Dosing & Uses
Dosage Forms & 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
Dosage Forms & 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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse 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 & Lactation
Pregnancy
A patient registry has been established that collects data on women who are treated during pregnancy; for information regarding registry program call 1-800-983-4587
There are no adequate and well-controlled studies in pregnant women; therapy should be administered during pregnancy only if potential benefit justifies potential risk to fetus
Available data from maternal Phenylketonuria Collaborative Study in PKU-affected women demonstrated that uncontrolled Phe levels above 600 micromol/L are associated with a very high incidence of neurological, cardiac, facial dysmorphism, and growth anomalies; good dietary control of Phe levels during pregnancy is essential to reduce incidence of Phe-induced teratogenic effects
Animal data
- An embryo-fetal development study in rats using oral doses up to 3 times maximum recommended human dose (MRHD) given during period of organogenesis showed no effects; in a rabbit study using oral administration of sapropterin dihydrochloride during period of organogenesis, a rare defect, holoprosencephaly, was noted at 10 times the MRHD
Lactation
Not known whether drug is present in human milk; it is present in milk of intravenously, but not orally, treated lactating rats; consider developmental and health benefits of human milk feeding along with mother’s clinical need for therapy and any potential adverse effects on human milk-fed child from drug or from underlying maternal condition; exercise caution when drug is administered to a nursing woman
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
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
Images
Patient Handout
Formulary
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