Dosing and uses of Kuvan (sapropterin)
Adult dosage forms and strengths
tablet
- 100mg
powder for oral solution
- 100mg/packet
Hyperphenylalaninemia
Indicated for hyperphenylalaninemia caused by tetrahydrobiopterin responsive phenylketonuria
10 mg/kg PO qDay initially with food; response to therapy is determined by change in blood Phe following treatment at 10 mg/kg/day for up to 1 month; blood Phe levels should be checked after 1 wk of therapy and periodically for up to a month; if blood Phe does not decrease from baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day; patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg/day are non-responders and treatment should be discontinued
Once responsiveness established, dosage may be adjusted within range of 5 to 20 mg/kg/day according to response to therapy; periodic blood Phe monitoring is recommended to assess blood Phe controL
Dosing Considerations
Measure baseline blood Phe level before initiating therapy
If 20 mg/kg/day starting dose used, response to therapy is determined by change in blood Phe following therapy at 20 mg/kg/day for a period of 1 month; blood Phe levels should be checked after 1 wk of therapy and periodically during first month; treatment should be discontinued in patients who do not respond to therapy
Administration
Take with food
Tablet
- Tablets may be swallowed either as whole tablets or dissolved
- Dissolve in 4-8 oz (120-240 mL) water or apple juice and take within 15 minutes of dissolution
- To make the tablets dissolve faster, stir or crush them
- Tablets may not dissolve completely; small tablet pieces may float on top of the water or apple juice, this is normal and safe to swallow
- If after drinking the medicine, add more water or apple juice to glass and drink to ensure the entire dose is taken
Powder for oral solution
- Dissolved in 4-8 oz (120 to 240 mL) of water or apple juice and drink within 30 minutes of dissolution
Pediatric dosage forms and strengths
tablet
- 100mg
Hyperphenylalaninemia
Indicated for hyperphenylalaninemia caused by tetrahydrobiopterin responsive phenylketonuria
1 month to 6 years: Recommended starting dose is 10 mg/kg taken once daily
≥ 7 years: 10 mg/kg PO qDay initially with food; if 10 mg/kg/day starting dose used, response to therapy is determined by change in blood Phe following treatment at 10 mg/kg/day for up to 1 month; blood Phe levels should be checked after 1 wk of therapy and periodically for up to a month; if blood Phe does not decrease from baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day; patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg/day are non-responders and treatment should be discontinued
Once responsiveness established, dosage may be adjusted within range of 5-20 mg/kg/day according to response to therapy; periodic blood Phe monitoring is recommended to assess blood Phe controL
Children aged <7 years treated with doses of 20 mg/kg/day are at increased risk for low levels of blood Phe
Dosing Considerations
Measure baseline blood Phe level before initiating therapy
Nonresponders: If 20 mg/kg/day starting dose used, response to therapy is determined by change in blood Phe following therapy at 20 mg/kg/day for a period of 1 month; blood Phe levels should be checked after 1 wk of therapy and periodically during first month; treatment should be discontinued in patients who do not respond to therapy
Administration
Take with food
Tablet
- Tablets may be swallowed either as whole tablets or dissolved
- Dissolve in 4-8 oz (120-240 mL) water or apple juice and take within 15 minutes of dissolution
- To make the tablets dissolve faster, stir or crush them
- Tablets may not dissolve completely; small tablet pieces may float on top of the water or apple juice, this is normal and safe to swallow
- If after drinking the medicine, add more water or apple juice to glass and drink to ensure the entire dose is taken
Powder for oral solution
- Dissolved in 4-8 oz (120 to 240 mL) of water or apple juice and drink within 30 minutes of dissolution
Kuvan (sapropterin) adverse (side) effects
>10%
Rhinorrhea (11%)
Headache (15%)
1-10%
Diarrhea (8%)
Pharyngolaryngeal pain (10%)
Cough (7%)
Nasal congestion (4%)
Vomiting (8%)
Nausea (8%)
<1%
Gastritis
Gastrointestinal bleeding
Thrombocytopenia
Spinal cord injury
Abdominal pain
Decreased appetite
Respiratory tract infection
Peripheral edema
Warnings
Contraindications
None listed in the manufacturer's labeL
Cautions
Do not eliminate ongoing Phe-restricted diet: treat all patients with a Phe-restricted diet
Children < 7 years treated with 20 mg/kg/day are at increased risk for low levels of blood Phe compared with patients 7 years and older
Treatment should be directed by physicians knowledgeable in management of PKU;. prolonged elevations in blood Phe levels in patients with PKU can result in severe neurologic damage, including severe mental retardation, microcephaly, delayed speech, seizures, and behavioral abnormalities; prolonged levels of blood Phe that are too low are associated with catabolism and protein breakdown; active management of dietary Phe intake while receiving therapy is required to ensure adequate Phe control and nutritional balance; monitor blood Phe levels during treatment to ensure adequate blood Phe level control; frequent blood monitoring is recommended in pediatric population
Hypersensitivity reactions including anaphylaxis and rash have occurred
Gastritis reported; monitor patients for signs and symptoms of gastritis
Use caution in renal and hepatic impairment
Patients that show no improvement after treating at 20 mg/kg/day for 1 month are considered nonresponders; response to treatment cannot be pre-determined by laboratory testing (e.g., molecular testing), and can only be determined by therapeutic triaL
Caution in coadministration of medications known to inhibit folate metabolism (eg, methotrexate), PDE-5 inhibitors, or levodopa
Hyperactivity behavior reported (rare)
Monitor patients for hypotension when co-administering drug with medications known to affect nitric oxide-mediated vasorelaxation
Pregnancy and lactation
Pregnancy category: C
Lactation: Excretion in breast milk unknown; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Kuvan (sapropterin)
Mechanism of action
Synthetic tetrahydrobiopterin (BH4), for phenylalanine hydroxylase (PAH); PAH hydroxylates Phe to form tyrosine; BH4 activates residual PAH enzyme, improving oxidative metabolism of Phe & thereby decreasing Phe blood levels
Pharmacokinetics
Half-Life: 7 hr; range: 3.9-17 hr
Onset: 24 hr; up to 2 month (maximum effect)
Peak Plasma Time: stable over 24-hr period
Duration: 24 hr
