Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Immedica Pharma AB, SE-113 29 Stockholm, Sweden
AMMONAPS 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 presentation (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.
AMMONAPS treatment should be supervised by a physician experienced in the treatment of urea cycle disorders.
The use of AMMONAPS tablets is indicated for adults and children who are able to swallow tablets. AMMONAPS is also available as granules for infants, children who are unable to swallow tablets and for patients with dysphagia.
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:
The safety and efficacy of doses in excess of 20 g/day (40 tablets) 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: AMMONAPS 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.
The total daily dose of AMMONAPS should be divided into equal amounts and given with each meal (e.g. three times per day). The tablets should be taken with a large volume of water.
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 diarrhoea, 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, hypacusis, disorientation, impaired memory and exacerbation of a pre-existing neuropathy.
In the event of an overdose, discontinue the treatment and institute supportive measures. Haemodialysis or peritoneal dialysis may be beneficial.
2 years.
Do not store above 30°C.
HDPE bottles, with child resistant caps, containing 250 or 500 tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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