Clopidogrel paclitaxel drug-drug interaction: A pharmacoepidemiologic study

K Agergaard, M Mau-Sørensen, T Bjerregaard Stage, T L Jørgensen, R E Hassel, K D Steffensen, J W Pedersen, Marie Louise Holm Milo, S H Poulsen, Anton Pottegård, J. Hallas, K. Brøsen, T K Bergmann

Research output: Contribution to journalJournal articleResearchpeer-review

25 Citations (Scopus)

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 1500 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% CI, 0.9-3.0). Among those receiving a high dose paclitaxel regimen, the hazard ratio was 2.3 (95% CI, 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. This article is protected by copyright. All rights reserved.

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

Keywords

  • Journal Article

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