From the FDA Drug Label
When patients presented with elevated transaminases, there were often other potential causative or contributory etiologies identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs In a placebo controlled study in which naltrexone hydrochloride was administered to obese subjects at a dose approximately five-fold that recommended for the blockade of opiate receptors (300 mg per day), 19% (5/26) of naltrexone hydrochloride recipients and 0% (0/24) of placebo-treated patients developed elevations of serum transaminases (i.e., peak ALT values ranging from 121 to 532; or 3 to 19 times their baseline values) after three to eight weeks of treatment.
The threshold for initiating naltrexone therapy regarding transaminitis (elevated liver enzymes) is not explicitly stated in the provided drug labels. However, it is mentioned that transaminase elevations occurred in patients receiving naltrexone hydrochloride, with peak ALT values ranging from 121 to 532, or 3 to 19 times their baseline values 1 1.
- Key points:
- No specific threshold is provided for initiating naltrexone therapy.
- Transaminase elevations have been observed in patients receiving naltrexone hydrochloride.
- Patients should be warned of the risk of hepatic injury and advised to seek medical attention if they experience symptoms of acute hepatitis.
- Use of naltrexone hydrochloride should be discontinued in the event of symptoms and/or signs of acute hepatitis.
From the Research
Naltrexone can be initiated when liver enzymes (transaminases) are less than 3-5 times the upper limit of normal (ULN). For patients with mild to moderate elevations below this threshold, naltrexone can generally be started with appropriate monitoring. The standard starting dose is 25-50 mg daily for oral naltrexone. Before initiating therapy, baseline liver function tests should be obtained, with follow-up testing recommended at 1 month after starting treatment and periodically thereafter. Caution is warranted in patients with existing liver disease, as naltrexone is metabolized by the liver and has been associated with hepatotoxicity at higher doses. If a patient develops transaminitis while on naltrexone, the medication should be discontinued if ALT/AST levels exceed 3-5 times ULN or if the patient develops symptoms of liver injury such as jaundice, abdominal pain, or fatigue. The concern with naltrexone-induced liver injury stems from its hepatic metabolism, which can produce potentially toxic metabolites in some individuals, particularly at doses higher than those typically used for alcohol or opioid use disorders 2.
Key Considerations
- Naltrexone is safe to use in patients with underlying liver disease, including those with compensated cirrhosis, as shown in a retrospective cohort study published in 2022 2.
- The study found that naltrexone hepatic safety was determined by liver enzyme changes during and after compared to before naltrexone prescription, with lower adjusted mean aspartate aminotransferase and alanine aminotransferase levels after versus before naltrexone prescription (p < 0.001) 2.
- However, caution is still necessary, and patients should be monitored closely for signs of liver injury, particularly those with pre-existing liver disease.
- Other studies, such as those on oxandrolone-treated adult burn patients and buprenorphine-naloxone treatment in opioid dependence, have also investigated the risk of liver enzyme elevation, but the most relevant and recent evidence for naltrexone initiation comes from the 2022 study 2.
Monitoring and Dosing
- Baseline liver function tests should be obtained before initiating naltrexone therapy.
- Follow-up testing is recommended at 1 month after starting treatment and periodically thereafter.
- The standard starting dose is 25-50 mg daily for oral naltrexone.
- Patients should be monitored for signs of liver injury, such as jaundice, abdominal pain, or fatigue, and the medication should be discontinued if ALT/AST levels exceed 3-5 times ULN or if symptoms develop.