Oral Hyperphenylalaninaemia due to phenylketonuria
Adult: In conjunction with phenylalanine-restricted diet: Initially, 10-20 mg/kg once daily, preferably in the morning; adjust dose according to blood phenylalanine levels. Usual maintenance dose: 5-20 mg/kg once daily. Dietary phenylalanine and overall protein intake should be actively managed during treatment to ensure adequate blood phenylalanine control. Discontinue treatment if phenylalanine levels do not decrease after 1 month at 20 mg/kg daily dose. Dosage and treatment recommendations may vary among countries and between individual products (refer to specific product guidelines). Child: 1 month to 6 years Initially, 10 mg/kg once daily; ≥7 years Same as adult dose. Usual maintenance dose: 5-20 mg/kg once daily. All doses should be taken preferably in the morning; adjust dose according to blood phenylalanine levels. Dietary phenylalanine and overall protein intake should be actively managed during treatment to ensure adequate blood phenylalanine control. Discontinue treatment if phenylalanine levels do not decrease after 1 month at 20 mg/kg daily dose. Dosage recommendations and approved starting age of use may vary among countries and between individual products (refer to specific product guidelines).
Oral Hyperphenylalaninaemia due to tetrahydrobiopterin (BH4) deficiency
Adult: In conjunction with phenylalanine-restricted diet: Initially, 2-5 mg/kg daily in 2-3 divided doses; adjust dose according to blood phenylalanine levels. Max: 20 mg/kg daily in 2-3 divided doses. Dietary phenylalanine and overall protein intake should be actively managed during treatment to ensure adequate blood phenylalanine control. Treatment recommendations may vary among countries and between individual products (refer to specific product guidelines). Child: Same as adult dose.
Administration
Sapropterin Should be taken with food. Tab: May crush/dissolve tab & mix w/ soft foods. Oral soln: Dissolve contents in water or soft foods.
Reconstitution
Tab: Dissolve tab in 120-240 mL of water or apple juice; may crush or stir the tab to help dissolve faster but complete dissolution may not occur. Powder for oral solution: Patients weighing ≤10 kg: Dissolve the contents of 1 packet in 5 mL or 10 mL of water or apple juice, then withdraw the required dose using an oral syringe; >10 kg: Dissolve the required number of packets in 120-240 mL of water or apple juice or in a small amount of soft food (e.g. applesauce or pudding); mix thoroughly until the powder is completely dissolved. Recommendations for preparation may vary among countries and between individual products (refer to specific product guidelines).
Special Precautions
Patient with history of convulsions. Not recommended for use in patients with history of anaphylaxis to sapropterin. Renal and hepatic impairment. Children. Pregnancy and lactation.
Monitor serum phenylalanine concentration at baseline, after 1 week of therapy, periodically for the 1st month, and regularly thereafter. Assess for signs and symptoms of upper gastrointestinal mucosal inflammation and hyperactivity; changes in neurological status (particularly in patients who are receiving levodopa during treatment).
Overdosage
Symptoms: Headache, dizziness, shortening of QT interval.
Management: Supportive and symptomatic treatment.
Drug Interactions
May cause or exacerbate convulsions and increase excitability and irritability with levodopa, particularly in BH4-deficient patients. Concomitant use with folate synthesis inhibitors (e.g. methotrexate, phenobarbital, trimethoprim, valproic acid) may reduce the efficacy of sapropterin due to the reduction of bioavailability of endogenous BH4. May cause additive vascular relaxation and reduction in blood pressure when used concomitantly with drugs that affect nitric oxide-mediated vascular relaxation, including phosphodiesterase 5 inhibitors (e.g. sildenafil, tadalafil, vardenafil), glyceryl trinitrate, isosorbide dinitrate, sodium nitroprusside, and minoxidil.
Food Interaction
Increased absorption with food (high-fat, high-calorie meal).
Action
Description: Overview: Sapropterin is a synthetic form of tetrahydrobiopterin (BH4), an endogenous cofactor for the enzyme phenylalanine hydroxylase (PAH) in the hydroxylation of phenylalanine (Phe) to tyrosine. Mechanism of Action: Sapropterin reduces Phe levels by enhancing the activity of the deficient PAH enzyme in patients with BH4-responsive phenylketonuria (PKU), which leads to an increased or restored oxidative metabolism of phenylalanine. In patients with BH4-deficiency, sapropterin acts as a replacement for endogenous BH4 to restore PAH activity. Pharmacodynamics: In an open-label study, the mean blood Phe levels decreased with increasing doses of sapropterin, demonstrating an inverse relationship. Onset: Within 24 hours. Duration: 24 hours. Pharmacokinetics: Absorption: Increased absorption with food (high-fat, high-calorie meal). Time to peak plasma concentration: 3-4 hours (fasted state); 4-5 hours (fed state). Distribution: Distributed mainly to the kidneys, adrenal glands, and liver. Metabolism: Metabolised mainly in the liver into dihydrobiopterin and biopterin. Excretion: Elimination half-life: Approx 6.7 hours (range: 3.9-17 hours).
Chemical Structure
Sapropterin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135398654, Sapropterin. https://pubchem.ncbi.nlm.nih.gov/compound/Sapropterin. Accessed Nov. 24, 2025.
Storage
Tab/Powder for oral solution: Store between 15-30°C. Protect from moisture.
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