Brand Names

BUPHENYL
OLPRUVA
PHEBURANE
RELYVRIO
SODIUM PHENYLBUTYRATE

Sodium

Indications and Usage

Sodium Phenylbutyrate Tablets is indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy. It is important that the diagnosis be made early and treatment initiated immediately to improve survival. Any episode of acute hyperammonemia should be treated as a life-threatening emergency. Sodium Phenylbutyrate Tablets must be combined with dietary protein restriction and, in some cases, essential amino acid supplementation. (See Nutritional Supplementation subsection of the DOSAGE AND ADMINISTRATION section.) Previously, neonatal-onset disease was almost universally fatal within the first year of life, even when treated with peritoneal dialysis and essential amino acids or their nitrogen-free analogs. However, with hemodialysis, use of alternative waste nitrogen excretion pathways (sodium phenylbutyrate, sodium benzoate, and sodium phenylacetate), dietary protein restriction, and, in some cases, essential amino acid supplementation, the survival rate in newborns diagnosed after birth but within the first month of life is almost 80%. Most deaths have occurred during an episode of acute hyperammonemic encephalopathy. Patients with neonatal-onset disease have a high incidence of mental retardation. Those who had IQ tests administered had an incidence of mental retardation as follows: ornithine transcarbamylase deficiency, 100% (14/14 patients tested); argininosuccinic acid synthetase deficiency, 88% (15/17 patients tested); and carbamylphosphate synthetase deficiency, 57% (4/7 patient

Dosage and Administration

For oral use only. The use of Sodium Phenylbutyrate Tablets is indicated for children weighing more than 20 kg and for adults. The usual total daily dose of Sodium Phenylbutyrate Tablets for patients with urea cycle disorders is 450 to 600 mg/kg/day in patients weighing less than 20 kg, or 9.9 to 13 g/m2/day in larger patients. The tablets is to be taken in equally divided amounts with each meal or feeding (i.e., three to six times per day). The safety or efficacy of doses in excess of 20 grams per day has not been established. NUTRITIONAL MANAGEMENT To promote growth and development, plasma levels of ammonia, arginine, branched-chain amino acids, and serum protein should be maintained within normal limits while plasma glutamine is maintained at levels less than 1,000 µmol/L. Minimum daily protein intake for a patient of a particular age should be taken from, for example, “Recommended Dietary Allowances”, 10th ed., Food and Nutrition Board, National Academy of Sciences, 1989. The allocation of dietary nitrogen into natural protein and essential amino acids is a function of age, residual urea-cycle enzyme activity, and the dose of sodium phenylbutyrate. At the recommended dose of sodium phenylbutyrate, it is suggested that infants with neonatal-onset CPS and OTC deficiencies initially receive a daily dietary protein intake limited to approximately 1.6 g/kg/day for the first 4 months of life. If tolerated, the daily protein intake may be increased to 1.9 g/kg/day during this period. Protein tolerance will decrease as the growth rate decreases, requiring a reduction in dietary nitrogen intake. From 4 months to 1 year of age, it is recommended that the infant receive at least 1.4 g/kg/day, but 1.7 g/kg/day is advisable. From 1 to 3 years of age, the protein intake should not be less than 1.2 g/kg/day; 1.4 g/kg/day is advisable during this period. For neonatal-onset patients with carbamylphosphate synthetase deficiency or ornithine transcarbamylase deficiency who are at

Contraindications

Sodium phenylbutyrate tablets should not be used to manage acute hyperammonemia, which is a medical emergency.

Adverse Reactions

The assessment of clinical adverse events came from 206 patients treated with sodium phenylbutyrate. Adverse events (both clinical and laboratory) were not collected systematically in these patients, but were obtained from patient-visit reports by the 65 co-investigators. Causality of adverse effects is sometimes difficult to determine in this patient population because they may result from either the underlying disease, the patient’s restricted diet, intercurrent illness, or sodium phenylbutyrate. Furthermore, the rates may be under-estimated because they were reported primarily by parent or guardian and not the patient. CLINICAL ADVERSE EVENTS In female patients, the most common clinical adverse event reported was amenorrhea/menstrual dysfunction (irregular menstrual cycles), which occurred in 23% of the menstruating patients. Decreased appetite occurred in 4% of all patients. Body odor (probably caused by the metabolite, phenylacetate) and bad taste or taste aversion were each reported in 3% of patients. Other adverse events reported in 2% or fewer patients were: Gastrointestinal: abdominal pain, gastritis, nausea and vomiting; constipation, rectal bleeding, peptic ulcer disease, and pancreatitis each occurred in one patient. Hematologic: aplastic anemia and ecchymoses each occurred in one patient. Cardiovascular: arrhythmia and edema each occurred in one patient. Renal: renal tubular acidosis Psychiatric: depression Skin: rash Miscellaneous: headache, syncope, and weight gain Neurotoxicity was reported in cancer patients receiving intravenous phenylacetate, 250 to 300 mg/kg/day for 14 days, repeated at 4-week intervals. Manifestations were predominately somnolence, fatigue, and lightheadedness; with less frequent headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of a pre-existing neuropathy. These adverse events were mainly mild in severity. The acute onset and reversibility when the phenylacetate infusion was discontinued sugges

Overdosage

No adverse experiences have been reported involving overdoses of sodium phenylbutyrate in patients with urea cycle disorders. In the event of an overdose, discontinue the drug and institute supportive measures. Hemodialysis or peritoneal dialysis may be beneficial.

⚠ Caution

Medical Disclaimer: This information is for educational purposes only. Always consult a healthcare professional before taking any medication.