Sapropterin
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Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
Recommended Dosage and Administration The recommended starting dosage of KUVAN is: Pediatric Patients 1 month to 6 years : 10 mg/kg (actual body weight) administered orally once daily. Patients 7 years and older : 10 to 20 mg/kg (actual body weight) administered orally once daily. Administer KUVAN with a meal, preferably at the same time each day [see Clinical Pharmacology ] .
A missed dose should be administered as soon as possible, but two doses should not be administered on the same day. 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 KUVAN at 10 mg/kg per day for a period of up to 1 month.
Blood Phe levels should be checked after 1 week of KUVAN 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 KUVAN 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 KUVAN at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of KUVAN 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] .
Dosage Adjustment Once responsiveness to KUVAN 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] .
Preparation and Administration Instructions KUVAN Tablets KUVAN tablets may be swallowed either as whole tablets or dissolved in 120 to 240 mL of water or apple juice and taken orally within 15 minutes of dissolution. It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster, tablets may be stirred or crushed.
The tablets may not dissolve completely. Patients may see small pieces floating on top of the water or apple juice. This is normal and safe for patients to swallow. If after drinking the medicine, patients still see pieces of the tablet in the container, more water or apple juice can be added to make sure all of the medicine is consumed.
KUVAN tablets may also be crushed and then mixed in a small amount of soft foods such as apple sauce or pudding. KUVAN Powder for Oral Solution Patients weighing greater than 10 kg KUVAN 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.
KUVAN powder for oral solution may also be stirred in a small amount of soft food 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, KUVAN 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 [See table below.] 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 KUVAN per packet. ‡ Volume of water or apple juice to dissolve KUVAN 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 [See table below.] 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 KUVAN per packet. † Volume of water or apple juice to dissolve KUVAN Powder for Oral Solution. § Discard remainder of mixture after volume to be administered is drawn.
Recommended Dosage and Administration The recommended starting dosage of KUVAN is: Pediatric Patients 1 month to 6 years : 10 mg/kg (actual body weight) administered orally once daily. Patients 7 years and older : 10 to 20 mg/kg (actual body weight) administered orally once daily. Administer KUVAN with a meal, preferably at the same time each day [see Clinical Pharmacology ] .
A missed dose should be administered as soon as possible, but two doses should not be administered on the same day. 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 KUVAN at 10 mg/kg per day for a period of up to 1 month.
Blood Phe levels should be checked after 1 week of KUVAN 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 KUVAN 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 KUVAN at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of KUVAN 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] .
Dosage Adjustment Once responsiveness to KUVAN 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] .
| PatientWeight (kg) | Starting Dose: 10 mg/kg per day* | |||
| Dose (mg) | KUVAN 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 |
| PatientWeight (kg) | 20 mg/kg per day | |||
| Dose (mg) | KUVAN 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 |
Drug interactions
Check sapropterin against a medication listLabel text (4 paragraphs)
Table 4 includes drugs with clinically important drug interactions when administered with sapropterin dihydrochloride and instructions for preventing or managing them. Table 4: Clinically Relevant Drug Interactions Levodopa Clinical Impact Sapropterin dihydrochloride may increase the availability of tyrosine, a precursor of levodopa. Neurologic events were reported postmarketing in patients receiving sapropterin and levodopa concomitantly for a non-PKU indication [see Warnings and Precautions ( 5.5 )] . Intervention Monitor patients for a change in neurologic status.
Inhibitors of Folate Synthesis (e.g., methotrexate, valproic acid, phenobarbital, trimethoprim) Clinical Impact In vitro and in vivo nonclinical data suggest that drugs that inhibit folate synthesis may decrease the bioavailability of endogenous BH4 by inhibiting the enzyme dihydrofolate reductase, which is involved in the recycling (regeneration) of BH4. This reduction in net BH4 levels may increase Phe levels. Intervention Consider monitoring blood Phe levels more frequently during concomitant administration. An increased dosage of KUVAN may be necessary to achieve a biochemical response.
Drugs Affecting Nitric Oxide‑Mediated Vasorelaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil) Clinical Impact Both sapropterin dihydrochloride and PDE-5 inhibitors may induce vasorelaxation. A reduction in blood pressure could occur; however, the combined use of these medications has not been evaluated in humans. Intervention Monitor blood pressure. Inhibitors of Folate Synthesis (e.g., methotrexate, valproic acid, phenobarbital, trimethoprim) : Can decrease endogenous BH4 levels; monitor blood Phe levels more frequently and adjust KUVAN dosage as needed.
(7 ) Drugs Affecting Nitric Oxide‑Mediated Vasorelaxation (e.g., PDE-5 inhibitors) : Potential for vasorelaxation; monitor blood pressure. ( 7 )
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Available data from pregnancy safety studies, pharmacovigilance, and published case reports with KUVAN use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . Uncontrolled blood phenylalanine concentrations before and during pregnancy are associated with an increased risk of adverse pregnancy outcomes and fetal adverse effects (see Clinical Considerations ) . 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 Dosage and Administration 2.2) ] . 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. Pregnancy Registry Data Available data from pregnancy sub-registries within the Phenylketonuria Developmental Outcomes and Safety (PKUDOS) Registry and the KUVAN Adult Maternal Pediatric…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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