Naltrexone Side Effects and What to Avoid
A plain guide to naltrexone side effects — usually mild nausea, headache, dizziness, and fatigue — plus the critical thing to avoid: opioids, and the overdose risk after the block wears off.
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Naltrexone Side Effects and the One Thing You Have to Avoid
Here is the plain answer most people are looking for. The most common naltrexone side effects are nausea, headache, dizziness, and fatigue, and they usually ease within the first few days to a couple of weeks. Most are mild, and most people who start naltrexone keep taking it. The side effect that actually matters is not on that list, though, and it is the reason this page exists: the most important thing to avoid is opioids.
That is the whole headline. Day to day, naltrexone is well tolerated. The real risk lives in what you mix it with and what happens if you stop, and an honest guide leads with that rather than burying it.
- Everyday naltrexone side effects are usually mild and short-lived—nausea, headache, dizziness, and tiredness that tend to fade as your body settles[1].
- The thing to avoid is opioids. While naltrexone is in your system, opioids will not work, and trying to overpower the block with a big dose can be fatal.
- After naltrexone wears off, your tolerance is low. Going back to your old opioid dose can kill you, so the safe path is staying opioid-free and keeping naloxone (Narcan) on hand[2].
This page covers the side effects worth knowing, whether naltrexone makes you sleepy, what to steer clear of, and how it treats your liver. For the full picture of how the medicine works and who it fits, start with the main guide on how naltrexone treats opioid addiction.
Common Naltrexone Side Effects
Most people tolerate naltrexone well, and when side effects do show up they are usually the mild, settle-down-on-their-own kind. They tend to be loudest in the first week or two and quieter after that.
The ones people notice most:
- Nausea or an upset stomach—the single most common complaint, and usually the first to fade. Taking the pill with food helps.
- Headache—common early, generally mild.
- Dizziness or lightheadedness—more likely when you stand up fast in the first few days.
- Fatigue or feeling sleepy—real but usually short-lived; more on that below.
- Trouble sleeping, low appetite, or anxiety—less common, and they tend to ease as you adjust.
If you get the monthly Vivitrol injection rather than the daily pill, add one more: soreness, swelling, or a small lump where the shot went in. That is normal and usually minor. What is not normal is severe pain, a hard knot, blistering, or an open sore at the site—call your provider if that happens.
The reassuring part is what the evidence shows about how well people stick with it. In a large analysis of naltrexone for alcohol dependence, side effects led to only a small share of people stopping the medicine, and most stayed on it[1]. The takeaway is simple: for most people the side effects are a brief nuisance, not a wall.
Does Naltrexone Make You Sleepy
Sometimes, yes—especially early on. Fatigue and drowsiness are recognized naltrexone side effects, and they show up most in the first days or weeks, then usually settle as your body gets used to the medicine. For most people the tiredness is mild and passes.
A few honest qualifiers, because the picture is rarely one thing:
- Early recovery is tiring on its own. Sleep, mood, and energy are often a mess in the first weeks off opioids, and it can be hard to tell what is the medicine and what is your body relearning how to rest.
- Low mood can look like fatigue. Feeling flat or worn down deserves attention in its own right, since untreated low mood is one of the most common reasons people quit treatment early. Tell your provider—pairing naltrexone with counseling or mental-health support is part of what makes it work.
Call your prescriber if the tiredness is heavy rather than mild, if it does not start lifting after the first couple of weeks, or if it comes with feeling down or hopeless. Those are worth a conversation, not a quiet exit from treatment.
Naltrexone is not a sedative and it carries no high of its own—there is nothing in it to feel buzzed or doped up on. So when tiredness shows up early, it is usually your body adjusting, not the medicine knocking you out. For most people it fades, and the steadiness that replaces it is the point.
What to Avoid When Taking Naltrexone
This is the part that matters most, so here it is straight. The number-one thing to avoid on naltrexone is opioids—heroin, fentanyl, oxycodone, hydrocodone, codeine, and the rest of the family.
Two reasons, and the second one can kill you:
- They will not work. Naltrexone is a opioid blocker that sits on the same receptors opioids need. Use on top of it and you get little or nothing—no high, no relief, just wasted money and risk.
- Trying to overpower the block can be fatal. Some people take more and more to “break through” the blockade. That is one of the most dangerous things you can do on naltrexone, because the dose it takes to override the block can be the dose that stops your breathing.
A few more things to clear with a provider before they catch you off guard:
- Be fully opioid-free before your first dose. Because naltrexone shoves opioids off their receptors, starting before you are clear sets off precipitated withdrawal—a fast, brutal version of being dope sick. The usual wait is 7 to 10 days, longer for fentanyl, which is why a medical detox is the safe on-ramp.
- Tell every provider you take it. Surgeons, dentists, and ER staff need to know, because standard opioid painkillers may not work on you. In a planned surgery, your team can choose non-opioid pain control. In an emergency, that information can change your whole treatment.
- Go easy on alcohol. Naltrexone is also used to treat alcohol use disorder, and it is not dangerous to mix the two the way opioids are. Still, both can stress the liver, so heavy drinking is worth avoiding.
Why the Real Danger Comes After Naltrexone Wears Off
Here is the safety point that too often goes unsaid, and it is the most important thing on this page after the warning above. The greatest risk with naltrexone is not a side effect of taking it. It is what can happen when you stop.
While you are on naltrexone and not using, your opioid tolerance falls. That is good—until someone stops the medicine and goes back to the dose that used to feel normal. The body that once handled that dose no longer can, and today’s supply is often laced with fentanyl, which is far stronger and far less forgiving. The dose that felt routine a month ago can now be the one that kills you[2].
That risk is real for everyone leaving a period of forced opioid abstinence, which is exactly why naltrexone is so useful at reentry from jail or prison—and exactly why the days around a missed shot demand care. A review of naltrexone in justice-involved people found it improved retention and reduced relapse, while underlining that release is a window of very high overdose risk because tolerance has dropped[3].
The point is not fear. It is the path: the safe move is to stay opioid-free, keep your doses on schedule, and keep naloxone within reach the way you keep a smoke detector. A missed dose is a reason to call your provider, not a reason to use.
Naltrexone and Your Liver
Naltrexone carries a long-standing caution about the liver, and it is worth understanding plainly rather than fearing. At the doses used to treat addiction, naltrexone is considered safe for the liver for most people. The warning comes from old studies that used very high doses for a different purpose, where liver enzymes rose; at standard treatment doses, that has not borne out as a common problem.
What that means in practice:
- You will usually get a baseline blood test before starting and sometimes a check later on. That liver panel is routine care, not a red flag about you.
- People with existing liver disease need a closer look. If you have hepatitis, cirrhosis, or another liver condition, naltrexone is not automatically off the table, but it is a conversation to have with a provider who knows your history.
- Stacking liver stressors is what to avoid—heavy drinking and certain other medications, for instance. This is one more reason to list everything you take and drink, so nothing piles up quietly.
Across the treatment-dose evidence, naltrexone is generally well tolerated, and the share of people who stop because of side effects is small[1][3]. The liver caution is a reason to monitor, not a reason to skip a medicine that can keep you alive. For the detail on how the drug lingers and clears, and how long the block lasts, learn how naltrexone treats opioid addiction.
Getting Help
If you are reading this far down a page about side effects, you are not looking for a reason to quit treatment—you are trying to do it right. Hold on to the plain version. The everyday side effects of naltrexone are usually mild and short-lived, and the one thing that truly matters is staying away from opioids while you are on it and after you stop. That is a rule you can live by, and a life that gets bigger from there.
You do not have to figure this out alone. A provider can walk you through whether naltrexone, buprenorphine (Suboxone), or another medicine fits your situation, and none of those choices is a failure. The path is more walkable than the fear makes it look.
When you are ready to find help near you, explore treatment centers →. For free, confidential help any time, call SAMHSA’s National Helpline at 1-800-662-HELP (4357). And if you or someone you love is in danger right now, call or text 988, or call 911 for a medical emergency—and keep naloxone close.
If any of this lands, the next step doesn’t have to be a big one. You can find treatment now and get matched with someone who can help you find the right care and take the next step. Reaching out today is a real step forward — and one you can make right now.
Frequently asked questions
How long do naltrexone side effects last?
For most people, not long. The common side effects—nausea, headache, dizziness, and fatigue—tend to be loudest in the first few days to two weeks and then ease as your body adjusts. Taking the pill with food helps with nausea. If a side effect is severe, or it is not starting to fade after a couple of weeks, call your provider rather than stopping on your own. In studies, only a small share of people stopped naltrexone because of side effects[1].
Does naltrexone affect the liver?
At the doses used to treat addiction, naltrexone is considered safe for the liver for most people. The caution comes from older studies using much higher doses, where liver enzymes rose. You will usually get a baseline blood test before starting, and people with existing liver disease need a closer look from their provider. The main thing to avoid is stacking liver stressors like heavy drinking. The liver warning is a reason to monitor, not a reason to skip an effective medicine that is well tolerated by most people[1].
Can you take painkillers while on naltrexone?
Standard opioid painkillers will not work while naltrexone is in your system, because it blocks the same receptors. For everyday aches, non-opioid options like acetaminophen or ibuprofen are fine. For surgery or a real injury, tell your care team you take naltrexone so they can plan non-opioid pain control or manage timing safely. In an emergency, that information can change your whole treatment, so wear a medical alert if you can and tell every doctor and dentist you take it.
What happens if you use opioids while on naltrexone?
Two things, and the second can kill you. First, the opioid will not work—naltrexone blocks the high and the pain relief, so you get little or nothing. Second, some people try to overpower the block with a large dose, which is one of the most dangerous things you can do on naltrexone, because the amount it takes to break through can stop your breathing. The risk is even higher after the medicine wears off, when your tolerance is low. Keep naloxone (Narcan) on hand and stay opioid-free[2].
Does naltrexone interact with alcohol?
Not in a dangerous way. Naltrexone is actually FDA-approved to treat alcohol use disorder, and mixing the two does not cause the kind of medical emergency that mixing opioids does. It does not make you sick if you drink, the way disulfiram (Antabuse) can. The reason to go easy on alcohol is that heavy drinking stresses the liver, and so can naltrexone at the margins, so it is worth avoiding while you are on the medicine.
Does naltrexone make you tired or sleepy?
It can, especially in the first days or weeks, and for most people the tiredness is mild and passes as the body adjusts. Naltrexone is not a sedative and has no high of its own, so early fatigue is usually your body settling rather than the medicine knocking you out. Early recovery is tiring on its own, and low mood can also look like fatigue. Call your provider if the tiredness is heavy, lasts beyond the first couple of weeks, or comes with feeling down.
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