페닐부틸산나트륨

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. Glycerol phenylbutyrate is a nitrogen-binding agent indicated 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. ( 1 ) Limitations of Use: • Glycerol phenylbutyrate oral liquid is not indicated for treatment of acute hyperammonemia in patients with UCDs. ( 1 ) • Safety and efficacy for treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established. ( 1 )

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. Known hypersensitivity to phenylbutyrate. ( 4 )

• Neurotoxicity: Phenylacetate (PAA), the active moiety of glycerol phenylbutyrate, may be toxic; reduce dosage for symptoms of neurotoxicity. ( 5.1 ) • Pancreatic Insufficiency or Intestinal Malabsorption: Monitor ammonia levels closely. ( 5.2 ) 5.1 Neurotoxicity Increased exposure to PAA, the major metabolite of glycerol phenylbutyrate, may be associated with neurotoxicity in patients with UCDs. In a study of adult cancer patients, subjects received sodium phenylacetate administered as a 1-hour infusion twice daily at two dose levels of 125 and 150 mg/kg for a 2-week period. Of 18 subjects enrolled, 7 had a history of primary central nervous system tumor. Signs and symptoms of potential PAA neurotoxicity, which were reversible, were reported at plasma PAA concentrations above 500 micrograms/mL and included somnolence, fatigue, lightheadedness, headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of preexisting neuropathy. PAA concentrations were not measured when symptoms resolved. In healthy subjects, after administration of 4 mL and 6 mL glycerol phenylbutyrate 3 times daily (13.2 g/day and 19.8 g/day, respectively) for 3 days, a dosedependent increase in non-serious nervous system adverse reactions were observed. In subjects who had nervous system adverse reactions, plasma PAA concentrations, which were measured on Day 3 per protocol and not always at onset of symptoms, ranged from 8 to 56 micrograms/mL with 4 mL glycerol phenylbutyrate 3 …

8.1 Pregnancy Risk Summary Limited available data with glycerol phenylbutyrate use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of oral glycerol phenylbutyrate to pregnant rabbits during organogenesis at doses up to 2.7–times the dose of 6.87 mL/m 2 /day in adult patients resulted in maternal toxicity, but had no effects on embryo-fetal development. In addition, there were no adverse developmental effects with administration of oral glycerol phenylbutyrate to pregnant rats during organogenesis at 1.9 times the dose of 6.87 mL/m 2 /day in adult patients; however, maternal toxicity, …