Drug Interaction Report

MONITOR: Coadministration with phenylbutyrate/taurursodiol (ursodoxicoltaurine) may increase the plasma concentrations of drugs that are substrates of CYP450 2C19, 2C8, 2C9, 2D6, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and/or organic anion transporter 1 (OAT1). Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Caution is advised if phenylbutyrate/taurursodiol is used concomitantly with substrates of CYP450 2C19, 2C8, 2C9, 2D6, P-gp, BCRP, and/or OAT1, particularly sensitive substrates or those with a narrow therapeutic range. The prescribing information for taurursodiol combined with sodium phenylbutyrate recommends avoiding coadministration with substrates of these isoenzymes and transporters for which minimal concentration changes may lead to therapeutic failure or serious toxicities. If coadministration is required, dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever phenylbutyrate/taurursodiol is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

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).