title: Transient elevation of international normalized ratio during cisplatin-based chemotherapy in patients who are taking warfarin.
abstract: OBJECTIVE
  To report 2 cases of a probable interaction between cisplatin and warfarin.
  
  
  METHODS
  Two cases of transient elevation of international normalized ratio (INR) during irinotecan (60 mg/m2 on days 1, 8, and 15) plus cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are presented. In both cases, warfarin dosages were stable at the therapeutic target range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on days 1, 8, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3, 8, and 15) were used prior to irinotecan administration in both patients. In addition, aprepitant was administered to both patients for 3-5 days with cisplatin. One of these patients also received aprepitant with irinotecan on days 8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over baseline level on day 3. This variation did not occur in subsequent irinotecan cycles on days 8 and 15. The timing of these increases was similar in each of the cycles.
  
  
  CONCLUSIONS
  Cisplatin was the common drug in the cases presented and therefore could be related to the INR elevations. To our knowledge, these are the first reports of an interaction between warfarin and irinotecan-cisplatin chemotherapy, but reports of a similar interaction with chemotherapy including platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale indicated a probable interaction between warfarin and cisplatin.
  
  
  CONCLUSIONS
  Cisplatin might affect the anticoagulation function of warfarin. Careful INR monitoring is necessary during antineoplastic chemotherapy with cisplatin in patients taking warfarin.
authors: Department of Pharmacy, University of Fukui Hospital, Fukui, Japan. yanor@u-fukui.ac.jp
authors: Ryoichi
authors: R
authors: Yano
authors: Tetsuji
authors: T
authors: Kurokawa
authors: Hideaki
authors: H
authors: Tsuyoshi
authors: Akiko
authors: A
authors: Shinagawa
authors: Yoko
authors: Y
authors: Sawamura
authors: Akiko
authors: A
authors: Matsunaga
authors: Toshiaki
authors: T
authors: Nakamura
authors: Yoshio
authors: Y
authors: Yoshida
authors: Makoto
authors: M
authors: Yoneda
authors: Fumikazu
authors: F
authors: Kotsuji
authors: Mikio
authors: M
authors: Masada
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D005833:Genital Neoplasms, Female / Q000150:complications / Q000188:drug therapy; D006801:Humans; D019934:International Normalized Ratio; D000077146:Irinotecan; D008875:Middle Aged; D013923:Thromboembolism / Q000517:prevention & control; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000150:complications / Q000188:drug therapy; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D014859:Warfarin; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin