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Rigshospitalet - a part of Copenhagen University Hospital
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Clopidogrel-Paclitaxel Drug-Drug Interaction: A Pharmacoepidemiologic Study

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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.

Original languageEnglish
JournalClinical Pharmacology and Therapeutics
Volume102
Issue number3
Pages (from-to)547-553
Number of pages7
ISSN0009-9236
DOIs
Publication statusPublished - Sep 2017

    Research areas

  • Aged, Aspirin, Cytochrome P-450 CYP2C8, Dose-Response Relationship, Drug, Drug Interactions, Female, Humans, Liver, Male, Middle Aged, Paclitaxel, Peripheral Nervous System Diseases, Pharmacoepidemiology, Platelet Aggregation Inhibitors, Retrospective Studies, Severity of Illness Index, Ticlopidine, Journal Article

ID: 52073264