Naltrexone is the mu opioid receptor antagonist with the unusual property of being effective in two distinct substance use disorders: alcohol use disorder and opioid use disorder. The mechanism in each is related but different, and the same drug serves both with the same clinical philosophy.
- Class
- Opioid receptor antagonist
- Mechanism
- Competitive mu opioid receptor antagonist. Blocks opioid reward; reduces alcohol-induced opioid-mediated reward (alcohol stimulates endogenous opioid release driving reward).
- Typical dose
- Oral 50 mg/day. LAI (Vivitrol) 380 mg IM every 4 weeks.
- Half-life
- Oral ~4 hours; LAI ~5-10 days
- FDA indications
- Alcohol use disorder, opioid use disorder (after detoxification)
- Key adverse effects
- Nausea (early), headache, fatigue, hepatotoxicity (rare, dose-dependent — monitor LFTs), injection site reactions (LAI), precipitated opioid withdrawal if active opioid use
Black box: No current FDA boxed warning — the hepatotoxicity boxed warning was removed in 2013. Hepatotoxicity at high doses (uncommon at therapeutic doses) and precipitated withdrawal in active opioid dependence remain labeled warnings.
For OUD: must be opioid-free (7-10 days) before starting — otherwise severe precipitated withdrawal. For AUD: can start while patient drinking. LAI Vivitrol simplifies adherence — monthly injection means daily decision removed. Effective for both AUD and OUD; should be offered to every patient with these disorders.
In OUD, the mechanism is direct: naltrexone blocks mu opioid receptors. An opioid taken on naltrexone produces no reward — the receptor is occupied. The patient who relapses on opioids while on naltrexone experiences blunted effect rather than reinforcement.
In AUD, the mechanism is indirect: alcohol stimulates endogenous opioid release in reward pathways, which contributes to the reward and reinforcement of drinking. Naltrexone blocks the downstream opioid effect, reducing the reinforcement of alcohol use and the craving cycle. Trial data show reduced heavy drinking days, reduced craving, and improved abstinence rates.
Naltrexone is an opioid receptor antagonist used in both alcohol and opioid use disorder — blocking opioid signaling to reduce reward and craving.
Mechanism note: Naltrexone blocks opioid-mediated reward — first-line for AUD (reduces heavy drinking) and an option for OUD (full blockade), but it requires complete opioid clearance before initiation.
Two formulations matter clinically. Oral naltrexone 50 milligrams daily — straightforward, inexpensive. The challenge is adherence: a patient who doesn't take naltrexone before drinking gets no benefit. Long-acting injectable naltrexone (Vivitrol) 380 milligrams IM monthly removes the daily decision entirely. For OUD especially, where lapses can be fatal, the LAI offers substantial advantages over oral.
- Cost
- Oral generic ~$30-80/month. Vivitrol (LAI) ~$1,500/month.
- Generic status
- Oral generic for years. Vivitrol brand-only.
- Formulary typical
- Oral Tier 1-2. Vivitrol: covered by most Medicaid plans and many commercial; PA typical.
- Access friction
- Vivitrol patient support program (Alkermes) navigates insurance. Some clinics buy-and-bill; some use specialty pharmacy. Pre-administration confirmation of opioid-free state critical.
Prescriber tip: For OUD, Vivitrol's adherence advantage is substantial — many patients who fail oral do well with LAI. Plan the 7-10 day opioid-free window before first injection; coordinate with patient and pharmacy.
Precipitated withdrawal is the central safety concern in OUD initiation. Naltrexone given to a patient with opioids on board produces severe, abrupt withdrawal — much more uncomfortable than spontaneous withdrawal. Before starting naltrexone, the patient must be opioid-free for 7-10 days. Urine toxicology negative. Naloxone challenge sometimes used to confirm.
Patient education matters. After naltrexone wears off (oral overnight, LAI over weeks), opioid tolerance is reduced. A patient who relapses to their pre-treatment dose can overdose fatally. Counsel explicitly: relapse after naltrexone carries elevated overdose risk. Naloxone availability for the patient and household is essential.
For AUD: can start while patient is still drinking. No washout required. For OUD: opioid-free required.