Drug Interactions between conivaptan and fostamatinib

MONITOR CLOSELY: Coadministration of fostamatinib with potent inhibitors of CYP450 3A4 may significantly increase 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 80 mg dose of fostamatinib (0.53 times the 150 mg dosage) was administered with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 3.5 days), R406 peak plasma concentration (Cmax) and systemic exposure (AUC) increased on average by 37% and 102%, respectively, compared to fostamatinib administered alone. Increased exposure to R406 may result in increased risk of adverse effects such as diarrhea, hepatotoxicity, hypertension, and neutropenia.

MANAGEMENT: Patients should be monitored for toxicities of fostamatinib during concomitant use of potent CYP450 3A4 inhibitors, and the fostamatinib dosage adjusted as necessary in accordance with the product labeling.