Abstract
Case We describe two cases in which treatment with aprepitant persistently altered antithrombotic control in patients receiving warfarin. A 60-year-old man received 5 weekly cycles of chemotherapy. Aprepitant was administered as a 3-day regimen from the second cycle of chemotherapy. In each of the chemotherapy cycles that included aprepitant, the therapeutic international normalized ratio (INR) decreased markedly to <1.6, and slowly recovered over several weeks. A 47-year-old woman was treated with 4 weekly cycles of chemotherapy. Aprepitant was administered as a 3-day regimen. On day 8 of the first cycle of chemotherapy, the patient’s INR fell markedly to 1.1. Although warfarin dosage was steadily increased over the four subsequent cycles of chemotherapy, therapeutic target range was not recovered. INR gradually returned to normal during the 2 months after the final cycle of chemotherapy. Conclusion To our knowledge, this is the first case report to document the effects of aprepitant in cancer patients receiving anticoagulation therapy.
References
Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant Protocol 052 Study Group. J Clin Oncol. 2003;21(22):4112–9.
Depre M, Van Hecken A, Oeyen M, De Lepeleire I, Laethem T, Rothenberg P, et al. Effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin. Eur J Clin Pharmacol. 2005;61(5–6):341–6.
Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, et al. Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. J Clin Pharmacol. 2004;44(3):215–23.
Harder S, Thurmann P. Clinically important drug interactions with anticoagulants. An update. Clin Pharmacokinet. 1996;30(6):416–44.
Emend (Aprepitant). Merck & Co., Inc. US Prescribing infomation. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021549s024lbl.pdf (2014). Accessed 25 Aug 2014.
Inoue H, Okumura K, Atarashi H, Yamashita T, Origasa H, Kumagai N, et al. Target international normalized ratio values for preventing thromboembolic and hemorrhagic events in Japanese patients with non-valvular atrial fibrillation: results of the J-RHYTHM Registry. Circ J. 2013;77(9):2264–70.
Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007;41(4):674–80.
Le AT, Hasson NK, Lum BL. Enhancement of warfarin response in a patient receiving etoposide and carboplatin chemotherapy. Ann Pharmacother. 1997;31(9):1006–8.
Gerbal-Chaloin S, Pascussi JM, Pichard-Garcia L, et al. Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab Dispos. 2001;29:242–51.
Sellam J, Costedoat-Chalumeau N, Amoura Z, Aymard G, Choquet S, Trad S, et al. Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis. Joint Bone Spine. 2007;74(5):446–52.
Miners JO, Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol. 1998;45(6):525–38.
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Ohno, Y., Yamada, M., Yamaguchi, R. et al. Persistent drug interaction between aprepitant and warfarin in patients receiving anticancer chemotherapy. Int J Clin Pharm 36, 1134–1137 (2014). https://doi.org/10.1007/s11096-014-0022-y
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DOI: https://doi.org/10.1007/s11096-014-0022-y