Vivitrol Side Effects: Trial Rates, Injection-Site Reactions and When to Get Help

This page covers the shot. For naltrexone tablets, see naltrexone side effects.

Key takeaways

• A lot of the list happened on placebo too. Half the people given a placebo shot had an injection-site reaction, and 18% had a headache.¹
• In the main opioid trial, side effects were reported less often than in a longer US opioid study. Liver-enzyme rises led the list, in a group where 89% had hepatitis C.¹
• Since approval there have been reports of injection-site reactions that needed surgery, mostly in women.¹
• A shot can't be taken back out. It lasts about a month, so a side effect can last as long as the drug does.¹
• In the alcohol trials, 9% on Vivitrol and 7% on placebo stopped treatment because of a side effect.¹

Side effects at a glance

Rates and sources for each are below.¹ If you have side effects now, When to get help lists who to call.

Alcohol trials: every side effect in the label's table

The label's main table covers adults in placebo-controlled trials for alcohol dependence. It lists every event reported during treatment, whether or not the drug caused it, so the placebo column is the comparison. The last column is the Vivitrol rate minus the placebo rate.¹

† Our arithmetic from the label's rounded percentages; not a measure of how many reactions the drug caused. ‡ Listed because the rate across all Vivitrol doses was 13%.¹

For most people on Vivitrol, the worst side effect they had was mild or moderate. On Vivitrol, 3% stopped because of injection-site reactions and 2% because of nausea.¹ In the main 24-week trial on its own, 14.1% on the 380 mg dose stopped because of side effects, against 6.7% on placebo.²

Opioid trial: fewer reported side effects, more liver-test rises

The label's opioid table comes from a 24-week placebo-controlled trial of 250 adults in Russia who had just finished detox. Side effects were reported less often than in a longer US study of people with opioid dependence, and all were rated mild or moderate.¹

At the start, 89% of the people in this trial had hepatitis C and 41% had HIV.¹ Two people in each group stopped because of side effects, and no one on Vivitrol died or overdosed during the trial.³ In a longer US study without a placebo group, injection-site reactions, nausea and diarrhea each affected more than 5% of people with opioid dependence, and 48% had at least one infection, most often a cold, sinus infection or urinary tract infection.¹ In a US trial against Suboxone, side effects other than mild-to-moderate injection-site reactions, overdose included, did not differ between the two groups.⁴

Injection-site reactions are common, usually mild, and sometimes need surgery

Vivitrol goes deep into a buttock muscle, switching sides each month. Tenderness, hardening, pain, lumps, redness, bruising or itching can follow.¹

Some reactions are severe. In the trials, one person developed a hard area that kept growing after 4 weeks, and the tissue died and had to be cut out. Since approval there have been reports of hardening, skin infection (cellulitis), pooled blood (hematoma), abscesses and dead tissue (necrosis). Some people needed surgery to remove dead tissue, some were left with significant scars, and most of these reports were in women.¹

What raises the risk. A shot that lands under the skin instead of in the muscle may make a severe reaction more likely. The carton holds a 1½-inch and a 2-inch needle, and the provider picks one to fit your build at each visit. Serious reactions, including some that led to a hospital stay, have followed shots people gave themselves.¹ Vivitrol has to be prepared and given by a healthcare provider.

When to call. Call your provider right away if a site has intense pain, feels hard, swells over a large area, or forms lumps, blisters, an open wound or a dark scab. Also call about any reaction that worries you, gets worse, or isn't better 2 weeks after the shot.¹ Signs of an abscess, infection, dead tissue or wide swelling call for a doctor's exam, which may lead to a surgeon.¹ What a normal visit looks like is described in the injection visit.

Opioids still in your body can set off sudden withdrawal

Vivitrol pushes opioids off the receptors they act on. If opioids are still in your body, a shot can start withdrawal all at once. In some cases this was severe enough for a hospital stay, sometimes in intensive care.¹ Some cases were in people being treated for alcohol whose prescriber didn't know they used opioids.¹

You need to be off opioids for at least 7 to 10 days before the first shot (the Medication Guide says 7 to 14 days). People switching from buprenorphine or methadone can be at risk of withdrawal for as long as 2 weeks. That includes tramadol and opioid cough, cold or diarrhea medicines.¹ Withdrawal signs include anxiety, sweating, yawning, a runny nose, teary eyes, goose bumps, shaking, muscle aches, vomiting, diarrhea and stomach cramps.¹ Call your provider right away if they start after a shot. How clinics check first is described in before the first shot.

Overdose risk rises as the shot wears off

If you miss a shot, get the next one as soon as you can.¹

A label liver warning, with enzyme rises clearest in the opioid trial

Hepatitis and clinically significant liver problems have been seen with Vivitrol, in trials and since approval, along with brief rises in liver enzymes that caused no symptoms. When enzymes were high, there was often another possible cause, such as alcohol-related liver disease, hepatitis B or C, or other drugs that can harm the liver.¹

• Alcohol trials: AST rose in 1.5% of people on Vivitrol and 1.5% on naltrexone tablets, against 0.9% on placebo.¹
• Opioid trial: liver enzymes rose above 3 times the upper limit of normal in 20% on Vivitrol and 13% on placebo.¹

Sudden opioid withdrawal can itself injure the liver. Vivitrol should be stopped if signs of acute hepatitis appear.¹ Call your provider about stomach-area pain lasting more than a few days, dark urine, yellowing of the whites of your eyes, or tiredness.¹ Liver tests, the tablet warning and how the shot compares are on naltrexone and your liver.

No boxed warning now. In October 2010, Vivitrol carried a boxed "WARNING: HEPATOTOXICITY", and that box also stated that "VIVITROL does not appear to be a hepatotoxin at the recommended doses."⁵ The May 2026 label has none.¹

Depression and suicidal thoughts

In the alcohol trials, suicide-related events (thoughts, attempts and deaths) were uncommon but more frequent on Vivitrol: 1% against 0% on placebo. Two people died by suicide, both on Vivitrol. Some suicidal thoughts came after people had left a study, during a depression that began while they were on it. In the main trial, low mood was reported by 10% on Vivitrol and 5% on placebo.¹

Opioid-study rates were lower. In a US study without a placebo group, low mood or suicidal thoughts or actions were reported by 5% of 101 people on Vivitrol and 10% of 20 on naltrexone tablets. In the placebo-controlled trial in Russia, no one in either group reported them.¹

The label asks families and caregivers to watch for depression. You or someone close to you should call your provider right away about sadness or crying spells, losing interest in friends or activities, sleeping much more or less, feeling hopeless, being more irritable or angry, a big change in appetite or weight, trouble paying attention, feeling tired all the time, or thoughts of hurting yourself.¹ If you are thinking about suicide, call or text 988. The 988 Lifeline is free, confidential and open 24/7.⁶

Two trial cases of eosinophilic pneumonia, both hospitalized

The Medication Guide describes eosinophilic pneumonia as a type of pneumonia caused by an allergic reaction. The trials had one diagnosed case and one suspected case. Both people needed a hospital stay and got better with antibiotics and steroids, and similar cases have been reported since approval.¹ Call your provider right away about shortness of breath, wheezing, or a cough that won't go away.¹ This warning is in the Vivitrol label and not in the tablet label.^1,7

Severe allergic reactions end treatment

Hives, deep swelling of the skin (angioedema) and anaphylaxis have been reported, in trials and since approval.¹ Get medical help right away for a rash, swelling of your face, eyes, mouth or tongue, trouble breathing or wheezing, chest pain, or feeling dizzy or faint. After a hypersensitivity reaction, no more Vivitrol should be given.¹ People allergic to naltrexone or to the shot's other ingredients, such as its polymer (PLG) or carboxymethylcellulose, should not get it.¹

Lab changes you won't feel

• Platelets, the blood cells that help clotting, dropped more on Vivitrol. In the alcohol trials the average maximum drop was 17.8 thousand per microliter, against 2.6 on placebo, with no rise in bleeding problems in the randomized trials.¹ As with any muscle shot, people with low platelets or a bleeding disorder such as hemophilia need extra care.¹
• Eosinophils (one type of white blood cell)⁸ rose compared with placebo, then returned to normal over several months of continued shots.¹
• CPK, a muscle enzyme, moved from normal to abnormal in 11% on Vivitrol, 17% on naltrexone tablets and 8% on placebo in short alcohol trials, and in 39% on Vivitrol against 32% on placebo in the opioid trial.¹
• Urine drug tests: Vivitrol may cross-react with some urine tests for opioids.¹ See drug tests.

Weight, sleep, sex drive and hair

Beyond the tables, the label lists events reported at least once across Vivitrol trials, with no rates and no finding that the drug caused them. That list includes weight loss, weight gain, a bigger appetite, abnormal dreams, lower sex drive and blurred vision.¹

• Weight: no rate is given for weight change in either direction. Poor appetite was 14% against 3% on placebo. A big change in appetite or weight is also on the label's list of depression signs.¹
• Sleep and alertness: Vivitrol may make you dizzy or sleepy, so don't drive or use machinery until you know how it affects you.¹
• Sex drive: lower libido is on the no-rate list only.¹
• Hair: hair loss does not appear in the Vivitrol label. The tablet label lists it among events seen in under 1% of people in its opioid-treatment trials.^1,7

How long side effects last when the shot lasts a month

No day counts are given for how long headache, tiredness, trouble sleeping or injection-site soreness last. These are the time points in the label.¹

Nausea is less likely with later shots.¹ Because a shot can't be removed, you are exposed to the drug for about a month after each one, even if you decide to stop.¹ Stopping Vivitrol does not cause withdrawal, because it does not create tolerance or dependence.¹ The full timeline is on Vivitrol in your system.

When to get help

Call 911 if, after using opioids, you or someone with you has trouble breathing, slow or shallow breathing, is very drowsy with slowed breathing, or feels faint, very dizzy or confused. Give naloxone or nalmefene if you have it.¹

Get medical help right away for swelling of the face, eyes, mouth or tongue, trouble breathing, wheezing or chest pain.¹

Call your provider right away for:

• an injection site with intense pain, hardness, wide swelling, lumps, blisters, an open wound or a dark scab
• withdrawal symptoms after a shot
• liver signs: stomach-area pain lasting more than a few days, dark urine, yellow eyes, tiredness
• shortness of breath, wheezing or a cough that won't go away
• new or worse depression, or thoughts of self-harm (or call or text 988)^1,6

Tell your provider about any side effect that bothers you or doesn't go away, and if you are pregnant, plan to be, or are breastfeeding. Naltrexone passes into breast milk.¹ You can also report side effects to the FDA at 1-800-FDA-1088.¹

At any medical visit, say that you get Vivitrol and when your last shot was. Vivitrol blocks opioid pain medicines, which changes how pain is treated in an emergency. Ask your provider for a wallet card.¹

Vivitrol vs naltrexone tablets

The tablet is a daily pill, usually 50 mg, and blocks opioids for up to about a day. The shot releases 380 mg over a month.^1,7

• Where the rates come from: the shot's rates come from placebo-controlled trials. The tablet label's rates come from an open-label safety study of about 570 people, where 10% reported new nausea and 7% new headache.⁷ The figures aren't a head-to-head comparison.
• Only on the shot: injection-site reactions and the eosinophilic pneumonia warning.^1,7
• On both: liver warnings, sudden opioid withdrawal, overdose risk once the block fades, and depression warnings.^1,7
• If a side effect starts: you can stop a tablet the same day, while a shot stays in your body for weeks.¹

The full tablet list is on naltrexone side effects. For choosing between them, see Naltrexone vs Vivitrol.

What the label does and doesn't say

• No boxed warning now. The box was in the October 2010 label and is gone from the current one.^1,5
• No sickness reaction with alcohol. It is not aversive therapy and does not cause a disulfiram-like reaction with alcohol or opioids.¹ See naltrexone and alcohol.
• No set duration for most side effects. The label gives a few days for first-shot nausea and a 2-week check for injection-site reactions, and no duration for the rest.¹
• Same side effects on the unbranded version. Unbranded Vivitrol (Amneal) carries the same two side-effect tables, number for number.^1,9

Had side effects from the Vivitrol shot? Share what it was like, or read other people's naltrexone reviews.

How we checked

• Rates, warnings and Medication Guide wording come from the current Vivitrol prescribing information (May 2026), and the boxed-warning history from the 2010 label.^1,5
• The unbranded (Amneal) label's tables were compared with Vivitrol's row by row.⁹
• Trial figures come from the abstracts of Garbutt 2005, Krupitsky 2011 and X:BOT 2018, and tablet figures from the current tablet label.^2-4,7
• The extra-per-100 column is our own subtraction.