The most important thing to avoid when taking naltrexone is any opioid, whether it’s a prescription painkiller, heroin, or even an opioid-based cough suppressant. But opioids aren’t the only concern. Several other medications, substances, and situations can cause problems while you’re on naltrexone, and some of them aren’t obvious.
Opioids and Opioid-Containing Medications
Naltrexone works by locking onto the same receptors in your brain that opioids use. If you take an opioid while naltrexone is occupying those receptors, one of two things happens, and both are dangerous.
If you’ve recently used opioids and then start naltrexone, the medication can rip opioids off those receptors all at once, triggering what’s called precipitated withdrawal. Unlike normal withdrawal that builds gradually, this hits within minutes: sweating, vomiting, diarrhea, severe anxiety, muscle aches, and chills, all arriving simultaneously. Because naltrexone is long-acting, these symptoms can take a full day or more to resolve. Precipitated withdrawal can also destabilize other health conditions, worsening blood pressure control, blood sugar regulation, or psychiatric symptoms like anxiety and depression.
The second danger goes the other direction. If you try to overpower naltrexone’s blockade by taking large amounts of opioids, you risk fatal overdose. The FDA label states this plainly: attempting to overcome the block by administering large amounts of heroin or other opioids “may lead to serious injury, coma, or death.” Your tolerance drops while on naltrexone, so the amount of opioid needed to feel high becomes dangerously close to the amount that stops your breathing.
This applies to all opioids, not just street drugs. Prescription painkillers like oxycodone and hydrocodone won’t work properly while you’re on naltrexone. Some cough syrups contain codeine. Even certain anti-diarrheal medications like loperamide (Imodium) work through opioid receptors in the gut. Animal research shows that opioid-blocking drugs completely destroy loperamide’s anti-diarrheal effect, so taking it while on naltrexone is essentially pointless. If you need relief from diarrhea, talk to your pharmacist about non-opioid alternatives.
Surgery and Emergency Pain Management
One of the most practical things to plan for on naltrexone is what happens if you need surgery or end up in an emergency room. Standard opioid pain medications won’t work while the drug is active in your system, which creates a real problem for anesthesiologists and emergency physicians.
For planned surgeries, the oral tablet needs to be stopped at least 72 hours before the procedure to allow it to clear your system. If you’re on the monthly injection, surgery should ideally be scheduled at least four weeks after your last shot. This requires coordination between your prescriber and your surgical team, so bring it up early when scheduling any procedure.
Emergencies are trickier because you can’t plan for them. The American Academy of Family Physicians recommends several layers of preparation. Set up a medical ID on your smartphone that lists naltrexone. Carry a wallet-sized medication information card. Consider wearing a medical alert bracelet. Tell your emergency contacts about naltrexone so they can inform paramedics or ER staff if you’re unable to speak. If medical professionals don’t know you’re on an opioid blocker, they may waste critical time trying pain medications that won’t work, or they may need to use much higher doses with careful monitoring.
Heavy Alcohol Use and Liver Strain
Naltrexone is commonly prescribed specifically to help reduce drinking, so alcohol itself isn’t strictly off-limits. In fact, the largest safety study of naltrexone in people with alcohol use disorder, covering 570 patients on the medication, found no new safety concerns and no deaths. Many people drink while on naltrexone as part of a gradual reduction approach.
The bigger concern is your liver. Naltrexone is processed through the liver, and heavy drinking already taxes that organ. Studies from the 1980s linked high-dose naltrexone (up to 300 mg per day, six times the standard dose) to liver cell damage. This led the FDA to issue a prominent warning about liver toxicity. The FDA removed that warning in 2013 after finding no known cases of liver failure at normal doses, but monitoring is still standard practice.
Your doctor will typically check liver enzymes within a few weeks of starting naltrexone and then every six months going forward. In one large clinical trial, about 1.8% of patients on naltrexone developed significantly elevated liver enzymes, but levels returned to normal after stopping the medication. If you have active liver disease or acute hepatitis, naltrexone may not be appropriate for you, though mild to moderate liver enzyme elevations alone aren’t necessarily a barrier.
Mood Changes to Watch For
Early studies reported that naltrexone could cause low mood or a flat emotional state, which raised concerns about prescribing it to people with depression. The picture has gotten clearer since then. A large naturalistic study found that only 1.4% of patients on naltrexone reported new depressive symptoms, nearly identical to the 1.7% rate in people not taking the drug. A recent review of clinical evidence concluded that naltrexone does not produce mood problems as a serious side effect, and that depression should not be considered a reason to avoid the medication.
That said, people with severe major depression or high suicide risk were excluded from most clinical trials, so the safety data in that specific group is limited. If you have a history of depression, naltrexone is generally still considered safe, but it’s worth paying attention to your mood in the first few weeks and letting your prescriber know if something feels off.
Quick Reference: What to Avoid
- All opioid medications, including prescription painkillers, codeine cough syrups, and opioid-based anti-diarrheal drugs like loperamide
- Starting naltrexone too soon after your last opioid use, which risks precipitated withdrawal
- Attempting to “push through” the opioid block with higher doses, which risks fatal overdose
- Scheduling surgery without informing your surgical team (stop oral naltrexone at least 72 hours prior, or the injection at least 4 weeks prior)
- Going without medical identification that lists naltrexone for emergency situations
- Ignoring liver monitoring, especially if you’re still drinking or have a history of liver problems