Naltrexone and Your Liver: What Liver Tests Show at the Usual Dose

The liver warning started with 300 mg a day

In a placebo-controlled study, people with obesity took 300 mg of naltrexone a day (the usual dose is 50 mg). After 3 to 8 weeks, 5 of 26 (19%) had raised liver enzymes, against 0 of 24 on placebo. Their peak ALT was 3 to 19 times their own starting level. Most had no symptoms, and in everyone who was followed up, levels returned to or toward baseline within weeks.¹

The 2010 box explained the worry: "The margin of separation between the apparently safe dose of naltrexone and the dose causing hepatic injury appears to be only five-fold or less." The same box said Vivitrol did not appear to be a liver toxin at the recommended dose.⁸

The current warning covers hepatitis seen with naltrexone in trials and after approval. When enzymes were high, another possible cause (alcohol-related liver disease, hepatitis B or C, other drugs) was often found, and single doses above 50 mg may carry a higher risk.¹ Sudden withdrawal set off by naltrexone may also injure the liver.^1,11

At usual doses, liver injury is rare

LiverTox, the National Institutes of Health database on drug-caused liver injury, last updated its naltrexone entry in March 2020. It reports liver-enzyme rises above 3 times the upper limit of normal in about 1% of people, and several studies found ALT rises as often on placebo. Most rises were mild and settled, even when the drug was continued. It rates naltrexone E*, a suspected but unproven cause. In its words, "naltrexone has not been definitively linked to cases of clinically apparent liver injury."²

• US liver-injury registry (DILIN), 2004 to 2024. Of 1,975 cases judged at least probably caused by a drug, 13 involved alcohol use disorder medicines: 11 disulfiram, 1 naltrexone (a woman taking 4.5 mg of low-dose naltrexone; mild, resolved), 1 baclofen and none acamprosate. Three disulfiram cases ended in a liver transplant or death.⁶
• A 570-person open-label study in alcohol treatment centers (not randomized) found liver tests on naltrexone similar to a comparison group that did not take it.¹²
• Vivitrol's alcohol trials. AST rose in 1.5% on the shot and 1.5% on tablets, against 0.9% on placebo.¹¹

The exception in the Vivitrol label is a 6-month opioid trial in which 89% of people had hepatitis C. Rises above 3 times the upper limit of normal were more common on the shot (20% vs 13% on placebo).¹¹ How naltrexone compares with disulfiram overall is on naltrexone vs disulfiram.

Which liver tests to expect, and when

The current tablet label tells prescribers to warn patients about liver injury, but it gives no timetable for blood tests. Its precautions section on laboratory tests covers only urine drug screens.¹

Reading ALT, AST and GGT results

• ALT is an enzyme found mainly in the liver. Damaged liver cells release it into the blood.¹⁵
• AST is found in the liver but also in the heart and muscles, so it is less specific to the liver.¹⁶
• GGT rises with drinking, and most people with alcohol use disorder have high levels.¹⁷
• "Times the upper limit of normal" compares your result with the top of the lab's normal range. Studies on this page flagged AST or ALT above 3 or 5 times that limit; the VA study also counted ALP above 2 times.^2,4,5

A high result does not always mean a condition that needs treatment. Age, weight, some medicines and supplements, and hard exercise can all affect ALT.¹⁵

In a study of 2,940 US veterans with cirrhosis who started naltrexone, 2% had a large rise in liver tests (AST, ALT or ALP) within 3 months. A cause other than naltrexone was found in 77% of them, and 60% were intoxicated when the blood was drawn. No case was rated as possibly or probably caused by the drug. Median AST and ALT went down slightly after starting.⁴

A frequent cut-off, AST or ALT more than 5 times the upper limit, "emerged from prior hepatotoxicity concerns and clinical trial inclusion criteria" without specific evidence, according to a 2025 review in the Journal of Hospital Medicine.⁵

Cirrhosis raises naltrexone levels; studies found no drug-caused liver injury

In cirrhosis, the amount of naltrexone in the blood is about 5 times higher when the cirrhosis is compensated (stable) and about 10 times higher when it is decompensated, the stage when the liver starts to fail. The label adds that adequate studies in severe liver impairment have not been done.¹

Child-Pugh is a score of liver disease severity: class A is mild, B moderate and C severe.^5,11 The gaps are at the severe end. The VA study was 96% men, and the 2026 trial enrolled only compensated cirrhosis.^4,18 As of a 2025 review, no study had examined naltrexone's safety in acute alcoholic hepatitis.⁵

Guidelines advise against it in liver failure but differ on cirrhosis

Guidelines agree on liver failure and acute hepatitis and differ on cirrhosis:

The AASLD guidance came out before the 2022 to 2026 cirrhosis studies above.

The monthly shot skips the first pass through the liver

Vivitrol, the 380 mg monthly shot, carries the same hepatotoxicity warning as the tablets.¹¹ Because it goes into muscle, it skips the first pass through the liver, so the body makes less of naltrexone's main breakdown product, 6β-naltrexol.^1,11 Its levels are not changed in mild or moderate liver impairment (Child-Pugh A or B), and it was not studied in severe impairment.¹¹

A 2025 case series of 14 people with alcohol-related liver disease found no liver toxicity over a median of 127 days.²³ The VA cirrhosis study had too few shot users to judge it separately.⁴

Low-dose naltrexone and the one registry case

The only naltrexone case in the 20-year US liver-injury registry was a woman taking 4.5 mg a day of low-dose naltrexone (LDN). Her ALT was 730 U/L when the injury was found 8 days after starting. She had no symptoms and recovered fully within a week of stopping. She had known fatty liver. The case was rated as probably caused by naltrexone and mild.⁶ LDN trial data on side effects are on low-dose naltrexone side effects.

Call your prescriber about signs of liver trouble

Call your prescriber about¹¹:

• stomach-area pain that lasts more than a few days
• dark urine
• yellowing of the whites of your eyes
• tiredness

The label tells prescribers to stop naltrexone if signs of acute hepatitis appear.¹ If you use opioids, also know the overdose risk after stopping or missing doses: see the opioid warnings.

Your experience: Did liver tests change your naltrexone plans? Tell us how it went, or read other people's naltrexone reviews.

Programs that prescribe naltrexone

To compare online programs that prescribe naltrexone for alcohol, with posted prices, see where to get naltrexone online. Whoever prescribes, tell them about any liver disease, hepatitis and recent liver test results before the first dose.

How we checked

• Labels: current tablet and Vivitrol labels (May 2026), the 2010 and July 2013 Vivitrol labels with FDA's 2013 approval letter, FDA's 2013 ReVia notice, and the SAMHSA advisory table (PDF).^1,3,8-11,13
• Full texts: LiverTox, DILIN, the VA, records and case-series studies, and the ACG, AASLD and J Hosp Med papers. Abstracts only: NAL-CI, the AGA review and the 570-person study.^{2,4-6,12,18,19,21-24}
• Not used: a COMBINE enzyme figure that two reviews report differently.^5,6