Vivitrol vs Naltrexone (Oral)

How they're similar

Vivitrol and oral naltrexone share the same molecule, so they share most of the profile.

• Both are naltrexone, which is a mu-opioid antagonist. It blocks the opioid receptor without activating it.
• Both are FDA-approved for alcohol use disorder and for opioid use disorder maintenance.
• Both have no abuse potential. Naltrexone doesn't produce a high, doesn't cause dependence, and doesn't cause withdrawal when stopped.
• Both have no respiratory depression risk. Since naltrexone is an antagonist, it doesn't suppress breathing.
• Neither is a controlled substance. Any prescriber can write for them.
• Both require the patient to be opioid-free for 7 to 10 days before starting, or the drug will kick residual opioids off the receptor and cause a sudden and severe withdrawal.
• Both require liver function testing at baseline and periodically. Elevated LFTs are the reason for monitoring.
• Both work by reducing the reward from alcohol or opioid use, so if a patient drinks or uses on top of naltrexone, they get little pleasure from it and are protected from opioid overdose while the drug is active.

The similar-molecule point is important. When people ask which one works better, the honest answer is that they're the same drug. What differs is how often the level dips and whether the patient has to take a daily dose.

How they differ

The delivery difference drives everything practical. The table below covers the main points.

Vivitrol is a 380 mg intramuscular injection, given monthly in the buttock. The injection releases naltrexone gradually over the month, keeping levels relatively steady. The next dose is due about every four weeks. It's given in a clinical setting, mostly because of the injection itself but also because reviewing symptoms and doing labs happens at the same visit.

Oral naltrexone is 50 mg per day for most patients. There are also flexible regimens, especially for alcohol use disorder, where the dose can be 100 mg every other day or 150 mg every third day to fit around the schedule. Some patients take a dose only on days they're most at risk of drinking, though the evidence base for that approach is weaker than for daily use.

Cost is a real difference. Oral naltrexone is generic and inexpensive, often filled at a regular pharmacy for a low copay or a modest cash price. Vivitrol is significantly more expensive and is billed as a medical benefit rather than a pharmacy benefit, because it's administered in a clinical setting. Prior authorization is common, and access can be a barrier without good insurance. The manufacturer runs patient assistance programs.

Reversibility matters for pain management. If a patient on oral naltrexone needs surgery or an unexpected serious pain issue, the pill can be stopped and the naltrexone clears within a few days, allowing opioid pain medications to work if needed. If a patient on Vivitrol needs the same, the injection is already in the muscle and can't be removed. The block lasts until the depot is fully absorbed. That can be a real problem for planned surgery, and it's part of the pre-injection conversation.

Injection site reactions are a Vivitrol-specific issue. Most are mild, some are moderate, and there's a small but real risk of a more serious reaction requiring drainage or antibiotics. Good injection technique reduces the risk. Rotating between sides and using proper needle length for body habitus both matter.

Both forms carry the same starting requirement, which is the biggest barrier in practice for opioid use disorder. The patient has to be opioid-free for 7 to 10 days before the first dose. That means completing an opioid detox, whether at home or in a facility, before naltrexone can be started. Many patients don't make it through the detox, and drop-out during that window is high. That's the main reason retention in naltrexone-based OUD treatment often lags behind buprenorphine or methadone in real-world settings, even though naltrexone works well in patients who get through induction and stay on it.

For alcohol use disorder, the starting requirement is different. There's no opioid-free wait period. The patient can start naltrexone while still drinking, or after a brief pause of a day or two. That makes it much easier to initiate for alcohol than for opioid use disorder.

Side effect tendencies

Because they're the same molecule, the side effect profile is broadly the same. Nausea is the most common side effect, especially early and especially with oral naltrexone. It usually eases within the first week or two. Headache, fatigue, and insomnia are also common early. Neither form causes sedation, weight gain, or sexual dysfunction the way opioid agonists can.

Vivitrol has the injection site issues noted above. The injection can be uncomfortable, and site reactions of varying severity can occur.

Both can cause elevated liver enzymes. In most patients this is mild and stable, but it's the reason for baseline and periodic LFTs. Severe hepatotoxicity is rare, and higher doses (much above the standard) have been linked to it in older studies.

Neither drug produces a high or a euphoric effect. They work by blocking the reward from alcohol or opioid use rather than by producing any feeling of their own. Some patients notice reduced enjoyment of food or other rewarding activities early on, though this usually settles.

What tips the choice

For opioid use disorder, the main choice between forms comes down to adherence and access. Patients who can get through the 7 to 10 day opioid-free period and who want the monthly structure often do well on Vivitrol. Patients who want more flexibility, want the option to stop quickly, or can't afford Vivitrol may prefer oral. The reality is that many patients with OUD do better on buprenorphine or methadone than on either form of naltrexone, mostly because the induction barrier for naltrexone is a real hurdle. In the X:BOT trial, which compared Vivitrol and buprenorphine for OUD, Vivitrol was non-inferior in patients who actually got started on it, but a substantial number of patients randomized to Vivitrol never made it through detox. In practice, for OUD, naltrexone is often chosen for patients who have already completed detox, or who are motivated to complete it, and who prefer an antagonist over an agonist.

For alcohol use disorder, both forms are effective. The evidence shows moderate benefit for both, with number needed to treat around 12 to 20 to prevent a return to heavy drinking. The choice often comes down to adherence. Patients who reliably take a daily pill can do very well on oral naltrexone. Patients who don't often benefit from Vivitrol because the monthly injection removes the daily decision.

Some concrete scenarios. A 40-year-old with alcohol use disorder who wants to stay sober and is engaged in treatment is a good oral naltrexone candidate. A 40-year-old with alcohol use disorder who has trouble taking any daily medication is a better Vivitrol candidate. A 30-year-old with opioid use disorder who has just completed detox and doesn't want an agonist medication can be started on either form of naltrexone, though the monthly injection provides more built-in protection during the highest-risk relapse window. A patient facing planned surgery in the next few months should probably be on oral naltrexone rather than Vivitrol, so it can be stopped if needed for pain management.

Common questions

Do I have to be completely sober before starting? For opioid use disorder, yes. You have to be opioid-free for 7 to 10 days. Starting sooner than that will cause precipitated withdrawal, which is a sudden and severe withdrawal that happens because naltrexone kicks residual opioids off the receptor. For alcohol use disorder, no. You can start naltrexone while still drinking or after just a short pause. Some patients drink less right away, and some see the biggest change over a few weeks.

Why do people say the daily pill is easier to skip? Because it is. Not because the patient wants to skip, but because taking a pill every day for months or years is genuinely hard, and one missed day can be the start of a return to use. Vivitrol takes that decision away for the month. Some patients need that structure and some don't. It's an honest conversation to have.

Does naltrexone help with cravings? For alcohol, yes. Many patients report reduced cravings within the first few weeks, and the effect can be substantial. For opioids, naltrexone doesn't reduce cravings the way buprenorphine or methadone do. What it does is block the reward, so if the patient uses on top of it, they don't get high. That still helps some patients maintain sobriety, but the cravings themselves can persist.

What happens if I drink or use opioids while on naltrexone? For alcohol, drinking on naltrexone is safe but less rewarding. The naltrexone blocks the pleasant effects, so patients often drink less or stop mid-drink. There's no dangerous interaction. For opioids, using on top of naltrexone is more complicated. In the short term, the naltrexone blocks the opioid, so nothing happens. In the higher-risk situation, patients try to override the block with high doses, and if the naltrexone level drops (which happens toward the end of a Vivitrol cycle or a day or two after stopping oral), the opioid can then hit an opioid-naive body and cause a fatal overdose. This is a real risk that gets talked through before starting.

How long do I need to stay on it? As long as it helps. For alcohol use disorder, many patients stay on for 6 to 12 months, some longer. For opioid use disorder, longer treatment is associated with better outcomes, though the evidence base for naltrexone is less mature than for buprenorphine or methadone. Stopping is done with a prescriber, and there's no withdrawal from naltrexone itself, so the drug can be stopped abruptly if needed.

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes.

1. U.S. Food and Drug Administration. Naltrexone prescribing information.
2. U.S. Food and Drug Administration. Vivitrol prescribing information.
3. Substance Abuse and Mental Health Services Administration. Medications for alcohol use disorder and opioid use disorder.
4. American Society of Addiction Medicine. National practice guideline for the treatment of alcohol use disorder and opioid use disorder.
5. National Institute on Alcohol Abuse and Alcoholism. Medications for the treatment of alcohol use disorder.