Drug Interaction Report

Coadministration with inhibitors of CYP450 2C19 may increase the plasma concentrations of abrocitinib, which is primarily metabolized 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 100 mg dose of abrocitinib was coadministered with fluvoxamine, a potent CYP450 2C19 inhibitor and a weak to moderate CYP450 2C9 and 3A4 inhibitor, or fluconazole, a potent CYP450 2C19 inhibitor and a moderate CYP450 2C9 and 3A inhibitor, the sum systemic exposure (AUC) of unbound abrocitinib plus its two active mono-hydroxylated metabolites, M1 (3-hydroxypropyl) and M2 (2-hydroxypropyl), increased by 91% and 155%, respectively. No data are available for other, less potent CYP450 2C19 inhibitors; however, clinically significant interactions are not expected.

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.