Negative Naltrexone Drug Combinations: What To Avoid

Naltrexone, sold under the brand names Vivitrol and Revia, is a prescription medication used to treat alcohol use disorder and opioid use disorder as part of medication-assisted treatment (MAT). While naltrexone is generally safe and effective when taken as prescribed, it can interact with certain medications, substances, and health conditions in ways that may be dangerous or reduce its effectiveness.

Taking naltrexone with certain drugs, including opioid pain medications, alcohol, or specific prescription medications, can result in serious side effects, reduced effectiveness, or life-threatening complications. Some interactions may cause severe withdrawal symptoms, liver damage, or prevent the medication from working properly.

Learn more about taking Naltrexone for addiction treatment

Naltrexone Drug Interactions

Drugs that interact with one another may counteract, enhance, or otherwise alter the effects of the drugs taken. Naltrexone is an opioid antagonist. While it is safe and effective when taken as prescribed, it should not be combined with the use of certain substances. Below are drug combinations that should be avoided while taking naltrexone.

Opioid Drugs And Naltrexone

Opioids, also known as opiates, should be avoided while taking naltrexone.

Common opioid drugs include:

• morphine
• oxycodone (OxyContin)
• hydrocodone (Vicodin)
• codeine
• tramadol (Ultram)
• methadone (Methadose, Dolophine)
• buprenorphine
• fentanyl
• oxymorphone (Opana)
• hydromorphone (Dilaudid)

Naltrexone can block the effects of opioids. However, it can’t prevent an overdose, in the event that a very high dose of one or more opioids is taken. Naltrexone should also not be taken with opioids still in a person’s system. This can precipitate acute opioid withdrawal.

Read more about what happens when you take naltrexone with opioids in your system

Alcohol And Naltrexone

Naltrexone is a medication that is known to help reduce cravings for alcohol and block its euphoric effects. Naltrexone should not be taken by people who are still drinking heavily or those who are alcohol-dependent.

Taking naltrexone in conjunction with alcohol will not:

• prevent alcohol-related physical or cognitive impairment
• prevent alcohol poisoning
• prevent negative side effects associated with heavy drinking
• prevent consequences of chronic alcohol misuse, such as liver damage
• enhance or reduce effects of alcohol (besides euphoria)

Unlike other medications for alcohol use disorder, such as disulfiram, naltrexone will not make a person violently ill if they drink. However, combining the two should be avoided.

Antidiarrheal Medications And Naltrexone

Naltrexone may interact with some antidiarrheal medications (medications for diarrhea), specifically those that contain opioids.

Antidiarrheal medications that might interact with naltrexone:

• diphenoxylate
• loperamide

Naltrexone can reduce the effectiveness of these medications and may precipitate opioid withdrawal symptoms such as severe vomiting, anxiety, or sweating.

Cold Medicine And Naltrexone

Certain cold and cough medicines should be avoided while taking naltrexone.

Cold and cough medicines that can interact with naltrexone:

• Tylenol with codeine
• Robitussin
• dextromethorphan (DXM)
• any opioid-containing pain relievers

Before starting naltrexone, tell your doctor if you are taking or have recently taken medicine for cough, cold, or pain. This includes the use of over-the-counter medications.

Illicit Drugs And Naltrexone

The use of illicit drugs, or street drugs, should be avoided while taking naltrexone for a drug or alcohol use disorder. This could result in adverse effects.

Common illicit drugs include:

• heroin
• cocaine
• methamphetamine (meth)
• illicitly manufactured fentanyl

Taking opioid street drugs, such as heroin, with naltrexone can be particularly dangerous. Naltrexone can make you not feel the effects of these drugs, which can increase the risk for accidental overdose, injury, coma, and death.

Thioridazine And Naltrexone

Thioridazine is an antipsychotic medication that can interact with naltrexone. Taken together, this combination could potentially cause sedation or excessive sleepiness.

Brand names for this drug include:

• Mellaril
• Melleril

No other antipsychotic medications have a known interaction with naltrexone.

Yohimbine And Naltrexone

Yohimbine is a supplement derived from the bark of an African evergreen tree. It is sold in the form of a tablet, pill, or extract. It is commonly taken to treat erectile dysfunction (ED). Yohimbine and naltrexone can interact. Taken together, this may cause increased anxiety, heart rate, and blood pressure.

Drug And Alcohol Addiction Medications And Naltrexone

Naltrexone is one of several medications that are FDA-approved to treat opioid and alcohol use disorder. Taking naltrexone with other MAT medications (excepting acamprosate) is not advised.

Naltrexone may interact with the following addiction medications:

• disulfiram
• buprenorphine
• buprenorphine/naloxone (Suboxone)
• methadone

Do not combine the use of naltrexone with other medication-assisted treatment (MAT) options unless you are directed to do so by a licensed MAT practitioner.

How To Prevent Negative Drug Interactions With Naltrexone

Negative drug interactions involving naltrexone can be serious.

What can help prevent a negative drug interaction:

• tell your doctor if you are taking any prescription medications, supplements, over-the-counter medications
• tell your doctor of any illicit drug use
• avoid drinking alcohol while taking naltrexone

If you or someone you know experiences adverse effects after taking naltrexone, contact your doctor right away.

Medical Conditions That Affect Naltrexone Use

Certain medical conditions can make naltrexone unsafe or require special monitoring during treatment. People with liver disease or hepatitis should use naltrexone with extreme caution or avoid it entirely, as the medication is processed through the liver and can cause liver damage at higher doses. Before starting naltrexone, doctors typically order liver function tests to check for existing problems. Anyone with liver issues needs regular monitoring or alternative treatment options.

Other conditions affecting naltrexone use include kidney disease, which impacts how the body processes the medication, and bleeding disorders, particularly for Vivitrol injections. People with depression or suicidal thoughts history need close monitoring, as some patients report worsening mood symptoms. Anyone currently taking opioid pain medication should not start naltrexone until they’ve been opioid-free for at least seven to ten days, as it will block pain relief and trigger severe withdrawal.

What To Do If You Need Pain Relief While Taking Naltrexone

Managing pain while taking naltrexone presents challenges because the medication blocks opioid pain medications. If you experience an injury, dental procedure, or other situation requiring pain management, inform all healthcare providers immediately that you’re taking naltrexone. For minor pain, non-opioid options like acetaminophen (Tylenol), ibuprofen (Advil), or naproxen (Aleve) work effectively and don’t interact with naltrexone.

For severe pain, doctors may need higher opioid doses to overcome naltrexone’s blocking effects (increasing overdose risk) or wait for naltrexone to clear your system. In emergencies requiring surgery, medical staff can use non-opioid pain management like nerve blocks, regional anesthesia, IV ketamine, or other methods. Some doctors may temporarily discontinue naltrexone for planned surgery.

Find Drug Or Alcohol Treatment Today

Naltrexone is a medication that can help reduce the desire to drink alcohol and prevent opioid cravings, including urges to use heroin. If you or a loved one are trying to find addiction treatment, reach out to the Substance Abuse and Mental Health Services Administration (SAMHSA) or browse our directory.

Written by the Addiction Resource Editorial Staff