Isosorbide and Hydralazine

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

The FDA highlight pharmacogenomic information regarding the biomarkers NAT1 and NAT2 for the clinical pharmacology of Isosorbide and Hydralazine. However, the latest drug label available (2005) does not specifically mention genetic or biomarker testing. Hydralazine hydrochloride and isosorbide dinitrate (trade name: BiDil) is used for the treatment of heart failure.

Excerpt from the Hydralazine hydrochloride and isosorbide dinitrate drug label:

"Metabolism and Elimination: Metabolism is the main route for the elimination of hydralazine. Negligible amounts of unchanged hydralazine are excreted in urine. Hydralazine is metabolized by acetylation, ring oxidation and conjugation with endogenous compounds including pyruvic acid. Acetylation occurs predominantly during the first pass after oral administration which explains the dependence of the absolute bioavailability on the acetylator phenotype. About 50% of patients are fast acetylators and have lower exposure."

SUMMARY
Individuals who are "fast acetylators" have reduced exposure to hydralazine and the FDA have highlighted the NAT1 and NAT2 biomarkers in the clinical pharmacology of this drug label. Though NAT1 and NAT2 are not specifically mentioned in the drug label available, both are acetyltransferases, therefore genetic variants within these genes may influence the bioavailability of Hydralazine.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Isosorbide and Hydralazine drug label PDF.