naltrexone extended release

General Information

Extended-release naltrexone (Vivitrol) is a monthly intramuscular (IM) formulation of naltrexone, an opioid receptor antagonist. It is indicated for alcohol dependence and for opioid dependence relapse prevention after detoxification (label).

An opioid-free interval is required before initiation. Labeling recommends at least 7–10 opioid-free days to avoid precipitated withdrawal that can be severe enough to require hospitalization (label).

Because it is long acting and cannot be removed once injected, success depends on safe initiation, injection access, and follow-up reliability (label/clinical).

The X:BOT trial highlights a key implementation tradeoff: among patients who successfully initiate, outcomes with extended-release naltrexone and buprenorphine/naloxone were similar, but induction onto extended-release naltrexone had higher early failure due to the detoxification barrier (trial/clinical).

The compare view, extended-release naltrexone evidence feed, and print page support shared decision-making in patients with overlapping alcohol use disorder and opioid use disorder.

Often selected when patients prefer an opioid-antagonist approach, can complete detoxification, and can reliably attend monthly injections. Barriers include detoxification requirements, injection logistics, and boxed safety considerations (label/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Naltrexone is a competitive opioid receptor antagonist with highest affinity for μ-opioid receptors. It blocks the effects of exogenous opioids and is used for relapse prevention in OUD and for reducing heavy drinking outcomes in some patients with alcohol use disorder (AUD) (label/clinical).

Because blockade can be overcome by very high opioid doses, attempts to “override” naltrexone can result in fatal opioid overdose; this is a central safety counseling point (label/clinical).

• Opioid receptor antagonism (μ-opioid receptor blockade; primary clinical effect).

Metabolism and Pharmacokinetics

• Vivitrol is an extended-release microsphere formulation given by IM gluteal injection every 4 weeks. After injection, there is an initial peak (~2 hours) and a second peak (~2–3 days), followed by gradual decline with measurable levels for >1 month (label).
• Elimination half-life of naltrexone and 6β-naltrexol following Vivitrol administration is ~5–10 days, driven by polymer erosion (label).
• Naltrexone is extensively metabolized to 6β-naltrexol via dihydrodiol dehydrogenase (cytosolic enzymes); CYP450 is not involved. Metabolites are conjugated (glucuronides) and eliminated primarily in urine, with minimal unchanged naltrexone excretion (label).

Dosing and Administration

• Recommended dose is 380 mg as a deep IM gluteal injection every 4 weeks or once a month, alternating buttocks each injection (label).
• Must only be administered as a deep IM gluteal injection using the carton components. Needle selection and body habitus assessment matter to ensure true IM delivery (label/clinical).
• Prior to initiation, labeling recommends an opioid-free interval of at least 7–10 days. Patients transitioning from methadone or buprenorphine may remain vulnerable to precipitated withdrawal for as long as two weeks (label/clinical).

Monitoring & Labs

• Confirm opioid-free status before initiation; plan for higher-risk transitions from methadone or buprenorphine (label/clinical).
• Monitor injection sites for severe reactions and ensure appropriate administration technique (deep IM gluteal) (label/clinical).
• Monitor liver symptoms and liver enzymes when indicated, especially in alcohol-related liver disease (label/clinical).
• Monitor mood and suicidality, particularly in patients with comorbid depression (label/clinical).
• Review overdose risk education and consider naloxone access planning (label/clinical).

Because missed injections can create predictable gaps in blockade, adherence planning and follow-up scheduling are practical determinants of benefit (clinical).

Adverse Effects

Interactions

• Opioid-containing medications (analgesics, antidiarrheals, cough suppressants) will be blocked and may be ineffective; perioperative and acute pain planning is clinically important (label/clinical).
• Because naltrexone is not CYP-metabolized, pharmacokinetic interactions are limited; regimen review often focuses on liver risk and opioid exposure risk (label/clinical).

Other Useful Information

• For OUD, the X:BOT trial provides comparative effectiveness evidence versus buprenorphine/naloxone, highlighting the induction barrier for antagonist therapy but similar outcomes among those successfully started (trial/clinical).
• Guidelines include naltrexone among first-line pharmacotherapies for alcohol use disorder and as an option for OUD relapse prevention after detoxification, with selection guided by patient preference, medical comorbidity, and feasibility of induction (guideline/clinical).

References

1. Vivitrol (naltrexone FOR Extended Release Injectable Suspension) Prescribing Information — DailyMed (2026)
2. The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update — Journal of Addiction Medicine (2020)
3. TIP 63: Medications for Opioid Use Disorder — SAMHSA (2021)
4. Comparative Effectiveness OF Extended Release Naltrexone Versus Buprenorphine Naloxone FOR Opioid Relapse Prevention (x:bot): A Multicentre, Open Label, Randomised Controlled Trial — The Lancet (2018)
5. The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder — American Journal of Psychiatry (2018)