Clopidogrel–Paclitaxel Drug–Drug Interaction: A Pharmacoepidemiologic Study

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 regis...

Full description

Saved in:
Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2017-09, Vol.102 (3), p.547-553
Main Authors: Agergaard, K, Mau‐Sørensen, M, Stage, TB, Jørgensen, TL, Hassel, RE, Steffensen, KD, Pedersen, JW, Milo, MLH, Poulsen, SH, Pottegård, A, Hallas, J, Brøsen, K, Bergmann, TK
Format: Article
Language:English
Subjects:
Aged
Aspirin - administration & dosage
Cytochrome P-450 CYP2C8 - metabolism
Dose-Response Relationship, Drug
Drug Interactions
Female
Humans
Liver - metabolism
Male
Middle Aged
Paclitaxel - administration & dosage
Paclitaxel - adverse effects
Paclitaxel - pharmacokinetics
Peripheral Nervous System Diseases - chemically induced
Peripheral Nervous System Diseases - epidemiology
Pharmacoepidemiology
Platelet Aggregation Inhibitors - administration & dosage
Platelet Aggregation Inhibitors - adverse effects
Platelet Aggregation Inhibitors - pharmacokinetics
Retrospective Studies
Severity of Illness Index
Ticlopidine - administration & dosage
Ticlopidine - adverse effects
Ticlopidine - analogs & derivatives
Ticlopidine - pharmacokinetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0009-9236
1532-6535
DOI:10.1002/cpt.674