Clinical Pharmacogenetics Implementation Consortium Guideline for NAT2 Genotype and Hydralazine Therapy

Area of Science:

• Pharmacogenomics
• Drug Metabolism
• Cardiovascular Therapeutics

Background:

• Hydralazine is a vasodilator for hypertension and heart failure.
• N-acetyltransferase 2 (NAT2) metabolizes hydralazine into inactive forms.
• NAT2 genotype influences hydralazine metabolism and patient response.

Purpose of the Study:

• To review literature on NAT2 and hydralazine interactions.
• To provide evidence-based recommendations for hydralazine prescribing.
• To guide clinical practice based on NAT2 genotype-predicted acetylator phenotype.

Main Methods:

• Literature review of NAT2/hydralazine evidence.
• Analysis of genotype-phenotype correlations for NAT2.
• Development of clinical practice guidelines.

Main Results:

• NAT2 poor metabolizers are predicted to have higher hydralazine plasma concentrations.
• Increased concentrations may lead to enhanced efficacy and adverse events, including drug-induced systemic lupus erythematosus.
• NAT2 genotype impacts hydralazine pharmacokinetics and pharmacodynamics.

Conclusions:

• NAT2 genotype influences hydralazine treatment outcomes.
• Prescribing hydralazine based on NAT2 acetylator phenotype can optimize therapy.
• Guidelines are updated at www.cpicpgx.org for current recommendations.