title: Potential drug interaction between paclitaxel and clopidogrel.
abstract: Paclitaxel is mainly inactivatedin vivoby cytochrome P5402C8 (CYP2C8). In recent years, the clopidogrel metabolite has been reported to potently inhibit CYP2C8. However, clinical information regarding the interaction between these two drugs is limited. To the best of our knowledge, this is the first retrospective study investigating the potential for the drug interaction between paclitaxel and clopidogrel. A total of 8 cases in which clopidogrel and paclitaxel were used in combination were examined. The incidence of adverse events and discontinuation rate in these cases were assessed. Neutrophil counts were compared in patients prior and subsequent to the combined administration of clopidogrel and paclitaxel. Grade 3 neutropenia occurred in all cases of combination therapy and grade 4 occurred in 7 cases (88%). In addition, 4 cases (50%) showed febrile neutropenia. Four cases (50%) involved a severe adverse event requiring discontinuation of drug administration. In 1 case involving 6 courses of paclitaxel and nedaplatin therapy prior and subsequent to clopidogrel, there was a significant reduction in the average neutrophil count after 8 days of combination treatment (1,240±395 counts/mm3without clopidogrel; 370±148 counts/mm3with clopidogrel; mean ± standard deviation, P<0.01). Drug interactions during co-administration of clopidogrel and paclitaxel may cause severe neutropenia. To avoid these interactions, alternative medications should be considered. If these two drugs are used in combination, it may be necessary to monitor for adverse events more carefully.
authors.affiliation: Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Shinoda
authors.affiliation: Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Eiseki
authors.initials: E
authors.lastname: Usami
authors.affiliation: Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Asano
authors.affiliation: Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshimura
keywords: CYP2C8; clopidogrel; cytochrome P450; drug interaction; paclitaxel