Drug Interaction Report

GENERALLY AVOID: Coadministration of fostamatinib with potent inducers of CYP450 3A4 may significantly 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.

MANAGEMENT: Concomitant use of fostamatinib with potent CYP450 3A4 inducers is not recommended.

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.