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: Fat-rich food enhances the absorption of mitotane. One study evaluated blood levels of mitotane (o,p'-DDD) after subjects ingested a single dose of 2 g administered using various delivery vehicles (e.g., tablets, granules, milk, chocolate or oil emulsion). Mitotane plasma levels were significantly higher for milk, chocolate, and oil emulsion when compared to those who received tablets or granules alone. In the same study, mitotane levels were evaluated in subjects following long-term treatment (total dose of 200 g over 30 to 60 days) in tablet, oil emulsion, or milk formulations. Significantly higher mean plasma levels were recorded in subjects who received mitotane as an oil emulsion or mixed in milk, when compared to tablets alone. Additionally, the recovery of o,p'-DDD from the feces was about 5 times higher in subjects who received tablets alone, suggesting absorption was reduced when compared to subjects who received mitotane mixed with a fat-rich vehicle (e.g., oil emulsion or milk).

GENERALLY AVOID: Concomitant use of mitotane with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: According to product labeling, mitotane tablets should be taken during meals containing fat-rich food (e.g., milk, chocolate, or oil) and with a full glass of water. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.