Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit

Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).

Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org).