Naltrexone Drug Interactions: What to Avoid and What to Tell Your Doctor

Naltrexone is generally considered a safe medication with a favorable interaction profile compared to many other drugs. But it does have important interactions — especially with opioids — that every patient taking it must understand. Being informed about these interactions could, in certain situations, be life-saving.

This guide covers naltrexone's most important drug interactions, what symptoms to watch for, and what information to share with every healthcare provider you see while on naltrexone.

The Most Important Interaction: Opioids (Major — Avoid)

The most critical interaction with naltrexone is with all opioid medications. Naltrexone blocks opioid receptors, so:

Starting naltrexone while on opioids: This causes precipitated opioid withdrawal — a sudden, severe withdrawal reaction. Symptoms include severe cramping, vomiting, diarrhea, muscle aches, agitation, and sweating. This can be severe enough to require hospitalization. Never start naltrexone until you have been opioid-free for at least 7-10 days.

Taking opioids for pain while on naltrexone: Opioid pain medications (oxycodone, hydrocodone, morphine, codeine, tramadol) will not work at standard doses because naltrexone blocks the receptors. In emergency situations where opioid analgesia is absolutely necessary, very high doses may be required — which increases the risk of respiratory depression. Alert all treating providers and emergency room staff that you take naltrexone.

Taking opioids to override the blockade: Attempting to overcome naltrexone's block by taking very large amounts of opioids is extremely dangerous and can cause overdose, coma, and death. Never attempt this.

Opioid-containing medications to be aware of (including unexpected sources):

Prescription pain medications: oxycodone (OxyContin, Percocet), hydrocodone (Vicodin), morphine, codeine, fentanyl, tramadol

Cough medications containing codeine (some prescription cough syrups)

Diarrhea medication: loperamide (Imodium) — technically an opioid-class drug, though it doesn't cross the blood-brain barrier at standard doses

OUD medications: methadone, buprenorphine (Suboxone, Sublocade) — cannot be taken with naltrexone

Thioridazine — Avoid

Thioridazine is an antipsychotic medication. When combined with naltrexone, cases of excessive lethargy and somnolence (extreme drowsiness) have been reported. This combination should be avoided. If you take thioridazine or any antipsychotic medication, tell your naltrexone prescriber.

Disulfiram (Antabuse) — Use With Caution

Both naltrexone and disulfiram (Antabuse) can cause liver damage. Taking both together increases the risk of hepatotoxicity. Combining them is generally not recommended unless your provider determines the benefit clearly outweighs the risk. If you take both, your liver function will need to be monitored closely.

Bremelanotide (Vyleesi) — Avoid

Bremelanotide is a medication for hypoactive sexual desire disorder (HSDD) in women. It slows gastric emptying, which can reduce the rate and extent of absorption of oral naltrexone. The FDA recommends avoiding this combination when naltrexone is being used to treat AUD or OUD, due to the risk of treatment failure.

Acamprosate — Monitor (Minor Interaction)

Naltrexone increases blood levels of acamprosate (Campral), which is sometimes used together with naltrexone for AUD. This interaction is generally minor and no dose adjustment is typically required, but your provider should be aware of it. Taking both medications is sometimes done intentionally to combine their complementary mechanisms of action.

Lofexidine (Lucemyra) — Modify Therapy

Lofexidine is used to manage opioid withdrawal symptoms. Research shows it can reduce naltrexone blood levels when taken within 2 hours of oral naltrexone. If you need to take both, space the doses appropriately and inform your provider.

Antidepressants — Generally Safe, Monitor

Most antidepressants (SSRIs, SNRIs, tricyclics) are considered generally safe to take with naltrexone. Some studies have even suggested naltrexone may enhance antidepressant effectiveness in some patients. However, as with any combination of psychiatric medications, your prescriber should be informed and monitor for any unusual side effects.

Cannabinoids (Cannabis/THC) — Monitor

Naltrexone may enhance the effects of cannabinoids (dronabinol, THC). There are also anecdotal reports that naltrexone can reduce or heighten the effects of cannabis in different individuals. If you use medical cannabis, notify your prescriber so any interactions can be monitored.

What to Tell Every Healthcare Provider

Because naltrexone blocks opioid pain medications from working, it is critical that all healthcare providers know you are taking it. Tell:

Your primary care physician and all specialists

Your dentist (dental procedures often use opioid pain medications)

Anesthesiologists before any surgery — opioid anesthetics may not work, and alternative anesthesia methods will need to be used

Emergency room staff — carry a medical alert card if possible

Your pharmacist every time you fill a new prescription

Food and Supplement Interactions

There are no known significant interactions between naltrexone and food. There are also no known interactions with alcohol from a pharmaceutical standpoint (though alcohol use defeats the purpose of taking naltrexone for AUD).

Supplements: Kratom (mitragynine) interacts with opioid receptors and may interact with naltrexone. St. John's Wort and immune-modulating herbs should be discussed with your provider. Always tell your provider about all supplements you take.

Also see: Naltrexone Side Effects: What to Expect and When to Call Your Doctor for a complete list of adverse effects to monitor.

Having trouble finding naltrexone? medfinder.com calls pharmacies near you to find which ones have it in stock.