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Clin Pharmacol Ther. 2017 Sep;102(3):547-553. doi: 10.1002/cpt.674. Epub 2017 May 26.

Clopidogrel-Paclitaxel Drug-Drug Interaction: A Pharmacoepidemiologic Study.

Author information

1
Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
2
Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
3
Department of Bioengineering and Therapeutics Sciences, University of California San Francisco, San Francisco, California, USA.
4
Department of Oncology, Odense University Hospital, Odense, Denmark.
5
AgeCare, Academy of Geriatric Cancer Research, Odense University Hospital, Odense, Denmark.
6
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
7
Department of Oncology, Lillebaelt Hospital, Vejle, Denmark.
8
Department of Oncology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
9
Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
10
OPEN, Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark.
11
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
12
Hospital Pharmacy, Hospital of South West Denmark, Esbjerg, Denmark.

Abstract

Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-β-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age- and sex-matched controls treated with paclitaxel and low-dose aspirin. By a cumulative dose of 1,500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% confidence interval, 0.9-3.0). Among those receiving a high-dose paclitaxel regimen, the hazard ratio was 2.3 (95% confidence interval, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy in patients treated with high-dose paclitaxel.

PMID:
28224612
DOI:
10.1002/cpt.674
[Indexed for MEDLINE]

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