Drug Interaction Report

MONITOR: Coadministration with abrocitinib may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp), an efflux transporter inhibited in vitro by abrocitinib. Concomitant administration of dabigatran etexilate, a P-gp substrate, and abrocitinib (200 mg single dose) increased the dabigatran peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 40% and 53%, respectively. The effect of abrocitinib on pharmacokinetics of other P-gp substrates has not been evaluated.

MANAGEMENT: Caution is advised if abrocitinib is coadministered with P-gp substrates, particularly sensitive substrates or those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever abrocitinib is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Food reduces the oral bioavailability of betrixaban. When administered with a low-fat (900 calories; 20% fat) or high-fat (900 calories; 60% fat) meal, betrixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased relative to administration in the fasting state by an average of 70% and 61%, respectively, with the low-fat meal and 50% and 48%, respectively, with the high-fat meal. The effect of food on betrixaban pharmacokinetics could be observed for up to 6 hours after meal intake.

MANAGEMENT: The manufacturer recommends taking betrixaban at the same time each day with food.

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.