Sapropterin Dihydrochloride
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Sapropterin Dihydrochloride Prescribing Information
Warnings and Precautions
Upper Gastrointestinal Mucosal Inflammation (
Gastrointestinal (GI) adverse reactions suggestive of upper GI mucosal inflammation have been reported with sapropterin dihydrochloride. Serious adverse reactions included esophagitis and gastritis
[see Adverse Reactions (6.2)]
. If left untreated, these could lead to severe sequelae including esophageal stricture, esophageal ulcer, gastric ulcer, and bleeding and such complications have been reported in patients receiving sapropterin dihydrochloride. Monitor patients for signs and symptoms of upper GI mucosal inflammation.Sapropterin dihydrochloride powder for oral solution is indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin-(BH4-) responsive Phenylketonuria (PKU). Sapropterin dihydrochloride powder for oral solution is to be used in conjunction with a Phe-restricted diet.
All patients with PKU who are being treated with sapropterin dihydrochloride powder for oral solution should also be treated with a Phe-restricted diet, including dietary protein and Phe restriction. (
Treatment with sapropterin dihydrochloride powder for oral solution should be directed by physicians knowledgeable in the management of PKU.
All patients with PKU who are being treated with sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution is 10 mg/kg taken once daily.Patients 7 years and older
: The recommended starting dose of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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)]
.Starting Dosage
•
Pediatric patients 1 month to 6 years
: The recommended starting dose of sapropterin dihydrochloride powder for oral solution is 10 mg/kg taken once daily. (Treatment with sapropterin dihydrochloride powder for oral solution should be directed by physicians knowledgeable in the management of PKU.
All patients with PKU who are being treated with sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution is 10 mg/kg taken once daily.Patients 7 years and older
: The recommended starting dose of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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)]
.•
Patients 7 years and older
: The recommended starting dose of sapropterin dihydrochloride powder for oral solution is 10 to 20 mg/kg taken once daily. (Treatment with sapropterin dihydrochloride powder for oral solution should be directed by physicians knowledgeable in the management of PKU.
All patients with PKU who are being treated with sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution is 10 mg/kg taken once daily.Patients 7 years and older
: The recommended starting dose of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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)]
.Dosage Adjustment
• Doses of sapropterin dihydrochloride powder for oral solution may be adjusted in the range of 5 to 20 mg/kg taken once daily. (
Treatment with sapropterin dihydrochloride powder for oral solution should be directed by physicians knowledgeable in the management of PKU.
All patients with PKU who are being treated with sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution is 10 mg/kg taken once daily.Patients 7 years and older
: The recommended starting dose of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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)]
.• Monitor blood Phe regularly, especially in pediatric patients. (
Treatment with sapropterin dihydrochloride powder for oral solution should be directed by physicians knowledgeable in the management of PKU.
All patients with PKU who are being treated with sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution is 10 mg/kg taken once daily.Patients 7 years and older
: The recommended starting dose of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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)]
.In clinical trials of sapropterin dihydrochloride, some PKU patients experienced hypophenylalaninemia (low blood Phe) during treatment with sapropterin dihydrochloride. In a clinical study of pediatric patients younger than 7 years old treated with sapropterin dihydrochloride 20 mg/kg per day, the incidence of hypophenylalaninemia was higher than in clinical trials of older patients
[see Adverse Reactions (6.1)]
.Preparation and Administration
• Take with a meal. (
Take sapropterin dihydrochloride powder for oral solution 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.Sapropterin Dihydrochloride Powder for Oral Solution
Patients weighing greater than 10 kg
Sapropterin dihydrochloride 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. Sapropterin dihydrochloride 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, sapropterin dihydrochloride 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
Patient Weight (kg) | Starting Dose: 10 mg/kg per day* | |||
Dose (mg) | Sapropterin Dihydrochloride Powder for Oral Solution 100 mg Packets Dissolved † | Dilution Volume (mL) ‡ | Administered Dose volume (mL) § | |
| 1 | 10 | 1 | 10 | 1 |
| 2 | 20 | 1 | 10 | 2 |
| 3 | 30 | 1 | 10 | 3 |
| 4 | 40 | 1 | 10 | 4 |
| 5 | 50 | 1 | 10 | 5 |
| 6 | 60 | 1 | 5 | 3 |
| 7 | 70 | 1 | 5 | 3.5 |
| 8 | 80 | 1 | 5 | 4 |
| 9 | 90 | 1 | 5 | 4.5 |
| 10 | 100 | 1 | 5 | 5 |
*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 per packet
‡Volume of water or apple juice to dissolve sapropterin dihydrochloride 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
Patient Weight (kg) | 20 mg/kg per day | |||
Dose (mg) | Sapropterin Dihydrochloride Powder for Oral Solution 100 mg Packets*Dissolved | Dilution Volume (mL) † | Administered Dose volume (mL) § | |
| 1 | 20 | 1 | 5 | 1 |
| 2 | 40 | 1 | 5 | 2 |
| 3 | 60 | 1 | 5 | 3 |
| 4 | 80 | 1 | 5 | 4 |
| 5 | 100 | 1 | 5 | 5 |
| 6 | 120 | 2 | 5 | 3 |
| 7 | 140 | 2 | 5 | 3.5 |
| 8 | 160 | 2 | 5 | 4 |
| 9 | 180 | 2 | 5 | 4.5 |
| 10 | 200 | 2 | 5 | 5 |
*Powder for oral solution provided in single use packets containing 100 mg sapropterin dihydrochloride per packet
†Volume of water or apple juice to dissolve sapropterin dihydrochloride powder for oral solution.
§Discard remainder of mixture after volume to be administered is drawn.
• Swallow oral solution after mixing powder in a small amount of soft foods or dissolving in recommended liquids. See full prescribing information for complete information on mixing with food or liquid. (
Take sapropterin dihydrochloride powder for oral solution 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.Sapropterin Dihydrochloride Powder for Oral Solution
Patients weighing greater than 10 kg
Sapropterin dihydrochloride 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. Sapropterin dihydrochloride 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, sapropterin dihydrochloride 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
Patient Weight (kg) | Starting Dose: 10 mg/kg per day* | |||
Dose (mg) | Sapropterin Dihydrochloride Powder for Oral Solution 100 mg Packets Dissolved † | Dilution Volume (mL) ‡ | Administered Dose volume (mL) § | |
| 1 | 10 | 1 | 10 | 1 |
| 2 | 20 | 1 | 10 | 2 |
| 3 | 30 | 1 | 10 | 3 |
| 4 | 40 | 1 | 10 | 4 |
| 5 | 50 | 1 | 10 | 5 |
| 6 | 60 | 1 | 5 | 3 |
| 7 | 70 | 1 | 5 | 3.5 |
| 8 | 80 | 1 | 5 | 4 |
| 9 | 90 | 1 | 5 | 4.5 |
| 10 | 100 | 1 | 5 | 5 |
*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 per packet
‡Volume of water or apple juice to dissolve sapropterin dihydrochloride 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
Patient Weight (kg) | 20 mg/kg per day | |||
Dose (mg) | Sapropterin Dihydrochloride Powder for Oral Solution 100 mg Packets*Dissolved | Dilution Volume (mL) † | Administered Dose volume (mL) § | |
| 1 | 20 | 1 | 5 | 1 |
| 2 | 40 | 1 | 5 | 2 |
| 3 | 60 | 1 | 5 | 3 |
| 4 | 80 | 1 | 5 | 4 |
| 5 | 100 | 1 | 5 | 5 |
| 6 | 120 | 2 | 5 | 3 |
| 7 | 140 | 2 | 5 | 3.5 |
| 8 | 160 | 2 | 5 | 4 |
| 9 | 180 | 2 | 5 | 4.5 |
| 10 | 200 | 2 | 5 | 5 |
*Powder for oral solution provided in single use packets containing 100 mg sapropterin dihydrochloride per packet
†Volume of water or apple juice to dissolve sapropterin dihydrochloride powder for oral solution.
§Discard remainder of mixture after volume to be administered is drawn.
Sapropterin dihydrochloride powder for oral solution is available as a unit dose packet containing 100 mg of sapropterin dihydrochloride and as a unit dose packet containing 500 mg of sapropterin dihydrochloride. The powder is off-white to yellow in color.
Risk Summary
Available pregnancy registry data have not reported an association with sapropterin dihydrochloride and major birth defects, miscarriage, or adverse maternal or fetal outcomes when sapropterin dihydrochloride was used during pregnancy (
see Data
). An embryo-fetal development study with sapropterin dihydrochloride in rats using oral doses up to 3 times the maximum recommended human dose (MRHD) given during the period of organogenesis showed no effects. In a rabbit study using oral administration of sapropterin dihydrochloride during the period of organogenesis, a rare defect, holoprosencephaly, was noted at 10 times the MRHD.
All pregnancies have a background risk of major birth defects, pregnancy loss, or other adverse pregnancy outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The estimated background risk of major birth defects and miscarriage in pregnant women with PKU who maintain blood phenylalanine concentrations greater than 600 micromol/L during pregnancy is greater than the corresponding background risk for pregnant women without PKU.
Clinical Considerations
Disease-Associated Maternal and/or Embryo-Fetal Risk
Uncontrolled blood phenylalanine concentrations before and during pregnancy are associated with an increased risk of adverse pregnancy outcomes and fetal adverse effects. To reduce the risk of hyperphenylalaninemia-induced fetal adverse effects, blood phenylalanine concentrations should be maintained between 120 and 360 micromol/L during pregnancy and during the 3 months before conception
[see
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 sapropterin dihydrochloride powder for oral solution at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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
Once responsiveness to sapropterin dihydrochloride powder for oral solution 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].
Treatment with sapropterin dihydrochloride powder for oral solution should be directed by physicians knowledgeable in the management of PKU.
All patients with PKU who are being treated with sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution is 10 mg/kg taken once daily.Patients 7 years and older
: The recommended starting dose of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of sapropterin dihydrochloride powder for oral solution 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 sapropterin dihydrochloride powder for oral solution 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)]
.Data
Human Data
Uncontrolled Maternal PKU
Available data from the Maternal Phenylketonuria Collaborative Study on 468 pregnancies and 331 live births 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. Control of blood phenylalanine during pregnancy is essential to reduce the incidence of Phe-induced teratogenic effects.
Animal Data
No effects on embryo-fetal development were observed in a reproduction study in rats using oral doses of up to 400 mg/kg per day sapropterin dihydrochloride (about 3 times the MRHD of 20 mg/kg per day, based on body surface area) administered during the period of organogenesis. However, in a rabbit reproduction study, oral administration of a maximum dose of 600 mg/kg per day (about 10 times the MRHD, based on body surface area) during the period of organogenesis was associated with a non-statistically significant increase in the incidence of holoprosencephaly in two high dose-treated litters (4 fetuses), compared to one control-treated litter (1 fetus).
None.
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