Drug Interactions between Jemperli and ketoconazole

Consumer information for this interaction is not currently available.

MONITOR: Concomitant use of immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 monoclonal antibodies and/or inhibitors of programmed cell death-1 (PD-1) or programmed death ligand-1 (PD-L1) with ketoconazole (and possibly with its enantiomer, levoketoconazole) may potentiate the risk of liver injury. The mechanism of this interaction is unknown. In one case series, 2 consecutive patients with different types of metastatic cancer (pituitary carcinoma and adrenal cortical carcinoma) received ketoconazole (800 mg/day) for Cushing syndrome and were later initiated on ICI therapy (nivolumab 3 mg/kg every 2 weeks for one and pembrolizumab 200 mg intravenous every 3 weeks for the other). Both patients exhibited normal liver function while on ketoconazole. However, after initiation of the ICI, the levels of each patient's alanine transaminase (ALT) and aspartate transaminase (AST) increased by 10- to 20-fold. Liver biopsies obtained for each patient were consistent with drug-induced hepatic injury. In both cases, the ICI and ketoconazole were discontinued, and treatment with methylprednisolone (62.5 mg/day) was initiated for hepatic injury. Liver function gradually improved and both patients recovered. Clinical data with levoketoconazole are not readily available.

MANAGEMENT: The risk of hepatic injury should be considered when immune checkpoint inhibitors (ICIs) are used in combination with ketoconazole and possibly levoketoconazole. Liver function tests should be monitored as clinically indicated and patients should be counseled to report any symptoms of liver damage such as fever, rash, right upper quadrant pain, dark urine, pale stools, and/or jaundice. Refer to the individual product labeling for the ICI in question as well as ketoconazole or levoketoconazole for more specific recommendations should signs or symptoms of hepatotoxicity occur.