Background
Phenylalanine is an essential amino acid that is not produced by the human organism itself. Phenylalanine ingested with food is produced by the enzyme phenylalanine hydroxylase and its cofactor 6-tetrahydrobiopterin (6-BH4) metabolized to tyrosine. Phenylketonuria is an autosomal recessive disorder caused by insufficient activity of phenylalanine hydroxylase, resulting in elevated blood phenylalanine levels, i.e., hyperphenylalaninemia. If left untreated, it leads to severe clinical symptoms such as developmental disabilities, mental retardation, and skin disorders. A lifelong phenylalanine-free diet is necessary. A less common disorder of biosynthesis or regeneration of cofactor BH4 can also lead to hyperphenylalaninemia (so-called BH4 deficiency).
Products
Kuvan, tablets for oral solution preparation.
Structure and properties
Sapropterin is synthetically produced 6-tetrahydrobiopterin (6-BH4) and corresponds to the cofactor of phenylalanine hydroxylase.
Effects
ATC A16AX07 In a proportion of patients with hyperphenylalaninemia, ingestion of sapropterin allows an increase in phenylalanine hydroxylase activity and a decrease in blood phenylalanine levels.
Indications
Sapropterin is used to treat hyperphenylalaninemia in patients with phenylketonuria or tetrahydrobiopterin deficiency if they respond.
Dosage
Dosage is based on body weight. Sapropterin is taken in the morning with food as a single dose always at the same time of day. For this purpose, the ready-to-drink solution must first be prepared by dissolving the tablets in water. The treatment must be monitored by a doctor.
Contraindications
- Hypersensitivity
- Pregnancy and lactation: see SmPC
- Children < 4 years (no data)
Further precautions according to the expert information.
Interactions
Dihydrofolate reductase inhibitors such as methotrexate and trimethoprim may potentially affect BH4 metabolism. Caution with drugs affecting NO degradation or its action: nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, nitroprusside, molsidomine, phosphodiesterase-5 inhibitors, minoxidil. Concurrent therapy with levodopa may result in increased excitability and irritability.
Adverse effects
Very common:
- Headache
- Runny nose
Common:
- Throat and larynx pain
- Blocked nose
- Cough
- Diarrhea
- Vomiting
- Abdominal pain
- Hypophenylalaninemia
