Quick answers
- What is Sapropterin dihydrochloride used for?
- The FDA-approved label (Kuvan, BioMarin Pharmaceutical Inc., August 26, 2024) says: “KUVAN ® 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). KUVAN is to be used in conjunction with a Phe-restricted diet. …” This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.
- What are the side effects of Sapropterin dihydrochloride?
- The “Adverse Reactions” section of the FDA label (Kuvan, BioMarin Pharmaceutical Inc., August 26, 2024) begins: “Most common adverse reactions (≥4%) are: headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.” … This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.
- What are the drug interactions of Sapropterin dihydrochloride?
- The “Drug Interactions” section of the FDA label (Kuvan, BioMarin Pharmaceutical Inc., August 26, 2024) begins: “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.” … This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.
- Does Sapropterin dihydrochloride have a boxed warning?
- No. None of the 16 FDA labels we found for this medicine has a boxed warning.
- Is there a shortage of Sapropterin dihydrochloride?
- No current shortage is listed by the FDA for the products of this medicine (FDA data from October 30, 2026).
- Has Sapropterin dihydrochloride been recalled?
- FDA enforcement reports list 2 recalls of products of this medicine; the newest started November 22, 2024 (Class III). A recall usually concerns specific lots, not every product.
- Who makes Sapropterin dihydrochloride?
- 10 companies list prescription products of Sapropterin dihydrochloride in the FDA NDC Directory, including NorthStar RxLLC, Camber Pharmaceuticals, Inc. and Par Health USA, LLC.
What Sapropterin dihydrochloride is used for
Quoted from the “Indications and Usage” section of the FDA-approved label.
KUVAN ® 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). KUVAN is to be used in conjunction with a Phe-restricted diet. …
— FDA label: Kuvan, BioMarin Pharmaceutical Inc., effective August 26, 2024. Read the full label on DailyMed →
Label quoted: the one for the most common form (powder, for solution, oral), Kuvan, BioMarin Pharmaceutical Inc.; it covers 3 products in the FDA NDC Directory. The side effects, interactions, dosage and pregnancy quotes below come from this same label.
The FDA has 16 labels for products of this medicine (different makers and forms); uses can differ between them. Check the label that comes with your own medicine.
This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.
Boxed warning
A boxed warning (“black box”) is the FDA’s strongest warning on a drug label, for serious or life-threatening risks.
The label quoted above has no boxed warning.
0 of 16 FDA labels for this medicine have a boxed warning.
Sapropterin dihydrochloride side effects
Quoted from the “Adverse Reactions” section of the FDA-approved label. Tell your doctor about any side effect that worries you.
Most common adverse reactions (≥4%) are: headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.
Read more of this section
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-877-695-8826, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. PKU Clinical Studies The safety of KUVAN was evaluated in 7 clinical studies in patients with PKU (aged 1 month to 50 years) [see Clinical Studies (14)]. In Studies 1-4 (controlled and uncontrolled studies), 579 patients with PKU aged 4 to 49 years received KUVAN in doses ranging from 5 to 20 mg/kg per day for lengths of treatment ranging from 1 to 164 weeks. The patient population was evenly distributed in gender, and approximately 95% of patients were Caucasian. The most common adverse reactions (≥4% of patients) were headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion. The data described in Table 3 reflect exposure of 74 patients with PKU to KUVAN at doses of 10 to 20 mg/kg per day for 6 to 10 weeks in two double-blind, placebo-controlled clinical trials (Studies 2 and 4). Table 3 enumerates adverse reactions occurring in at least 4% of patients treated with KUVAN in the double-blind, placebo-controlled clinical trials described above. Table 3: Summary of Adverse Reactions Occurring in ≥4% of Patients in Placebo-Controlled Clinical Studies with KUVAN MedDRA Preferred Term Treatment KUVAN (N=74) Placebo (N=59) No. Patients (%) No. Patients (%) Headache 11 (15) 8 (14) Rhinorrhea 8 (11) 0 Pharyngolaryngeal pain 7 (10) 1 (2) Diarrhea 6 (8) 3 (5) Vomiting 6 (8) 4 (7) Cough 5 (7) 3 (5) Nasal congestion 3 (4) 0 In open-label, uncontrolled clinical trials (Studies 1 and 3) all patients received KUVAN in doses of 5 to 20 mg/kg per day, and adverse reactions were similar in type and frequency to those reported in the double-blind, placebo-controlled clinical trials [see Clinical Studies (14)]. In Study 5, 65 pediatric patients with PKU aged 1 month to 6 years received KUVAN 20 mg/kg per day for 6 months. Adverse reactions in these patients were similar in frequency and type as those seen in other KUVAN clinical trials except for an increased incidence of low Phe levels. Twenty-five percent (16 out of 65) of patients developed Phe levels below normal for age [see Warnings and Precautions (5.3), Use In Specific Populations (8.4), and Clinical Studies (14)].
Table from the label
| MedDRA Preferred Term | Treatment | |
|---|---|---|
| KUVAN(N=74) | Placebo(N=59) | |
| No. Patients (%) | No. Patients (%) | |
| Headache | 11 (15) | 8 (14) |
| Rhinorrhea | 8 (11) | 0 |
| Pharyngolaryngeal pain | 7 (10) | 1 (2) |
| Diarrhea | 6 (8) | 3 (5) |
| Vomiting | 6 (8) | 4 (7) |
| Cough | 5 (7) | 3 (5) |
| Nasal congestion | 3 (4) | 0 |
— FDA label: Kuvan, BioMarin Pharmaceutical Inc., effective August 26, 2024. This is part of the section. Read the full label on DailyMed →
Sapropterin dihydrochloride drug interactions
Quoted from the “Drug Interactions” section of the FDA-approved label. Tell your pharmacist about every medicine, vitamin and herbal product you take.
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.
Read more of this section
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)
— FDA label: Kuvan, BioMarin Pharmaceutical Inc., effective August 26, 2024. This is part of the section. Read the full label on DailyMed →
Sapropterin dihydrochloride dosage
Quoted from the “Dosage and Administration” section of the FDA-approved label. Your own dose is the one your doctor prescribes: do not change it on your own.
All patients with PKU who are being treated with KUVAN should also be treated with a Phe-restricted diet, including dietary protein and Phe restriction. (2.1) Starting Dosage Pediatric patients 1 month to 6 years: The recommended starting dosage of KUVAN is 10 mg/kg administered orally once daily. (2.2) Patients 7 years and older: The recommended starting dosage of KUVAN is 10 to 20 mg/kg administered orally once daily.
Read more of this section
(2.2) Dosage Adjustment Doses of KUVAN may be adjusted in the range of 5 to 20 mg/kg taken once daily. (2.2) Monitor blood Phe regularly, especially in pediatric patients. (2.2, 5.3) Preparation and Administration See the full prescribing information for preparation and administration instructions. (2.3) 2.1 Recommendations Prior to KUVAN Treatment Treatment with KUVAN should be directed by physicians knowledgeable in the management of PKU. All patients with PKU who are being treated with KUVAN should also be treated with a Phe-restricted diet, including dietary protein and Phe restriction. 2.2 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 (12.3)]. 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 (5.4)]. 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).
Table from the label
| 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 |
— FDA label: Kuvan, BioMarin Pharmaceutical Inc., effective August 26, 2024. This is part of the section. Read the full label on DailyMed →
Sapropterin dihydrochloride in pregnancy
Quoted from the pregnancy part of the FDA-approved label. Ask your doctor before you take any medicine while pregnant or planning a 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).
Read more of this section
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 European Registry (KAMPER) have identified 72 live births (79 pregnancies) in women with PKU exposed to sapropterin during pregnancy. Three birth defects were reported, including one case each of microcephaly, cleft palate, and tongue tie. The two major birth defects (microcephaly and cleft palate) were associated with Phe levels greater than 360 micromol/L during pregnancy. 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.
— FDA label: Kuvan, BioMarin Pharmaceutical Inc., effective August 26, 2024. This is part of the section. Read the full label on DailyMed →
Sapropterin dihydrochloride overdose
Quoted from the “Overdosage” section of the FDA-approved label. If someone may have taken too much, call Poison Help at 1-800-222-1222 (or 911 in an emergency).
Two unintentional overdosages with KUVAN have been reported. One adult patient in a KUVAN clinical trial received a single KUVAN dose of 4,500 mg (36 mg/kg) instead of 2,600 mg (20 mg/kg). The patient reported mild headache and mild dizziness immediately after taking the dose; both symptoms resolved within 1 hour with no treatment intervention. There were no associated laboratory test abnormalities.
Read more of this section
The patient suspended therapy for 24 hours and then restarted KUVAN with no reports of abnormal signs or symptoms. In postmarketing, one pediatric patient received KUVAN doses of 45 mg/kg per day instead of 20 mg/kg per day. The patient reported hyperactivity that began at an unspecified time after overdosage and resolved after the KUVAN dose was reduced to 20 mg/kg per day. In a clinical study to evaluate the effects of KUVAN on cardiac repolarization, a single supra-therapeutic dose of 100 mg/kg (5 times the maximum recommended dose) was administered to 54 healthy adults. No serious adverse reactions were reported during the study. The only adverse reactions reported in more than 1 subject who received the supra-therapeutic dose were upper abdominal pain (6%) and dizziness (4%). A dose-dependent shortening of the QT interval was observed [see Clinical Pharmacology (12.2)]. Patients should be advised to notify their physicians in cases of overdosage.
— FDA label: Kuvan, BioMarin Pharmaceutical Inc., effective August 26, 2024. Read the full label on DailyMed →
Forms and how it is given
Companies that list this medicine
Labelers in the FDA NDC Directory: the company named on the package (maker or distributor), with the number of prescription products.
- NorthStar RxLLC3 products
- Camber Pharmaceuticals, Inc.3 products
- Par Health USA, LLC3 products
- BioMarin Pharmaceutical Inc.3 products
- Dr.Reddys Laboratories Inc3 products
- Aucta Pharmaceuticals, Inc.2 products
- Micro Labs Limited2 products
- TruPharma, LLC2 products
- Aurobindo Pharma Limited1 product
- Hikma Pharmaceuticals USA Inc.1 product
FDA approval history
- NDA: New Drug Application: how a new (usually brand-name) medicine is approved.
- ANDA: Abbreviated New Drug Application: how a generic version is approved.
| Application | Sponsor | Approved | Later changes approved |
|---|---|---|---|
| NDA022181 KUVAN | Biomarin Pharm | December 13, 2007 | 12, latest August 26, 2024 2024: Labeling · 2020: Labeling · 2019: Labeling |
| NDA205065 KUVAN | Biomarin Pharm | December 19, 2013 | 6, latest August 26, 2024 2024: Labeling · 2020: Labeling · 2019: Labeling |
Generic approvals (13)
- ANDA207200Ph Health · May 10, 2019
- ANDA207207Ph Health · August 20, 2019
- ANDA210027Ph Health · August 20, 2019
- ANDA209452DR Reddys · March 30, 2021
- ANDA207685DR Reddys · June 15, 2021
- ANDA215798DR Reddys · May 13, 2022
- ANDA215420Annora Pharma · August 18, 2022
- ANDA215534Annora Pharma · August 23, 2022
- ANDA218645Aucta · April 29, 2025
- ANDA216797Aurobindo Pharma · June 9, 2025
- ANDA218797Hikma · June 11, 2025
- ANDA216432Hopewell Pharma · September 3, 2025
- ANDA219511Micro Labs · January 8, 2026
Shortage status
The FDA drug shortage list does not show these products.
Recalls
From FDA enforcement reports, matched by the product’s NDC code. A recall usually covers specific lots only: check the lot number on your package and ask your pharmacist. Do not stop a medicine on your own.
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November 22, 2024 · Class III · Ongoing · D-0117-2025
Failed Impurities/Degradation Specifications
Javygtor (sapropterin dihydrochloride) Tablets 100mg, 120-count bottle, Rx Only, Distributor: Dr. Reddy's Laboratories Inc., Princeton, NJ 08540 Made in India, NDC 43598-096-04. — Dr. Reddy's Laboratories, Inc.
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April 8, 2024 · Class I · Ongoing · D-0485-2024
Sub-potent Drug; powder discoloration associated with decreased potency
Javygtor (sapropterin dihydrochloride) Powder for Oral Solution 100mg, 30 individual packets per carton, Rx Only, Distributor: Dr. Reddy's Laboratories Inc., Princeton, NJ 08540 Made in India, NDC 43598-097-30. — Dr. Reddy's Laboratories, Inc.
What do the recall classes mean?
Class I: The most serious type: there is a reasonable chance that using the product will cause serious health problems or death.
Class II: Using the product may cause temporary or medically reversible health problems, or the chance of serious problems is remote.
Class III: Using the product is not likely to cause health problems (for example a labeling or packaging issue).
Official identifiers
Next steps
- Find a pharmacy near youAsk which price applies to you and whether your product is affected by a recall
- Latest FDA drug recallsAll medicines, newest first
- JavygtorBrand page: products, maker and price
- KuvanBrand page: products, maker and price
- ZelvysiaBrand page: products, maker and price
- NorthStar RxLLCMaker or distributor
- Camber Pharmaceuticals, Inc.Maker or distributor
- Par Health USA, LLCMaker or distributor
- All prescription drugs A to ZSearch by generic, brand or Spanish name
Sources
- FDA-approved label on DailyMed (National Library of Medicine) — Kuvan, BioMarin Pharmaceutical Inc., effective August 26, 2024; via openFDA, FDA data exported October 30, 2026, retrieved October 31, 2026
- NDC Directory (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
- Drugs@FDA (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
- Drug recall enforcement reports (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 27, 2026, retrieved October 31, 2026
- Drug shortages (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
openFDA data is provided by the FDA as is; it may be incomplete. Always rely on the label that comes with your medicine. FDA Enforcement Report search →