Urea cycle disorders

Active Ingredient: Sodium phenylbutyrate

Indication for Sodium phenylbutyrate

Population group: only children (1 year - 12 years old) , adolescents (12 years - 18 years old) , adults (18 - 65 years old)

Sodium phenylbutyrate is indicated as adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase.

It is indicated in all patients with neonatal-onset disease (complete enzyme deficiencies, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy.

For this indication, competent medicine agencies globally authorize below treatments:

9.9-13.0 g/m² in 3 divided doses daily

Route of admnistration

Oral

Defined daily dose

9.9 - 13 g per m² of body surface area (BSA)

Dosage regimen

From 3.3 To 4.333 g per m² of body surface area (BSA) 3 time(s) per day every day

Detailed description

The daily dose should be individually adjusted according to the patient’s protein tolerance and the daily dietary protein intake needed to promote growth and development.

The usual total daily dose of sodium phenylbutyrate in clinical experience is:

  • 450-600 mg/kg/day in neonates, infants and children weighing less than 20 kg.
  • 9.9-13.0 g/m²/day in children weighing more than 20 kg, adolescents and adults.

The safety and efficacy of doses in excess of 20 g/day have not been established.

Therapeutic monitoring

Plasma levels of ammonia, arginine, essential amino acids (especially branched chain amino acids), carnitine and serum proteins should be maintained within normal limits. Plasma glutamine should be maintained at levels less than 1,000 μmol/L.

Nutritional management

Sodium phenylbutyrate must be combined with dietary protein restriction and, in some cases, essential amino acid and carnitine supplementation.

Citrulline or arginine supplementation is required for patients diagnosed with neonatal-onset form of carbamyl phosphate synthetase or ornithine transcarbamylase deficiency at a dose of 0.17 g/kg/day or 3.8 g/m²/day.

Arginine supplementation is required for patients diagnosed with deficiency of argininosuccinate synthetase at a dose of 0.4-0.7 g/kg/day or 8.8-15.4 g/m²/day.

If caloric supplementation is indicated, a protein-free product is recommended.

Dosage considerations

The total daily dose should be divided into equal amounts and given with each meal or feeding (e.g. 4-6 times per day in small children).

Active ingredient

Sodium phenylbutyrate

Sodium phenylbutyrate is a pro-drug and is rapidly metabolised to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine which is then excreted by the kidneys. On a molar basis, phenylacetylglutamine is comparable to urea (each containing 2 moles of nitrogen) and therefore provides an alternate vehicle for waste nitrogen excretion.

Read more about Sodium phenylbutyrate

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