Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 2C19 and/or 2C9 may decrease the plasma concentrations of abrocitinib, which is primarily metabolised by CYP450 2C19 (approximately 53%) and 2C9 (30%) and to a lesser extent by CYP450 3A4 (11%) and 2B6 (6%) based on in vitro data. When a 200 mg dose of abrocitinib was administered following multiple dosing with rifampicin, a potent CYP450 2C19 and 3A4 inducer and a moderate CYP450 2C9 and 2B6 inducer, the sum systemic exposure (AUC) of unbound abrocitinib plus its two active mono-hydroxylated metabolites, M1 (3-hydroxypropyl) and M2 (2-hydroxypropyl), decreased by approximately 56%. Reduced efficacy of abrocitinib may occur.

MANAGEMENT: Concomitant use of abrocitinib with potent CYP450 2C19 and/or 2C9 inducers should generally be avoided.

MONITOR: Smoking during treatment with abrocitinib may increase the risk of major adverse cardiovascular events (MACE) and the risk of developing malignancies. During abrocitinib clinical studies, current or past smokers had an additional increased risk of overall malignancies. Also, abrocitinib may increase patients' risk of MACE, including myocardial infarction, stroke, and cardiovascular death.

Administration of abrocitinib with high-fat, high-calorie food increased abrocitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 29% and 26%, respectively, and prolonged the time to reach Cmax by 2 hours. These changes are not considered clinically relevant.

MANAGEMENT: Caution is advised if abrocitinib is prescribed to current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. The manufacturer recommends discontinuing abrocitinib in patients that have experienced a myocardial infarction or stroke. Abrocitinib may be taken with or without food.