What are the implications of using Olanzapine (Zyprexa) and Risperidone in patients with liver failure?

From the Guidelines

Both Zyprexa and risperidone should be used with caution in patients with liver failure, with careful monitoring of liver function and potential dose adjustments. When considering the use of these medications in patients with liver failure, it is essential to weigh the potential benefits against the risks of hepatic impairment. According to the practice parameter for the assessment and treatment of children and adolescents with schizophrenia 1, atypical agents like Zyprexa and risperidone may produce elevations in hepatic transaminase levels, which are often transient but can be a concern in patients with pre-existing liver disease. Some key points to consider when using these medications in patients with liver failure include:

• Starting with lower doses and gradually increasing as tolerated to minimize the risk of adverse effects
• Regular monitoring of liver function to detect any potential abnormalities
• Being aware of the potential for increased sedation, orthostatic hypotension, and extrapyramidal symptoms, which may indicate toxicity
• Considering alternative antipsychotics with less hepatic metabolism, such as paliperidone, for patients with severe liver dysfunction It is crucial to consult with both psychiatry and hepatology specialists for optimal management of patients with liver failure who require antipsychotic medication, as they can provide guidance on the best course of treatment and help mitigate potential risks.

From the FDA Drug Label

Hepatic Impairment — Although the presence of hepatic impairment may be expected to reduce the clearance of olanzapine, a study of the effect of impaired liver function in subjects (n=6) with clinically significant (Childs Pugh Classification A and B) cirrhosis revealed little effect on the pharmacokinetics of olanzapine

The FDA drug label does not provide sufficient information to directly answer the question about the use of Zyprexa (olanzapine) and risperidone in liver failure. However, it does mention that olanzapine is highly metabolized and that hepatic impairment may be expected to reduce its clearance, but a study in patients with cirrhosis showed little effect on the pharmacokinetics of olanzapine. Caution should be exercised in patients with signs and symptoms of hepatic impairment.

There is no information provided about risperidone in the given drug labels.

Key points:

• Olanzapine is highly metabolized
• Hepatic impairment may reduce olanzapine clearance
• A study in patients with cirrhosis showed little effect on olanzapine pharmacokinetics
• Caution should be exercised in patients with hepatic impairment 2

From the Research

Zyprexa and Risperidone in Liver Failure

• Zyprexa (olanzapine) and risperidone are atypical antipsychotics that can cause liver dysfunction, although the risk is considered uncommon to rare 3.
• Risperidone is classified as a moderate-risk agent for causing or worsening liver disease, while olanzapine poses a higher risk of hepatotoxicity 3.
• A study found that 27.2% of patients treated with atypical antipsychotics, including risperidone, showed asymptomatic increases in liver enzymes, while 1.8% presented with significant liver enzyme elevations that required treatment discontinuation 4.
• In patients with cirrhosis, most medications, including those that are potentially hepatotoxic, can be used safely, but lower doses or reduced dosing frequency is often recommended due to altered pharmacokinetics 5.
• Risperidone and olanzapine have been shown to alter the hepatic proteomic signature in mice, leading to the development of steatosis and affecting multiple pathways relating to energy metabolism, NAFLD, and immune function 6.

Liver Injury and Monitoring

• The most common antipsychotic-induced liver injury is mild and self-limiting transaminitis, followed by hepatocellular disease, steatosis, and mixed liver injury 3.
• A careful risk-benefit analysis should guide the decision to discontinue the antipsychotic in cases of severe liver disease, and dose adjustments and careful monitoring are recommended for mild to moderate disease 3.
• Patients without an existing liver disease initiating treatment with a higher-risk antipsychotic should be counseled to report symptoms of liver injuries along with regular lab monitoring 3.
• Baseline liver enzyme tests should be obtained before atypical antipsychotic therapy, and monitoring should be done regularly, especially in patients with risk factors for liver damage 4.