Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 lossof-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 clopidogreltreated 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).

Selective Serotonin Reuptake Inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).

The slow rate at which pharmacogenetic tests are being adopted in clinical practice is partly due to the lack of specific guidelines on how to adjust medications on the basis of the genetic test results. One of the goals of the Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health’s Pharmacogenomics Research Network (http://www.pgrn.org) and the Pharmacogenomics Knowledge Base (PharmGKB, http://www.pharmgkb.org) is to provide peer-reviewed, updated, evidence-based, freely accessible guidelines for gene/drug pairs. These guidelines will facilitate the translation of pharmacogenomic knowledge from bench to bedside.

This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.