Common Side Effects of the Vivitrol Shot: What Patients Should Know

Vivitrol is the brand name for extended-release injectable naltrexone, an FDA-approved medication used to treat opioid use disorder and alcohol use disorder. Unlike other addiction medications, it is not an opioid and produces no physical dependence — but it does have a distinct side effect profile that patients should understand before the first injection. The most common side effects are manageable; a smaller number are serious enough to require medical attention. This guide covers both, along with the specific precautions that make Vivitrol different from other addiction treatment medications.

What Vivitrol Is and How It Works

Vivitrol is a 380 mg dose of naltrexone formulated into a slow-release suspension that is injected into the gluteal muscle once every four weeks. Over the month following the injection, the medication is gradually released into the bloodstream, providing continuous opioid receptor blockade at therapeutic levels. Naltrexone binds to opioid receptors without activating them, preventing heroin, fentanyl, oxycodone, or any other opioid from producing a high. For alcohol use disorder, it reduces the rewarding effects of drinking and diminishes cravings, though the mechanism there is less completely understood.

Vivitrol was FDA-approved for alcohol dependence in 2006 and for opioid dependence in 2010. It is manufactured by Alkermes and is currently the only long-acting injectable formulation of naltrexone available in the United States.

Most Common Side Effects

In clinical trials, the side effects reported by at least 5% of patients on Vivitrol were:

• Injection site reactions — pain, tenderness, induration, swelling, itching, or bruising at the injection site, reported by about 69% of patients
• Nausea — reported by 33% of patients, typically worst after the first injection and diminishing with subsequent doses
• Headache — 25%
• Fatigue and weakness — 23%
• Insomnia or sleep disturbances — 14%
• Vomiting — 14%
• Decreased appetite — 14%
• Dizziness — 13%
• Toothache — 10%
• Muscle cramps or joint pain — 8%
• Anxiety — 7%

Injection site reactions are nearly universal. Most are mild and resolve within a few days, but some patients develop more significant reactions including induration (hardening), deep bruising, or in rare cases, necrotic tissue damage requiring surgical intervention. The 2 mL injection volume is larger than most intramuscular injections, which contributes to the site reactions. Proper injection technique — deep IM injection into the gluteal muscle, alternating sides each month — significantly reduces the risk.

Nausea typically peaks in the days following the first injection and becomes noticeably milder with subsequent monthly doses. Patients who cannot tolerate the nausea sometimes find it helps to take anti-nausea medications prophylactically around the time of each injection for the first two or three months.

Serious Side Effects Requiring Medical Attention

A smaller number of side effects are serious enough that patients should contact their prescribing physician or seek emergency care:

• Severe injection site reactions — if the injection site becomes intensely painful, hot, hard, or develops open sores or dark patches, this can indicate tissue necrosis and requires immediate medical evaluation
• Allergic reactions — hives, rash, swelling of the face or throat, difficulty breathing, or wheezing may indicate a serious allergic reaction. Anaphylaxis is rare but has been reported
• Liver toxicity — naltrexone is processed by the liver and can cause hepatitis or hepatic damage, particularly at higher doses. Patients with pre-existing liver disease require careful evaluation before starting Vivitrol. Signs of liver problems include yellow skin or eyes, dark urine, right-upper-quadrant abdominal pain, and severe fatigue
• Depression or suicidal thoughts — some patients experience worsening depression on Vivitrol, and suicidal ideation has been reported. Any patient with a history of depression should be monitored closely, and any new or worsening depressive symptoms should be reported to the prescriber immediately
• Pneumonia — Vivitrol has been associated with eosinophilic pneumonia, a rare but serious allergic lung reaction. New onset cough, shortness of breath, or chest pain warrants evaluation

Any persistent or severe symptom after an injection should be reported. The injection is active for approximately one month, so adverse effects cannot simply be "waited out" the way they could with daily oral medications.

The Most Important Precaution: Precipitated Withdrawal

This is not exactly a side effect, but it is the most critical safety issue with Vivitrol and the one patients must understand before their first injection. Because naltrexone blocks opioid receptors completely, giving Vivitrol to someone who still has opioids in their system will precipitate immediate, severe withdrawal — much worse than natural withdrawal, and lasting the entire 30-day duration of the injection with no way to reverse it.

For this reason, patients must be fully detoxified from opioids before their first Vivitrol injection. Guidelines typically require:

• 7-10 days opioid-free for short-acting opioids (heroin, fentanyl, oxycodone, hydrocodone)
• 10-14 days opioid-free for long-acting opioids (methadone, extended-release formulations)
• A negative oral naltrexone challenge — some physicians give a small oral dose first to confirm the patient will tolerate the injection without precipitated withdrawal

This detox requirement is the main reason Vivitrol is less widely used than buprenorphine for opioid use disorder. It is also the reason many MAT programs use clonidine and supportive medications during the opioid-free window before starting Vivitrol. Patients considering Vivitrol who cannot tolerate the detox phase may be better candidates for buprenorphine, which can be started during active withdrawal.

The Reduced Opioid Tolerance Warning

Patients need to understand one additional safety issue: while on Vivitrol, opioid tolerance drops significantly. If a patient stops Vivitrol (either by missing a scheduled injection or by discontinuing treatment) and then uses opioids at their previous dose, they face a dramatically elevated overdose risk. This is the leading cause of Vivitrol-associated deaths. The medication does not cause the overdose; the return to opioid use at a dose the body can no longer handle does.

Patients should be counseled repeatedly that any relapse after starting Vivitrol should be at much lower doses than before, and ideally should occur in the presence of someone who can administer naloxone if needed.

Talking to Your Doctor About Side Effects

If you are on Vivitrol and experiencing side effects, the most important thing is to communicate with your prescribing physician rather than stopping treatment on your own. Most side effects improve over time, can be managed with supportive medications, or indicate a need for dose adjustment — but only your physician can evaluate which category your specific symptoms fall into.

Stopping Vivitrol is straightforward in that there is no physical withdrawal from the medication itself, but the loss of opioid receptor blockade creates the dangerous tolerance situation described above. Anyone considering stopping Vivitrol should discuss the decision with their physician and have a plan for the transition, which often includes starting buprenorphine, intensifying behavioral therapy, or both.

For more information about Vivitrol in the context of alcohol use disorder specifically, see our companion article on Vivitrol for alcoholism.

Finding a Vivitrol Provider

Vivitrol can be prescribed by any physician, nurse practitioner, or physician assistant — it does not require a special DEA registration the way buprenorphine historically did. It is typically administered in a doctor's office, addiction treatment program, or sometimes in hospital outpatient settings. Many MAT programs offer Vivitrol as an alternative to buprenorphine for patients who prefer a non-opioid medication.

Liberation Way's helpline can help you find MAT programs in your area that offer Vivitrol and walk you through insurance coverage questions. The helpline is free, confidential, and available 24 hours a day. Call (866) 275-3142 to speak with a treatment specialist.