Drug Interaction Report

MONITOR: Drugs that can increase plasma ammonia levels such as corticosteroids, haloperidol, or the anticonvulsants carbamazepine, topiramate, and phenobarbital may interfere with the therapeutic effects of phenylbutyrate therapy in the management of urea cycle disorders. Corticosteroids can cause the breakdown of body protein, which may lead to increased ammonia levels. The use of haloperidol has been associated with hyperammonemia in a young child with citrullinemia, an inherited disorder of ammonia excretion. The mechanism for haloperidol, carbamazepine, topiramate, and phenobarbital has not been established.

MANAGEMENT: Plasma ammonia levels should be closely monitored when corticosteroids, haloperidol, carbamazepine, topiramate, or phenobarbital are used in patients with urea cycle disorders receiving phenylbutyrate therapy.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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).