Naltrexone Side Effects: What to Expect and How to Manage Them

Key Takeaways

• Most naltrexone side effects, like nausea, headache, and fatigue, are mild and tend to ease as your body adjusts to the medication.
• Serious reactions, including confusion, hallucinations, or severe injection-site damage, require prompt contact with a clinician.
• Mental health changes, such as depression or thoughts of self-harm, can occur and require immediate professional attention.

Naltrexone is a Food and Drug Administration (FDA)-approved medication available in oral and extended-release injectable forms that works by blocking opioid receptors in the brain. It’s commonly prescribed to help reduce alcohol cravings and support recovery from opioid use disorder.

Starting a new medication can make you hyperaware of every physical or emotional change. If you’re beginning treatment with naltrexone for alcohol use disorder (AUD) or opioid use disorder (OUD), it’s completely understandable to wonder what side effects are normal, which ones are serious, and how long they might last. Most naltrexone side effects are temporary and manageable.

What are the Most Common Naltrexone Side Effects?

Most common naltrexone side effects involve digestive symptoms, headaches or dizziness, and temporary changes in sleep or energy levels during the first few weeks of treatment. They fall into the following clusters:

These clusters reflect the documented adverse effect profile for oral naltrexone. According to the FDA, clinical trials for injectable naltrexone found that nausea, headache, fatigue, dizziness, and injection-site reactions were among the most commonly reported side effects.

"The most common side effects seen with naltrexone can include some nausea and fatigue. These are often temporary and improve with time, dose adjustment, or even with timing of taking the medication."

- Talkspace Therapist, Svetlana Stuck, PA-C

Digestive symptoms (nausea, stomach upset)

Digestive symptoms are the most common early reaction to naltrexone. The medication changes how certain brain and gut receptors communicate, which can temporarily affect appetite and digestion while your body adjusts. In clinical studies of extended-release injectable naltrexone per the FDA, 33% of participants reported nausea compared to 11% receiving a placebo. Vomiting, diarrhea, and abdominal pain were also reported more often in the treatment group.

Eating smaller meals and taking naltrexone with food may help reduce stomach discomfort. Bland foods like toast, rice, bananas, or soup can feel easier on the stomach during the first few days. Some people also find ginger tea or peppermint helpful for mild nausea.

Most digestive side effects improve within the first few weeks of treatment. If nausea becomes severe or prevents you from eating or drinking normally, check in with your healthcare provider.

Neurological effects (headache, dizziness)

Headaches and dizziness are known side effects of both oral and injectable naltrexone. These symptoms may occur because the medication affects signaling pathways tied to pain perception, stress response, and balance.

Simple adjustments can make these symptoms easier to manage:

• Drink enough water throughout the day
• Change positions slowly when standing
• Take breaks from screens if headaches worsen
• Avoid skipping meals

Dizziness and headaches are usually temporary. If symptoms become intense, persistent, or noticeably worse over time, contact your healthcare provider.

Energy and sleep changes

Naltrexone can temporarily affect energy levels and sleep patterns while your body adapts to treatment. Some people feel more tired than usual, while others notice insomnia, restless sleep, or intense drowsiness.

A few basic sleep habits may help:

• Keep consistent sleep and wake times
• Limit caffeine later in the day
• Reduce screen time before bed
• Ask your provider whether morning dosing may help

Taking naltrexone at the same time every day may also help reduce fluctuations in side effects.

How Serious Can Naltrexone Side Effects Become?

Serious naltrexone side effects are uncommon, but symptoms involving liver problems, allergic reactions, or mental health changes require immediate medical attention.

You can use this color-coded risk scale to gauge the severity of your side effects:

• Green: Mild nausea, temporary headache, fatigue, mild dizziness
• Yellow: Persistent vomiting, worsening insomnia, severe headaches, increasing anxiety
• Red: Jaundice, hallucinations, suicidal thoughts, trouble breathing, severe injection-site damage

Liver warning signs

Naltrexone carries a warning for potential liver injury, particularly at higher doses. The FDA prescribing information notes that the risk of liver damage increases when oral doses exceed recommended therapeutic ranges.

Signs of possible liver stress include:

• Yellowing of the skin or eyes
• Dark urine
• Severe fatigue
• Pain in the upper-right abdomen
• Unusual nausea that doesn’t improve

According to research in LiverTox, liver enzyme elevations linked to naltrexone are often mild and temporary, but serious symptoms still require immediate medical attention. Contact your healthcare provider right away if you notice signs of jaundice or persistent abdominal pain.

Allergic or injection reactions

Injection-site reactions are common with extended-release injectable naltrexone. Clinical studies found that tenderness, swelling, bruising, and hardened skin around the injection site occurred more frequently in people receiving the medication. Most mild reactions improve with:

• Ice packs
• Gentle movement
• Avoiding pressure on the area

More serious reactions can include tissue damage, blistering, severe swelling, or open wounds. Rare cases have required surgical treatment. Seek urgent medical evaluation if pain becomes severe or the skin appears damaged. Signs of a serious allergic reaction may include:

• Hives
• Swelling of the lips or throat
• Trouble breathing
• Severe rash

Call emergency services immediately if these symptoms occur.

Prescription note: please note that Talkspace providers do not prescribe injectable-form naltrexone.

Mental health red flags

According to MedlinePlus, people with substance use challenges often experience depression, and receiving naltrexone does not reduce that risk. Concerning symptoms include:

• Sudden mood swings
• Severe anxiety
• Panic symptoms
• Depression that worsens quickly
• Thoughts of self-harm or suicide

Alcohol may cause anxiety symptoms, particularly during withdrawal or when cutting back on drinking. Recognizing this connection can help distinguish withdrawal-related anxiety from other mental health concerns.

How Can You Ease Side Effects at Home?

Managing day-to-day naltrexone side effects at home often comes down to a few consistent habits. None of these replaces your healthcare prescriber's guidance, but they can make the early weeks more comfortable.

Lifestyle tweaks

Healthy daily routines can make a meaningful difference when you’re adjusting to naltrexone. Focus on:

• Drinking enough water
• Eating regular meals
• Limiting excessive caffeine
• Prioritizing sleep
• Moving your body gently when possible

It’s also important to understand how naltrexone side effects and alcohol interactions may feel. Naltrexone can reduce alcohol’s rewarding effects, but drinking alcohol while taking the medication can still increase liver stress and worsen dehydration or stomach upset.

Additionally, alcohol can influence mood and exacerbate symptoms of depression, often leading to increased sadness, irritability, or emotional lows after drinking. Keeping a symptom journal or tracking symptoms in an app can help you notice patterns and identify triggers that worsen side effects.

Over-the-counter relief

Some over-the-counter (OTC) medications may help manage mild side effects like headaches or stomach discomfort. Examples may include:

• Antacids for nausea or heartburn
• Non-opioid pain relievers for headaches
• Electrolyte drinks for dehydration

Always check with a pharmacist or healthcare provider before combining OTC medications with naltrexone. Since naltrexone blocks opioid medications, it can complicate pain management during emergencies, surgeries, or dental procedures.

The same caution applies to antidepressants and other prescription mental health medications. For example, mixing alcohol and Lexapro or other similar medications may increase side effects such as drowsiness or dizziness.

Dose timing and adherence

Taking naltrexone consistently and exactly as prescribed may help reduce fluctuations in side effects over time. Oral naltrexone (Revia) is commonly prescribed at 50 mg once daily for alcohol use disorder, while treatment for opioid use disorder may begin with a lower 25 mg starting dose before increasing to 50 mg daily if withdrawal symptoms do not occur.

The Revia prescribing information also notes that the risk of liver injury increases with single doses above 50 mg, which is why it’s important to stay within your prescribed dose and avoid adjusting medication on your own.

Before starting either oral or injectable naltrexone, you should be opioid-free for at least 7–10 days, including avoiding tramadol, to reduce the risk of severe precipitated opioid withdrawal that may require hospitalization.

A few simple adherence habits can help:

• Take oral medication at the same time every day
• Use a phone reminder or pill organizer
• Keep a symptom journal to track side effects and patterns
• Record when symptoms appear and whether they improve or worsen
• Follow your provider’s instructions carefully if you miss a dose

Keeping a simple log of when you take your medication and any side effects you notice can help you and your healthcare provider identify patterns more easily. If a dose is missed, follow your prescriber’s instructions rather than doubling your next dose.

When Should You Call a Healthcare Professional?

Call your provider promptly if you experience:

• Vomiting or diarrhea lasting longer than 24 hours
• Severe headaches that keep worsening
• Confusion or hallucinations
• Significant dizziness or fainting
• Worsening depression or panic symptoms
• Yellowing of the skin or eyes
• Severe injection-site pain or skin breakdown

Go to the emergency room or call emergency services if you experience:

• Trouble breathing
• Swelling of the face or throat
• Thoughts of suicide
• Signs of overdose after opioid use

When contacting your healthcare provider, it can help to describe:

• When the symptom started
• How severe do they feel on a scale from 1–10
• Whether they're improving or worsening
• Anything that seems to trigger or relieve them

Here's a simple script you can follow or adapt when talking to your healthcare provider:

“I started naltrexone three days ago, and I’m having persistent nausea and dizziness that’s making it hard to function. I wanted to check whether this is expected and what steps I should take next.”

Low-dose naltrexone side effects may sometimes feel milder, but lower doses can still cause headaches, fatigue, sleep changes, or mood symptoms that deserve medical guidance.

Manage Naltrexone Side Effects with Support

Naltrexone can cause nausea, fatigue, or headaches, especially in the early weeks. Managing these side effects is easier when you have consistent professional guidance. That's where Talkspace comes in. Through ongoing prescription management, you can track how your body responds and adjust your treatment plan as needed.

Having someone in your corner makes a real difference. Talkspace connects you with licensed psychiatric providers who understand your history and can address concerns before they become setbacks. Support like this helps you stay on track and feel more confident throughout your recovery.

Frequently Asked Questions (FAQs)

Does low-dose naltrexone have different side effects?

Low-dose naltrexone is generally well-tolerated, and its side effects are usually mild, such as vivid dreams, insomnia, or temporary headaches. These effects are often less severe than those seen with standard-dose naltrexone used for addiction treatment.

Can I drink alcohol while on naltrexone?

It's not recommended to drink alcohol while taking naltrexone, as the medication blocks opioid receptors and may reduce alcohol tolerance. Drinking can increase the risk of liver damage and may also reduce the effectiveness of naltrexone in controlling cravings.

How long do naltrexone side effects usually last?

Naltrexone side effects typically appear within the first few days of starting the medication and usually subside within one to two weeks. If side effects persist or worsen, it’s important to consult a healthcare provider.

Will the side effects of naltrexone return if I miss a dose?

Missing a dose of naltrexone usually doesn’t cause side effects to return immediately, but stopping and restarting the medication can sometimes cause mild effects like nausea or headache. Consistent dosing helps minimize side effects and maintain the medication’s effectiveness.

Is it safe to combine naltrexone with pain relievers?

Naltrexone can block the effects of opioid pain relievers, making them ineffective, so combining them can be unsafe if strong pain relief is needed. Non-opioid pain relievers like acetaminophen or ibuprofen are generally safe to use, but it’s best to consult a healthcare provider before taking any pain medication.

Sources

1. U.S. Food and Drug Administration. Revia (naltrexone hydrochloride) tablets prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/018932s017lbl.pdf. 2013 Apr;1-19. Accessed May 7, 2026.
2. U.S. Food and Drug Administration. Vivitrol (naltrexone for extended-release injectable suspension) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021897s042lbl.pdf. 2018 Oct;1-39. Accessed May 7, 2026.
3. LiverTox: clinical and research information on drug-induced liver injury. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.ncbi.nlm.nih.gov/books/NBK548583/. 2012;1-24. Accessed May 7, 2026.
4. MedlinePlus. Naltrexone. National Library of Medicine. https://medlineplus.gov/druginfo/meds/a685041.html. Accessed May 7, 2026.

Talkspace articles are written by experienced mental health-wellness contributors; they are grounded in scientific research and evidence-based practices. Articles are extensively reviewed by our team of clinical experts (therapists and psychiatrists of various specialties) to ensure content is accurate and on par with current industry standards.

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