In 2007, KUVAN® (sapropterin dihydrochloride) Tablets or Powder for Oral Solution was approved as the first prescription medication for PKU
Here are 10 facts to remember about KUVAN:
KUVAN is available in 58 countries around the world1
Since FDA approval, more than 6,000 patients in the United States have been treated with KUVAN, together with a low-Phe diet*1
Experience with KUVAN totals more than 20,950 patient-years†1
The safety of KUVAN has been tested in clinical studies in more than 600 people, ranging in age from 1 month to 50 years. Common adverse reactions (incidence ≥4%) were headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion2
More than 420 children under 4 years of age in the United States have been treated with KUVAN, together with a low-Phe diet1
The American College of Medical Genetics and Genomics (ACMG) recommends a trial of KUVAN for all patients with PKU to test for response‡3
In a clinical study, patients treated with KUVAN showed the greatest reduction in blood Phe levels with the 20 mg/kg dose2
KUVAN is offered in 3 dosage forms: 100 mg Tablets, 100 mg Powder Packets, and 500 mg Powder Packets, which offer the convenience of fewer packets to open2
According to ACMG Guidelines, it’s never too late to return to treatment, including diet and medication. Many patients will likely see an improvement in symptoms3-6
To date, BioMarin RareConnections™ has helped approximately 7,000 patients with PKU1
*As of May 24, 2017. †As of December 1, 2015. ‡Except those with two null mutations in trans.
Data on file. Novato, CA: BioMarin Pharmaceutical Inc; 2016.
KUVAN [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2016.
Vockley J, Andersson HC, Antshel KM, et al; for the American College of Medical Genetics and Genomics Therapeutic Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16(2):188-200.
Christ SE, Moffitt AJ, Peck D, White DA. The effects of tetrahydrobiopterin (BH4) treatment on brain function in individuals with phenylketonuria. Neuroimage Clin. 2013;3:539-547.
Bik-Multanowski M, Didycz B, Mozrzymas R, et al. Quality of life in noncompliant adults with phenylketonuria after resumption of the diet. JIMD Short Report. 2008;133. doi:10.1007/s10545-008-0978-7.
Waisbren SE, Levy HL. Agoraphobia in phenylketonuria. J Inherit Metab Dis. 1991;14(5):755-764.
KUVAN® (sapropterin dihydrochloride) Tablets for Oral Use and Powder for Oral Solution are indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age or older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). KUVAN is to be used in conjunction with a Phe-restricted diet.
IMPORTANT SAFETY INFORMATION
Treatment with KUVAN should be directed by physicians knowledgeable in the management of PKU. Prolonged exposure to elevated blood Phe levels can result in severe neurologic damage in PKU patients.
The use of KUVAN does not eliminate the need for careful monitoring of blood Phe levels and ongoing dietary management to ensure adequate Phe control and nutritional balance. Response to KUVAN can only be determined by a therapeutic trial. Patients should be advised to notify their physicians in cases of overdose.
Warnings and Precautions
Hypersensitivity Reactions Including Anaphylaxis: KUVAN is not recommended in patients with a history of anaphylaxis to KUVAN. Hypersensitivity reactions, including anaphylaxis and rash, have occurred. Signs of anaphylaxis include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash. Discontinue KUVAN treatment in patients who experience anaphylaxis, and initiate appropriate medical treatment. Continue dietary Phe restrictions in patients who experience anaphylaxis.
Upper Gastrointestinal Mucosal Inflammation: Gastrointestinal (GI) adverse reactions suggestive of upper GI mucosal inflammation have been reported with KUVAN. Serious adverse reactions included esophagitis and gastritis. 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 KUVAN. Monitor patients for signs and symptoms of upper GI mucosal inflammation.
Hypophenylalaninemia: Some patients receiving KUVAN can experience significant drops in blood Phe levels, and children younger than 7 years old treated with KUVAN doses of 20 mg/kg per day are at an increased risk for low levels of blood Phe compared with children 7 years and older.
Monitoring Blood Phe Levels During Treatment: Prolonged elevations of blood Phe levels in patients with PKU can result in severe neurologic damage, including severe intellectual disability, developmental delay, microcephaly, delayed speech, seizures, and behavioral abnormalities. Conversely, prolonged levels of blood Phe that are too low have been associated with catabolism and endogenous protein breakdown, which has been associated with adverse developmental outcomes. Active management of dietary Phe intake and frequent blood Phe monitoring while taking KUVAN is required to ensure adequate Phe control and nutritional balance, especially in the pediatric population.
Lack of Biochemical Response to KUVAN: Not all patients with PKU respond to treatment with KUVAN. Biochemical response to KUVAN treatment cannot generally be pre-determined by laboratory testing (e.g., molecular testing), and should be determined through a therapeutic trial (evaluation) of KUVAN response.
Interactions with Levodopa: In a post-marketing safety surveillance program for a non- PKU indication using another formulation of the same active ingredient (sapropterin), there have been reports of an interaction with levodopa causing seizures, exacerbation of seizures, over-stimulation, and irritability. Monitor patients who are receiving levodopa for a change in neurologic status during treatment with KUVAN.
Hyperactivity: There have been post-marketing reports of hyperactivity with administration of KUVAN. Monitor patients for hyperactivity.
Most common: The most common adverse reactions (incidence ≥4%) were headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.
Additional adverse reactions reported in connection with worldwide marketing: hypersensitivity reactions including anaphylaxis and rash, esophagitis, gastritis, oropharyngeal pain, pharyngitis, esophageal pain, abdominal pain, dyspepsia, nausea, vomiting, and hyperactivity.
Additional Drug Interactions
Frequently monitor blood Phe levels when co-administering KUVAN with medications known to inhibit folate metabolism, such as methotrexate, valproic acid, phenobarbital, trimethoprim.
Monitor patients for hypotension when co-administering KUVAN with medications known to affect nitric oxide–mediated vasorelaxation such as PDE-5 inhibitors including sildenafil, vardenafil, or tadalafil.
To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please read the full Prescribing Information by clicking here.