Drug-Induced Liver Injury From a Novel Antifungal – Olorofim

Olorofim, an orotomide antifungal with orphan designation for coccidioidomycosis, has not been previously linked to drug-induced liver injury. We present a case of drug-induced liver injury in a 67-year-old man treated with olorofim for refractory disseminated coccidioidomycosis. The patient experienced an acute, almost 30-fold increase in liver enzymes in a hepatocellular pattern after administration of olorofim, followed by a rapid downtrend over the next few weeks. Rechallenge at a reduced dose did not reproduce the transaminase elevations, consistent with a probable Roussel-Uclaf Causality Assessment Method score of 8. Close hepatic monitoring and dose considerations are warranted as olorofim moves toward broader clinical use.