Transient elevation of international normalized ratio during cisplatin-based chemotherapy in patients who are taking warfarin

Ann Pharmacother. 2011 Oct;45(10):e55. doi: 10.1345/aph.1Q290. Epub 2011 Aug 31.

Abstract

Objective: To report 2 cases of a probable interaction between cisplatin and warfarin.

Case summary: 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.

Discussion: 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.

Publication types

  • Case Reports

MeSH terms

  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Cisplatin / therapeutic use
  • Drug Interactions
  • Drug Monitoring
  • Female
  • Genital Neoplasms, Female / complications
  • Genital Neoplasms, Female / drug therapy
  • Humans
  • International Normalized Ratio
  • Irinotecan
  • Middle Aged
  • Thromboembolism / prevention & control
  • Treatment Outcome
  • Venous Thrombosis / complications
  • Venous Thrombosis / drug therapy
  • Warfarin / administration & dosage
  • Warfarin / adverse effects*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Warfarin
  • Irinotecan
  • Cisplatin
  • Camptothecin