Naltrexone Side Effects: What to Expect and When to Call Your Doctor

Starting a new medication always brings questions about side effects, and naltrexone is no different. The good news: most patients tolerate naltrexone well, and many side effects — especially nausea — are temporary and most pronounced in the first few weeks of treatment.

This guide covers what side effects are common with naltrexone, which ones are serious and require medical attention, and practical tips for managing the side effects you're most likely to experience.

How Common Are Naltrexone Side Effects?

Clinical studies show naltrexone has a low incidence of serious adverse effects at recommended doses (50 mg daily for oral; 380 mg monthly for injectable). Most patients who discontinue naltrexone do so due to gastrointestinal side effects, primarily nausea — but these are often manageable and tend to improve within 1-2 weeks of starting treatment.

Common Side Effects of Naltrexone

These side effects are reported most frequently and are generally not dangerous:

Nausea — the most common side effect, especially at the start of treatment. Taking naltrexone with food or milk can significantly reduce nausea. Some patients find that starting with a lower dose (25 mg) for a few days before moving to 50 mg helps their stomach adjust.

Headache — reported in some patients, typically mild to moderate. Staying well hydrated helps.

Abdominal pain or cramping — discomfort in the stomach area, often linked to nausea. Taking naltrexone with food reduces this.

Loss of appetite — some patients notice reduced appetite, especially early in treatment. This typically resolves over time.

Dizziness and drowsiness — some patients feel lightheaded or fatigued. If this is an issue, your provider may recommend taking naltrexone at bedtime.

Insomnia (trouble sleeping) — some patients have difficulty sleeping, especially early in treatment. Discuss timing of your dose with your provider.

Joint and muscle pain — some patients experience musculoskeletal aches, particularly in the first few weeks.

Anxiety or nervousness — some patients feel more anxious when starting naltrexone. This is often related to early recovery itself rather than the medication.

Cold-like symptoms — stuffy nose, sneezing, sore throat, and toothache have been reported in some clinical studies.

Side Effects Specific to Vivitrol (Injectable Naltrexone)

In addition to the common side effects above, patients receiving the 380 mg monthly injection (Vivitrol) may experience:

Injection site reactions — pain, bruising, swelling, redness, or nodules at the injection site. These are generally mild to moderate. A small percentage of patients develop more serious reactions.

Severe injection site reactions (rare) — in rare cases, the injection site can develop cellulitis, necrosis, or hematoma. These require immediate medical attention. Report any significant injection site reaction (pain, swelling, hardening, or open sores) to your provider promptly.

Serious Side Effects: When to Call Your Doctor Immediately

These side effects require prompt medical attention. Contact your provider right away if you experience:

Liver damage signs: Naltrexone carries a boxed FDA warning for hepatotoxicity at high doses. Symptoms to watch for include yellowing of skin or eyes (jaundice), dark urine, light-colored stools, pain or tenderness in the upper right abdomen, unusual fatigue, or loss of appetite that doesn't resolve. Liver damage is rare at standard doses (50 mg) but requires monitoring.

Opioid withdrawal symptoms: If you still have opioids in your system when you start naltrexone, it can trigger sudden and severe opioid withdrawal (precipitated withdrawal). Symptoms include severe cramping, muscle aches, agitation, sweating, goosebumps, rapid heartbeat, and anxiety. This requires medical attention and is why patients must be opioid-free for 7-10 days before starting naltrexone.

Depressive symptoms or suicidal thoughts: Post-marketing reports have noted cases of depression and suicidal ideation in some naltrexone patients. If you notice worsening depression, unusual mood changes, or thoughts of self-harm, contact your provider or call the 988 Suicide & Crisis Lifeline immediately.

Allergic reaction: Hives, difficulty breathing, or swelling of the face, lips, tongue, or throat. Seek emergency medical care immediately.

Eosinophilic pneumonia (rare, injectable only): Progressive shortness of breath and low oxygen. Report any new or worsening respiratory symptoms to your provider.

Tips to Manage Common Naltrexone Side Effects

Take with food — the most effective way to reduce nausea and stomach discomfort. Even a small snack can help.

Start low, go slow — some providers start patients at 25 mg for the first few days before increasing to the standard 50 mg dose. Ask your prescriber if this approach makes sense for you.

Adjust timing — if naltrexone makes you drowsy, try taking it at night. If it causes insomnia, try taking it in the morning.

Stay hydrated — helps with headaches and general well-being during the first weeks of treatment.

Don't stop without talking to your provider — if side effects are troublesome, call your provider rather than stopping on your own. Dose adjustments or timing changes often resolve issues.

The Bottom Line on Naltrexone Side Effects

Naltrexone has a favorable side effect profile at standard doses. The most common issues — nausea, headache, and stomach discomfort — are manageable and usually improve with time. Serious adverse effects are rare when the medication is taken as directed and with appropriate baseline liver function monitoring.

For more on what to avoid while taking naltrexone, see: Naltrexone Drug Interactions: What to Avoid and What to Tell Your Doctor.

If you're having trouble finding naltrexone at a pharmacy near you, medfinder.com can call pharmacies on your behalf to locate it.