Drug Interaction Report

GENERALLY AVOID: Coadministration of histone deacetylase (HDAC) inhibitors and phenylbutyrate may lead to excess inhibition of HDAC and additive adverse effects. According to the prescribing information for sodium phenylbutyrate combined with taurursodiol (ursodoxicoltaurine), phenylbutyrate is a pan-HDAC inhibitor. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: The prescribing information for sodium phenylbutyrate combined with taurursodiol recommends avoiding concomitant use of phenylbutyrate and other HDAC inhibitors.

ADJUST DOSING INTERVAL: Coadministration with a high-fat meal may reduce the rate and extent of absorption of sodium phenylbutyrate. When a single 3 g-1 g dose of sodium phenylbutyrate-taurursodiol (sodium phenylbutyrate-ursodoxicoltaurine) was administered to healthy volunteers in the presence of a high-fat, high-calorie meal (approximately 800 to 1000 calories; 500 to 600 calories from fat, 250 calories from carbohydrate, 150 calories from protein), sodium phenylbutyrate peak plasma concentration (Cmax) decreased by 75% and systemic exposure (AUC) decreased by 55%. The Cmax for taurursodiol was not significantly affected, but AUC was increased by 46%. The clinical significance of these changes has not been established. In premarketing studies, patients were advised to take the drug before a meal.

MANAGEMENT: The prescribing information recommends administration of sodium phenylbutyrate-taurursodiol before a meal or snack, particularly in patients of low body weight (less than 70 kg).