Sapropterin Dihydrochloride (sapropterin dihydrochloride)

The recommended initial dosage of sapropterin dihydrochloride for the treatment of PKU in adults is 10-20 mg/kg once daily. In pediatric patients, the recommended initial dosage is 10 mg/kg once daily (for those 1 month to 6 years of age) or 10-20 mg/kg once daily (for those 7 year of age or older).

Blood phenylalanine concentrations should be measured after 1 week of treatment and periodically for up to 1 month. In patients initiating therapy with a dosage of 10 mg/kg daily who do not respond with a decrease in blood phenylalanine concentrations after 1 month of treatment, dosage may be increased to 20 mg/kg once daily; if a response is still not obtained after 1 month of treatment at a dosage of 20 mg/kg once daily, the patient is deemed a nonresponder and therapy should be discontinued. In patients initiating therapy with a dosage of 20 mg/kg daily who do not respond with a decrease in blood phenylalanine concentrations after 1 month of treatment, the drug should be discontinued. Once responsiveness to sapropterin has been established, dosage may be adjusted within the range of 5-20 mg/kg once daily based on response to therapy as indicated by blood phenylalanine concentrations.

Sapropterin dihydrochloride is administered orally once daily (as tablets or oral solution) with meals to increase absorption, preferably at the same time each day.

The tablets may be swallowed whole or may be dissolved in 120-240 mL of water or apple juice and consumed within 15 minutes. Dissolution of the tablets may take a few minutes; stirring the mixture or crushing the tablets may speed the rate of dissolution, but complete dissolution may not occur. If there are visible tablet fragments in the glass after the mixture has been consumed, the patient should rinse the glass with additional water or apple juice and then swallow the rinse to ensure that the entire dose is consumed. The tablets also may be crushed and mixed with a small amount of soft foods such as apple sauce or pudding.

Sapropterin dihydrochloride powder for oral solution is commercially available in single-use packets containing 100 or 500 mg of the drug. In patients weighing more than 10 kg, the contents of the required number of 100- and/or 500-mg packets (based on prescribed dose) should be dissolved in 120-240 mL of water or apple juice and consumed within 30 minutes. Alternatively, the powder may be mixed with a small amount of soft food such as apple sauce or pudding. In infants weighing 10 kg or less, the contents of the required number of 100-mg packets (based on prescribed dose) should be dissolved in 5 or 10 mL of water or apple juice and the appropriate portion of the solution (depending on the prescribed dose) administered with an oral dosing syringe; the remainder of the mixture should then be discarded. The manufacturer's prescribing information should be consulted for additional details on preparation of the oral solution.

If a dose of sapropterin is missed, the missed dose should be taken as soon as possible; however, 2 doses should not be taken on the same day.

Sapropterin should be used in conjunction with a phenylalanine-restricted diet. Patients must refrain from modifying their dietary phenylalanine intake while response to sapropterin therapy is being evaluated, so that the drug's effect on phenylalanine concentrations can be accurately assessed.

In vitro studies indicate that sapropterin does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5, and does not induce CYP1A2, 2B6, or 3A4/5.

In vitro studies indicate that sapropterin does not inhibit organic anion transporter (OAT) 1 or 3, and multidrug and toxin extrusion transporter (MATE) 1 or 2K. Although sapropterin inhibits breast cancer resistance protein (BCRP) in vitro, the potential for clinically important interactions appears to be low. The drug does not appear to affect P-glycoprotein (P-gp) substrates.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

Manufacturer states none known.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

Adverse effects reported in 4% or more of patients receiving sapropterin in placebo-controlled studies include headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.

Rare or Very Rare

• Anaphylaxis
• Gastritis

More Frequent

• Cough
• Headache disorder
• Rhinorrhea
• Sore throat
• Vomiting

Less Frequent

• Acute abdominal pain
• Diarrhea
• Nasal congestion
• Rhinitis

Rare or Very Rare

• Dyspepsia
• Esophageal pain
• Esophagitis
• Hyperkinesis
• Nausea
• Pain in oropharynx
• Skin rash

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Safety and efficacy of sapropterin have not been established in neonates. Clinical studies evaluating safety and efficacy of the drug have included children 1 month of age and older. Frequent monitoring of blood phenylalanine concentrations is recommended in children to ensure adequate control.

Category C. (See Users Guide.) There are no adequate and well-controlled studies of sapropterin in pregnant women; in animal reproductive studies, a rare defect (holoprosencephaly) was observed in the offspring of rabbits administered the drug at dosages 10 times the maximum recommended human dosage during the period of organogenesis. Sapropterin should be used during pregnancy only when the benefits justify the potential risks to the fetus.

Uncontrolled blood phenylalanine concentrations before and during pregnancy are associated with an increased risk of fetal loss (miscarriage), major birth defects (e.g., microcephaly, cardiac malformations), reduced fetal growth, and adverse effects on postnatal development (e.g., intellectual disability, low IQ). Blood phenylalanine concentrations should be maintained between 120-360 mcmol/L during pregnancy and for 3 months before conception to decrease the risk of adverse fetal effects.

A pregnancy registry has been established to monitor the outcomes of pregnant women with PKU exposed to sapropterin. Information on the registry may be obtained by calling 800-983-4587.

Sapropterin is distributed into milk in rats; it is not known whether the drug is distributed into human milk. The manufacturer recommends caution if the drug is used in nursing women. The known benefits of breast-feeding should be considered along with the woman's clinical need for sapropterin and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Experience in patients 65 years of age or older insufficient to determine whether they respond differently from younger patients.