Clopidogrel-Paclitaxel Drug-Drug Interaction: A Pharmacoepidemiologic Study

K Agergaard, M Mau-Sørensen, T B Stage, T L Jørgensen, R E Hassel, K D Steffensen, J W Pedersen, Mlh Milo, S H Poulsen, A Pottegård, J Hallas, K Brøsen, T K Bergmann

25 Citationer (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 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.

OriginalsprogEngelsk
TidsskriftClinical Pharmacology and Therapeutics
Vol/bind102
Udgave nummer3
Sider (fra-til)547-553
Antal sider7
ISSN0009-9236
DOI
StatusUdgivet - sep. 2017

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