title: Effect of gefitinib on warfarin antithrombotic activity.
abstract: BACKGROUND
  Despite the literature indicating adverse interactions between warfarin and cytotoxic agents, whether such an interaction occurs when warfarin and gefitinib are used concomitantly is unknown. We analyzed the prevalence of the concomitant use of warfarin and gefitinib, and the incidence of prothrombin time-international normalized ratio (PT-INR) alterations or adverse interactions in concomitant users of warfarin and gefitinib.
  
  
  METHODS
  We conducted a retrospective study of patients with non-small cell lung cancer treated at the Kitasato University Hospital who received concomitant warfarin and gefitinib between September 2002 and January 2007. Medical information, including the indication for warfarin use, warfarin dosing and dosing changes, and exposure to gefitinib were collected from computerized databases and medical records.
  
  
  RESULTS
  Twelve (4.1%) of 296 patients treated with gefitinib received warfarin. PT-INR elevation occurred in 6 patients (50.0%). Two (16.7%) of the 12 patients had liver metastases. Liver dysfunction was associated with PT-INR elevation (P = 0.0100).
  
  
  CONCLUSIONS
  As there is a possibility of PT-INR abnormalities occurring during the concomitant use of gefitinib and warfarin, clinicians should be aware of this interaction. Because of the potentially severe consequences of this interaction, close monitoring of PT-INR and warfarin dose adjustment are recommended for patients receiving warfarin and gefitinib, especially during the first 2 weeks in the beginning of warfarin therapy.
authors.affiliation: Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Arai
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mitsufuji
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Nishii
authors.forename: Sayaka
authors.initials: S
authors.lastname: Onoda
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ryuge
authors.forename: Mayuko
authors.initials: M
authors.lastname: Wada
authors.forename: Ken
authors.initials: K
authors.lastname: Katono
authors.forename: Maiko
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Takakura
authors.forename: Sakiko
authors.initials: S
authors.lastname: Otani
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yanaihara
authors.forename: Masanori
authors.initials: M
authors.lastname: Yokoba
authors.forename: Masaru
authors.initials: M
authors.lastname: Kubota
authors.forename: Masato
authors.initials: M
authors.lastname: Katagiri
authors.forename: Tomoya
authors.initials: T
authors.lastname: Fukui
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yanase
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hataishi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D004347:Drug Interactions; D005260:Female; D000077156:Gefitinib; D006801:Humans; D019934:International Normalized Ratio; D008113:Liver Neoplasms / Q000097:blood / Q000556:secondary; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011517:Prothrombin Time; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014859:Warfarin; D000077156:Gefitinib
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