Drug Interactions between abrocitinib and aspirin / omeprazole

CONTRAINDICATED: Coadministration of antiplatelet therapy 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. This interaction does not apply for low-dose aspirin (81 mg/day or less).

MANAGEMENT: Antiplatelet drugs, except for low-dose aspirin (81 mg/day or less), during the first 3 months of treatment with abrocitinib are considered contraindicated.

Coadministration with proton pump inhibitors may decrease the oral bioavailability of aspirin and other salicylates. The interaction has been studied with omeprazole and aspirin, although data are conflicting. In one study, pretreatment with omeprazole (20 mg/day for 2 days) in 11 healthy volunteers led to a significant and progressively greater reduction in the mean serum salicylate level at 30, 60, and 90 minutes after administration of aspirin (650 mg single dose). The investigators suggest that acid suppression may reduce the lipophilic nature of aspirin, thereby adversely affecting its absorption from the gastrointestinal tract. Another study found no effect of omeprazole pretreatment (20 mg/day for 4 days) on plasma salicylate and aspirin levels, skin bleeding times, or antiplatelet effect of low-dose aspirin (125 mg single dose) in 14 healthy volunteers. However, these results do not exclude the possibility that omeprazole might interfere with the analgesic, antipyretic, or anti-inflammatory effects of aspirin, which has been demonstrated in rats.

Proton pump inhibitors may enhance the release rate of salicylates from enteric-coated formulations due to premature disruption of the coating and intragastric release of the drug secondary to an increase in gastric pH. In eight healthy volunteers, omeprazole pretreatment (20 mg/day for 4 days) did not affect the bioavailability of salicylate from uncoated aspirin tablets but significantly increased the absorption rate of salicylate from enteric-coated sodium salicylate tablets. The clinical significance of this interaction is unknown. Theoretically, it may increase the risk of gastric adverse effects associated with salicylates.

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.