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 treatment, baseline liver function tests should be obtained, with follow-up testing recommended at 1 month after starting 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 1.
Some key points to consider when initiating naltrexone therapy include:
- Baseline liver function tests should be obtained before starting naltrexone
- Patients with existing liver disease should be monitored closely for signs of hepatotoxicity
- Naltrexone should be discontinued if ALT/AST levels exceed 3-5 times ULN or if the patient develops symptoms of liver injury
- The standard starting dose of naltrexone is 25-50 mg daily for oral naltrexone
- Follow-up liver function tests should be performed at 1 month after starting naltrexone and periodically thereafter
It's also important to note that the safety of naltrexone in patients with liver disease has been evaluated in several studies, including a retrospective cohort study published in 2022, which found that naltrexone was safe to use in patients with underlying liver disease, including those with compensated cirrhosis 1. However, more safety data are needed for those with decompensated cirrhosis.
In terms of the risk of transaminitis, a study published in 2019 found that younger patients and those with concurrent amiodarone or vasopressor use were at higher risk of developing oxandrolone-induced transaminitis, and should be monitored closely 2. However, this study was not specific to naltrexone, and more research is needed to fully understand the risk of transaminitis associated with naltrexone therapy.
Overall, the decision to initiate naltrexone therapy should be made on a case-by-case basis, taking into account the patient's individual risk factors and medical history. Naltrexone can be a safe and effective treatment option for patients with alcohol use disorder, but it's essential to monitor liver function tests closely and adjust the treatment plan as needed.