Synthetic tetrahydrobiopterin (BH4) Pregnancy: Limited data in pregnant women. Maternal blood phenylalanine levels must be strictly controlled before and during pregnancy; physician-supervised dietary phenylalanine restriction is the first choice of treatment, and sapropterin should be considered only if strict dietary management does not adequately reduce blood phenylalanine. Caution must be exercised when prescribing to pregnant women. Should not be used during breast-feeding.

Sapropterin dihydrochloride

Brand names: Kuvan

Sapropterin dihydrochloride is a synthetic form of tetrahydrobiopterin (BH4) used, alongside dietary management, to reduce blood phenylalanine in responsive patients with phenylketonuria or BH4 deficiency.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Phenylketonuria (PKU): starting dose 10 mg/kg body weight once daily, adjusted usually between 5 and 20 mg/kg/day to achieve and maintain adequate blood phenylalanine levels. BH4 deficiency: starting dose 2 to 5 mg/kg body weight total daily dose, which may be adjusted up to a total of 20 mg/kg per day

Route: Oral use, after dissolution — administer with a meal to increase absorption; the solution should be consumed within 30 minutes of initial dissolution

Frequency: PKU: a single daily dose at the same time each day, preferably in the morning. BH4 deficiency: total daily dose divided into 2 or 3 administrations distributed over the day

Max: 20 mg/kg/day

eMC SPC for Sapropterin Dihydrochloride 100 mg powder for oral solution. Treatment must be initiated and supervised by a physician experienced in the treatment of PKU and BH4 deficiency, with active management of dietary phenylalanine and overall protein intake. For patients above 20 kg body weight, the calculated daily dose based on body weight should be rounded to the nearest multiple of 100 mg. Determining response: check blood phenylalanine before starting and after 1 week at the recommended starting dose; if reduction is unsatisfactory the dose can be increased weekly to a maximum of 20 mg/kg/day with continued weekly monitoring over a one-month period, keeping dietary phenylalanine intake constant. A satisfactory response is a >= 30 percent reduction in blood phenylalanine or attainment of the individual therapeutic goal; patients who fail to respond within the one-month test period are non-responders and treatment should be discontinued. Once responsiveness is established the dose may be adjusted within 5 to 20 mg/kg/day; blood phenylalanine and tyrosine should be tested one to two weeks after each dose adjustment and monitored frequently thereafter. Discontinuation should only be done under physician supervision, as rebound hyperphenylalaninaemia may occur. Elderly: safety and efficacy above 65 years not established — caution. Contains 0.3 mmol (11.7 mg) potassium per 100 mg sachet.

Paediatric dose

Dose: 10 mg/kg

Route: Oral use, after dissolution, with a meal

Frequency: Once daily (PKU); for BH4 deficiency the total daily dose is divided into 2 or 3 administrations distributed over the day

Max: 20 mg/kg/day

The SPC states that the posology is the same in adults, children and adolescents. PKU: starting dose 10 mg/kg once daily, usually adjusted between 5 and 20 mg/kg/day. BH4 deficiency: starting dose 2 to 5 mg/kg total daily dose, adjustable up to a total of 20 mg/kg/day. Blood phenylalanine and tyrosine levels should be tested particularly in the paediatric population one to two weeks after each dose adjustment and monitored frequently thereafter. Prolonged exposure to low blood phenylalanine and tyrosine levels during infancy has been associated with impaired neurodevelopmental outcome. For patients above 20 kg the calculated daily dose should be rounded to the nearest multiple of 100 mg; for children up to 20 kg only the 100 mg powder sachets should be used, with the dissolution volumes and measuring devices described in the SPC. Clinician to verify against a children's formulary.

Dose adjustments

Renal

Safety and efficacy in patients with renal (or hepatic) insufficiency have not been established; caution must be exercised when prescribing to such patients. No numeric dose adjustment is stated.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

Patient weight (kg)

Verify in a children's formulary

Contraindications

Hypersensitivity to the active substance or to any of the excipients

Side effects

Headache (very common)
Rhinorrhoea (very common)
Hypophenylalaninaemia (common)
Pharyngolaryngeal pain, nasal congestion, cough (common)
Diarrhoea, vomiting, abdominal pain, dyspepsia, nausea (common)
Hypersensitivity reactions including serious allergic reactions, and rash (frequency not known)

Interactions

Inhibitors of dihydrofolate reductase (e.g. methotrexate, trimethoprim) — may interfere with BH4 metabolism; caution recommended
Medicinal products causing vasodilation by affecting nitric oxide metabolism or action, including classical NO donors (glyceryl trinitrate, isosorbide dinitrate, sodium nitroprusside, molsidomine), phosphodiesterase type 5 inhibitors and minoxidil (including topically administered) — caution recommended, as BH4 is a cofactor for nitric oxide synthetase
Levodopa — caution; cases of convulsion, exacerbation of convulsion, increased excitability and irritability have been observed with co-administration in BH4-deficient patients

Clinical monograph

How it works

It acts as a cofactor for phenylalanine hydroxylase, enhancing residual enzyme activity in responsive patients so that phenylalanine is more effectively metabolised.

Prescribing in practice

It is only effective in patients shown to be responsive, and treatment must always be combined with continued phenylalanine-restricted dietary control under specialist supervision.
Blood phenylalanine must be monitored to confirm response and to avoid levels falling too low, which can itself be harmful.
It should be used within a specialist metabolic service, with dietary intake adjusted in response to monitoring.

Monitoring

Regularly monitor blood phenylalanine to assess responsiveness, guide dietary phenylalanine intake and ensure levels remain within the target range.

Counselling the patient

This medicine works together with your low-phenylalanine diet, not instead of it.
Regular blood tests are essential to keep phenylalanine in the right range.
Keep all specialist metabolic clinic appointments.

Evidence & guidelines

Sapropterin is an established adjunct in responsive phenylketonuria, used within specialist metabolic services per national commissioning guidance.

Reference: NICE HST7; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Pathways