Naltrexone side effects and how to avoid them

Nausea, fatigue, and loss of appetite are some common naltrexone side effects

By Georgia C. Yalanis, MD | Aug. 3, 2021 Medically reviewed by Anne Jacobson, MD, MPH

Naltrexone is a medication approved by the U.S. Food and Drug Administration (FDA) to treat alcohol use disorder (AUD), alcohol dependence, and opioid addiction. Naltrexone and its active metabolite, naltrexol, are opioid antagonists. They competitively bind opioid receptors, reversibly blocking or reducing the effects of opioids.

In this manner, naltrexone is used for what is known as medication-assisted treatment (MAT), where medicines are used to assist with treating alcohol and opioid use disorders. Naltrexone is sometimes preferred over methadone and buprenorphine as its use and availability are not as restricted.

It’s important to note that medication in isolation is not recommended when treating any type of substance use disorder. Comprehensive treatment programs for any type of substance use disorder should involve counseling, support groups, or other behavioral health therapies.

Naltrexone is sometimes used as part of a treatment regimen for compulsive behaviors, dissociative disorders, self-injurious behaviors, and sexual addiction. Naltrexone has also demonstrated a reduction in binging and purging behavior in adolescents and adults with eating disorders. It may be prescribed in combination with bupropion under the brand name Contrave for those that require significant weight loss.

Naltrexone is not an over-the-counter medication. It is a prescription drug and must be used under the supervision of a healthcare provider. The brands ReVia and Depade (naltrexone hydrochloride), have been discontinued in the United States, however, generic naltrexone HCl tablets and Vivitrol ( extended-release injectable suspension administered monthly), are available.

This article will discuss some of the side effects, warnings, and interactions associated with naltrexone use as well as how to avoid them.

Common side effects of naltrexone

As with any medication, naltrexone use is associated with some common, non-serious side effects. Most side effects associated with naltrexone use are mild and self-limiting. If any of the following adverse effects become bothersome, notify your healthcare provider.

Insomnia or trouble sleeping
Abdominal discomfort, stomach pain, nausea, vomiting, or constipation
Anxiety
Headache and dizziness
Muscle pain or joint pain
Rash
Fatigue, tiredness, somnolence (excessive sleepiness)
Anorexia, loss of appetite, or weight loss
Rigors (chills), shaking, or shivering
Liver function problems

Nausea

Nausea is a common side effect associated with the use of many medications, including naltrexone. Nausea associated with naltrexone use is generally mild and self-limiting. Severe nausea may be an indicator that something is wrong. Seek medical attention if you experience any of the symptoms of severe nausea below:

Persistent nausea for more than 48 hours
You are unable to eat for 24 hours or drink for 12 hours due to nausea
Nausea accompanied by:
- An intense headache, blurry vision, or confusion
- Difficulty breathing and a rapid heartbeat
- Severe abdominal pain, voluminous diarrhea, or projectile vomiting
- Symptoms associated with heart attack including sweating, chest pain or tightness, or pain in the jaw or arms

Fatigue

Fatigue, drowsiness, and sleepiness are very commonly associated with medications that exert effects on the opioid receptors in the brain. Naltrexone is more likely to exert this effect in higher doses. Paradoxically, low-dose naltrexone (LDN) has actually been used off-label to treat chronic fatigue.

Loss of appetite

Naltrexone alone is known to decrease appetite and reduce the appeal of food. Naltrexone use could lead to weight loss on its own, however, appetite reduction is generally a desired side effect for individuals concerned about increasing appetite or weight gain secondary to lifestyle changes or medication adjustments. This is typically the use for individuals attempting smoking cessation or beginning medications that are known to cause weight gain. Naltrexone is generally not used as a weight loss adjuvant on its own, though several compounding pharmacies market it as a weight-loss tool.

Naltrexone is sometimes used with a medication called bupropion for weight loss. This combination is available under the brand name, Contrave. In all clinical studies performed with this combination, individuals taking naltrexone-bupropion combined with a diet and exercise program for one year had greater weight loss than a placebo combined with a diet and exercise program.

Naltrexone has also demonstrated a reduction in binging and purging behavior in adolescents and adults with eating disorders, but this effect is secondary to its action on the opioid system and reward pathway involved in compulsive behavior.

Serious side effects of naltrexone

Individuals who use naltrexone may experience severe, and potentially irreversible adverse effects. It is possible that naltrexone may need to be discontinued, which should only be done with the guidance of your healthcare provider. Immediately notify your healthcare provider if you experience any of the following serious side effects.

Suicidality
Depression
Hypersensitivity reactions
Hepatotoxicity causing liver problems and impaired liver function

Liver damage

Naltrexone use has been associated with up to 50% of individuals experiencing serum liver enzyme elevations, which are often mild and self-limited. In approximately 1% of those taking naltrexone, those elevations reach more than three times the upper limit of normal and the medication needs to be stopped. Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses or large doses and is contraindicated for use in individuals with acute hepatitis or liver failure. If higher doses of naltrexone need to be administered for therapeutic benefit, liver function tests should be monitored on a periodic basis. Naltrexone should be immediately discontinued in the event of signs or symptoms of acute hepatitis listed below.

Fever, fatigue, and loss of appetite
Severe abdominal pain
Severe nausea or vomiting
Stool changes
Jaundice or yellowing of the skin and eyes
Brown or very dark urine

It is never safe or advisable to consume alcoholic beverages in the context of liver disease. Alcohol is very damaging to the cells in the liver, and liver disease may be one reason an individual has decided to reduce or eliminate alcohol from their diet. As naltrexone is used as a treatment option for individuals struggling to reduce or eliminate alcohol intake, treatment should be initiated in individuals who have demonstrated an ability to abstain from alcohol with complete alcohol abstinence as the goal.

If naltrexone must be discontinued, disulfiram may be prescribed for alcohol use disorder and Suboxone (buprenorphine-naloxone) for opioid use disorder.

How long do naltrexone side effects last?

Mild side effects (nausea, vomiting, constipation) associated with naltrexone use usually resolve within a few weeks of treatment or with discontinuation of the medication. Some serious side effects (liver damage, suicidality, hypersensitivity reactions) could be permanent and even fatal.

Naltrexone contraindications and warnings

Abuse and dependence

Naltrexone itself is not an opiate, it is not addictive, and it does not cause withdrawal symptoms with discontinuing use. Naltrexone is designed to suppress cravings for alcohol and opiates by blocking the euphoric sensation induced from ingesting those agents, thereby reducing an individual’s desire to drink alcohol or use opioids. It is important to note that naltrexone will not prevent you from being impaired while drinking or remove the risk from drinking or bodily harm from alcohol or opioid use.

Overdose

Naltrexone should always be taken exactly as it is prescribed. Side effects associated with naltrexone use are dose-dependent. Taking more medication than is prescribed will increase the likelihood of experiencing potentially fatal side effects.

Tolerance is the effect that happens with repeated exposure to a drug or alcohol. The more you are exposed to, the more you need to take to get the same “high” or “buzz.” Naltrexone effectively removes an individual’s tolerance to opioid drugs such that smaller doses of opioids or alcohol are required to achieve the effect that larger doses would have prior to naltrexone use. Clinically, this means that once you have started taking naltrexone, if you relapse, you are more likely to experience an opioid or alcohol overdose than someone who has not taken naltrexone.

A healthcare provider may prescribe naloxone together with naltrexone for those being treated for opioid use disorder. Naloxone is a medication given to reverse an opioid overdose.

Individuals who are worried about misusing opioids, alcohol, or medications can call a local or national hotline to receive addiction assistance. There is effective treatment available at low- to no cost.

Restrictions

Naltrexone is contraindicated for use in the following individuals:

Those with acute hepatitis or liver failure
Those taking opioid analgesics
Individuals with current physiologic opioid dependence
Individuals in acute opioid withdrawal
Any individual who has failed the naloxone challenge test or has a positive urine screen for opioids
Any individual receiving the injectable preparation who has previously exhibited hypersensitivity to naltrexone, polylactide-co-glycolide, carboxymethylcellulose, or any other components of the medication

Renal impairment

Naltrexone and its primary metabolite are excreted in the urine. Naltrexone should be used with caution in individuals with moderate to severe kidney disease.

Pregnancy and breastfeeding

Naltrexone has been shown to increase the incidence of early fetal loss in high doses in animal studies. There are no adequate or well-controlled studies of naltrexone in pregnant women. Naltrexone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Naltrexone has been found in human milk. As animal studies have demonstrated the potential for tumorigenicity and because of the potential for serious adverse reactions in nursing infants, an informed decision should be made between the patient and the mother as to whether there is more benefit to continue nursing or to continue taking naltrexone.

Naltrexone interactions

Naltrexone is absolutely contraindicated for use with the following medications:

Buprenorphine
Butorphanol
Codeine
Dihydrocodeine
Fentanyl
Hydrocodone
Hydromorphone
Levorphanol
Meperidine
Methadone
Morphine
Nalbuphine
Opium
Oxycodone
Oxymorphone
Pentazocine
Tapentadol
Tramadol

Other medications should be used with caution in combination with naltrexone. Advise your healthcare provider of all prescription and non-prescription medications you are taking.

RELATED: List of opioids

How to avoid naltrexone side effects

Follow medical advice while taking this medication. Take only the dose prescribed by a healthcare professional. Do not take more medication and do not take less. Take all of the doses how and when they are prescribed. For any missed dose, take the next dose as soon as possible. Injectable preparations should be administered by a healthcare provider. Read the medication guide for more drug information.
Disclose a full medication list, health history, and allergies before taking naltrexone. This includes all medications and supplements, medical conditions, allergic reactions, and substance use.
Store and dispose of the medication correctly and away from children. Naltrexone tablets should be stored at room temperature (68 to 77 degrees Fahrenheit). Naltrexone injectable preparations should be refrigerated and allowed to reach room temperature prior to use. Improper storage of the medication could affect the preparation.
Use the medication preparation exactly as it was prepared. Do not modify it in any way. Tablets should be taken whole. Liquid preparations need to be prepared using only the materials supplied in the carton and administered using only the needles supplied in the carton.
Avoid alcohol, opioids, illegal drugs, other CNS depressants, and medications with known interactions while taking naltrexone. Avoiding these substances can reduce the likelihood of overdose.
Be informed and aware about access to and availability of treatment for substance use disorders. There are many resources available for individuals who may have alcohol or opiate addiction. Getting help early could save lives.