Sodium Phenylbutyrate Tablets, 500 Mg
FDA Drug Information • Also known as: Sodium Phenylbutyrate
- Brand Names
- Sodium Phenylbutyrate
- Route
- ORAL
- Dosage Form
- TABLET
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
DESCRIPTION Sodium Phenylbutyrate Tablets, USP for oral administration contain Sodium phenylbutyrate, USP. Sodium Phenylbutyrate, USP is an off-white crystalline substance which is soluble in water and has a strong salty taste. Sodium Phenylbutyrate, USP also is freely soluble in methanol and practically insoluble in acetone and diethyl ether. It is known chemically as 4-phenylbutyric acid, sodium salt with a molecular weight of 186 and the molecular formula C 10 H 11 O 2 Na. Chemical Structure: Each tablet of Sodium Phenylbutyrate Tablets, USP contains 500 mg of Sodium Phenylbutyrate, USP and the inactive ingredients calcium stearate NF, colloidal silicon dioxide NF, magnesium stearate and microcrystalline cellulose. sodium-phenyl
What Is Sodium Phenylbutyrate Tablets, 500 Mg Used For?
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 patients tested). Retardation was severe in the majority of the retarded patients. In patients diagnosed during gestation and treated prior to any episode of hyperammonemic encephalopathy, survival is 100%, but even in these patients, most subsequently demonstrate cognitive impairment or other neurologic deficits. In late-onset deficiency patients, including females heterozygous for ornithine transcarbamylase deficiency, who recover from hyperammonemic encephalopathy and are then treated chronically with Sodium Phenylbutyrate Tablets and dietary protein restriction, the survival rate is 98%. The two deaths in this group of patients occurred during episodes of hyperammonemic encephalopathy. However, compliance with the therapeutic regimen has not been adequately documented to allow evaluation of the potential for Sodium Phenylbutyrate Tablets and dietary protein restriction to prevent mental deterioration and recurrence of hyperammonemic encephalopathy if carefully...
Dosage and Administration
DOSAGE & 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/m 2 /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 least 6 months of age, it is recommended that the daily protein intake be equally divided between natural protein and supplemental essential amino acids. Patients with argininosuccinic acid synthetase deficiency and those with late-onset disease (partial deficiencies, including females heterozygous for ornithine transcarbamylase), initially may receive a diet containing the age-determined minimal daily natural protein allowance. The protein intake may be increased as tolerated and determined by plasma glutamine and other amino acid levels. However, many patients with partial deficiencies avoid dietary protein. Citrulline supplementation is required and recommended for patients diagnosed with neonatal-onset deficiency of carbamylphosphate synthetase or ornithine transcarbamylase; citrulline daily intake is recommended at 0.17 g/kg/day or 3.8 g/m 2 /day. The free-base form of arginine may be used instead of citrulline in patients with milder forms of...
Side Effects (Adverse Reactions)
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 suggest a drug effect. LABORATORY ADVERSE EVENTS In patients with urea cycle disorders, the frequency of laboratory adverse events by body system were: Metabolic : acidosis (14%), alkalosis and hyperchloremia (each 7%), hypophosphatemia (6%), hyperuricemia and hyperphosphatemia (each 2%), and hypernatremia and hypokalemia (each 1%). Nutritional : hypoalbuminemia (11%) and decreased total protein (3%). Hepatic : increased alkaline phosphatase (6%), increased liver transaminases (4%), and hyperbilirubinemia (1%). Hematologic : anemia (9%), leukopenia and leukocytosis (each 4%), thrombocytopenia (3%), and thrombocytosis (1%). The clinician is advised to routinely perform urinalysis, blood chemistry profiles, and hematologic tests.
Warnings and Precautions
WARNINGS Each sodium phenylbutyrate tablet contains 62 mg of sodium (9.2 % w/w) (corresponding to 124 mg of sodium per gram of sodium phenylbutyrate [12.4% w/w]). Sodium phenylbutyrate should be used with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states in which there is sodium retention with edema. Because sodium phenylbutyrate is metabolized in the liver and kidney, and phenylacetylglutamine is primarily excreted by the kidney, use caution when administering the drug to patients with hepatic or renal insufficiency or inborn errors of beta oxidation. Probenecid is known to inhibit the renal transport of many organic compounds, including hippuric acid, and may affect renal excretion of the conjugated product of sodium phenylbutyrate as well as its metabolite. Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.
Contraindications
CONTRAINDICATIONS Sodium phenylbutyrate tablets should not be used to manage acute hyperammonemia, which is a medical emergency.
Overdosage
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.
How Supplied
HOW SUPPLIED Sodium Phenylbutyrate Tablets, USP are available as 500 mg in bottles of 250 Sodium Phenylbutyrate Tablets, USP (NDC 49884-170-04). The bottles are equipped with child-resistant caps. White to off-white, oval shaped tablet debossed 'EP 340' on one side and plain on the other side. Each tablet contains 500 mg of sodium phenylbutyrate, USP. Store at 20º to 25º C (68º to 77ºF); [see USP Controlled Temperature]; Excursions permitted to 15º to 30ºC (59º to 86ºF) . After opening, keep bottle tightly closed.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.