PHEBURANE Granules Ref.[7695] Active ingredients: Sodium phenylbutyrate

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 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.

A calibrated dosing spoon is provided which dispenses up to 3g of sodium phenylbutyrate by graduation of 250 mg.

One case of overdose occurred in a 5-month old infant with an accidental single dose of 10 g (1370 mg/kg). The patient developed diarrhea, irritability and metabolic acidosis with hypokalaemia. The patient recovered within 48 hours after symptomatic treatment. These symptoms are consistent with the accumulation of phenylacetate, which showed dose-limiting neurotoxicity when administered intravenously at doses up to 400 mg/kg/day. Manifestations of neurotoxicity were predominantly somnolence, fatigue and light-headedness. Less frequent manifestations were confusion, headache, dysgeusia, hypoacusis, disorientation, impaired memory and exacerbation of a pre-existing neuropathy.

In the event of an overdose, the treatment should be discontinued and supportive measures be instituted. Haemodialysis or peritoneal dialysis may be beneficial

Shelf life: 3 years.

After the first opening, to be used within 45 days.

Not applicable.

HDPE bottle, child-resistant closure with desiccant, containing 174 g of granules. Each carton contains one bottle.

A calibrated measuring spoon is provided.

In case of mixture of the granules with solid foods or liquid it is important that it is taken immediately after mixing.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.