2.1 Dosage

Treatment with JAVYGTOR should be directed by physicians knowledgeable in the management of PKU.

All patients with PKU who are being treated withJAVYGTOR should also be treated with a Phe-restricted diet, including dietary protein and Phe restriction.

Starting Dosage

Pediatric Patients 1 month to 6 years: The recommended starting dose of JAVYGTOR is 10 mg/kg taken once daily.

Patients 7 years and older: The recommended starting dose of JAVYGTOR is 10 to 20 mg/kg taken once daily.

Dosage Adjustment (Evaluation Period)

Existing dietary protein and Phe intake should not be modified during the evaluation period.

If a 10 mg/kg per day starting dose is used, then response to therapy is determined by change in blood Phe following treatment with JAVYGTOR at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of JAVYGTOR treatment and periodically for up to a month. If blood Phe does not decrease from baseline at 10 mg/kg per day, the dose may be increased to 20 mg/kg per day. Patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg per day do not show a biochemical response and treatment with JAVYGTOR should be discontinued in these patients.

If a 20 mg/kg per day starting dose is used, then response to therapy is determined by change in blood Phe following treatment with JAVYGTOR at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of JAVYGTOR treatment and periodically during the first month. Treatment should be discontinued in patients who do not show a biochemical response (blood Phe does not decrease) after 1 month of treatment at 20 mg/kg per day [see Warnings and Precautions (5.4)].

Once responsiveness to JAVYGTOR has been established, the dosage may be adjusted within the range of 5 to 20 mg/kg per day according to biochemical response to therapy (blood Phe). Periodic blood Phe monitoring is recommended to assess blood Phe control, especially in pediatric patients [see Warnings and Precautions (5.3)].

2.2 Preparation and Administration Instructions

Take JAVYGTOR orally with a meal, preferably at the same time each day [see Clinical Pharmacology (12.3)]. A missed dose should be taken as soon as possible, but two doses should not be taken on the same day.

JAVYGTOR (sapropterin Dihydrochloride) Powder for Oral Solution

Patients weighing greater than 10 kg

JAVYGTOR powder for oral solution should be dissolved in 120 to 240 mL of water or apple juice and taken orally within 30 minutes of dissolution. JAVYGTOR powder for oral solution may also be stirred in a small amount of soft foods such as apple sauce or pudding. Empty the contents of the packet(s) in water, apple juice, or a small amount of soft foods and mix thoroughly. The powder should dissolve completely.

Patients weighing 10 kg or less (use 100 mg packets)

For infants weighing 10 kg or less, JAVYGTOR powder for oral solution can be dissolved in as little as 5 mL of water or apple juice and a portion of this solution corresponding to a 10 mg/kg dose may be administered orally via an oral dosing syringe. Table 1 provides dosing information for infants at the recommended starting dose of 10 mg/kg per day. Refer to Table 2 for dosing information at 20 mg/kg per day if dosage adjustment is needed.

Table 1: 10 mg/kg per day Dosing Table for Infants Weighing 10 kg or less

*Starting dose for infants is 10 mg/kg per day. Dosing information for 20 mg/kg per day is provided in Table 2.

† Powder for oral solution provided in single use packets containing 100 mg sapropterin dihydrochloride powder per packet

‡ Volume of water or apple juice to dissolve JAVYGTOR Powder for Oral Solution.

§ Discard remainder of mixture after volume to be administered is drawn.

Table 2: 20 mg/kg per day Dosing Table for Infants Weighing 10 kg or less

*Powder for oral solution provided in single use packets containing 100 mg sapropterin dihydrochloride powder per packet

†Volume of water or apple juice to dissolve JAVYGTOR Powder for Oral Solution.

§ Discard remainder of mixture after volume to be administered is drawn.