Naltrexone does cause nausea in roughly one in three people, making it the most common side effect of the medication. Vomiting, diarrhea, and abdominal pain each affect 11% to 14% of users. These symptoms are usually mild and tend to fade as your body adjusts, but there’s a separate, more serious scenario where naltrexone can make you severely ill: if you take it while opioids are still in your system.
Common Stomach Side Effects
Nausea is by far the most frequently reported problem, hitting about 33% of people who take naltrexone. Vomiting occurs in around 14%, diarrhea in 13%, and abdominal pain in 11%. These gastrointestinal effects tend to be strongest after the first dose and generally diminish over the following days to weeks. Some people feel queasy for a few days and then adjust without any ongoing issues. Others find the nausea persistent enough that they stop the medication, though that’s less common.
Headache and fatigue are also frequently reported after the initial dose, whether you’re taking the daily pill or the monthly injection. These follow a similar pattern: worst at the start, then gradually improving.
How to Reduce Nausea
Starting at a lower dose is the most effective strategy for minimizing stomach problems. Rather than jumping straight to the standard 50 mg daily tablet, many prescribers recommend beginning at 12.5 mg (a quarter tablet) or 25 mg (a half tablet) for the first week or two, then gradually increasing. Taking the medication with food also helps. Women, younger patients, and those who haven’t been abstinent from alcohol for long tend to be more sensitive to side effects, so a slower ramp-up is especially useful for those groups.
In studies of adolescents taking naltrexone, only about 9% experienced nausea, and some who initially couldn’t tolerate it were able to restart the medication successfully on a second attempt. This suggests that timing, food intake, and starting dose all play a role in whether nausea becomes a dealbreaker.
Naltrexone Is Not Disulfiram
A common concern is whether drinking alcohol while on naltrexone will make you violently ill the way disulfiram (Antabuse) does. It won’t. Naltrexone works by blocking the receptors in your brain that produce the pleasurable buzz from alcohol or opioids. It doesn’t cause a punishing physical reaction when you drink. In a double-blind, placebo-controlled study published in JAMA Psychiatry, researchers found no significant difference in adverse effects between people taking naltrexone and those on placebo when both groups consumed alcohol.
What naltrexone does is make drinking feel less rewarding. You can still drink on it, but the “high” is blunted. That’s a very different mechanism from disulfiram, which causes intense flushing, nausea, and vomiting as a deliberate deterrent.
Precipitated Withdrawal: The Serious Risk
The scenario where naltrexone can make you genuinely, dangerously sick involves opioids. If you take naltrexone while opioids (including heroin, fentanyl, oxycodone, methadone, buprenorphine, or even tramadol) are still active in your body, it can trigger what’s called precipitated withdrawal. This isn’t ordinary nausea. It’s a rapid, severe withdrawal reaction that can hit within minutes.
In a study of 132 patients who experienced precipitated withdrawal, the symptoms were striking: 96% had severe agitation, nearly 39% had altered consciousness, 28% had nausea, 27% vomited, 24% had abdominal pain, and about 16% had bone and muscle pain. Rapid heart rate and dilated pupils were also common. This reaction requires emergency medical attention and is far more intense than the withdrawal someone would experience by simply stopping opioids on their own.
The reason is straightforward. Naltrexone is a powerful opioid receptor blocker. If opioids are sitting on those receptors when naltrexone arrives, it rips them off all at once, throwing the nervous system into immediate chaos. The effect is essentially compressed withdrawal, all happening in a very short window instead of over days.
Required Opioid-Free Period
To avoid precipitated withdrawal, you need to be completely free of opioids before your first dose. The recommended timeline, according to the Substance Abuse and Mental Health Services Administration, depends on what you were using:
- Short-acting opioids (heroin, oxycodone, hydrocodone, tramadol): 7 to 10 days opioid-free
- Long-acting opioids (methadone, buprenorphine): 10 to 14 days opioid-free
Your prescriber will typically verify your abstinence through a combination of your reported history, a physical exam, and sometimes a urine drug screen before giving you the first dose. Some clinicians also use a small test dose of naltrexone to check for any withdrawal reaction before prescribing the full amount.
Liver Concerns
You may have heard that naltrexone is hard on the liver. This concern traces back to studies in the 1980s where doses up to 300 mg per day (six times the standard dose) were linked to liver cell injury, which led the FDA to add a black box warning about liver damage. That warning was removed in 2013 after no cases of liver failure had been attributed to naltrexone at normal doses.
In the large COMBINE clinical trial, which included over 1,300 participants, only 0.9% had significant liver enzyme elevations while taking naltrexone at 100 mg per day (double the standard dose), and none developed serious liver disease. A separate study of nearly 3,000 VA patients with cirrhosis who started naltrexone found that liver enzymes actually decreased on average, and the 2% who had elevations at three months couldn’t be attributed to the medication.
Current guidelines still recommend caution if your liver enzymes are very elevated, and naltrexone isn’t typically the first choice for someone with acute alcoholic hepatitis. But for most people, including many with liver disease, it’s considered safe at the standard 50 mg dose.
Pill vs. Monthly Injection
Naltrexone comes in two forms: a daily 50 mg tablet and a monthly intramuscular injection (sold as Vivitrol). Both can cause nausea, headache, and fatigue, particularly around the first dose or first injection. The injection delivers the medication steadily over four weeks, so you can’t adjust the dose downward the way you can with tablets if side effects bother you. With the oral version, you have the flexibility to start low and increase gradually, which is why many prescribers begin patients on the pill before switching to the injection if adherence is a concern.
The injection can also cause soreness, hardness, or a lump at the injection site, which is unique to that form. For people who tolerate the oral version well, the transition to the injection is generally smooth.