Normal-Dose Naltrexone (Oral and Vivitrol)

Full-dose naltrexone — oral 50 mg daily and Vivitrol 380 mg monthly — for sustained abstinence after detox. With the precipitated-withdrawal safety warning.

SAFETY, read before anything else on this page.

Naltrexone is a full opioid receptor antagonist. Starting it while opioids are still on your receptors causes immediate, severe precipitated withdrawal: symptoms within ~5 minutes, lasting up to 48 hours, sometimes severe enough to require ICU admission (ReVia FDA label).

“Opioids” here includes 7-OH, kratom and the kratom synthetics (MGM-15, MIT-A, pseudo), buprenorphine (Suboxone, Subutex, Sublocade), methadone, and any prescription opioid.

Required opioid-free windows before initiation: at least 7 days for short-acting opioids and 10 to 14 days for long-acting opioids per SAMHSA TIP 63 and the ASAM National Practice Guideline. For the longer-acting kratom synthetics, prescribers experienced with this population often use windows at the longer end of that range or beyond.

Do not initiate naltrexone without a clinician confirming the timing. This is not a “try it and see” medication. If a wave of impending doom or suicidal thinking shows up while you’re trying to figure this out, call or text 988 (US Suicide & Crisis Lifeline) or see Crisis Hotlines.

This page covers full-dose naltrexone in its two formulations — oral tablets (typically 50 mg/day) and the extended-release intramuscular injection Vivitrol (380 mg every 4 weeks). It’s the most clinically established of the three naltrexone protocols covered on this site (see the parent overview for the comparison across normal-dose, LDN, and ULDN).

What it is and how it works

Naltrexone is a competitive, non-selective opioid receptor antagonist with strong preference for the mu receptor. It occupies the receptor without activating it; while it’s bound, opioid agonists can’t produce their effects. Practically, that means while a patient is adherent to naltrexone:

  • No euphoria from a use event
  • No analgesia from a standard opioid dose
  • No reinforcement of the use behavior
  • No respiratory depression from a typical opioid dose

It’s also why starting naltrexone while opioids are on the receptor produces precipitated withdrawal, the antagonist competitively displaces the agonist, dropping receptor activation to zero in minutes (ReVia FDA label, Warnings).

The two formulations

Oral naltrexone (Revia, Depade, generic)

  • FDA-approved dose for opioid dependence: initiate with 25 mg on day 1; if no precipitated withdrawal, increase to 50 mg/day. The FDA label also lists alternative schedules (100 mg every other day, 150 mg every third day) for adherence purposes, though higher single doses carry higher hepatotoxicity risk (ReVia label).
  • Trade-offs: cheap, no clinic visits required for ongoing dosing, reversible quickly if needed (~24 hour effect). But it requires daily adherence, and in the OUD population specifically, oral naltrexone is widely considered ineffective outside supervised-dosing settings because adherence collapses. This is the entire premise of the injectable formulation.

Vivitrol (extended-release naltrexone for injection, XR-NTX)

  • FDA-approved dose: 380 mg as a single IM gluteal injection, every 4 weeks (Vivitrol FDA label).
  • Trade-offs: removes daily decision-making, eliminates the adherence problem that limits oral naltrexone in OUD. But it requires a monthly in-clinic visit, runs about $1,500+ per dose list price (insurance often covers as MAT), and once injected cannot be removed, the depot lasts the full 4 weeks regardless.

Initiation, getting the timing right

This is the hard part of starting naltrexone, and the part where a clinician matters most.

Required abstinence:

  • Short-acting opioids (most kratom synthetics, oxycodone, hydrocodone, heroin): at least 7 days opioid-free
  • Long-acting opioids (methadone, sometimes buprenorphine, possibly the longer-acting kratom synthetics): 10 to 14 days, with methadone potentially requiring complete withdrawal beforehand (SAMHSA TIP 63; ASAM NPG)

Naloxone challenge test: the FDA label describes an optional pre-initiation test where a small dose of IV or subcutaneous naloxone is administered to detect occult opioid dependence before the first naltrexone dose (0.2 mg IV → observe 30 sec → if negative, 0.6 mg → observe 20 min; or 0.8 mg SC, observe 20 min) (ReVia label, Dosage and Administration). In current practice, many clinicians rely on urine toxicology, a COWS score, and a careful history rather than the formal challenge — but it remains on the label and some inpatient programs still use it.

For 7-OH and the kratom synthetics specifically: there is no peer-reviewed guidance on the exact abstinence window. Clinicians working with this population extrapolate from the OUD literature, often using longer windows for the longer-acting synthetics (MGM-15, pseudo) out of caution. If you’re considering this, find a prescriber familiar with these compounds (see Telehealth Providers for the fact-checked comparison).

Evidence base

For alcohol use disorder (AUD): strong. The COMBINE trial (Anton et al., JAMA 2006, n=1,383) showed naltrexone with medical management improved drinking outcomes versus placebo on percent days abstinent and time to relapse to heavy drinking.

For opioid use disorder (OUD): the evidence is more complicated. The X:BOT trial (Lee et al., Lancet 2018, n=570) compared Vivitrol against buprenorphine-naloxone for OUD relapse prevention. Two important findings, both real:

  1. Among patients who successfully completed induction, the two medications were equally safe and effective.
  2. But induction itself was the obstacle for Vivitrol, 28% of XR-NTX assignees couldn’t get through the required opioid-free window, versus 6% for bupe-nx. On intention-to-treat analysis, bupe-nx had a lower relapse rate (HR 1.36, 95% CI 1.10–1.68 favoring bupe-nx) primarily because more patients made it onto bupe-nx in the first place.

The lesson for the 7-OH/kratom population: the induction hurdle is the hard part. If you can clear the abstinence window, Vivitrol works comparably to bupe; if the abstinence window is what keeps collapsing your attempts, bupe (with its lower initiation barrier) may be the better fit. Per ASAM, this is a patient-and-situation choice, not a ranking.

Side effects

Common, generally mild: nausea, headache, fatigue, dizziness, sleep disturbance.

Serious, less common:

  • Hepatotoxicity. Both FDA labels carry warnings. Transaminase elevations were documented at ~300 mg/day (about 5× the standard dose, in obese subjects) but not at standard dosing (ReVia label; Vivitrol label, black box). Standard liver-function monitoring is reasonable.
  • Injection-site reactions with Vivitrol (induration, nodules, in rare cases more severe local reactions).
  • Depression and suicidality have been reported in some patients starting naltrexone; the causal relationship is unclear but the signal exists on the FDA labels.

The post-discontinuation overdose risk

This is the one that kills people. Naltrexone occupies opioid receptors, which over time reduces opioid tolerance. If a patient discontinues naltrexone, by stopping oral doses, by reaching the end of a Vivitrol injection’s effect, or by leaving treatment, and then uses opioids again, their reduced tolerance plus a dose calibrated to their pre-treatment tolerance is the documented fatal pattern.

The NEPOD cohort study (Digiusto et al., Addiction 2004) found naltrexone-treated patients had 39 overdoses per 100 person-years after leaving treatment, eight times the rate of agonist-treatment leavers, with 44% of those overdoses occurring within 2 weeks of stopping naltrexone.

If you stop naltrexone and there’s any chance you’ll use opioids again, known craving pattern, prior relapse history, environmental risk, keep naloxone (Narcan) in the house, tell someone you’re with, and read Thinking About Using? so the information is in your head before the moment.

For 7-OH dependence specifically

The OUD evidence base above is the closest reference for someone coming off 7-OH or kratom synthetics. There is no peer-reviewed clinical literature specifically on naltrexone for 7-OH dependence. Clinicians prescribing it for this population are using the broader OUD evidence, which is reasonable, since the underlying pharmacology (mu-opioid agonist dependence) is the same, but it should be named as extrapolation rather than 7-OH-specific evidence.

Where this fits in the recovery picture

Normal-dose naltrexone is not a withdrawal medication and not a quitting tool. It’s for after acute withdrawal is over, as a relapse-prevention scaffold for someone who has decided to stay opioid-free.

For the actual quitting process, see Withdrawal Help for the four community-documented paths off 7-OH and the synthetics. For the post-acute symptoms naltrexone doesn’t directly address, see What is PAWS and Depression and Anhedonia.

For finding a prescriber, Telehealth Providers lists the fact-checked options with kratom and 7-OH experience.

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