Document Detail

Drug interaction between capecitabine and warfarin: a case report and review of the literature.
MedLine Citation:
PMID:  16502767     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To report on possible adverse interaction between capecitabine and warfarin in a patient with cancer, who developed subconjunctival and nose bleeding during treatment with these drugs and review of the previously reported five cases in the literature.
CASE SUMMARY: In the second week of capecitabine treatment the patient was hospitalized owing to subconjunctival hemorrhage and nose bleeding. Her international normalized ratio (INR) level was found to have increased, and both drugs were discontinued. Fresh frozen plasma replacement was administered. Warfarin and capecitabine treatment were restarted again but the warfarin dose was decreased. The patients INR was kept between 2.5-3 with the reduced dose of warfarin.
DISCUSSION: Capecitabine is an orally active prodrug of fluorouracil (FU) and is extensively used as an antineoplastic agent. It is converted to 5-FU in the liver and tumor tissues. Warfarin is an antithrombolytic agent and is metabolized by liver cytochorom P450 (CYP) isoenzymes in liver. Preclinical in vitro studies using human liver microsomes report no inhibitory effects between capecitabine and substrates of CYP. However, the concomitant administration of capecitabine and warfarin resulted in gastrointestinal, retroperitoneal bleeding and hemorrhagic blisters in the five cases previously reported. The exact mechanism of this interaction is unknown; however, a significant pharmacokinetic interaction between capecitabine and S-warfarin resulting in exaggerated anticoagulant activity has recently been demonstrated. Here, we describe another case and use of the Naranjo adverse drug reaction (ADR) probability scale, which indicated a probable relationship between subconjunctival bleeding and epistaxis in this patient after concomitant warfarin and capecitabine use.
CONCLUSION: Capecitabine is extensively used in outpatient clinics, and physicians should be aware of ADRs arising from combined used of capecitabine and warfarin. In the light of the current data, INR levels should be closely monitored in patients using this medication regimen.
Y Yildirim; O Ozyilkan; Z Akcali; B Basturk
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  44     ISSN:  0946-1965     ISO Abbreviation:  Int J Clin Pharmacol Ther     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-28     Completed Date:  2006-04-27     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  80-2     Citation Subset:  IM    
Department of Medical Oncology, Baskent University Faculty of Medicine, Bahcelievler, Ankara, Turkey.
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MeSH Terms
Anticoagulants / adverse effects*,  pharmacology
Antimetabolites, Antineoplastic / adverse effects*,  pharmacology
Breast Neoplasms / drug therapy*
Deoxycytidine / adverse effects,  analogs & derivatives*,  pharmacology
Dose-Response Relationship, Drug
Drug Interactions / physiology
Fluorouracil / analogs & derivatives
Hemorrhage / chemically induced*
International Normalized Ratio
Neoplasm Recurrence, Local
Warfarin / adverse effects*,  pharmacology
Reg. No./Substance:
0/Anticoagulants; 0/Antimetabolites, Antineoplastic; 51-21-8/Fluorouracil; 6804DJ8Z9U/capecitabine; 81-81-2/Warfarin; 951-77-9/Deoxycytidine

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