Included in the formulation
Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):VED
АТХ:A.16.A.X Other drugs for the treatment of digestive and metabolic diseases
A.16.A.X.07 Saprotherin
Pharmacodynamics:Hyperphenylalaninemia - disease are caused by autosomal recessive mutations in the genes encoding phenylalanine hydroxylase enzyme (for phenylketonuria), or enzymes involved in the biosynthesis or regeneration (in the case of BH4 deficiency) 6R-tetrahydrobiopterin (6R -BH4). Lack of BH4 - a group of diseases associated with mutations or deletions in the genes encoding one of the five enzymes involved in the biosynthesis or recycling of BH4. In both cases, phenylalanine can not be effectively converted into an amino acid tyrosine, which leads to an increase in the level of phenylalanine in the blood.
Sapropterin is a synthetic analogue of the natural 6R-BH4, which is a factor hydroxylases to phenylalanine, tyrosine and tryptophan.
Pharmacokinetics:Sapropterin absorbed after oral administration of dissolved tablets, the maximum blood concentration reached in 3-4 hours after ingestion fasting.The speed and extent of absorption of sapropeterine is affected by food. Absorption increases with the use of high-calorie foods with a high fat content. When compared with the use in empty stomach, the average maximum blood concentration at 40-85% higher in 4-5 hours after administration. Bioavailability for a person after ingestion is unknown.
Metabolized in the liver in dihydrobiopterin and biopterin. The metabolic cycle is similar to 6R-BH4.
At oral reception basically it is deduced with faeces, a small part - with urine.
Indications:Hyperphenylalanineemia in adults and children older than 4 years suffering from phenylketonuria.
Hyperphenylalanineemia in adults and children older than 4 years with a deficiency of tetrahydrobioperin.
IV.E70-E90.E70.1 Other types of hyperphenylalaninemia
IV.E70-E90.E70.2 Violations of tyrosine metabolism
IV.E70-E90.E70.3 Albinism
IV.E70-E90.E70.9 Disturbances in the exchange of aromatic amino acids, unspecified
IV.E70-E90.E70.8 Other metabolic disturbances of aromatic amino acids
IV.E70-E90.E70 Disturbances in the exchange of aromatic amino acids
Contraindications:Hypersensitivity.
Carefully:Patients with predisposition to convulsions.
Despite the fact that the concomitant use of methotrexate inhibitor dihydrofolate reductase and sapropterin has not been studied,should be cautiously appointed methotrexate with the simultaneous use of sapropeter.
Pregnancy and lactation:Action category for the fetus by FDA - FROM.
Animal studies have identified a negative effect of the drug on the fetus, and there have not been proper studies in pregnant women, but the potential benefits associated with the use of this medication in pregnant women can justify its use, despite the risk.
Dosing and Administration:Phenylketonuria:
The initial dose for adults and children is 10 mg / kg of body weight once daily. The dose is usually adjusted from 5 to 20 mg / kg / day until adequate levels of phenylalanine are achieved and maintained.
Deficit of BH4:
The initial dose for adults and children is from 2 to 5 mg / kg of body weight once daily. The dose can be adjusted to 20 mg / kg / day. It is possible to divide the total daily dose by 2-3 injections during the day.
Side effects:Often: headache, rhinorrhea. Often: pain in the throat and larynx, nasal congestion, cough, diarrhea, vomiting, abdominal pain, hypophenylalaninemia.
At the termination of treatment with the drug, it is possible to increase the level of phenylalanine in the blood above the levels fixed before the drug therapy.
Overdose:Symptoms: headache and dizziness.
Treatment: symptomatic.
Interaction:Use with caution with vardenafil, sildenafil, tadalafil - PDE-5 inhibitors that have a vasodilating effect, with isosorbide dinitrate and other nitrates, with molisidomine - NO donors due to its effect on the metabolism and / or mechanism of action of NO.
Combination therapy with levodopa and sapropterin in patients with tetrahydrobiopterin insufficiency (BH4) may increase excitability and irritability, as well as cause or occur seizures, especially at the beginning of therapy. In this case, correction of the dose of levodopa may be required.
With sildenafil, tadalafil - an inhibitor of PDE-5, which has a vasodilating effect due to its effect on the metabolism and / or mechanism of action of NO.
Special instructions:Patients during therapy should continue to adhere to a diet that prohibits the reception of phenylalanine, and to undergo regular monitoring of phenylalanine and tyrosine levels in the blood, the intake of phenylalanine with food, and control of psychomotor development.
Constant or periodic dysfunction of the metabolic chain of phenylalanine-tyrosine-dihydroxy-L-phenylalanine (DOPA) can lead to a deficiency of proteins in the body and an inadequate synthesis of neurotransmitters.A prolonged lack of phenylalanine and tyrosine levels in infancy may be associated with impaired development of the nervous system. To ensure an adequate level of phenylalanine and tyrosine in the blood and balance of nutrients, an active control of the intake of phenylalanine and proteins with food during treatment is required.
Data on long-term use are limited.
Special studies in the treatment of children under 4 years old were not conducted.
Safety and efficacy in elderly patients are not established.
Studies of safety and efficacy in patients with renal and hepatic insufficiency have not been conducted.