Clopidogrel-Paclitaxel Drug-Drug Interaction: A Pharmacoepidemiologic Study

  • Clin Pharmacol Ther. 2017 Sep;102(3):547-553. doi: 10.1002/cpt.674.
K Agergaard  1 ,  M Mau-Sørensen  2 ,  T B Stage  1  3 ,  T L Jørgensen  4  5 ,  R E Hassel  6 ,  K D Steffensen  7 ,  J W Pedersen  8 ,  Mlh Milo  9 ,  S H Poulsen  2 ,  A Pottegård  1 ,  J Hallas  1 ,  K Brøsen  1  10 ,  T K Bergmann  11  12
Affiliations
  • 1. Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
  • 2. Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • 3. Department of Bioengineering and Therapeutics Sciences, University of California San Francisco, San Francisco, California, USA.
  • 4. Department of Oncology, Odense University Hospital, Odense, Denmark.
  • 5. AgeCare, Academy of Geriatric Cancer Research, Odense University Hospital, Odense, Denmark.
  • 6. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
  • 7. Department of Oncology, Lillebaelt Hospital, Vejle, Denmark.
  • 8. Department of Oncology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • 9. Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
  • 10. OPEN, Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark.
  • 11. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
  • 12. Hospital Pharmacy, Hospital of South West Denmark, Esbjerg, Denmark.
PMID: 28224612 DOI: 10.1002/cpt.674
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.

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