CPIC Guideline for NAT2 Genotype and Hydralazline Therapy

The CPIC Guideline for NAT2 Genotype and Hydralazine Therapy has been published in the journal Clinical Pharmacology and Therapeutics. This new guideline summarizes and evaluates literature evidence regarding the impact of genetic variants on NAT2's metabolism of hydralazine, a vasodilator typically used in the treatment of resistant hypertension and heart failure, into inactive metabolites. This is the first CPIC guideline for NAT2 (N-acetyltransferase 2). From the guideline: "NAT2 poor metabolizers (historically referred to as “slow acetylators”) are predicted to have increased plasma hydralazine concentrations compared with NAT2 rapid and intermediate metabolizers (historically referred to as “rapid acetylators” and “intermediate acetylators,” respectively), which may lead to both increased clinical efficacy and adverse effects, including drug-induced systemic lupus erythematosus." For more information, including the guideline manuscript, supplement and supporting gene and drug resources, please go to the ClinPGx and CPIC websites.

The guideline annotation includes an interactive interface for retrieving specific recommendations based on user-entered genotypes or phenotypes. The NAT2 resources created to support this guideline enable us to map genotypes to FDA-approved drug label annotations and annotated Table of Pharmacogenetic Associations entries for NAT2 and "Nonspecific (NAT)". Annotations for amifampridine, amifampridine phosphate, hydralazine, isoniazid, procainamide, sulfamethoxazole/trimethoprim and sulfasalazine are now included in our precision guidance tools PharmDOG/GSI and are coming soon to PharmCAT.