Naltrexone Liver Effects: How Metabolism, Dosage and Pre-Existing Conditions Impact Liver Function

Naltrexone’s effect on liver function is usually not a concern for the vast majority of patients. However, because of how naltrexone is processed by the liver there’s a very low risk for people with certain pre-existing conditions.

What You’ll Learn:

• How naltrexone medication is processed by the liver.
• The possible naltrexone liver contraindications.
• How the naltrexone dose level plays a role. 
• The actual likelihood of liver damage.
• Who is susceptible to naltrexone liver side effects.
• Ways to monitor and test liver function before and during naltrexone treatment.

One reason that prescription naltrexone is a first-line alcohol use treatment is because, in addition to being effective, it’s well-tolerated by the vast majority of people and there’s a low risk of side effects. The only real concern that clinicians have when prescribing naltrexone is its hepatotoxic potential.  

Naltrexone is generally considered safe for the liver at standard therapeutic doses, but certain people have to be careful because of the way that the medication is processed.

How Naltrexone Medication is Processed by the Liver

Is naltrexone bad for liver function? Naltrexone side effects on the liver are possible for certain individuals with pre-existing conditions, but it’s very rare. 

Naltrexone undergoes first-pass hepatic metabolism, which means it is processed by the liver soon after ingestion. This exposes the liver to high concentrations of naltrexone as it metabolizes the medication into the active metabolite 6-β-naltrexol. 

This is why naltrexone is potentially hepatotoxic. When a substance is hepatotoxic it could cause liver damage and inflammation that impedes function and can lead to liver disease.

Interestingly, alcohol is also hepatotoxic. It’s a toxin that is processed by the liver, damaging liver cells, creating inflammation and eventually tissue scarring in the liver known as cirrhosis. 

For people with liver concerns who are taking naltrexone for alcohol use, there’s a risk-benefit assessment. You have to consider that:

• Alcohol is far more hepatotoxic than naltrexone.
• Naltrexone may reduce drinking, thereby improving liver outcomes overall.

This clinical trade-off means that naltrexone can still be beneficial when patients have mild to moderate liver issues.

How the Naltrexone Dose Level Plays a Role

As with other side effects, naltrexone dosage plays a role in the likelihood of liver damage. Essentially, the higher the dose, the more concern there is with hepatotoxic potential. 

Studies have found that with naltrexone 50 mg tablets (the standard dose) there’s very low risk. Even upping the daily dose to 100 mg appears to be safe. It isn’t until the dosage reaches 300 mg a day that clinically significant liver injury has been observed. 

The Actual Likelihood of Liver Damage

Does naltrexone affect liver enzymes? Yes, but not always and sometimes the effect can be positive.

The overall incidence of liver damage from naltrexone is extremely low, especially when taken at the recommended standard dose. But some people will experience liver enzyme changes.

Approximately 1-10% of people taking naltrexone have mild AST and ALT liver enzyme elevations. Fortunately, the elevation is typically short-term and resolves without discontinuing naltrexone. It’s also an asymptomatic issue, so there shouldn’t be any discomfort or side effects to manage.

The Possible Naltrexone Liver Contraindications

There are absolute and relative contraindications associated with naltrexone use. Clinicians consider the contraindications whenever they are prescribing the medication. 

Absolute Naltrexone Liver Contraindications

Naltrexone is not recommended for people with:

• Acute hepatitis
• Liver failure
• Severe cirrhosis

The risk for liver damage is higher in the situations noted above. Also, someone with one of these conditions won’t be able to metabolize naltrexone properly.

Relative Naltrexone Liver Contraindications

Rather than ruling naltrexone out, clinicians will often prescribe it with close monitoring if a patient has:

• Moderate hepatic impairment
• Elevated baseline AST/ALT that’s < 3–5× upper limit of normal (ULN)
• Chronic liver disease

Anyone with one of these conditions should have regular liver function tests to ensure there are no adverse effects. 

Who is Susceptible to Naltrexone Liver Side Effects

There are certain high risk groups that need to be more cautious when taking naltrexone. They include:

Patients With Active Liver Disease

• Acute hepatitis (viral, alcoholic, drug-induced)
• Cirrhosis (especially decompensated)

These patients have reduced metabolic capacity and increased susceptibility.

Heavy Alcohol Users With Advanced Damage

• Ironically, naltrexone is used to treat alcohol use disorder
• But patients with advanced alcoholic hepatitis are at higher risk

Mild–moderate liver disease is often still acceptable with monitoring.

Patients Taking High Doses

• Hepatotoxicity is strongly dose-dependent
• High doses are rarely used clinically now

Patients on Other Hepatotoxic Medications

Examples of hepatotoxic medications include:

• Acetaminophen (high doses)
• Certain antibiotics
• Anticonvulsants

Combined exposure increases cumulative liver stress.

Patients With Metabolic Risk Factors

• Obesity
• Nonalcoholic fatty liver disease (NAFLD)
• Diabetes

These conditions can increase baseline liver vulnerability.

Testing Your Liver Function Before and During Naltrexone Treatment

If you’re in the small group of people who are concerned about contraindications, the best thing to do is test your liver function to get a better idea of how healthy it is. This also provides a valuable benchmark once naltrexone treatment starts that can be used to monitor how your liver is responding.

Before Starting Naltrexone

Measure your baseline metrics for:

• AST
• ALT
• Bilirubin
  

As long as everything looks good, proceed with the naltrexone treatment.

During Treatment

Once you’ve started taking prescription naltrexone you can gauge how your liver is handling the medication by testing liver function again at:

• 1 month
• 3 months
• Periodically thereafter as needed

Don’t be surprised if your liver enzyme markers actually improve after starting naltrexone treatment. Drinking less alcohol can improve liver function even while you’re taking naltrexone.

Signs You Need to Stop or Lower the Naltrexone Dose

The goal with the testing is to ensure safety. Since liver damage is asymptomatic at first, changing biomarkers are often the only early warning sign. You may need to lower the naltrexone dose or stop treatment if AST/ALT rise to:

• >3–5× ULN with symptoms, or
• >5× ULN without symptoms

Choose Health offers one of the most extensive at-home liver testing kits available today. You’ll be able to easily test liver function and track it over time to see how your health is improving. 

It’s also important to discuss naltrexone side effects on the liver with a knowledgeable clinician who can provide personalized recommendations. If you’re interested in discussing treatment options with a professional, take our Alcohol Use Assessment. It provides valuable information on your Audit-C score and is the first step in receiving a naltrexone online prescription.