Generic drug of the therapeutic class: Metabolism and nutrition
active ingredients: Sodium phenylbutyrate
laboratory: Swedish Orphan Inter AB
Box of 1 Bottle (+ measure of 1.2g or 3.3g or 9.7g) of 266 g
AMMONAPS is indicated as adjunctive therapy in the long-term management of urea cycle disorders involving deficiency of carbamylphosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase.
It is indicated in all neonatal forms (complete enzyme deficiency occurring in the first 28 days of life) and also in the forms of late revelation (partial enzymatic deficit occurring after the first month of life) with a history of encephalopathy hyperammonaemic.
Dosage AMMONAPS 940 mg / g Granule Box of 1 Bottle (+ measure of 1.2g or 3.3g or 9.7g) of 266 g
Treatment with AMMONAPS should be supervised by a physician experienced in the treatment of urea cycle disorders.
AMMONAPS granules should be administered orally (in infants and children unable to swallow tablets and in dysphagic patients), by gastrostomy tube or nasogastric tube.
The daily dose must be adapted individually according to the protein tolerance of the patient and the food protein intake necessary for its growth and development.
The total daily dose of sodium phenylbutyrate usually used in clinical practice is:
. 450 - 600 mg / kg / day in neonates, infants and children under 20 kg,
. 9.9 - 13.0 g / m² / day in children over 20 kg, adolescents and adults.
The safety and efficacy of doses greater than 20 g / day have not been established.
Therapeutic monitoring : Plasma levels of ammonia, arginine, essential amino acids (especially branched amino acids), carnitine and proteins should be kept within normal limits and that of glutamine levels below 1000 μmol / L.
Nutritional Surveillance : AMMONAPS should be combined with a low protein diet and in some cases supplemented with essential amino acids and carnitine.
In neonatal forms deficient in carbamylphosphate synthetase or ornithine transcarbamylase, supplementation with citrulline or arginine is required at a dose of 0.17 g / kg / day or 3.8 g / m² / day.
In arginine succinate synthetase deficiency, supplementation with arginine is necessary at a dose of 0.4 to 0.7 g / kg / day or 8.8 to 15.4 g / m² / day.
If caloric supplementation is indicated, it is recommended to use a protein free preparation.
The total daily dose should be divided into equal doses given at each meal or by eating (for example, 4 to 6 times a day in young children). When administered orally, the granules should be mixed with solid foods (such as mashed potatoes or applesauce) or liquid foods (such as water, apple juice, juice). of orange or infantile preparations without proteins).
Three measuring spoons are provided which deliver 1.2 g, 3.3 g or 9.7 g of sodium phenylbutyrate.
Shake the bottle slightly before use.
• Hypersensitivity to the active substance or to any of the excipients listed under Composition.
Adverse effects Ammonaps
In clinical trials with AMMONAPS, 56% of patients experienced at least one adverse event and 78% of these adverse events were considered unrelated to AMMONAPS.
These undesirable effects mainly concern the reproductive and gastrointestinal tract.
Adverse reactions are listed below by organ system class and frequency. Frequency is defined as: very common (≥ 1/10), frequent (≥ 1/100, <1/10), uncommon (≥ 1/1000, <1/100), rare (≥ 1/10) 000, <1/1000), very rare (<1 / 10, 000) and undetermined (can not be estimated from the available data). Within each frequency group, adverse effects should be presented in order of decreasing severity.
Hematological and lymphatic system disorders:
Common: Anemia, thrombocytopenia, leukopenia, leukocytosis, thrombocytosis.
Uncommon: Aplastic anemia, bruising.
Metabolism and nutrition disorders:
Common: Metabolic acidosis, alkalosis, decreased appetite.
Frequent: Depression, irritability.
Nervous system disorders:
Frequent: Syncope, headache.
Common : Abdominal pain, vomiting, nausea, constipation, dysgeusia
Uncommon : Pancreatitis, peptic ulcer, rectal hemorrhage, gastritis.
Skin and subcutaneous tissue disorders:
Common : Rash, abnormal smell of the skin.
Renal and urinary disorders:
Common: Renal tubular acidosis.
Disorders of the reproductive organs and the breast:
Very common : Amenorrhea, irregular menstruation.
Frequent: Decreased blood levels of potassium, albumin, total protein and phosphate. Increased blood levels of alkaline phosphatase, transaminases, bilirubin, uric acid, chloride, phosphate and sodium. Weight gain.
A probable case of AMMONAPS toxicity (450 mg / kg / day) has been reported in an 18-year-old anorexic patient with metabolic encephalopathy associated with lactic acidosis, severe hypokalemia, pancytopenia, peripheral neuropathy and pancreatitis .
She was cured after dose reduction with the exception of recurrent episodes of pancreatitis which ultimately led to discontinuation of treatment.
Reporting of suspected adverse reactions
The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the reporting system - see Annex V.