From the Guidelines
Naltrexone should be used with caution in patients with elevated liver enzymes, and the decision to use it should be made on a case-by-case basis, considering the risks and benefits, as recommended by the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines 1. When considering the use of naltrexone in patients with liver disease, it is essential to weigh the potential benefits against the risks of hepatotoxicity. According to the American Family Physician study, naltrexone has been associated with hepatic injury at supratherapeutic doses, and liver function tests are recommended at baseline and every three to six months 1. The management of patients with liver disease requires careful consideration of the potential risks and benefits of naltrexone treatment. The Journal of Hepatology study highlights the importance of careful patient selection and monitoring, particularly in patients with severe liver disease 1. Some key points to consider when using naltrexone in patients with elevated liver enzymes include:
- Obtaining baseline liver function tests before starting naltrexone
- Monitoring liver enzymes regularly, particularly in the first few months of treatment
- Considering lower doses or alternative medications, such as extended-release naltrexone injections, in patients with a history of liver disease
- Discontinuing naltrexone if liver enzymes rise to 3-5 times the upper limit of normal or if symptoms of hepatotoxicity occur By carefully evaluating the risks and benefits of naltrexone treatment and monitoring patients closely, healthcare providers can minimize the risk of hepatotoxicity and ensure the safe use of this medication in patients with elevated liver enzymes.
From the FDA Drug Label
Cases of hepatitis and clinically significant liver dysfunction were observed in association with naltrexone hydrochloride exposure during the clinical development program and in the postmarketing period. Transient, asymptomatic hepatic transaminase elevations were also observed in the clinical trials and postmarketing period 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 Although clinically significant liver dysfunction is not typically recognized as a manifestation of opioid withdrawal, opioid withdrawal that is precipitated abruptly may lead to systemic sequelae, including acute liver injury. 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.
Naltraxone and Elevated Liver Enzymes: Naltrexone hydrochloride has been associated with elevated liver enzymes and hepatotoxicity. Patients should be warned of the risk of hepatic injury and advised to seek medical attention if they experience symptoms of acute hepatitis. The use of naltrexone hydrochloride should be discontinued in the event of symptoms and/or signs of acute hepatitis 2.
- Key Points:
- Naltrexone hydrochloride can cause elevated liver enzymes and hepatotoxicity.
- Patients should be warned of the risk of hepatic injury.
- Use of naltrexone hydrochloride should be discontinued in the event of symptoms and/or signs of acute hepatitis.
- Recommendations:
- Monitor patients for elevated liver enzymes and hepatotoxicity.
- Discontinue naltrexone hydrochloride in the event of symptoms and/or signs of acute hepatitis.
- Warn patients of the risk of hepatic injury and advise them to seek medical attention if they experience symptoms of acute hepatitis 2.
From the Research
Naltraxone and Elevated Liver Enzymes
- Naltrexone has been studied for its potential impact on liver enzymes, with some studies suggesting it may not have a significant effect on hepatic enzymes 3.
- A study published in 1988 found that naltrexone actually decreased lactic acid dehydrogenase (LDH) and serum glutamic oxalacetic transaminase (SGOT) levels in patients with elevated hepatic enzymes 3.
- More recent studies have also investigated the safety of naltrexone in patients with liver disease, including those with cirrhosis 4, 5.
- A 2022 study found that naltrexone was safe to use in patients with underlying liver disease, including those with compensated cirrhosis, and that it may even lower liver enzyme levels 4.
- Another study published in 2024 found that naltrexone was not associated with drug-induced liver injury in patients with cirrhosis, and that it may be a safe and effective treatment option for alcohol use disorder in this population 5.
High-Dose Naltrexone and Liver Function
- High-dose naltrexone has been studied for its potential impact on liver function, with some studies suggesting it may not have a significant effect on liver enzymes 6.
- A 1997 study found that high-dose naltrexone (100-200 mg bid) did not cause any adverse clinical or laboratory changes in liver function in patients with eating disorders 6.
Effect of Liver Cirrhosis on Naltrexone Availability
- Liver cirrhosis has been shown to affect the systemic availability of naltrexone, with studies suggesting that the severity of liver disease may impact the reduction of naltrexone to its active metabolite, 6 beta-naltrexol 7.
- A 1997 study found that patients with severe cirrhosis had higher circulating levels of naltrexone and lower levels of 6 beta-naltrexol compared to controls, suggesting that liver disease may alter the pharmacokinetics of naltrexone 7.