Dutch Pharmacogenetics Working Group (DPWG) guideline information
for clopidogrel and CYP2C19

last updated 08/10/2011

Summary

The Dutch Pharmacogenetics Working Group Guideline for clopidogrel recommends to consider an alternative drug for CYP2C19 poor or intermediate metabolizers, because of increased risk for reduced response to clopidogrel. Prasugrel might be associated with an increased bleeding risk compared to clopidogrel.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for clopidogrel based on the CYP2C19 genotype [Article:21412232]. For the CYP2C19 PM and IM phenotype they conclude an increased risk for reduced response to clopidogrel and recommend to consider an alternative drug. Prasugrel is not or to a much smaller extent metabolized by CYP2C19 but is associated with an increased bleeding risk compared to clopidogrel.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
CYP2C19 PM (*2/*2, *2/*3, *3/*3)Increased risk for reduced response to clopidogrel. Consider alternative drug. Prasugrel is not or to a much smaller extent metabolized by CYP2C19 but is associated with an increased bleeding risk compared to clopidogrelPublished controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpointsClinical effect (statistically significant difference): death; arrhythmia; unanticipated myelosuppression
CYP2C19 IM (*1/*2, *1/*3, *17/*2, *17/*3)Increased risk for reduced response to clopidogrel. Consider alternative drug. Prasugrel is not or to a much smaller extent metabolized by CYP2C19 but is associated with an increased bleeding risk compared to clopidogrelPublished controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpointsClinical effect (statistically significant difference): death; arrhythmia; unanticipated myelosuppression
CYP2C19 UM (*17/*17)NonePublished controlled studies of moderate quality# relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpointsMinor clinical effect (statistically significant difference): QTc prolongation (<450 ms female, <470 ms male); international normalized ratio increase < 4.5 Kinetic effect (statistically significant difference)
  • *See Methods or [Article:18253145] for definition of "good quality."
  • #wherever one or more of the "good quality" criteria was missing, the quality of the study was considered to be "moderate"

DPWG Guideline publication

Total publications: 1

Reference
1. Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee A H, Mulder H, Rongen G A P J M, van Schaik R H N, Schalekamp T, Touw D J, van der Weide J, Wilffert B, Deneer V H M, Guchelaar H-J. PubMed

Guideline History