Hepatic adverse events associated with ketamine and esketamine: A population-based disproportionality analysis.

An analysis of the FDA Adverse Event Reporting System found that reports of hepatobiliary disorders differ between ketamine and esketamine. Compared to acetaminophen, ketamine was associated with disproportionately lower reporting of hepatitis, liver injury, drug-induced liver injury, hepatic failure, and acute hepatic failure, but disproportionately higher reporting of hepatic function abnormalities and hepatic cytolysis. For esketamine, there was no disproportionate reporting of most hepatobiliary toxicities relative to acetaminophen, except for disproportionately higher reporting of hepatic failure. The authors recommend periodic monitoring of liver function tests and clinical surveillance for signs of hepatobiliary disease in individuals receiving chronic ketamine or esketamine, though causality has not been established.

Study at a glance

Abstract

To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine. We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders. Formulations of ketamine and esketamine were evaluated for the proportionality of reporting for each hepatobiliary disorder parameter using the reporting odds ratio (ROR). We also estimated the lower limits of 95 % confidence intervals of information components (IC025) to determine whether the association was significant. Acetaminophen was used as the positive reference agent and lithium as the neutral reference agent. We observed disproportionately lower reporting of hepatitis, liver disorder, liver injury, drug-induced liver injury, hepatic failure, and acute hepatic failure for ketamine compared to acetaminophen. Additionally, we observed disproportionately higher reporting of hepatic function abnormalities and hepatic cytolysis for ketamine compared to acetaminophen. For esketamine, we did not find disproportionate reporting of any hepatobiliary toxicity relative to acetaminophen. However, for ketamine, there was disproportionate lower reporting of hepatic function abnormalities, liver disorder and hepatic cirrhosis. In contrast, for esketamine, there was disproportionately higher reporting of hepatic failure. Although causality has not been established, the data support recommendations for periodic monitoring of liver function tests, as well as clinical surveillance for stigmata of hepatobiliary disease in individuals receiving chronic exposure to ketamine and esketamine.