Drug Interaction Report

MONITOR: Coadministration of fostamatinib with inducers of CYP450 3A4 may decrease exposure to the active metabolite known as R406, the predominant moiety in the systemic circulation following fostamatinib administration. Fostamatinib is metabolized in the gut by alkaline phosphatase to R406, which then undergoes oxidation via CYP450 3A4 and glucuronidation via UGT1A9. When a single 150 mg dose of fostamatinib was administered with the potent CYP450 3A4 and UGT1A1 inducer rifampin (600 mg once daily for 8 days), R406 peak plasma concentration (Cmax) and systemic exposure (AUC) decreased on average by 59% and 75%, respectively, compared to fostamatinib administered alone. Reduced efficacy of fostamatinib may occur. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of fostamatinib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.