Potential drug interaction between paclitaxel and clopidogrel

Shinoda,Yasutaka; Kimura,Michio; Usami,Eiseki; Asano,Hiroki; Yoshimura,Tomoaki

doi:10.3892/br.2016.685

July-2016 Volume 5 Issue 1

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July-2016 Volume 5 Issue 1

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Article

Potential drug interaction between paclitaxel and clopidogrel

Authors:
- Yasutaka Shinoda
- Michio Kimura
- Eiseki Usami
- Hiroki Asano
- Tomoaki Yoshimura
View Affiliations / Copyright

Affiliations: Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503‑8502, Japan
Pages: 141-145
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Published online on: May 20, 2016

https://doi.org/10.3892/br.2016.685
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Abstract

Paclitaxel is mainly inactivated in vivo by 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/mm3 without clopidogrel; 370±148 counts/mm3 with 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.

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1	Rahman A, Korzekwa KR, Grogan J, Gonzalez FJ and Harris JW: Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res. 54:5543–5546. 1994.PubMed/NCBI
2	Tornio A, Filppula AM, Kailari O, Neuvonen M, Nyrönen TH, Tapaninen T, Neuvonen PJ, Niemi M and Backman JT: Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: A phase II metabolite as a perpetrator of drug-drug interactions. Clin Pharmacol Ther. 96:498–507. 2014. View Article : Google Scholar : PubMed/NCBI
3	Bergmann TK, Filppula AM, Launiainen T, Nielsen F, Backman J and Brosen K: Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60 year old Caucasian woman with ovarian carcinoma. Br J Clin Pharmacol. Oct 7–2015.(Epub ahead of print).
4	Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM and Baergen R: Gynecologic Oncology Group: Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol. 21:3194–3200. 2003. View Article : Google Scholar : PubMed/NCBI
5	Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, et al: Japanese Gynecologic Oncology Group: Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: A phase 3, open-label, randomised controlled trial. Lancet. 374:1331–1338. 2009. View Article : Google Scholar : PubMed/NCBI
6	Kanda Y: Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 48:452–458. 2013. View Article : Google Scholar : PubMed/NCBI
7	Bergmann TK, Brasch-Andersen C, Gréen H, Mirza M, Pedersen RS, Nielsen F, Skougaard K, Wihl J, Keldsen N, Damkier P, et al: Impact of CYP2C8*3 on paclitaxel clearance: A population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer. Pharmacogenomics J. 11:113–120. 2011. View Article : Google Scholar : PubMed/NCBI
8	Hertz DL, Roy S, Motsinger-Reif AA, Drobish A, Clark LS, McLeod HL, Carey LA and Dees EC: CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel. Ann Oncol. 24:1472–1478. 2013. View Article : Google Scholar : PubMed/NCBI
9	Hertz DL, Motsinger-Reif AA, Drobish A, Winham SJ, McLeod HL, Carey LA and Dees EC: CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel. Breast Cancer Res Treat. 134:401–410. 2012. View Article : Google Scholar : PubMed/NCBI
10	Huizing MT, Vermorken JB, Rosing H, ten Bokkel Huinink WW, Mandjes I, Pinedo HM and Beijnen JH: Pharmacokinetics of paclitaxel and three major metabolites in patients with advanced breast carcinoma refractory to anthracycline therapy treated with a 3-hour paclitaxel infusion: A European Cancer Centre (ECC) trial. Ann Oncol. 6:699–704. 1995.PubMed/NCBI
11	Nakajima M, Fujiki Y, Kyo S, Kanaya T, Nakamura M, Maida Y, Tanaka M, Inoue M and Yokoi T: Pharmacokinetics of paclitaxel in ovarian cancer patients and genetic polymorphisms of CYP2C8, CYP3A4, and MDR1. J Clin Pharmacol. 45:674–682. 2005. View Article : Google Scholar : PubMed/NCBI
12	National Comprehensive Cancer Network: Prevention and treatment of cancer-related infections. Version 1.2013. http://oralcancerfoundation.org/treatment/pdf/infections.pdfAccessed. February 05–2013

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Potential drug interaction between paclitaxel and clopidogrel

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Abstract

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