Sapropterin

Sapropterin dihydrochloride is a synthetic form of BH4, the cofactor for the enzyme phenylalanine hydroxylase (PAH). PAH hydroxylates Phe through an oxidative reaction to form tyrosine.

• Sapropterin dihydrochloride tablets are 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 tablets are to be used in conjunction with a Phe-restricted diet.

• None. None.contraindicated

All patients with PKU who are being treated with sapropterin dihydrochloride tablets 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 sapropterin dihydrochloride tablets is 10 mg/kg administered orally once daily. ( 2.2 ) Patients 7 years and older : The recommended starting dosage of sapropterin dihydrochloride tablets is 10 to 20 mg/kg administered orally once daily. ( 2.2 ) Dosage Adjustment Doses of sapropterin dihydrochloride tablets 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 Sapropterin Dihydrochloride Tablets Treatment Treatment with sapropterin dihydrochloride tablets should be directed by physicians knowledgeable in the management of PKU. All patients with PKU who are being treated with sapropterin dihydrochloride tablets 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 sapropterin dihydrochloride tablets are: 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.

Hypersensitivity Reactions Including Anaphylaxis : Sapropterin dihydrochloride is not recommended in patients with a history of anaphylaxis to sapropterin dihydrochloride; discontinue treatment in patients who experience anaphylaxis and initiate appropriate medical treatment. Continue dietary Phe restrictions. ( 5.1 ) Upper Gastrointestinal Mucosal Inflammation : Monitor patients for signs and symptoms of these conditions including esophagitis and gastritis. ( 5.2 ) Hypophenylalaninemia : Pediatric patients younger than 7 years treated with sapropterin dihydrochloride doses of 20 mg/kg per day are at increased risk for low levels of blood Phe compared with patients 7 years and older. ( 5.3 ) Monitoring Blood Phe Levels During Treatment : Ensure adequate blood Phe control and nutritional balance during treatment with sapropterin dihydrochloride. Frequent blood monitoring is recommended, especially in pediatric patients. ( 5.4 , 2.1 ) Lack of Biochemical Response to sapropterin dihydrochloride Treatment : Response to sapropterin dihydrochloride treatment cannot be pre-determined by laboratory (e.g., molecular) testing and can only be determined by a therapeutic trial of sapropterin dihydrochloride. ( 5.5 , 2.1 ) Interaction with Levodopa : Seizures, over-stimulation or irritability may occur; monitor patients for a change in neurologic status. ( 5.6 , 7 ) Hyperactivity : Monitor patients for hyperactivity.

Most common adverse reactions (≥4%) are: headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876, 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 sapropterin dihydrochloride was evaluated in 7 clinical studies in patients with PKU (aged 1 month to 50 years) [see Clinical Studies (14) ] . In Studies 1 to 4 (controlled and uncontrolled studies), 579 patients with PKU aged 4 to 49 years received sapropterin dihydrochloride 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 sapropterin dihydrochloride 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).

8.1 Pregnancy Risk Summary Available data from pregnancy safety studies, pharmacovigilance, and published case reports with sapropterin dihydrochloride 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.

Metabolism

Studies in healthy subjects have shown comparable absorption of sapropterin when tablets are dissolved in water or orange juice and taken under fasted conditions. Administration of dissolved tablets after a high-fat/high-calorie meal resulted in mean increases in C max of 84% and AUC of 87% (dissolved in water).

Two unintentional overdosages with sapropterin dihydrochloride have been reported. One adult patient in a sapropterin dihydrochloride clinical trial received a single sapropterin dihydrochloride 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. The patient suspended therapy for 24 hours and then restarted sapropterin dihydrochloride with no reports of abnormal signs or symptoms. In postmarketing, one pediatric patient received sapropterin dihydrochloride 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 sapropterin dihydrochloride dose was reduced to 20 mg/kg per day. In a clinical study to evaluate the effects of sapropterin dihydrochloride 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.

• Dec 13, 2007NDANDA022181Biomarin Pharm
• Dec 19, 2013NDANDA205065Biomarin Pharm
• May 10, 2019ANDAANDA207200Ph Health
• Aug 20, 2019ANDAANDA210027Ph Health
• Aug 20, 2019ANDAANDA207207Ph Health
• Mar 30, 2021ANDAANDA209452Dr Reddys
• Jun 15, 2021ANDAANDA207685Dr Reddys
• May 13, 2022ANDAANDA215798Dr Reddys

1. 1Headache3705.9%
2. 2Drug Ineffective3695.9%
3. 3Therapy Non-responder3615.8%
4. 4Vomiting3074.9%
5. 5Maternal Exposure During Pregnancy2964.7%
6. 6Diarrhoea2784.5%
7. 7Nausea2293.7%
8. 8Abdominal Pain Upper2153.4%
9. 9Amino Acid Level Increased2083.3%
10. 10Anxiety1863.0%
11. 11Abdominal Discomfort1752.8%
12. 12Cough1612.6%
13. 13Nasopharyngitis1582.5%
14. 14Arthralgia1482.4%
15. 15Dizziness1462.3%

The 10 most recently updated of 93 ClinicalTrials.gov registrations naming Sapropterin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Neurovascular Transduction During Exercise in Chronic Kidney Disease
  Recruiting · Phase 2 · Interventional · 150 enrolled · Emory University
  NCT02947750updated 2026-05-18
• A Single Patient Study of Sapropterin for Multisystem Smooth Muscle Dysfunction Syndrome
  Not yet recruiting · Interventional · 1 enrolled · Gregor Andelfinger
  NCT07574034updated 2026-05-07
• Clinical Antenatal Randomised Study to CharactErise Key Roles of TetrahydroFOLate in HyperTensive Pregnancies
  Recruiting · Interventional · 128 enrolled · University of Oxford
  NCT05434195updated 2026-04-29
• Study on Sapropterin Dihydrochloride Oral Suspension in Healthy Subjects Under Fed Conditions
  Completed · Phase 1 · Interventional · 42 enrolled · APR Applied Pharma Research s.a.
  NCT06987773updated 2026-04-28
• Novel Approaches for Improving Vascular Function in Veterans With HFpEF
  Recruiting · Phase 1 · Interventional · 90 enrolled · VA Office of Research and Development
  NCT06312748updated 2026-04-23
• The Effects of ATLAS Therapy on Nitric Oxide Bioavailability in Patients With Intermittent Claudication
  Active not recruiting · Phase 1 · Interventional · 10 enrolled · Louis Messina
  NCT04800692updated 2026-04-15
• Evaluation of BH4 Responsiveness in Our PKU Patients
  Active not recruiting · Phase 1 · Interventional · 20 enrolled · Sohag University
  NCT07255599updated 2025-12-01
• : Vascular Function in Health and Disease
  Recruiting · Phase 1 · Interventional · 420 enrolled · Russell Richardson
  NCT02966665updated 2025-09-26
• Exercise and NO in HFrEF
  Completed · Early phase 1 · Interventional · 68 enrolled · VA Office of Research and Development
  NCT03136029updated 2025-08-06
• Rhode Island Diastolic Dysfunction - Heart Failure
  Completed · Interventional · 28 enrolled · Providence VA Medical Center
  NCT02353312updated 2025-07-03

Frequently asked questions

How does Sapropterin work?

Sapropterin dihydrochloride is a synthetic form of BH4, the cofactor for the enzyme phenylalanine hydroxylase (PAH). PAH hydroxylates Phe through an oxidative reaction to form tyrosine.

What is Sapropterin used for?

According to FDA labeling, Sapropterin carries indications including: Sapropterin dihydrochloride tablets are 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 tablets are to be used in conjunction with a Phe-restricted diet.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Sapropterin?

Sapropterin is classified as Various alimentary tract and metabolism products, Phenylalanine Hydroxylase Activator, Breast Cancer Resistance Protein Inhibitors, P-Glycoprotein Inhibitors, Phenylalanine Hydroxylase Activators, Peptide Metabolism Alteration.

What are the brand names for Sapropterin?

Sapropterin is marketed under brand names including Javygtor, Kuvan, Zelvysia.

What are the contraindications for Sapropterin?

Sapropterin labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.