Naltrexone & Vivitrol® Side Effects: What to Expect and How Long They Last

‍Quick answer: The most common naltrexone side effects are nausea, headache, dizziness, fatigue and trouble sleeping. Most are mild and fade within the first one to two weeks. Vivitrol®, the monthly extended-release naltrexone shot, can also cause injection-site soreness or a firm lump. Serious risks are uncommon but include liver problems and a higher chance of opioid overdose after stopping.

Naltrexone treats both alcohol use disorder and opioid use disorder by reducing cravings and blocking opioid effects. Knowing what to expect makes it easier to stay on it long enough to work. If you have questions about whether naltrexone is right for you, call MATClinics at 410-220-0720 or schedule an appointment.

Common Naltrexone Side Effects

Nausea is the most common naltrexone side effect, followed by headache and tiredness. In clinical trials of Vivitrol for alcohol use disorder, these were the side effects reported more often than with a placebo shot (Vivitrol prescribing information):

• Nausea: 33% of patients (vs. 11% on placebo)
• Headache: 25% (vs. 18%)
• Fatigue or low energy: 23% (vs. 12%)
• Vomiting: 14% (vs. 6%)
• Trouble sleeping: 14% (vs. 12%)
• Dizziness or fainting: 13% (vs. 4%)
• Muscle cramps: 8% (vs. 1%)
• Sleepiness: 4% (vs. 1%)

Oral naltrexone tablets cause a similar list. MedlinePlus also notes stomach cramps, diarrhea or constipation, loss of appetite, anxiety, irritability, joint or muscle pain and rash.

Tips for Managing Mild Side Effects

• Take tablets with food if they upset your stomach.
• Drink plenty of water, especially if you have nausea or vomiting.
• Wait to drive until you know whether naltrexone makes you dizzy or drowsy.
• Ask your provider about starting at a lower dose if nausea is a problem.

Most people find these effects ease after the first week or two. Don't stop on your own; talk to your provider first.

Vivitrol Shot Side Effects at the Injection Site

Injection-site reactions are the side effect most specific to Vivitrol. The shot is given deep into the buttock muscle once every four weeks, alternating sides. In alcohol trials, 69% of patients had some injection-site reaction, compared with 50% after a placebo shot.

Common reactions include:

• Pain or tenderness
• A firm lump under the skin (induration), reported by about 35% of patients
• Swelling, redness or bruising
• Itching

These usually improve within days to a few weeks. A cold pack in the first day and mild over-the-counter pain relief can help; ask your provider what is safe for you.

When to Call Your Provider

Rarely, the injection site becomes infected or the tissue is damaged. The label reports cases of cellulitis, abscesses and tissue death (necrosis), some needing surgery. Call your provider if the area:

• Hurts more over time instead of less
• Turns hot, very red or spreads
• Develops a blister, open sore or dark scab
• Is still swollen or lumpy after two weeks

The right needle length and a deep intramuscular injection lower this risk, which is one reason Vivitrol must be given by a trained provider.

Does Naltrexone Hurt Your Liver?

At standard doses, serious liver injury from naltrexone is uncommon. Older labels carried a boxed warning about liver damage, but that warning is no longer on the current Vivitrol label. The label still lists hepatitis and liver dysfunction as a precaution, so providers watch for it.

In the opioid trial, mild rises in liver enzymes (ALT and AST) were more common on Vivitrol than placebo. Many people starting naltrexone already have some liver strain from alcohol, hepatitis C or other medications, which can make results harder to read.

How Your Provider Monitors Your Liver

• Liver blood tests before you start, especially if you drink heavily or have liver disease
• Follow-up tests if you have symptoms or risk factors
• Stopping naltrexone if signs of acute hepatitis appear

Signs of Liver Problems

Get medical care right away if you notice:

• Yellowing of the skin or eyes
• Dark urine or pale stools
• Pain in the upper right side of your belly
• Unusual tiredness, bruising or bleeding

For people with alcohol use disorder, cutting back on drinking usually does much more for liver health than the small liver risk naltrexone carries.

Mood and Sleep Effects

Some people notice changes in mood or sleep on naltrexone. Trouble sleeping, anxiety, irritability and low energy are listed side effects, and they often overlap with early recovery itself. In the main Vivitrol alcohol trial, depressed mood was reported by 10% of patients, compared with 5% on placebo.

The label also warns about depression and suicidal thoughts, which are more common in people with substance use disorders whether or not they take naltrexone. Tell your provider if you have a history of depression, and let family know what to watch for.

Seek help right away if you or a loved one notices:

• New or worsening depression or hopelessness
• Thoughts of self-harm or suicide
• Sudden changes in behavior

If you are in crisis, call or text 988 to reach the Suicide & Crisis Lifeline. MATClinics' mental health therapy and psychiatry services can treat depression and anxiety alongside naltrexone.

Reduced Tolerance and Overdose Risk

The most serious risk of naltrexone isn't a side effect of the drug itself. It is what can happen if someone uses opioids after their tolerance has dropped. Naltrexone blocks opioids for as long as it's active, and during that time the body loses its tolerance.

According to the Vivitrol label, overdose risk rises:

• Near the end of a dosing month, as the blockade wears off
• After a missed dose
• After stopping naltrexone completely

An amount of opioids someone used safely before treatment can now be fatal. Trying to "push through" the blockade by taking large amounts of opioids is also extremely dangerous.

How to Stay Safe

• Keep naloxone (Narcan) at home and make sure family knows how to use it.
• Don't miss or delay injections; call your clinic to reschedule right away.
• Talk to your provider before stopping, and make a plan for what comes next.
• Tell any doctor or dentist that you take naltrexone, since it also blocks opioid pain medicine.

Starting Naltrexone After Opioids

You must be opioid-free for at least 7 to 10 days before your first dose, or longer after buprenorphine or methadone. Starting too soon can cause sudden, severe withdrawal. Your provider may use a urine test or a naloxone challenge first. Learn more in 6 Things to Know About Opiate-Blocking Shots.

How Long Do Naltrexone Side Effects Last?

For most people, side effects like nausea and headache are strongest in the first few days and fade within one to two weeks as the body adjusts. With Vivitrol, side effects may be more noticeable in the first few days after each shot.

• Oral naltrexone: Side effects usually ease within the first week or two. Because each tablet wears off within about a day, effects stop soon after a dose is stopped.
• Vivitrol: Blood levels peak about 2 to 3 days after the injection, then slowly decline. Nausea and fatigue are usually worst in those first days, especially after the first shot.
• Injection-site soreness or lumps: Usually improve over days to a few weeks.

How Long Does Vivitrol Last?

One Vivitrol shot blocks opioids for about 28 days, which is why it's given every four weeks. Naltrexone stays measurable in the blood for more than a month, and its half-life is 5 to 10 days. This means side effects from a shot can't be stopped quickly, which is one reason some providers suggest trying oral naltrexone first.

Vivitrol vs. Naltrexone Pills: Which Has Fewer Side Effects?

Vivitrol and naltrexone tablets contain the same medication, so their side effects are similar. The main differences are how often you take them and how steady the dose is.

• How it's taken: Oral naltrexone is a daily tablet, usually 50 mg. Vivitrol is a 380 mg shot given by a provider every four weeks.
• Side effects: Both commonly cause nausea, headache and fatigue. Only Vivitrol causes injection-site reactions.
• Stopping: Tablet effects end within about a day. A Vivitrol shot keeps working for about a month.
• Adherence: Daily pills are easy to skip, especially when cravings are strong. Vivitrol removes that daily choice, which is its biggest advantage.
• Exposure: Over 28 days, Vivitrol delivers about 3 to 4 times more total naltrexone than 50 mg daily tablets.

Many people do well starting with tablets to check how they feel, then switching to Vivitrol for steadier coverage. Your provider can help you choose. For how Vivitrol compares with buprenorphine for opioid use disorder, see Vivitrol vs. Suboxone.

Naltrexone vs. Low-Dose Naltrexone (LDN)

If you've seen naltrexone discussed for pain or autoimmune conditions, that's usually low-dose naltrexone, or LDN. LDN uses a small fraction of the standard dose, typically a few milligrams a day compared with 50 mg. It is prescribed off-label, often compounded by a pharmacy, for conditions like fibromyalgia and chronic pain.

LDN is not used to treat alcohol or opioid use disorder, and its side effects (most often vivid dreams or trouble sleeping) are generally milder. Everything else in this article refers to standard-dose naltrexone and Vivitrol.

Who Shouldn't Take Naltrexone?

Naltrexone isn't right for everyone. According to the Vivitrol label, you should not take it if you:

• Take opioid pain medicine, or expect to need it
• Are currently dependent on opioids or are in opioid withdrawal
• Have a positive opioid urine test or fail a naloxone challenge
• Have had an allergic reaction to naltrexone or Vivitrol's ingredients

Your provider will also use extra caution if you have liver or kidney disease, a bleeding disorder (because of the injection), depression, or are pregnant or breastfeeding. For people still dependent on opioids, buprenorphine treatment like Suboxone may be a better first step.

How MATClinics Can Help

MATClinics offers Vivitrol treatment for both alcohol and opioid use disorder at eight locations across Maryland. Our providers check your liver health before you start, give each injection in the office and help you manage side effects so you can stay on track. Treatment includes access to substance use counseling, therapy and psychiatry.

We accept all Maryland Medicaid plans, Medicare Part B and CareFirst, offer evening and Saturday hours and often see new patients the same day. Call 410-220-0720 or schedule an appointment.

Frequently Asked Questions About Naltrexone Side Effects

What Is the Most Common Side Effect of Naltrexone?

Nausea. In Vivitrol's alcohol trials, about one in three patients had nausea, usually mild and mostly in the first days after starting or after a shot.

Do Naltrexone Side Effects Go Away?

Usually, yes. Most side effects fade within one to two weeks as your body adjusts. Tell your provider if they don't, since a dose change or switch in form may help.

Can Naltrexone Cause Weight Loss or Weight Gain?

Weight change isn't a common side effect on its own. Nausea or lower appetite can lead to small weight loss early on, and some people's weight changes as they drink less.

Can You Drink Alcohol on Naltrexone?

Naltrexone doesn't make you sick if you drink, unlike Antabuse. It reduces the rewarding effect of alcohol so cravings ease, but drinking still carries its usual risks. Talk with your provider about your goals.

What Happens If You Take Opioids on Vivitrol?

Naltrexone blocks normal opioid doses, so they won't work as expected. Taking large amounts to overcome the block can cause a fatal overdose.

How Long Does Vivitrol Stay in Your System?

One shot works for about 28 days, and naltrexone stays measurable in the blood for more than a month.

Is Vivitrol Better Than Naltrexone Pills?

They use the same medicine. Many people find a monthly shot easier to stick with than a daily pill, while tablets are easier to stop if side effects are a problem.