Naltrexone

Alcohol Use Disorder

Naltrexone is used to help people with alcohol dependence remain abstinent or reduce their consumption of alcohol. It is most effective when used as part of a complete treatment program that includes counseling, support groups, and lifestyle changes.

Opioid Dependence

This medication is used to prevent relapse in individuals who have previously been dependent on opioid medicines or illegal drugs. It is only intended for use after a person has successfully completed detoxification and has been free from opioids for a period of time. It works by blocking the effects of opioid medications and street drugs.

Weight Management

When combined with bupropion, naltrexone is used to help adults who are obese or overweight with weight-related medical conditions lose weight and keep it off. This use is intended to be paired with a reduced-calorie diet and increased physical activity.

Mechanism of Action

Naltrexone is classified as an opioid antagonist. It works by attaching to opioid receptors in the brain and blocking them. This action serves two primary purposes depending on the condition being treated:

• For Opioid Use Disorder: By blocking the receptors, naltrexone prevents opioid drugs (such as heroin or prescription painkillers) from producing a "high" or feelings of euphoria. If a person uses opioids while taking naltrexone, they will not feel the typical effects of the drug.
• For Alcohol Use Disorder: The exact way naltrexone works for alcohol is not fully established, but it is believed to interact with the brain's reward system. It helps reduce the urge or craving to drink and may make the consumption of alcohol feel less rewarding.

Naltrexone is not a narcotic and does not cause physical dependence. It does not treat withdrawal symptoms; instead, it works by preventing the pleasurable effects of opioids and alcohol to help support long-term recovery.

Common Side Effects

Many people using naltrexone experience mild side effects. These often improve as the body adjusts to the medication. Common symptoms include:

• Nausea and vomiting
• Headache
• Dizziness or lightheadedness
• Nervousness or anxiety
• Difficulty sleeping or feeling tired
• Muscle or joint pain
• Stomach pain or cramping
• Loss of appetite

For those receiving the injectable form of naltrexone, reactions at the injection site are common, such as pain, redness, bruising, or itching.

Serious Side Effects

While less common, some side effects can be severe. Seek medical attention immediately if you experience:

• Liver problems: Symptoms include yellowing of the eyes or skin, dark urine, or severe pain in the upper right stomach area.
• Depression or mood changes: This includes feeling unusually sad, hopeless, or having thoughts of self-harm.
• Severe allergic reactions: Signs include skin rash, hives, swelling of the face or throat, and trouble breathing.
• Pneumonia: A specific type of lung inflammation may occur, causing cough, fever, or shortness of breath.
• Severe injection site reactions: For the injectable form, seek help if the site becomes very hard, develops an open sore, or does not heal.

Naltrexone can also cause sudden, severe opioid withdrawal symptoms if opioids are still in your system when you start the medication.

Opioid Withdrawal and Overdose Risk

Naltrexone blocks the effects of opioids. If it is taken while opioids are still in the body, it can cause sudden and severe withdrawal symptoms. Individuals are typically required to be opioid-free for at least 7 to 14 days before starting treatment. A naloxone challenge test or urine screening may be used to confirm the absence of opioids.

There is a significant risk of fatal overdose if a person attempts to overcome the blockade by taking large amounts of opioids. Additionally, because naltrexone reduces tolerance to opioids, resuming opioid use after stopping the medication—even at previously used doses—can lead to life-threatening respiratory depression and death.

Liver Health

Naltrexone has the potential to cause liver injury or hepatitis, particularly when taken in high doses. Healthcare providers usually monitor liver function through blood tests before and during treatment. Signs of liver problems include dark urine, yellowing of the eyes or skin (jaundice), and pain in the upper right abdomen.

Mental Health and Other Concerns

• Depression and Suicidality: Some people taking naltrexone may experience depression, suicidal thoughts, or suicidal behavior.
• Injection Site Reactions: For the injectable form, severe reactions at the site of administration can occur, sometimes requiring medical or surgical intervention.
• Eosinophilic Pneumonia: A rare but serious lung inflammation has been reported with the use of naltrexone.
• Allergic Reactions: Severe allergic reactions, including hives, rashes, and swelling of the face, can occur.

Contraindications

Naltrexone is not recommended for individuals who:

• Are currently using or dependent on opioids.
• Are experiencing acute opioid withdrawal.
• Have failed a naloxone challenge test or have a positive urine screen for opioids.
• Have acute hepatitis or liver failure.
• Have a known hypersensitivity to naltrexone or any of its ingredients.

Pregnancy

There is limited information regarding the safety of naltrexone in pregnant women. In animal studies, high doses of the medication were associated with an increased risk of early pregnancy loss. Because well-controlled human studies are lacking, naltrexone is generally only recommended during pregnancy if the clinical need clearly justifies the potential risk to the fetus.

If you are pregnant or planning to become pregnant, discuss your treatment options with your healthcare provider to weigh the risks and benefits.

Breastfeeding

Naltrexone and its active metabolites are excreted into human breast milk. The effects of this exposure on a nursing infant are not well understood. Due to the potential for side effects in the infant, healthcare providers may recommend either stopping breastfeeding or stopping the medication, depending on the mother's medical needs.

It is important to consult with a clinician to evaluate the risks to the infant versus the benefits of the medication for the mother.

Available Forms

Naltrexone is provided in the following formulations:

• Oral Tablet: This form is taken by mouth.
• Extended-Release Injectable Suspension: This is a long-acting formulation administered as an intramuscular injection by a healthcare professional.

FDA Approved Indications

Naltrexone is approved by the U.S. Food and Drug Administration (FDA) for the following uses:

• Alcohol Dependence: To help patients maintain abstinence from alcohol and reduce cravings.
• Opioid Dependence: To prevent relapse following opioid detoxification. It is intended for patients who have been opioid-free for a minimum of 7 to 10 days.

The medication is available in two primary forms: a daily oral tablet and a long-acting injectable suspension administered once a month by a healthcare professional.

Boxed Warning and Safety Information

The oral form of naltrexone carries a boxed warning regarding the risk of liver injury (hepatotoxicity). This risk is primarily associated with high doses of the medication. Healthcare providers typically perform liver function tests before starting treatment and monitor them periodically thereafter. Naltrexone is not recommended for patients with acute hepatitis or liver failure.

There is also a significant regulatory focus on the risk of opioid overdose. Because naltrexone blocks opioid receptors, patients may attempt to overcome the blockade by taking large amounts of opioids, which can lead to fatal respiratory depression. Furthermore, patients have a lower tolerance for opioids after stopping naltrexone, increasing the risk of overdose if they return to previous levels of drug use.

Regulatory Classification

Naltrexone is a prescription medication but is not classified as a controlled substance. Unlike other medications used for opioid use disorder, such as methadone or buprenorphine, naltrexone does not have a potential for abuse or physical dependence.

Precipitated Withdrawal

Naltrexone is an opioid antagonist that blocks the effects of narcotics. If you have opioids in your body when you take naltrexone, it will cause sudden and severe withdrawal symptoms. This is called precipitated withdrawal and can be life-threatening.

To prevent this, you must be completely opioid-free for at least 7 to 14 days before your first dose. This includes avoiding medications like methadone, buprenorphine, and tramadol. Symptoms of precipitated withdrawal can include:

• Nausea, vomiting, or diarrhea
• Stomach cramps
• Muscle aches and joint pain
• Anxiety, nervousness, or irritability
• Sweating, fever, or chills
• Confusion or hallucinations

Discontinuing Naltrexone

Naltrexone is not habit-forming and does not cause physical dependence. Therefore, you will not experience withdrawal symptoms if you stop taking the medication.

It is important to note that after stopping naltrexone, you may be more sensitive to the effects of opioids. If you resume opioid use at the same doses you used in the past, there is a high risk of a fatal overdose because your body has lost its previous tolerance during treatment.