What to Avoid When Taking Naltrexone

Taking low-dose naltrexone (LDN) for pain or an autoimmune condition? The evidence differs at low doses; see what to avoid on low-dose naltrexone. Shot-specific advice, such as driving after an injection, is on Vivitrol side effects.

Naltrexone interactions, from opioids to coffee

No listed interaction means the current labels name none. For most pairs no one has run a study, so it is not a finding of safety. Bring a full list of your medicines, vitamins and herbal supplements to the prescriber.²

Why the label's list is so short

The tablet label states that interaction studies with drugs other than opioids "have not been performed," and advises caution whenever another drug is needed.¹ Beyond opioids, it names only disulfiram and thioridazine; the Vivitrol label names opioid-containing medicines alone. Naltrexone is not processed by the liver's main drug-handling (CYP) enzymes and does not block or boost them in lab tests, so drugs that change those enzymes are unlikely to change naltrexone levels.² A 2018 review of interactions among alcohol-treatment drugs rated naltrexone relatively safe, apart from withdrawal when it meets an opioid.¹⁸

Until October 2013 the tablet label carried a boxed warning about liver injury; FDA removed it that year.¹⁹ The current label keeps a liver warning but names no painkiller other than opioids.¹

Opioids may not work, and forcing them through is dangerous

Naltrexone sits on opioid receptors and blocks them. While the block lasts:

• Opioid medicines may give little relief. For pain care in an emergency, see the box below.¹
• Overriding the block can kill. Taking large amounts of heroin or another opioid to get past it can cause serious injury, coma or death.¹
• Opioids already in your body set off withdrawal. Sudden (precipitated) withdrawal usually starts within 5 minutes of a tablet and can last up to 48 hours; some people have needed intensive care.¹ Timing and treatment are on sudden (precipitated) withdrawal; symptoms are on opioid reactions on naltrexone.

After you stop, or when a dose is late, tolerance is lower and an opioid dose you once took can cause an overdose. Both labels ask prescribers to discuss keeping naloxone or nalmefene on hand.^1,2

Cough syrups, diarrhea pills and kratom can contain opioids

Cough and cold medicines. Vivitrol's Medication Guide asks you to tell your provider about any you take.² Check the active ingredients, or ask a pharmacist.

Diarrhea medicines. Lomotil contains diphenoxylate, which its label describes as chemically related to the opioid painkiller meperidine; naloxone is the treatment for its overdose.⁸ Loperamide (Imodium) is "a mu-opioid agonist" that binds opioid receptors in the gut wall.¹⁰ If loperamide seems not to work, ask before taking more: doses above the recommended amount have caused dangerous heart rhythms.¹⁰

Kratom. FDA says kratom is not lawfully marketed in the US as a drug or a dietary supplement, and that its main compounds bind the same brain receptors as opioid drugs.⁵ In one case report, a 56-year-old man with heavy daily kratom use took his first 50 mg tablet, prescribed for weight loss, and spent 48 hours in intensive care with withdrawal that lasted about 36 hours.⁶ A second report describes withdrawal after a naltrexone injection in a kratom user.⁷ Tell your prescriber about kratom before the first dose.

For pain, non-opioid painkillers are the first option

SAMHSA's 2021 advisory on alcohol-use-disorder medicines says people taking naltrexone may use non-opioid painkillers such as acetaminophen, aspirin and ibuprofen for mild pain.¹¹

The warnings that matter are on the painkillers' own packages. Acetaminophen (Tylenol) can cause severe liver damage above 4,000 mg in 24 hours, when combined with other acetaminophen products, or with 3 or more alcoholic drinks a day; its label says to ask a doctor first if you have liver disease.³ Ibuprofen (Advil) and aspirin are NSAIDs, which can cause severe stomach bleeding, more likely with 3 or more drinks a day; ask first if you have cirrhosis or kidney disease.⁴ That matters on naltrexone, which is prescribed for alcohol dependence.

Starting after Suboxone, methadone or pain pills takes 7 days or more

You need to be off all opioids, including opioid-containing medicines, for at least 7 to 10 days before the first tablet. After buprenorphine (Suboxone) or methadone, withdrawal can still be set off for up to 2 weeks.¹ The Vivitrol Medication Guide gives 7 to 14 days before a first shot.² This applies to people starting naltrexone for alcohol as well. Precipitated withdrawal has happened when the prescriber did not know about recent opioid use.¹ How the switch is timed is explained on switching from Suboxone to naltrexone.

Alcohol does not trigger a reaction

Naltrexone does not cause a disulfiram-like reaction when you drink, and treating alcohol dependence is one of its two approved uses. It can cause dizziness, so the label advises against driving until you know how it affects you.¹ SAMHSA's naltrexone page, in its section on opioid use disorder, says patients taking naltrexone should not drink alcohol or take sedatives or tranquilizers; the drug labels list no reaction with alcohol, and your prescriber can say what applies to you.^1,16 Drinking on naltrexone has its own page, naltrexone and alcohol.

Antidepressants, gabapentin and benzodiazepines

None of these appear in either label's interaction list.^1,2 Several have been given with naltrexone on purpose in trials of treatment, not of interactions.

Antidepressants. In a 14-week trial of 170 people with depression and alcohol dependence, 42 took sertraline (200 mg a day) with naltrexone (100 mg a day; the usual dose is 50 mg). Serious adverse events were reported in 11.9% of that group, fewer than in the other three groups; across the trial the rate was 25.9%.^1,12 In a 12-week trial, 138 depressed adults with alcohol dependence all took naltrexone and were randomly assigned citalopram or placebo on top; both medicines were reasonably well tolerated.¹³ Bupropion is the other half of Contrave, which should not be added to naltrexone you already take.⁹ See Wellbutrin and naltrexone.

Gabapentin. In a 16-week trial of 150 people with alcohol dependence, 50 took naltrexone 50 mg a day plus gabapentin, up to 1,200 mg a day, for the first 6 weeks.¹⁴ The trials of gabapentin for alcohol on its own are summarized on our medicines page.

Benzodiazepines. The tablet label's emergency pain plan includes sedation with a benzodiazepine.¹ These drugs carry their own boxed warning: with opioids, they can cause profound sedation, slowed breathing, coma and death. Their label also warns against drinking alcohol with them.¹⁵ That matters most for anyone tempted to override the block with opioids.

Stimulants, cannabis and caffeine. The labels name no interaction with stimulants such as Adderall and set no food or caffeine rules.^1,2 In a lab study of 51 daily cannabis smokers, the 23 given naltrexone 50 mg for 16 days chose to smoke less active cannabis and rated its "good effect" lower than the placebo group. They also reported more stomach upset and headaches.¹⁷

Disulfiram and thioridazine need a prescriber's go-ahead; Contrave doubles up

Disulfiram (Antabuse). The safety of taking it with naltrexone is unknown, and combining two drugs that can harm the liver is "not ordinarily recommended unless the probable benefits outweigh the known risks."¹ Trials of the pair are on naltrexone vs disulfiram.

Thioridazine. Lethargy and sleepiness have been reported with naltrexone plus thioridazine.¹ Thioridazine is an antipsychotic reserved for schizophrenia that has not responded to other drugs.²⁰

Contrave. Contrave already contains naltrexone (with bupropion), so taking it with other naltrexone products is not recommended.⁹

With liver disease, ask about every other medicine

If you have liver disease, ask before adding any medicine or supplement, acetaminophen included; other drugs were among the causes found when liver enzymes rose on naltrexone.¹ Kratom has also been linked to liver inflammation.⁷ Which liver tests to expect is covered on naltrexone and your liver.

Feeling strange in the first week? Side effect or hidden opioid

In a study of about 570 people taking naltrexone for alcohol, 10% had new nausea, 7% headache and 4% dizziness.¹ A small fraction get a withdrawal-like mix of tearfulness, mild nausea, cramps, restlessness, joint or muscle aches and nasal symptoms. That may mean an opioid you didn't know you were taking, such as kratom or a cough medicine, or it may come from naltrexone itself.¹ Vomiting, diarrhea, confusion or hallucinations soon after a dose point to precipitated withdrawal and need urgent care.¹ Rates and timing are on naltrexone side effects.

Your experience: If you take naltrexone, you can share your story on our naltrexone reviews page.

How we checked

• Read on October 17, 2026: the current naltrexone tablet and Vivitrol labels, FDA's 2013 ReVia labeling notice, SAMHSA's 2021 advisory and naltrexone page, and the Imodium, Lomotil, thioridazine, Xanax, Tylenol and Advil labels.
• Read as abstracts only: the trials and the 2018 review. The Jarka kratom case was read in full.