BLACK BOX WARNING
- hepatotoxicity at excessive doses; not approved for non-opioid-dependent patients
naltrexone
Brand: ReVia, Vivitrol (extended-release injectable)
⚠ BBW Prototype: naloxone
Drug Class: opioid antagonist
Drug Family: opioid antagonist
Subclass: full mu- and kappa-opioid receptor antagonist
Organ Systems: cns
Mechanism of Action
Competitively blocks all opioid receptor subtypes with high affinity and no intrinsic agonist activity; unlike naloxone, naltrexone has a long half-life suitable for once-daily oral or monthly injectable use. Also reduces alcohol craving by blocking endogenous opioid-mediated reward pathways in the limbic system.
mu-opioid receptor (MOR)kappa-opioid receptor (KOR)delta-opioid receptor (DOR)
Indications
- opioid use disorder (maintenance treatment after detoxification)
- alcohol use disorder
Contraindications
- current opioid use or acute opioid withdrawal
- anticipated need for opioid analgesia within 7-10 days (oral) or 30 days (injectable)
- hepatic failure
Adverse Effects
Common
- nausea
- headache
- fatigue
- insomnia
- anxiety
- injection site reactions (Vivitrol)
Serious
- precipitated opioid withdrawal (if opioids present when naltrexone initiated)
- hepatotoxicity (at supratherapeutic doses)
- depression and suicidal ideation (rare)
Pharmacokinetics (ADME)
| Absorption | oral: bioavailability ~5-12% due to first-pass; injectable: sustained release over 30 days |
| Distribution | protein binding ~21%; Vd ~1350 L |
| Metabolism | hepatic reduction to 6-beta-naltrexol (active); glucuronidation |
| Excretion | primarily renal |
| Half-life | 4 hours (naltrexone); 13 hours (6-beta-naltrexol); injectable: 5-10 days effective |
| Onset | oral: within hours; injectable: 2-3 hours |
| Peak | oral: 1 hour |
| Duration | oral: 24-72 hours; injectable: 30 days |
| Protein Binding | 21% |
| Vd | 1350 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| opioid analgesics | complete blockade of opioid-mediated analgesia; large doses of opioids may overcome blockade with dangerous respiratory depression | major |
| opioid-containing medications (cough preparations, antidiarrheals) | loss of opioid effect | moderate |
Nursing Considerations
- Patient must be opioid-free for a minimum of 7-10 days (oral short-acting opioids) or 10-14 days (long-acting opioids, methadone) before initiating naltrexone; naloxone challenge test confirms opioid-free status before first dose.
- Educate patients that their opioid tolerance is lost while on naltrexone; if they relapse and use their previous opioid dose, it will not work initially (blocked), but once the drug clears they face full lethal risk without tolerance.
- For alcohol use disorder, naltrexone reduces craving and the reinforcing effects of alcohol; it works best combined with counseling and does not require abstinence to initiate.
- Vivitrol (monthly injectable) greatly improves adherence for OUD treatment; ensure gluteal injection technique is correct — this is a deep IM injection that should not be administered subcutaneously.
Clinical Pearls
- Naltrexone's efficacy for alcohol use disorder, though modest, is achieved through a completely different mechanism than alcohol — by blocking endorphin-mediated reward from alcohol, it reduces the positive reinforcement that drives continued drinking.
- The combination of naltrexone with acamprosate (targets GABA/glutamate) for alcohol use disorder is supported by the COMBINE trial, showing additive benefit compared to either alone.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.