Naltrexone Side Effects: How Common Each One Is and When to Call a Doctor

Side effects at a glance

This table covers the 50 mg tablet unless it says otherwise.

The numbers, with placebo for comparison

A study with no placebo group counts everything people felt while on the drug, whether the drug caused it or not. A placebo-controlled trial shows how much extra the drug adds. In Vivitrol's trials, for example, 11% of people on a placebo shot had nausea and 18% had a headache.⁵

The pooled figures come from three reviews: a 2010 Cochrane review of 50 trials, a 2023 JAMA review of 118 trials, and a 2019 review of 89 trials across all doses and uses.^3,4,8 The 2019 authors warn that side-effect reporting was poor: fewer than 21 trials contributed to each analysis of a specific side effect, such as nausea or dizziness.⁴

Nausea is the side effect that makes people stop

Nausea is the most common side effect in the tablet studies and the most common reason people stopped. In the 570-person study, 15.0% stopped naltrexone because of side effects, most often nausea.² In the two placebo-controlled trials behind the alcohol approval, 5 of 93 people on naltrexone stopped because of nausea, and no serious adverse events were reported.¹

Pooled across trials, the gap with placebo is small. For every 48 people treated with naltrexone, one more left a trial because of side effects than would have on placebo.⁹ The benefit side of that trade-off is on how well naltrexone works.

Most side effects show up early and pass

Reports collected after the tablet's approval show most events come early in treatment and are short-lived, though some are hard to tell apart from opioid withdrawal.¹

A small share of people get a cluster that looks like mild withdrawal: tearfulness, mild nausea, stomach cramps, restlessness, bone or joint pain, muscle aches and a runny or stuffy nose. The label says this may be hidden opioid use coming to light, or an effect of naltrexone itself.¹

For the Vivitrol shot the timing is clearer. Nausea after the first injection tends to be mild and to ease within a few days, and it is less likely with later shots.⁵ Side effects often arrive before any change in drinking; that timeline is on how long naltrexone takes to work.

Depression, liver symptoms and withdrawal are not side effects to wait out. Contact your prescriber about them right away; when to call a doctor lists the signs.

Opioids in your system cause the worst reactions

Aside from liver injury at high doses and precipitated withdrawal, the tablet label says the available evidence does not link naltrexone, at any dose, to any other serious reaction in people who are opioid-free.¹

Sudden (precipitated) withdrawal. Naltrexone pushes opioids off their receptors. In someone who is physically dependent on opioids, that sets off withdrawal all at once. Symptoms usually start within 5 minutes of a tablet and can last up to 48 hours. Some people have become confused or had hallucinations, and some lost so much fluid from vomiting and diarrhea that they needed an IV. Some needed intensive care.¹ This can happen to people taking naltrexone for alcohol whose prescriber didn't know about their opioid use.¹ How long it lasts and how clinicians treat it are on precipitated withdrawal.

To avoid it, you need to be off all opioids first, including tramadol and opioid cough, cold or diarrhea medicines. The usual gap is at least 7 to 10 days after short-acting opioids, and up to 2 weeks after buprenorphine or methadone.^1,5 Tell your prescriber about any recent opioid use.¹

Opioid medicines may not work. On naltrexone, opioid pain relievers and opioid cough or diarrhea medicines may do little. Carry a wallet card or other ID that says you take naltrexone, so you can get the right treatment in an emergency.¹ For planned surgery, see stopping naltrexone before surgery.

Overdose after stopping. Tolerance to opioids falls after detox. When naltrexone wears off, a dose you used to take can be fatal, and fatal overdoses have been reported after people stopped treatment. Trying to overpower the block with large doses is also dangerous. Both labels tell prescribers to discuss having naloxone or nalmefene on hand.^1,5 For more on the rescue drugs, see naltrexone vs naloxone.

Liver injury is a label warning, tied mostly to high doses

The tablet and Vivitrol labels warn that hepatitis and serious liver problems have been seen with naltrexone and say to stop it if signs of acute hepatitis appear, though neither current label has a boxed warning.^1,5 Enzyme rises were clearest at 300 mg a day, six times the usual dose, where 5 of 26 people (19%) developed raised liver enzymes against 0 of 24 on placebo; at 50 mg, liver tests in the 570-person study were similar to those of a comparison group not taking it.^1,2 Which liver tests to expect, what ALT and AST results mean, the boxed-warning history and what studies found in people with cirrhosis are on naltrexone and your liver.

Signs to report. Stomach pain that lasts more than a few days, dark urine, yellowing of the whites of the eyes, or tiredness.⁵

Tablet trials found similar depression rates on placebo

In the tablet's alcohol trials, depression ranged from 0% to 15% on naltrexone and 0% to 17% on placebo. Suicide attempts or thoughts ranged from 0% to 1% on naltrexone and 0% to 3% on placebo.¹ Depression and suicide have been reported in people using naltrexone for opioid dependence; for the tablet, the label says "No causal relationship has been demonstrated."¹

The shot's numbers lean the other way. In Vivitrol's alcohol trials, suicide-related events were 1% vs 0% on placebo, and two people on Vivitrol died by suicide. In the main 24-week trial, low mood was reported by 10% on Vivitrol and 5% on placebo.⁵

Both labels give the same advice: tell family you are taking it, and call a doctor right away if you feel depressed.^1,5 If you have thoughts of suicide, call or text 988, the Suicide & Crisis Lifeline. It is free, confidential and open 24/7.¹³

Daytime sleepiness is more common than on placebo

Tiredness and sleepiness are both on the 570-person list.¹ The 2010 Cochrane review named sedative effects, along with stomach problems, as the main side effects: daytime sleepiness affected about 9 more people per 100 than placebo.³ Dizziness was about 1.45 times as common as on placebo.⁴ The label advises not driving or using heavy machinery until you know how naltrexone affects you.¹ Placebo rates, insomnia and timing are covered on does naltrexone make you sleepy?

One interaction is listed: lethargy and sleepiness after naltrexone with thioridazine.¹ Beyond opioids, interactions with other drugs have not been studied, so tell your prescriber everything you take; common medicines are covered in what to avoid on naltrexone.¹

Rare effects reported in opioid-treatment trials

These come from the tablet's opioid-treatment trials, where effects were reported both before and during treatment. There was no placebo group, so these lists can't show cause.¹

• Sexual: delayed ejaculation and lower potency were under 10%. Raised or lowered sexual interest was under 1%.¹
• Hair: hair loss was under 1%.¹
• Weight: weight loss, weight gain and increased appetite were each under 1%.¹
• Dreams: nightmares and bad dreams were under 1%.¹
• Hormones: opioid blockers have been linked with changes in some hormone levels, including sex hormones. What this means clinically is not fully understood.¹
• Blood: reports after approval include idiopathic thrombocytopenic purpura, a low-platelet disorder.¹

Vivitrol adds injection-site reactions

Vivitrol is naltrexone given as a 380 mg shot into the buttock muscle once a month. It shares the tablet's warnings and adds some of its own.⁵ This section is a summary; the shot gets its own page, Vivitrol side effects.

Source: Vivitrol label, Table 1 and section 6.1.⁵ Most reactions were mild or moderate.⁵ In the main trial, 14.1% on the 380 mg dose stopped because of side effects, against 6.7% on placebo.¹⁷

Serious but rare risks specific to the shot⁵:

• Severe injection-site reactions. Some have caused tissue death (necrosis) and needed surgery. Call your provider right away for intense pain, a hard area, large swelling, lumps, blisters, an open wound or a dark scab, or for any reaction that isn't better 2 weeks after the shot.
• A type of allergic pneumonia (eosinophilic pneumonia). Report shortness of breath, wheezing or a cough that won't go away.
• Serious allergic reactions, during or soon after a shot.
• A month-long commitment. Once injected, it can't be removed. Its opioid block lasts about 28 days.

Low-dose naltrexone (off-label)

Low-dose naltrexone (LDN) is off-label in the US. There is no FDA-approved low-dose product: every single-ingredient oral naltrexone listing in the FDA's drug directory is a 50 mg tablet.¹⁸ Its side-effect data come from small trials in other conditions. A fibromyalgia review linked LDN with more vivid dreams and nausea, and a chronic-pain review found side effects about 1.4 times as often as on placebo.^19,20 The 2019 review found no increase in serious adverse events, and the result held across the doses studied.⁴ The opioid warnings above still apply. Which medicines and procedures need care on LDN, graded by how much evidence backs each warning, is on what to avoid on low-dose naltrexone. Trial-by-trial rates at LDN doses, how long they last and stopping LDN are on low-dose naltrexone side effects.

When to call a doctor

Call 911 or get emergency help if you or someone with you⁵:

• has trouble breathing, or slow, shallow breathing
• is very drowsy with slowed breathing
• feels faint, very dizzy or confused after using opioids

Give naloxone if you have it, and call 911 even if it works.¹

Get medical help right away for:

• withdrawal symptoms after a dose: vomiting, diarrhea, sweating, shaking, anxiety, confusion^1,5
• signs of liver trouble: stomach pain lasting more than a few days, dark urine, yellow eyes⁵
• new or worse depression, or thoughts of hurting yourself (call or text 988)^1,13
• swelling of the face, eyes, mouth or tongue, trouble breathing, or a rash after a Vivitrol shot⁵

Tell your prescriber about any side effect that bothers you or does not go away, and if you become pregnant or are breastfeeding (naltrexone and pregnancy).^1,5 You can also report side effects to the FDA at 1-800-FDA-1088.⁵

What the labels do and don't say

1. No boxed warning on current labels. Neither the tablet label nor the Vivitrol label has one, though liver injury is still a listed warning. The 2010 Vivitrol label had one.^1,5,6
2. Liver or kidney problems are not automatic bars. The tablet's contraindications are opioid use, opioid withdrawal and allergy to the drug. Kidney problems call for caution, and the APA advises against it in acute hepatitis or liver failure.^1,21
3. The pneumonia warning is for the shot. It is in the Vivitrol label, from the shot's trials and later reports.⁵
4. No sickness reaction with alcohol. Both labels say naltrexone "does not cause a disulfiram-like reaction" (the Antabuse reaction) with alcohol.^1,5 For what drinking on it does feel like, see what happens if you drink on naltrexone.
5. No withdrawal when you stop. Naltrexone does not lead to physical or psychological dependence.¹ The risk when you stop is opioid overdose, covered above.

How we checked

• Rates come from the current tablet and Vivitrol labels, the 1997 study behind the tablet's 570-person figures, and three systematic reviews.^1-5,8
• The boxed-warning history comes from the 2010 Vivitrol label, the 2013 ReVia label and an archived copy of FDA's 2013 safety-labeling notice.^6,22,23
• Each number was checked against our saved copy on October 17, 2026. The reviews' harms tables were read as abstracts only.