Sapropterin Oral Solution

Generic name:

Sapropterin dihydrochloride

Drug class:

Protein replacement therapy; Synthetic form of tetrahydrobiopterin (BH4), a cofactor for phenylalanine hydroxylase

Dosage form:

• Oral solution
• Tablets (varies by formulation; primarily oral solution for pediatric use)

Route of administration:

Oral

Dose:

• Initial: 10 mg/kg/day
• Maintenance dose: 5 to 20 mg/kg/day
• Maximum dose: 20 mg/kg/day or 1,000 mg/day (whichever is less)
• Dosing individualized based on response to therapy and phenylalanine levels
• Administered once daily or divided doses depending on clinical judgment

Mechanism of action:

Sapropterin is a synthetic form of tetrahydrobiopterin (BH4), an essential cofactor for the enzyme phenylalanine hydroxylase (PAH). PAH catalyzes the conversion of the amino acid phenylalanine to tyrosine. In patients with phenylketonuria (PKU), PAH deficiency or dysfunction leads to accumulation of phenylalanine, which can be neurotoxic. Sapropterin enhances residual PAH activity, lowering blood phenylalanine levels.

Drug usage cases:

• Phenylketonuria (PKU), mild to moderate forms, responsive to BH4
• Adjunctive therapy with a phenylalanine-restricted diet for PKU patients
• Varies by indication; consult label for any off-label use

Drug contraindications:

• Known hypersensitivity to sapropterin dihydrochloride or any of its components
• Use in patients with phenylalanine hydroxylase deficiency who are non-responsive to sapropterin (no therapeutic benefit)
• Varies by indication; consult label

Side effects:

• Headache
• Runny nose (nasopharyngitis)
• Diarrhea
• Cough
• Vomit
• Upper respiratory tract infection
• Oral ulcers
• Hypersensitivity reactions including rash and urticaria
• Potential for anemia (rare)
• Varies by individual tolerance and dose

Warnings:

• Monitor blood phenylalanine levels regularly to adjust dosing and avoid toxicity
• Not effective in all patients with PKU; assess responsiveness before long-term treatment
• Use caution in patients with pre-existing anemia or other blood disorders
• Avoid abrupt discontinuation to prevent rebound increase in phenylalanine levels
• Potential hypersensitivity: discontinue if serious allergic reaction occurs
• Monitor for gastrointestinal symptoms and adjust dose if necessary
• Use with caution in patients with hepatic impairment; data limited
• Varies by indication; consult label for additional warnings

Use during pregnancy or breastfeeding:

There are limited data on the use of sapropterin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. However, sapropterin should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus. Phenylketonuria itself poses risks during pregnancy, making metabolic control important.

Breastfeeding: It is unknown whether sapropterin is excreted in human milk. Caution should be exercised when administered to a nursing mother. Benefits of breastfeeding should be weighed against the mother’s need for sapropterin therapy and any potential adverse effects on the infant.