Drug Interactions between abrocitinib and Prevacid NapraPAC

GENERALLY AVOID: Theoretically, proton pump inhibitors may decrease the gastrointestinal absorption of enteric-coated naproxen, which requires an acidic environment for dissolution. The proposed mechanism is an increase in gastric pH (i.e. decreased gastric acidity) induced by proton pump inhibitors. In patients treated with proton pump inhibitors, the possibility of a reduced or subtherapeutic response to enteric-coated naproxen should be considered.

MANAGEMENT: Concomitant use of these drugs is generally not recommended.

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MONITOR: Systemically and topically administered nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of bleeding in patients treated with anticoagulants and other drugs that affect hemostasis such as platelet inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause thrombocytopenia. The pharmacologic effects of NSAIDs that contribute to this interaction include prolongation of prothrombin time and inhibition of platelet adhesion and aggregation.

MANAGEMENT: Caution is advised if NSAIDs are used in combination with other drugs that affect hemostasis. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their doctor, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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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.

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