Disproportionality analysis of acetaminophen-induced hepatic disorders with and without immune checkpoint inhibitors

Background: Although acetaminophen is recommended for the treatment of mild-to-moderate cancer pain, acetaminophen-induced hepatic disorders pose an important clinical challenge. Concomitant prescription of immune checkpoint inhibitors (ICIs) may further increase the risk of hepatic disorders in patients taking acetaminophen; however, there are few clinical studies that confirm this.

Aim: To evaluate the risk of hepatic disorders in patients taking concomitant acetaminophen and ICIs using a disproportionality analysis from the Japanese Adverse Drug Event Report database.

Method: Acetaminophen users aged ≥ 20 years were included; factors that can affect the risk of acetaminophen-induced hepatic disorders were collated. Similar data on the widely used analgesic, loxoprofen, were used for comparison.

Results: Among 233,594 patients surveyed, 10,403 were prescribed acetaminophen, and among them, 1,245 patients developed hepatic disorders. The disproportionality of hepatic disorders was observed in acetaminophen users regardless of concomitant ICI use (without ICI: reporting odds ratio [ROR], 1.18; 95% confidence intervals [CI], 1.10-1.26; with ICI: ROR 1.87, 95%CI 1.59-2.20); it was even higher in concomitant acetaminophen and ICI users (ROR 1.94, 95%CI 1.65-2.29). However, increased disproportionality of hepatic disorders was not observed in patients taking concomitant loxoprofen and ICI. Multivariable logistic regression showed that the risk of hepatic disorders in acetaminophen users was associated with concomitant use of ICI (ROR, 1.91; 95% CI, 1.49-2.45); (P < 0.01).

Conclusion: Our findings suggest that the risk of hepatic disorders is greater with concomitant acetaminophen and ICI treatment than with acetaminophen alone.