Glycerol Phenylbutyrate (2 brand names, 1 dosage form, 1 route)
Available dosage forms: LIQUID.
Routes of administration: ORAL.
Brand Names
- GLYCEROL PHENYLBUTYRATE
- RAVICTI
Indications and Usage
Glycerol phenylbutyrate oral liquid is indicated for use as a nitrogen-binding agent for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Glycerol phenylbutyrate oral liquid must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements). Limitations of Use: Glycerol phenylbutyrate oral liquid is not indicated for the treatment of acute hyperammonemia in patients with UCDs because more rapidly acting interventions are essential to reduce plasma ammonia levels. The safety and efficacy of glycerol phenylbutyrate oral liquid for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.
Contraindications
Glycerol phenylbutyrate oral liquid is contraindicated in patients with known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: • Neurotoxicity [see Warnings and Precautions (5.1)] • Pancreatic insufficiency or Intestinal Malabsorption [see Warnings and Precautions (5.2)]
Mechanism of Action
UCDs are inherited deficiencies of enzymes or transporters necessary for the synthesis of urea from ammonia (NH3, NH4 +). Absence of these enzymes or transporters results in the accumulation of toxic levels of ammonia in the blood and brain of affected patients. Glycerol phenylbutyrate is a triglyceride containing 3 molecules of PBA. PAA, the major metabolite of PBA, is the active moiety of glycerol phenylbutyrate. PAA conjugates with glutamine (which contains 2 molecules of nitrogen) via acetylation in the liver and kidneys to form PAGN, which is excreted by the kidneys (Figure 1). On a molar basis, PAGN, like urea, contains 2 moles of nitrogen and provides an alternate vehicle for waste nitrogen excretion. Figure 1: Glycerol phenylbutyrate Mechanism of Action
Overdosage
While there is no experience with overdosage in human clinical trials, PAA, a toxic metabolite of glycerol phenylbutyrate oral liquid, can accumulate in patients who receive an overdose [see Warnings and Precautions (5.1)]. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.