Posology : מינונים

4.2     Posology and method of administration

PHEBURANE treatment should be supervised by a physician experienced in the treatment of urea cycle disorders.

Posology
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 of sodium phenylbutyrate 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
PHEBURANE 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.

Special populations
Renal and hepatic impairment
Since the metabolism and excretion of sodium phenylbutyrate involves the liver and kidneys, PHEBURANE should be used with caution in patients with hepatic or renal insufficiency.

Method of administration
PHEBURANE should be administered orally. Because of its slow dissolution, PHEBURANE should not be administered by nasogastric or gastrostomy tubes.

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). The granules can be directly swallowed with a drink (water, fruit juices, protein-free infant formulas) or sprinkled on to a spoonful of solid foods (mashed potatoes or apple sauce); in this case, it is important that it is taken immediately in order to preserve the taste-masking.

The dose of PHEBURANE is expressed in grams of sodium phenylbutyrate. A calibrated measuring spoon is provided. It dispenses up to 3g of sodium phenylbutyrate by graduation of 250 mg.