naltrexone
opioid antagonist· Brands: Revia, VivitrolIMPO
Mechanism of action
Naltrexone is a competitive antagonist at mu, delta and kappa opioid receptors. It binds with high affinity, blocking the effects of exogenous opioids. In alcohol dependence, it reduces the reinforcing effects of alcohol by modulating the endogenous opioid system, leading to decreased craving and relapse.
Pharmacokinetics
Well absorbed orally, but undergoes extensive first-pass hepatic metabolism to the active metabolite 6-beta-naltrexol. Bioavailability is about 5-40%. Peak plasma concentrations occur within 1 hour. Elimination half-life of naltrexone is about 4 hours, and that of 6-beta-naltrexol is about 13 hours. Excreted mainly in urine as conjugates. Duration of action is longer than suggested by half-life due to persistent receptor blockade.
Indications & dosing
Alcohol dependence
Start with 25 mg once daily for 1 week, then increase to 50 mg once daily.
- adult · PO: 50 mg once daily · Start with 25 mg once daily for 1 week, then increase to 50 mg once daily.
Opioid dependence
Initiate after detoxification; start with 25 mg once daily for 1 week, then increase to 50 mg once daily.
- adult · PO: 50 mg once daily · Initiate after detoxification; start with 25 mg once daily for 1 week, then increase to 50 mg once daily.
Alcohol dependence (extended-release)
Administer as deep intramuscular injection for relapse prevention.
- adult · IM: 380 mg every 4 weeks · Administer as deep intramuscular injection for relapse prevention.
Opioid dependence (extended-release)
Administer as deep intramuscular injection for relapse prevention after detoxification.
- adult · IM: 380 mg every 4 weeks · Administer as deep intramuscular injection for relapse prevention after detoxification.
Contraindications & precautions
- Current opioid use or opioid dependence · Precipitates acute opioid withdrawal.
- Acute hepatitis or liver failure · Hepatotoxicity risk; monitor liver function.
- Hypersensitivity to naltrexone or any component · Avoid in allergic reactions.
- Patients currently receiving opioid analgesics · Blocks opioid effects; may precipitate withdrawal.
- Monitor liver function tests before and during therapy.
- Patients must be opioid-free for at least 7-10 days before starting naltrexone.
- Advise patients to avoid use of opioids during therapy.
- Use with caution in patients with renal impairment.
- Patients should carry a card or wear a bracelet to alert medical personnel of naltrexone use.
Adverse effects
- Nausea
- Headache
- Dizziness
- Fatigue
- Insomnia
- Hepatotoxicityserious
- Precipitated opioid withdrawalserious
- Depressionserious
Renal & hepatic adjustment
- eGFR 0–30: Use with caution; no formal adjustment required but active metabolite may accumulate.
- Hepatic impairment (mild): No dose adjustment required; monitor liver function before and during treatment.
- Hepatic impairment (moderate): Use with caution; monitor liver function closely.
- Hepatic impairment (severe): Contraindicated in acute hepatitis or liver failure; avoid. (avoid)
Monitoring, pregnancy & toxicity
- Liver function tests · Before starting and periodically during treatment
- Signs of opioid withdrawal · At initiation, especially if the patient has recent opioid use
- Adherence to treatment · At each visit
- Mood and mental health · Monitor for depression or suicidal ideation
- Injection site reactions · At each visit if using depot formulation
- Pregnancy: Not recommended during pregnancy; use only if potential benefit outweighs risk. Discuss with specialist.
- Toxicity: Opioid withdrawal syndrome in patients with recent opioid use: agitation, hypertension, tachycardia, nausea, vomiting, diarrhoea, piloerection · Supportive care; monitor vital signs. Do not attempt to overcome with opioids; consider supportive treatment and specialist input.
- Toxicity: Hepatotoxicity with high doses: elevated transaminases, jaundice · Discontinue naltrexone; monitor liver function; provide supportive care.
Clinical notes
Used for maintenance of opioid abstinence in detoxified patients and for alcohol dependence. It can precipitate severe opioid withdrawal if administered to patients who are opioid-dependent. Must be initiated at least 7-10 days after last opioid use. Monitor liver function. The long-acting intramuscular formulation is given monthly. It is not a controlled substance, but requires careful prescribing. Discontinuation may lead to relapse.
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BNF; local formulary