8 Naltrexone Side Effects You Should Know About

Naltrexone is a prescription medication that comes as an oral tablet and intramuscular (IM) injection called Vivitrol. Both forms are approved to treat alcohol use disorder. The IM form is also approved to treat opioid use disorder. The tablet is usually taken daily, while the injection is given every 4 weeks in a healthcare provider’s office.

Both forms of naltrexone are usually well-tolerated. Still, naltrexone side effects are possible. If you do experience them, it’s helpful to know when they can be managed at home and when you should contact your healthcare provider.

Naltrexone side effects at a glance

Naltrexone tablets and the injection are usually well-tolerated. But there are some common side effects you may experience. Common IM and oral naltrexone side effects include:

• Nausea

• Stomach pain

• Diarrhea

• Headache

• Dizziness

• Nervousness and anxiety

• Trouble sleeping

• Tiredness

• Joint and muscle pain

• Decreased appetite

• Opioid withdrawal if opioids are in the body

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Additionally, IM naltrexone may cause injection site reactions like redness, itching, and swelling. It’s also more likely than oral naltrexone to cause dizziness, decreased appetite, and mood changes like depression and anxiety.

Serious naltrexone side effects are also possible. These include:

• Increased opioid sensitivity in the event of an opioid relapse

• Liver damage

• Suicidal thoughts or actions

• Severe allergic reactions

Below, we’ll go into more detail about eight of these naltrexone side effects and how to manage them.

Good to know: Some naltrexone side effects — like nausea and headaches — are also symptoms of alcohol and opioid withdrawal. Avoid taking opioids in the days before starting (and during) naltrexone treatment. We’ll talk more about this below. For now, just know that if you experience any severe symptoms of alcohol or opioid withdrawal (like seizures, confusion, or hallucinations), you should seek emergency care. These severe symptoms are unlikely to be caused by naltrexone.

1. Nausea

Nausea is the most common side effect of oral and IM naltrexone. It may occur with other gastrointestinal side effects, like diarrhea and stomach pain. With IM naltrexone, nausea is most common after your first injection. 

Usually, nausea from naltrexone is mild, can be managed at home, and gets better within a few days. If you take oral naltrexone, try taking it with a meal or just afterwards. If this doesn’t help, focus on staying hydrated and eating smaller, more frequent meals. You can also try avoiding spicy, fried, or fatty foods. These changes may help relieve your nausea.

If nausea continues, you may be able to try an over-the-counter (OTC) or prescription nausea medication. Talk to your healthcare provider or pharmacist about your options.

2. Injection site reactions

Injection site reactions are the most common IM naltrexone side effect. Typically, this occurs within a few days of the injection. But rarely, reactions can occur more than a week later.

Injection site reactions can include any of the following symptoms in the area where naltrexone was injected (the buttocks):

• Redness

• Itching

• Swelling

• Pain

• Bruising

Injection site reactions are usually mild and go away on their own within a few days. To ease discomfort in the meantime, try applying a warm compress to the affected area if your muscles are sore. You can also try ice packs if the area is red or swollen. And OTC pain relievers like ibuprofen (Advil, Motrin) can relieve pain.

Keep in mind that it’s common for a small lump to show up at the injection site, and it can take weeks to go away. If it isn’t painful or inflamed, there’s likely nothing to worry about. 

Good to know: Injection site reactions aren’t the same as serious allergic reactions, which can also occur with IM naltrexone. If you experience a skin rash, swelling anywhere on your face, or trouble breathing, seek emergency care immediately or call 911.

3. Headache

Headaches are a possible naltrexone side effect. If you experience this, you can try some tactics at home:

• Drinking water, since dehydration can worsen headaches

• Getting enough sleep at night (usually 7 to 9 hours for adults)

• Lowering your stress levels with meditation or breathing exercises

You can also ask your healthcare provider or pharmacist about taking an OTC pain reliever, like  acetaminophen (Tylenol) or ibuprofen. But if your headaches don’t improve or become worse, talk to your provider about what to do next.

4. Dizziness

Oral and IM naltrexone can cause dizziness. This can make it hard to complete your daily activities.

When you’re first starting naltrexone, it’s a good idea to avoid driving or operating heavy machinery until you know how naltrexone affects you. If your dizziness doesn’t improve, talk to your healthcare provider. They may recommend trying another medication.

5. Muscle pain and cramps

Muscle cramps are another side effect to watch out for with IM naltrexone. Muscle pain can also happen with oral naltrexone.

Most of the time, muscle cramps go away on their own. In the meantime, walking around or stretching the affected area may help provide some relief. Taking a hot shower or using a warm compress may also help.

If your muscle cramps are extremely painful or seem severe, contact your healthcare provider for further guidance.

6. Withdrawal symptoms

Naltrexone works by blocking the effects of opioids. So if you take naltrexone with opioids present in your body, opioid withdrawal symptoms may occur. Examples of withdrawal symptoms include:

• Nausea and vomiting

• Sweating

• Diarrhea

• Irritability

• Runny nose

• Stomach cramping

• Increased yawning

Opioid withdrawal is rarely life-threatening, but it can be extremely uncomfortable. To avoid opioid withdrawal symptoms, avoid taking any opioid medications for 7 to 10 days before starting naltrexone.

Good to know: Methadone (Methadose), buprenorphine/naloxone (Suboxone, Zubsolv), and buprenorphine (Belbuca, Butrans, Suboclade) are other medications that treat opioid use disorder. Methadone is an opioid, and buprenorphine is an “opioid agonist.” Buprenorphine attaches to the same receptors as opioids do, but less strongly. If you’re switching from methadone or buprenorphine to naltrexone, you may need to wait even longer than usual to start naltrexone — up to 2 weeks.

7. Increased opioid sensitivity

Some people may relapse to opioids after taking naltrexone. Anytime you stop taking opioids, even if for a brief period, your tolerance for opioids may be lowered. When this happens, you’re more likely to experience an opioid overdose when you use them again, even with opioid doses that are lower than what you used to take. 

Additionally, people who try to overcome the opioid-blocking effects of naltrexone by taking a large amount of opioids can also experience an overdose.

If you’re taking naltrexone and you relapse to opioids, let your healthcare provider know immediately. They may recommend stopping naltrexone and trying another medication for opioid use disorder.

8. Liver damage

Naltrexone may rarely cause liver damage. This is more likely if you have existing liver problems. In severe cases, liver failure can occur.

If you experience symptoms of liver damage, seek emergency medical care. You’ll likely be told to stop taking naltrexone. Symptoms of liver damage to watch out for include:

• Right upper abdominal pain

• Swelling in the abdominal area

• Yellow skin (jaundice) or eyes

• Dark-colored urine

• Clay-colored or light-colored stools

• Frequent bruising and bleeding

When should you contact your healthcare provider about naltrexone side effects?

Many naltrexone side effects are mild. Nausea, injection site reactions, and headache can usually be managed at home. Dizziness and muscle cramps are also easily managed in most cases. But if you’re experiencing these side effects and they’re bothersome, or they don’t improve after a few days, talk to your pharmacist or healthcare provider about next steps.

Rarely, naltrexone can cause serious side effects that warrant immediate medical attention. Seek emergency care if you notice side effects like vomiting, trouble breathing, or producing less urine. 

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Written by:

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP, has over a decade of experience as a pharmacist, professor, and researcher. She was a full-time clinical professor in the pharmacy practice department at D’Youville School of Pharmacy before subsequently joining the faculty of the pharmacy practice department at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

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