Drug Interaction Report

MONITOR CLOSELY: Probenecid may inhibit the renal excretion of metabolites of phenylbutyrate, including phenylacetate (PAA) and phenylacetylglutamine (PAGN). PAA is associated with neurotoxic effects such as somnolence, fatigue, lightheadedness, headache, dysgeusia, hypoacusis, disorientation, memory impairment, tremor, peripheral neuropathy, and seizures.

MANAGEMENT: Since plasma PAA and urinary PAGN levels may be used to help guide dosing of phenylbutyrate therapy, caution is advised if probenecid is coadministered. The potential for increased risk of PAA-induced neurotoxicity should also be considered. The prescribing information for sodium phenylbutyrate combined with taurursodiol (ursodoxicoltaurine) recommends avoiding concomitant use of probenecid.

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).