Aprepitant and Warfarin Drug Interaction

Abstract

Aprepitant is a novel, potent, selective, oral non-peptide substance P/ NK1 receptor antagonist that inhibits chemotherapy induced nausea and vomiting (CINV), Aprepitant represents a new class of anti-emetics and it’s the first to gain regulatory approval for the management of chemotherapy induced nausea and vomiting. Warfarin is an oral coumarin that inhibits vitamin K dependent clotting factors leading to its anti-coagulant effect. It is a key medicine in the prophylaxis and treatment of thromboembolic diseases and in the prevention of complications that might rise after prosthetic cardiac valve replacement. Drug- drug interaction is a major concern for health care professionals. Though not all interactions have clinical consequences; as many as 20-30% of adverse drug events results from those interactions. The NK1 receptor antagonist Aprepitant is a key medication in the management and prevention of CINV resulting from high emetogenic chemotherapeutic protocols, especially high dose Cisplatin, as it improved patients’ side effect profile regarding nausea and vomiting, which highlights the importance of its use in cancer patients. Metabolized by liver and with a high protein binding capacity one might expect drug- drug interaction between Aprepitant and other medications. Warfarin - the anticoagulant of vast drug - drug interactions - is used commonly among cancer patients, as prophylaxis or treatment of hypercoagulable state. When used with Aprepitant care should be taken as after the 3 days dosing of Aprepitant the INR levels will start to decrease resulting in sub-therapeutic ranges of INR, this interaction is the result of Aprepitant effect on CYP2C9. It is recommended to monitor INR levels for 2 weeks after the three days Aprepitant dosing, especially days 7- 10, and to adjust Warfarin dose accordingly.