered with monitoring

Monitoring in infant Feeding adequacy, weight gain, irritability, gastrointestinal disturbances

Parameter Recommendation

Starting dose 25 mg once daily

Titration Slower than younger adults; assess tolerance over 1 week before increasing

Extra risks Increased susceptibility to hepatotoxicity, cognitive effects, dehydration; more likely to have reduced hepatic or renal reserve

Special considerations Baseline and frequent LFT monitoring; assess renal function; evaluate for cognitive impairment affecting medication adherence; lower threshold for discontinuation if adverse effects emerge

Interacting Drug Effect Recommendation

Opioid Analgesics (Morphine, Fentanyl, Codeine, Tramadol, Oxycodone) Complete blockade of opioid effects — analgesic failure Avoid combination; if urgent analgesia needed, use non-opioid alternatives; if opioids essential, requires higher doses under close monitoring (risk of respiratory depression when naltrexone wears off)

Opioid Agonist Therapy (Methadone, Buprenorphine) Precipitates severe withdrawal if patient on agonist; blocks therapeutic effect Contraindicated; ensure complete detoxification before naltrexone initiation

Disulfiram Additive hepatotoxicity risk Avoid combination unless strictly supervised with frequent LFT monitoring

Thioridazine Potential for increased sedation and hepatotoxicity Avoid combination

Interacting Drug Effect Recommendation

Isoniazid Additive hepatotoxicity risk Monitor LFTs more frequently (every 2 weeks initially); consider alternative TB regimen if possible

Rifampicin Additive hepatotoxicity; may also alter naltrexone metabolism Monitor LFTs; use with caution

Methotrexate Additive hepatotoxicity Monitor LFTs closely

Warfarin May alter INR in some patients (mechanism unclear) Monitor INR when initiating or stopping naltrexone

NSAIDs Additive hepatotoxicity risk with chronic use Use with caution; monitor LFTs

Antidepressants (SSRIs, SNRIs) No significant pharmacokinetic interaction Generally safe; monitor mood closely as both conditions increase depression risk

CNS Depressants (Benzodiazepines, Alcohol) No pharmacodynamic synergy with naltrexone, but patients may have comorbid use Monitor for sedation; counsel about alcohol use

• Nausea (most common — often improves after first week)

• Headache

• Dizziness

• Fatigue, lethargy

• Anxiety, nervousness

• Insomnia

• Abdominal pain, cramping

• Decreased appetite

• Joint and muscle pain

• Transient elevation of transaminases

• Hepatotoxicity — dose-dependent; presents with elevated transaminases, jaundice, right upper quadrant pain; requires immediate discontinuation and hepatology consultation if transaminases >3–5× ULN

• Precipitated Opioid Withdrawal — if initiated in patient with opioids in system; severe, prolonged withdrawal (up to 48 hours); requires supportive care

• Depression and Suicidal Ideation — monitor psychiatric status closely; requires immediate psychiatric evaluation if emergent suicidal thoughts

• Eosinophilic Pneumonia — rare; presents with dyspnoea, cough, fever; requires discontinuation

• Hypersensitivity Reactions — rash, urticaria, angioedema (rare)

• Injection Site Reactions — NOT applicable in India (depot formulation not available)

Phase Parameters to Monitor

Baseline Liver function tests (AST, ALT, bilirubin, ALP), renal function, urine drug screen (confirm opioid-negative), psychiatric assessment (depression, suicidal ideation screening), informed consent documentation

Before initiation Consider naloxone challenge test if opioid abstinence uncertain

After initiation (1 month) LFTs, clinical assessment for abstinence, mood evaluation, medication adherence

Short-term (Monthly for first 3 months) LFTs, psychiatric status, abstinence verification, adverse effect assessment

Long-term (Every 3 months thereafter) LFTs, clinical assessment for relapse, ongoing psychosocial engagement, mood monitoring

Note: Extended-release injectable formulation (Vivitrol) is NOT AVAILABLE in India.

Note: Naltrexone IS included in NLEM India 2022. Available at subsidised rates in government de-addiction centres and through Jan Aushadhi outlets.

• Confirm opioid abstinence before initiation: Minimum 7–10 days for short-acting opioids, 10–14 days for long-acting opioids; urine drug screen mandatory; consider naloxone challenge if uncertain — precipitated withdrawal is severe and prolonged.

• Hepatotoxicity monitoring is non-negotiable: Baseline LFTs mandatory; do not initiate if transaminases >3× ULN; monitor monthly for first 3 months.

• Not a substitute for naloxone in overdose: Naltrexone is for relapse prevention, NOT for reversing acute opioid overdose — ensure patients and families understand this distinction.

• Educate about analgesic implications: Opioid analgesics will NOT work while on naltrexone; patients should carry medical alert card; non-opioid analgesia (NSAIDs, paracetamol, regional anaesthesia) should be used for acute pain; if opioids essential, requires significantly higher doses under close monitoring.

• Reduced opioid tolerance is dangerous: During naltrexone treatment, opioid tolerance decreases; if patient relapses after stopping naltrexone, usual pre-treatment opioid doses may cause fatal overdose — counsel extensively.

• Best outcomes with motivated patients and psychosocial support: Naltrexone alone is insufficient; concurrent counselling, family involvement, and structured de-addiction programme significantly improve outcomes.

Naltrexone; opioid dependence; alcohol dependence; opioid antagonist; relapse prevention; hepatotoxicity; abstinence-focused; de-addiction; NLEM India; Schedule H; Psychiatry

RxIndia v1.0 — 11 Jun 2025

• CDSCO approved product inserts

• Indian Pharmacopoeia / National Formulary of India

• NLEM India 2022

• API Textbook of Medicine — Psychiatry and Addiction Medicine chapters

• AIIMS De-addiction Centre Protocols

• National Drug Dependence Treatment Centre (NDDTC) Clinical Guidelines

• Government of India Guidelines for Treatment of Substance Use Disorders

• WHO Model Guidelines for Opioid Antagonist Use in Dependence (supportive reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

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