title: Clopidogrel-Paclitaxel Drug-Drug Interaction: A Pharmacoepidemiologic Study.
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.
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Agergaard
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Mau-Sørensen
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Bioengineering and Therapeutics Sciences, University of California San Francisco, San Francisco, California, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Stage
authors.affiliation: Department of Oncology, Odense University Hospital, Odense, Denmark.|AgeCare, Academy of Geriatric Cancer Research, Odense University Hospital, Odense, Denmark.
authors.forename: T L
authors.initials: TL
authors.lastname: Jørgensen
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: R E
authors.initials: RE
authors.lastname: Hassel
authors.affiliation: Department of Oncology, Lillebaelt Hospital, Vejle, Denmark.
authors.forename: K D
authors.initials: KD
authors.lastname: Steffensen
authors.affiliation: Department of Oncology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: J W
authors.initials: JW
authors.lastname: Pedersen
authors.affiliation: Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Mlh
authors.initials: M
authors.lastname: Milo
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: S H
authors.initials: SH
authors.lastname: Poulsen
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Pottegård
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Hallas
authors.affiliation: Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.|OPEN, Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Brøsen
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.|Hospital Pharmacy, Hospital of South West Denmark, Esbjerg, Denmark.
authors.forename: T K
authors.initials: TK
authors.lastname: Bergmann
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D065727:Cytochrome P-450 CYP2C8 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology; D017891:Pharmacoepidemiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065727:Cytochrome P-450 CYP2C8; D013988:Ticlopidine; D017239:Paclitaxel; D001241:Aspirin