Drug Interactions between abrocitinib and fluvoxamine

CONTRAINDICATED: Coadministration of antiplatelet therapy or drugs that affect platelet function during the first 3 months of treatment with abrocitinib may increase the risk of bleeding with thrombocytopenia. Treatment with abrocitinib was associated with a transient, dose-dependent decrease in platelet count with the maximum decrease occurring at a median of 24 days after continuous administration of abrocitinib 200 mg/day. Recovery of platelet count (40% recovery) occurred by 12 weeks without discontinuation of the treatment.

ADJUST DOSE: Coadministration with potent 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. Increased exposure to abrocitinib and its metabolites may increase the risk of adverse reactions such as hematologic abnormalities, infections, venous thrombotic events including deep venous thrombosis and pulmonary embolism, and increases in blood lipids.

MANAGEMENT: Due to potential antiplatelet effects, concomitant use of potent CYP450 2C19 inhibitors such as fluoxetine, fluvoxamine, and ticlopidine are considered contraindicated for the first 3 months of abrocitinib treatment. For coadministration with potent CYP450 2C19 inhibitors without antiplatelet effects, or for concomitant use with potent CYP450 2C19 inhibitors with antiplatelet effects (after the first 3 months of abrocitinib), the abrocitinib dose should be reduced to 50 mg once daily. If an adequate response is not achieved with 50 mg once daily after 12 weeks, consider increasing the dose to 100 mg once daily. Discontinue if inadequate response remains after increase to 100 mg once daily.