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Clopidogrel–Paclitaxel Drug–Drug Interaction: A Pharmacoepidemiologic Study
Author(s) -
Agergaard K,
MauSørensen M,
Stage TB,
Jørgensen TL,
Hassel RE,
Steffensen KD,
Pedersen JW,
Milo MLH,
Poulsen SH,
Pottegård A,
Hallas J,
Brøsen K,
Bergmann TK
Publication year - 2017
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.674
Subject(s) - paclitaxel , clopidogrel , medicine , hazard ratio , confidence interval , peripheral neuropathy , cyp2c19 , aspirin , pharmacology , chemotherapy , endocrinology , diabetes mellitus , cytochrome p450 , metabolism
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.