kuvan
Kuvan (Sapropterin Dihydrochloride) is a phenylalanine hydroxylase activator used to treat Phenylketonurias.
Sapropterin Dihydrochloride · by Biomarin Pharm
Key facts
- Active ingredient
- Sapropterin Dihydrochloride
- Drug class
- Phenylalanine Hydroxylase Activator
- Form
- Powder, Tablet
- Strength
- Sapropterin Dihydrochloride 100MG
- Type
- Prescription (Rx)
- Brand or generic
- Brand-name
- May treat
- phenylketonurias
- Manufacturer
- Biomarin Pharm
- FDA application
- NDA022181
What is Kuvan?
From the FDA label:KUVAN (sapropterin dihydrochloride) is an orally administered Phenylalanine Hydroxylase activator (or PAH activator). Sapropterin dihydrochloride, the active pharmaceutical ingredient in KUVAN, is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Sapropterin dihydrochloride is an off-white to light yellow crystals or crystalline powder. The chemical name of sapropterin dihydrochloride is (6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride and the molecular formula is C 9 H 15 N 5 O 3 ·2HCl with a molecular weight of 314.17. Sapropterin dihydrochloride has the following structural formula: KUVAN is supplied as tablets and powder for oral solution containing 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base). KUVAN is also supplied as powder for oral solution containing 500 mg of sapropterin dihydrochloride (equivalent to 384 mg of sapropterin base). Tablets are round, off-white to light yellow, mottled, and debossed with “177”. Each tablet contains the following inactive ingredients: ascorbic acid (USP), crospovidone (NF), dibasic calcium phosphate (USP), D-mannitol (USP), riboflavin (USP), and sodium stearyl fumarate (NF). KUVAN powder for oral solution is off-white to yellow in color. Each unit dose packet contains the following inactive…
How to use
Kuvan is sold in more than one form (Powder and Tablet), and each is dosed differently. The instructions below come from the FDA label for application NDA022181 — follow the label that came with the product you were actually prescribed.
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. ( 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…
Side effects
Most common adverse reactions (≥4%) are: headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion. ( 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…
Warnings
Important safety information
Hypersensitivity Reactions Including Anaphylaxis : KUVAN is not recommended in patients with a history of anaphylaxis to KUVAN; 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 KUVAN 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 KUVAN. Frequent blood monitoring is recommended, especially in pediatric patients. ( 5.4 , 2.1 ) Lack of Biochemical Response to KUVAN T reatment : Response to KUVAN treatment cannot be pre-determined by laboratory (e.g., molecular) testing and can only be determined by a therapeutic trial of KUVAN. ( 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. ( 5.7 ) 5.1 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 [see Adverse Reactions ( 6.2 )] . Signs of anaphylaxis include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash. Discontinue treatment with KUVAN in patients who experience anaphylaxis and initiate appropriate medical treatment. Continue dietary protein and Phe restriction in patients who experience anaphylaxis. 5.2 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 [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 KUVAN. Monitor patients for signs and symptoms of upper GI mucosal inflammation. 5.3 Hypophenylalaninemia In clinical trials of KUVAN, some PKU patients experienced hypophenylalaninemia (low blood Phe) during treatment with KUVAN. In a clinical study of pediatric patients younger than 7 years old treated with KUVAN 20 mg/kg per day, the incidence of hypophenylalaninemia was higher than in clinical trials of older patients [see Adverse Reactions ( 6.1 )] . 5.4 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 while taking KUVAN is required to ensure adequate Phe control and nutritional balance. Monitor blood Phe levels during treatment to ensure adequate blood Phe level control. Frequent blood monitoring is recommended in the pediatric population [see Dosage and Administration ( 2.2 )] . 5.5 Lack of Biochemical Response to KUVAN Some patients with PKU do not show biochemical response (reduction in blood Phe) with treatment with KUVAN. In two clinical trials at a KUVAN dose of 20 mg/kg per day, 56% to 75% of pediatric PKU patients showed a biochemical response to KUVAN, and in one clinical trial at a dose of 10 mg/kg per day, 20% of adult and pediatric PKU patients showed a biochemical response to KUVAN [see Clinical Studies ( 14 )] . 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 [see Dosage and Administration ( 2.2 )] . 5.6 Interaction with Levodopa In a 10-year post-marketing safety surveillance program for a non-PKU indication using another sapropterin product, 3 patients with underlying neurological disorders experienced seizures, exacerbation of seizures, over-stimulation, and irritability during co-administration of levodopa and sapropterin. Monitor patients who are receiving levodopa for changes in neurological status during treatment with KUVAN [see Drug Interactions ( 7 )] . 5.7 Hyperactivity In the KUVAN postmarketing safety surveillance program, 2 patients with PKU experienced hyperactivity when treated with KUVAN [see Adverse Reactions ( 6.2 )] . Monitor patients for hyperactivity. 5.1 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 [see Adverse Reactions ( 6.2 )] . Signs of anaphylaxis include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash. Discontinue treatment with KUVAN in patients who experience anaphylaxis and initiate appropriate medical treatment. Continue dietary protein and Phe restriction in patients who experience anaphylaxis. 5.2 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 [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 KUVAN. Monitor patients for signs and symptoms of upper GI mucosal inflammation. 5.3 Hypophenylalaninemia In clinical trials of KUVAN, some PKU patients experienced hypophenylalaninemia (low blood Phe) during treatment with KUVAN. In a clinical study of pediatric patients younger than 7 years old treated with KUVAN 20 mg/kg per day, the incidence of hypophenylalaninemia was higher than in clinical trials of older patients [see Adverse Reactions ( 6.1 )] . 5.4 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 while taking KUVAN is required to ensure adequate Phe control and nutritional balance. Monitor blood Phe levels during treatment to ensure adequate blood Phe level control. Frequent blood monitoring is recommended in the pediatric population [see Dosage and Administration ( 2.2 )] . 5.5 Lack of Biochemical Response to KUVAN Some patients with PKU do not show biochemical response (reduction in blood Phe) with treatment with KUVAN. In two clinical trials at a KUVAN dose of 20 mg/kg per day, 56% to 75% of pediatric PKU patients showed a biochemical response to KUVAN, and in one clinical trial at a dose of 10 mg/kg per day, 20% of adult and pediatric PKU patients showed a biochemical response to KUVAN [see Clinical Studies ( 14 )] . 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 [see Dosage and Administration ( 2.2 )] . 5.6 Interaction with Levodopa In a 10-year post-marketing safety surveillance program for a non-PKU indication…
Who should not take Kuvan
None. None. ( 4 )
Overdose — what happens if you take too much
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. 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.
U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.
Interactions
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 )
Drug class
May treat (source: NIH RxClass)
Dosage forms
Powder and Tablet
The forms currently marketed in the U.S., per the FDA National Drug Code Directory.
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Frequently asked questions
- What does Kuvan treat?
- Kuvan (Sapropterin Dihydrochloride) may be used to treat phenylketonurias, based on NIH RxClass drug-classification data (conditions a drug may treat — not a verbatim copy of the FDA-approved label). This is general reference, not medical advice.
- Is there a coupon or discount for Kuvan?
- pharmaranks is an independent ratings site, not a pharmacy — we don't issue coupons or sell Kuvan. To pay less, ask your prescriber or pharmacist whether a generic equivalent exists, check the manufacturer's copay/savings card and patient-assistance program, and compare a pharmacy discount card against your insurance copay. Prices vary by pharmacy, insurance, and location, so always confirm at the counter. This is general reference, not medical or financial advice.
- Who makes Kuvan?
- Kuvan is marketed by Biomarin Pharm. You can see Biomarin Pharm's full profile, rating, and other products on pharmaranks.
- Is Kuvan a brand-name or generic drug?
- Kuvan is a brand-name product with the active ingredient Sapropterin Dihydrochloride.
- Is Kuvan available over the counter?
- No. Kuvan is a prescription (Rx) medication in the US — you need a prescription from a licensed clinician (in person or via telehealth); it isn't sold over the counter. For some conditions there are OTC alternatives — ask your pharmacist.
- What forms does Kuvan come in?
- Kuvan is currently marketed as powder and tablet, per the FDA's National Drug Code Directory.
- What class of drug is Kuvan?
- Kuvan is classified as phenylalanine hydroxylase activator, per the FDA's Established Pharmacologic Class.
- Is Kuvan FDA-registered?
- Kuvan is on record with the U.S. FDA under application number NDA022181. You can verify this on its official FDA label.
- Is Kuvan safe?
- There's no single safe-or-not verdict, and we don't yet have a composite recall-safety score for Kuvan. Review its FDA-label side effects and warnings below, and always consult a licensed professional.
- What are the side effects of Kuvan?
- Kuvan's side effects are taken directly from its FDA label. From the label: Most common adverse reactions (≥4%) are: headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion. ( 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 .… Both common and serious reactions are documented in full on this page. This is general reference from the FDA, not medical advice — always consult a professional.
Clinical content sourced from the FDA label via openFDA (U.S. FDA). View the FDA label on DailyMed → Provided for general reference only — not medical advice. Always consult a licensed professional and the current prescribing information.
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