Naltrexone’s most important drug interaction is with opioids. Because naltrexone blocks opioid receptors, it cancels the effect of opioid medicines and can trigger withdrawal if opioids are still in your body. It interacts with a few other medicines too. Always give your provider a full list of everything you take, including over-the-counter products and supplements.
What is the main naltrexone interaction?
The main interaction is with opioids. Naltrexone sits on the same receptors that opioids use, and it blocks them. This has two effects. First, any opioid you take will have little or no effect, so opioid painkillers will not relieve pain and will not produce a high. Second, if opioids are still in your body when naltrexone is started, the medication can force them off the receptors and cause a fast, intense withdrawal known as precipitated withdrawal.
This applies to all opioids, including oxycodone, hydrocodone, morphine, codeine, tramadol, fentanyl, methadone, buprenorphine, and heroin. To start naltrexone safely, you need to be opioid-free first, usually for 7 to 10 days.
Opioid-containing medicines to watch for
Some common medicines contain opioids even when it is not obvious. Prescription cough syrups often contain codeine or hydrocodone. Some anti-diarrhea products contain diphenoxylate or loperamide. A few cold and flu combination products include an opioid cough suppressant. On naltrexone, these will not work the way they normally do, and they are best avoided unless your provider clears them. If you are unsure, ask a pharmacist whether a product contains an opioid.
Other medications that interact with naltrexone
A handful of non-opioid medicines can also interact. Thioridazine, an older antipsychotic, can cause more drowsiness and sluggishness when combined with naltrexone. Disulfiram (Antabuse), another alcohol medication, can stress the liver, and since naltrexone is processed by the liver too, the two are combined only with careful monitoring. The Vivitrol injection label also notes a possible interaction with yohimbine, a supplement, which may increase anxiety and other reactions. Your provider will weigh these before prescribing.
Does naltrexone interact with alcohol?
Naltrexone does not have a dangerous interaction with alcohol. Unlike disulfiram, it will not make you sick if you drink. Instead, it blocks the reward you get from drinking, which is exactly how it helps. You will not have a flushing or vomiting reaction. The only caution is common sense: naltrexone is meant to help you cut back, and heavy drinking remains harmful to your health regardless of the medication.
Supplements and over-the-counter products
Most vitamins and supplements are fine with naltrexone, but a few, like yohimbine, can interact. Over-the-counter cough, cold, and anti-diarrhea products are the ones to watch, because some contain opioids. The safest habit is to give your provider and pharmacist a full list of everything you take, including things you would not think of as medicine, so they can flag anything that matters.
Naltrexone interactions at a glance
| Drug or substance | What happens | What to do |
|---|---|---|
| Opioid painkillers, heroin, methadone, buprenorphine | Blocked by naltrexone; can cause sudden withdrawal | Avoid; be opioid-free 7 to 10 days before starting |
| Opioid cough, cold, and diarrhea medicines | Contain hidden opioids; will not work as intended | Avoid unless your provider approves |
| Thioridazine | More drowsiness and sluggishness | Tell your provider; may need monitoring |
| Disulfiram (Antabuse) | Added stress on the liver | Combine only with close monitoring |
| Yohimbine (with Vivitrol) | Possible increased anxiety and reactions | Avoid unless cleared |
| Alcohol | No dangerous reaction; reward is blunted | Safe to take, but avoid heavy drinking |
See also our naltrexone for alcohol guide, what to avoid on naltrexone, and naltrexone side effects.
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No spam. We will only email you about naltrexone for alcohol at Recovery Delivered.Frequently asked questions
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Does naltrexone interact with antidepressants?
Daniel R. Karlin, MD, MA
Board-certified psychiatrist and addiction medicine specialist. Author of 21+ peer-reviewed publications (1,355 citations) including recent work in JAMA (2025) and the British Journal of Psychiatry (2023).
- Sources. U.S. Food and Drug Administration. Prescribing information for naltrexone (ReVia) and naltrexone extended-release injectable (Vivitrol), including drug interaction sections.
- Singh D, Saadabadi A. Naltrexone. StatPearls. National Library of Medicine.
This page is for education only and is not medical advice. Naltrexone is a prescription medication. Talk with a licensed provider about your specific medications before starting.
