Is Ondansetron (ondansetron) associated with liver failure?

From the Guidelines

Ondansetron can be used cautiously in patients with liver failure, but dose adjustments may be necessary, with a recommended total daily dose not exceeding 8 mg, as indicated in the most recent guidelines 1. When considering the use of ondansetron in patients with liver failure, it is crucial to understand the drug's metabolism and potential for hepatotoxicity. Ondansetron is primarily metabolized in the liver through the cytochrome P450 enzyme system, and when liver function is compromised, the drug's elimination half-life can be prolonged, potentially leading to higher blood levels and increased risk of side effects 1. The evidence suggests that ondansetron is generally considered safe for short-term use in patients with liver disease, but monitoring for adverse effects such as QT interval prolongation is important, especially in patients with electrolyte abnormalities which often accompany liver failure 1. Common side effects like headache and constipation may still occur, but serious hepatotoxicity directly caused by ondansetron is rare. For patients with both liver failure and kidney impairment, even greater caution is warranted as drug clearance may be further reduced. In the context of managing irritable bowel syndrome (IBS) with diarrhea, ondansetron, a 5-Hydroxytryptamine 3 receptor antagonist, can be considered as a second-line treatment option, titrated from a dose of 4 mg once a day to a maximum of 8 mg three times a day, as suggested by recent guidelines 1. It is essential to weigh the benefits and risks of using ondansetron in patients with liver failure, considering the potential for reduced drug clearance and increased risk of side effects, and to closely monitor patients for any adverse effects. Given the most recent evidence, ondansetron can be a viable option for patients with liver failure, provided that dose adjustments are made and the patient is closely monitored for potential side effects 1. Key considerations include:

• Dose adjustment to not exceed 8 mg total daily dose in severe hepatic impairment
• Monitoring for QT interval prolongation and other adverse effects
• Caution in patients with both liver and kidney impairment
• Consideration of ondansetron as a second-line treatment for IBS with diarrhea in patients with liver failure, with careful monitoring and dose titration.

From the Research

Ondansetron and Liver Failure

• Ondansetron is primarily eliminated via hepatic metabolism, and liver disease may affect its clearance 2.
• Studies have shown that patients with severe hepatic impairment have a lower mean plasma clearance of ondansetron, resulting in increased AUC and t1/2 2, 3.
• The dosing frequency of ondansetron should be limited to once daily in patients with severe hepatic impairment 2, 3.
• Elevation of aminotransferase levels is a rarely reported adverse effect of ondansetron, and it is not dose-related and has not been associated with liver injury 4.
• Low-dose ondansetron did not significantly change biochemical markers of liver injury in patients with alcohol use disorder 5.
• The safety of ondansetron has been reviewed, and increases in liver function tests were observed, but the incidence was similar to that of metoclopramide, and no end-organ toxicity was seen 6.

Pharmacokinetics of Ondansetron in Hepatic Insufficiency

• The pharmacokinetics of ondansetron were assessed in patients with different degrees of hepatic insufficiency, and the results showed a reduced first-pass effect in patients with liver disease, resulting in a higher AUC0-infinity 2.
• A correlation existed between clearance of ondansetron and decreased antipyrine clearance, and a smaller correlation existed between ondansetron clearance and indocyanine green clearance 2.
• Mean percent of ondansetron bound to plasma proteins was significantly lower in patients with liver disease than in control subjects 2.

Safety and Efficacy of Ondansetron in Patients with Liver Disease

• Ondansetron is well tolerated in patients with liver disease, and the principal side effects are constipation and headache 6.
• No severe adverse reactions attributed to ondansetron were reported in patients with hepatic impairment 2, 3.
• Low-dose ondansetron has the potential to be a safe treatment option for subjects with alcohol use disorder and alcohol-associated liver disease 5.