Erlotinib과 Warfarin의 동시 투여로 PT-INR이 연장된 1예

A Case of Elevated Prothrombin Time-International Normalized Ratio (PT-INR) Associated with Concurrent Use of Erlotinib and Warfarin

  • 김승경 (가톨릭대학교 의과대학 성모병원 내과) ;
  • 박경선 (가톨릭대학교 의과대학 성모병원 내과) ;
  • 최승화 (가톨릭대학교 의과대학 성모병원 내과) ;
  • 변재호 (가톨릭대학교 의과대학 성모병원 내과) ;
  • 우인숙 (가톨릭대학교 의과대학 성모병원 내과) ;
  • 한치화 (가톨릭대학교 의과대학 성모병원 내과) ;
  • 김효림 (가톨릭대학교 의과대학 성모병원 방사선과)
  • Kim, Seung-Kyoung (Department of Internal Medicine, St. Mary’s Hospital, The Catholic University of Korea School of Medicine) ;
  • Park, Kyung-Seon (Department of Internal Medicine, St. Mary’s Hospital, The Catholic University of Korea School of Medicine) ;
  • Choi, Seung-Hwa (Department of Internal Medicine, St. Mary’s Hospital, The Catholic University of Korea School of Medicine) ;
  • Byun, Jae-Ho (Department of Internal Medicine, St. Mary’s Hospital, The Catholic University of Korea School of Medicine) ;
  • Woo, In-Sook (Department of Internal Medicine, St. Mary’s Hospital, The Catholic University of Korea School of Medicine) ;
  • Han, Chi-Hwa (Department of Internal Medicine, St. Mary’s Hospital, The Catholic University of Korea School of Medicine) ;
  • Kim, Hyo-Lim (Department of Radiology, St. Mary’s Hospital, The Catholic University of Korea School of Medicine)
  • 발행 : 2011.06.01

초록

향후 활동성이 저하된 진행성 비소세포폐암 환자에서 EGFR TKI 표적치료제와 와파린을 병용하는 사례가 더욱 증가할 것으로 예상되므로 이들 약제의 잠재적인 상호작용을 고려하여 INR의 변화를 주의 깊게 관찰해야 하며 필요한 경우에는 와파린의 용량을 조절해야 한다.

Erlotinib, an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is indicated for EGFR mutation-positive patients with poor performance status. Erlotinib is also used as a second-line agent in patients who show disease progression after failure of first-line therapy. Warfarin is administered in patients with advanced cancer for the prevention or treatment of venous thromboembolism. Both erlotinib and warfarin are metabolized in the human liver primarily by the CYP3A4 enzyme system. Thus, erlotinib may inhibit the metabolism of warfarin and clinicians should pay attention to the possible interaction between the two drugs when they are administered concurrently. We report the case of a 50-year-old man who showed changes in the prothrombin time-international normalized ratio (PT-INR) after coadministration of erlotinib and warfarin.

키워드

참고문헌

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108. https://doi.org/10.3322/canjclin.55.2.74
  2. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatments, and survivorship. Mayo Clin Proc 2008;83:584-594. https://doi.org/10.1016/S0025-6196(11)60735-0
  3. Korean National Statistical Office. The cause of death statistics, Daejeon: Korean National statistical office, c2006. [cited 2010, March 10]. Available from: http://www.Cancer.go.kr/cms/statics/mortality/index.html.
  4. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa survival evaluation in lung cancer). Lancet 2005;366:1527-1537. https://doi.org/10.1016/S0140-6736(05)67625-8
  5. Arai S, Mitsufuji H, Nishii Y, et al. Effect of gefitinib on warfarin antithrombotic activity. Int J Clin Oncol 2009;14:332-336. https://doi.org/10.1007/s10147-008-0871-2
  6. Onoda S, Mitsufuji H, Yanase N, et al. Drug interaction between gefitinib and warfarin. Jpn J Clin Oncol 2005;35:478-482. https://doi.org/10.1093/jjco/hyi122
  7. Micromedex Products. Erlotinib. [cited 2010. March 10]. Available from: http://www.thomsonhc.com/ hcs/ librarian.
  8. Tarceva R[package insert]. Roche Pharma (Schweiz) Ltd. Schoenmattstrasse 2 4153 Reinach. Switzerland. Available from: http:// www.roche.co.kr./fmfiles/re7198001/product/insertpaper/Tarreva tab.pdf.
  9. Hidalgo M, Bloedow D. Pharmacokinetics and Pharmacodynamics: maximizing the clinical potential of Erlotinib (Tarceva). Semin Oncol 2003;30(3 Suppl 7):S25-S33.
  10. Smith J. Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer. Clin Ther 2005;27: 1513-1534. https://doi.org/10.1016/j.clinthera.2005.10.014
  11. Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 2007;25:1545-1552. https://doi.org/10.1200/JCO.2005.05.1474
  12. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-132. https://doi.org/10.1056/NEJMoa050753
  13. Francis CW. Prevention of venous thromboembolism in hospitalized patients with cancer. J Clin Oncol 2009;27:4874- 4680. https://doi.org/10.1200/JCO.2009.22.3644
  14. Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol 2003;41:1633-1652. https://doi.org/10.1016/S0735-1097(03)00416-9
  15. Kolesar JM, Johnson CL, Freeberg BL, Berlin JD, Schiller JH. Warfarin-5-FU interaction: a consecutive case series. Pharmacotherapy 1999;19:1445-1449. https://doi.org/10.1592/phco.19.18.1445.30897
  16. Yildirim Y, Ozyilkan O, Akcali Z, Basturk B. Drug interation between capecitabine and warfarin: a case report and review of the literature. Int J Clin Pharmacol Ther 2006;44:80-82. https://doi.org/10.5414/CPP44080
  17. Moretti LV, Montalvo RO. Elevated internationl normalized ratio associated with concurrent use of sorafenib and warfarin. Am J Health Syst Pharm 2009;66:2123-2125. https://doi.org/10.2146/ajhp080436
  18. Naranjo CA, Shear NH, Lanctot KL. Advances in the diagnosis of adverse drug reactions. J Clin Pharmacol 1992;32:897-909. https://doi.org/10.1002/j.1552-4604.1992.tb04635.x
  19. Cohen MH, Williams GA, Sridhara R, et al. United States food and drug administration drug approval summary: gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 2004;10:1212-1218. https://doi.org/10.1158/1078-0432.CCR-03-0564