Usual Adult Dose for Urea Cycle Disorders

Administer orally in equally divided doses with each meal or feeding (i.e., 3 to 6 times a day):

• Weight: Less than 20 kg: 450 to 600 mg/kg/day
• Weight: 20 kg or Greater: 9.9 to 13 g/m2/day

• Treatment should be combined with dietary protein restriction and, in some cases, essential amino acid

• Adjunctive therapy in the chronic management of urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase.
• Indicated for treatment of neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life) and late-onset disease (partial enzymatic deficiency, presenting after the first month of life) with history of hyperammonemic encephalopathy.

Usual Pediatric Dose for Urea Cycle Disorders

Administer orally in equally divided doses with each meal or feeding (i.e., 3 to 6 times a day):

• Weight: Less than 20 kg: 450 to 600 mg/kg/day
• Weight: 20 kg or Greater: 9.9 to 13 g/m2/day

• Treatment should be combined with dietary protein restriction and, in some cases, essential amino acid

• Tablets are not recommended in patients weighing less than 20 kg.

• Adjunctive therapy in the chronic management of UCDs involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase.
• Indicated for treatment of neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life) and late-onset disease (partial enzymatic deficiency, presenting after the first month of life) with history of hyperammonemic encephalopathy.

Renal Dose Adjustments

Use with caution

Liver Dose Adjustments

Use with caution

Dose Adjustments

To promote growth and development:

• Plasma levels of ammonia, arginine, branched-chain amino acids, and serum proteins should be maintained

• Plasma glutamine should be maintained at levels less than 1,000 micromol/L

Precautions

CONTRAINDICATIONS:

• Management of acute hyperammonemia
• This drug should not be administered to patients with known hypersensitivity to sodium phenylbutyrate or any component of this preparation

Dialysis

Data not available

Other Comments

Administration Advice:

• Take orally in equally divided doses with each meal or feeding (3 to 6 times per day)
• Shake lightly prior to use
• Powder formulation may be given via gastrostomy or nasogastric tube.

• When dissolved in water, the powder formulation is stable for up to one week at room temperature or under refrigeration.

• Mix the powder formulation with food (solid or liquid, e.g., mashed potatoes, apple sauce, water, apple juice, protein-free infant formula) for immediate use.
• When the powder formulation is added to a liquid, only the active substance will dissolve; the excipients will not dissolve.

• Treatment should be initiated as soon as possible to improve survival and clinical outcomes.
• Nutritional management is an important component of treating UCDs; the manufacturer product information may be consulted for nutritional management recommendations.
• For each gram of sodium phenylbutyrate administered, between 0.12 to 0.15 grams of phenylacetylglutamine nitrogen are produced.
• The safety and efficacy of doses in excess of 20 g/day have not been established.
• This drug may be required life-long unless orthotopic liver transplantation is elected.

• Urinalysis, hematological tests, blood chemistry profile, serum potassium, serum proteins, and plasma levels of glutamine, ammonia, arginine, branched-chain amino acids (routinely)
• Serum levels of phenylbutyrate, phenylacetate, phenylacetylglutamine (periodically)

• Patients/caregivers should be instructed to read the US FDA-approved patient labeling (Patient Package Insert).