For U.S. Healthcare ProfessionalsFor U.S. Patients & Caregivers
Select a treatment for support

We’re here to help.
For assistance, please call
1-833-PKU-CARE (1-833-758-2273)
Monday-Friday, 8AM-8PM ET

For assistance, please call 1-833-PKU-CARE (1-833-758-2273)

Enroll your PALYNZIQ patients for one-to-one access support

BioMarin RareConnections™ provides patients on PALYNZIQ with personalized Case Management and has Field Reimbursement Managers available to provide reimbursement education to your clinic, product access education, and logistics support. Learn more about our support services.

To get started, complete the Patient Enrollment Form (PEF) and have your patient complete the Patient Consent Form (PCF) via QUICK ENROLL.

Your office and the patient must enroll in the PALYNZIQ Risk Evaluation and Mitigation Strategy (REMS) program prior to treatment. The PEF serves as the prescription for PALYNZIQ.
Portal iconEnroll in PALYNZIQ REMS
+
Computer iconQUICK ENROLL e-enrollment
Download the forms for faxing
PALYNZIQ logo
Full Prescribing Information
PALYNZIQ.com/hcp
We’re here to help. For assistance, please call 1-833-PKU-CARE (1-833-758-2273) Monday-Friday, 8AM-8PM ET
BioMarin RareConnections provides one-to-one financial navigation to help patients start and stay on therapy. Learn more about our services and the following resources:
PALYNZIQ Coverage Authorization Guide
A comprehensive resource including sample Letter of Medical Necessity for accessing PALYNZIQ treatment for your patients.
Download the guide
RareConnections and Specialty Pharmacy Roadmap Flyer
An at-a-glance reference sheet outlining the patient journey.
Download the flyer
PKU Patient Support Program Brochure
A comprehensive guide to help your patients understand the PKU Support Program.
Download the brochure
Email to your patient
PKU Reimbursement Video Series
A video series to help clinics manage reimbursement and logistics.
Watch the videos >
Specialty Pharmacy Contact Sheet
An at-a-glance reference sheet for contacting specialty pharmacies.
Download the sheet
PALYNZIQ Co-Pay Assistance Flyer
A flyer describing the PALYNZIQ Co-Pay Assistance Program for eligible patients.
Download the flyer
Email to your patient
BioMarin RareConnections provides one-to-one financial navigation to help patients start and stay on therapy. Learn more about our services and the following resources:
KUVAN Coverage Authorization Guide
A comprehensive guide to help you access KUVAN treatment for your patients.
Download the guide
RareConnections and Specialty Pharmacy Patient Journey Flyer
An at-a-glance reference sheet outlining the patient journey.
Download the flyer
PKU Patient Support Program Brochure
A comprehensive guide to help your patients understand the PKU Support Program.
Download the brochure
PKU Reimbursement Video Series
A video series to help clinics manage reimbursement and logistics.
Watch the videos >
Specialty Pharmacy Contact Sheet
An at-a-glance reference sheet for contacting the specialty pharmacies.
Download the sheet
KUVAN Co-Pay Assistance Flyer
A flyer describing the KUVAN Co-Pay Assistance Program.
Download the flyer
Email to your patient

PALYNZIQ® (pegvaliase-pqpz) Injection Important Safety Information
WARNING: RISK OF ANAPHYLAXIS

INDICATION

PALYNZIQ is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe concentrations in adult patients with phenylketonuria who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management.

BOXED WARNING: RISK OF ANAPHYLAXIS
  • Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment with PALYNZIQ
  • Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient’s and observer’s (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable epinephrine, if needed
  • Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use
  • Prescribe auto-injectable epinephrine. Prior to the first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment
  • PALYNZIQ is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Further information, including a list of qualified pharmacies, is available at www.PALYNZIQREMS.com or by telephone at 1-855-758-REMS (1-855-758-7367)
WARNINGS AND PRECAUTIONS
Anaphylaxis
  • Signs and symptoms of anaphylaxis reported include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat tightness, skin flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea)
  • Anaphylaxis generally occurred within 1 hour after injection; however, delayed episodes occurred up to 48 hours after PALYNZIQ administration
  • Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use
  • Anaphylaxis requires immediate treatment with auto-injectable epinephrine. Prescribe auto-injectable epinephrine to all patients receiving PALYNZIQ and instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment. Prior to the first dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, how to properly administer auto-injectable epinephrine, and to seek immediate medical care upon its use. Consider the risks associated with auto-injectable epinephrine use when prescribing PALYNZIQ. Refer to the auto-injectable epinephrine prescribing information for complete information
  • Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. Subsequent PALYNZIQ dose titration should be based on patient tolerability and therapeutic response
  • Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to PALYNZIQ administration based upon individual patient tolerability
Other Hypersensitivity Reactions
  • Hypersensitivity reactions other than anaphylaxis have been reported in 204 of 285 (72%) patients treated with PALYNZIQ in clinical trials
  • Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgment of the healthcare provider, and may include dosage adjustment, temporary drug interruption, or treatment with antihistamines, antipyretics, and/or corticosteroids
ADVERSE REACTIONS
  • The most common adverse reactions (at least 20% of patients in either treatment phase) were injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety
  • Of the 285 patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. The most common adverse reactions leading to treatment discontinuation were hypersensitivity reactions (6% of patients) including anaphylaxis (3% of patients), angioedema (1% of patients), arthralgia (4% of patients), generalized skin reactions lasting at least 14 days (2% of patients), and injection site reactions (1% of patients)
  • The most common adverse reactions leading to dosage reduction were arthralgia (15% of patients), hypersensitivity reactions (9% of patients), injection site reactions (4% of patients), alopecia (3% of patients), and generalized skin reactions lasting at least 14 days (2% of patients)
  • The most common adverse reactions leading to temporary drug interruption were hypersensitivity reactions (14% of patients), arthralgia (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients)
  • Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema, and face edema) occurring independent of anaphylaxis. In clinical trials, serum sickness was reported in 7 out of 285 (2%) patients
Blood Phenylalanine Monitoring and Diet
  • Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe concentrations during maintenance therapy
  • Counsel patients to monitor dietary protein and Phe intake, and adjust as directed by their healthcare provider
DRUG INTERACTIONS

Effect of PALYNZIQ on Other PEGylated Products

  • In a single-dose study of PALYNZIQ in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced a hypersensitivity reaction. One of the two patients experienced anaphylaxis
  • The clinical effects of concomitant treatment with different PEGylated products are unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis
USE IN SPECIFIC POPULATIONS

Pregnancy and Lactation

  • PALYNZIQ may cause fetal harm when administered to a pregnant woman
  • Advise women who are exposed to PALYNZIQ during pregnancy or who become pregnant within one month following the last dose of PALYNZIQ that there is a pregnancy surveillance program that monitors pregnancy outcomes. Healthcare providers should report PALYNZIQ exposure and encourage these patients to report their pregnancy to BioMarin (1-866-906-6100)
  • Monitor blood Phe levels in breastfeeding women treated with PALYNZIQ
Pediatric Use
  • The safety and effectiveness of PALYNZIQ in pediatric patients have not been established
Geriatric Use
  • Clinical studies of PALYNZIQ did not include patients aged 65 years and older

You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information, with Boxed Warning for risk of anaphylaxis, and Medication Guide here.

KUVAN® (sapropterin dihydrochloride) Indication and Important Safety Information

INDICATION

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.
Adverse Reactions
  • 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.

PALYNZIQ® (pegvaliase-pqpz) Injection Important Safety Information
WARNING: RISK OF ANAPHYLAXIS

KUVAN® (sapropterin dihydrochloride) Indication and Important Safety Information

INDICATION

PALYNZIQ is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe concentrations in adult patients with phenylketonuria who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management.

BOXED WARNING: RISK OF ANAPHYLAXIS
  • Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment with PALYNZIQ
  • Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient’s and observer’s (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable epinephrine, if needed
  • Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use
  • Prescribe auto-injectable epinephrine. Prior to the first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment
  • PALYNZIQ is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Further information, including a list of qualified pharmacies, is available at www.PALYNZIQREMS.com or by telephone at 1-855-758-REMS (1-855-758-7367)
WARNINGS AND PRECAUTIONS
Anaphylaxis
  • Signs and symptoms of anaphylaxis reported include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat tightness, skin flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea)
  • Anaphylaxis generally occurred within 1 hour after injection; however, delayed episodes occurred up to 48 hours after PALYNZIQ administration
  • Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use
  • Anaphylaxis requires immediate treatment with auto-injectable epinephrine. Prescribe auto-injectable epinephrine to all patients receiving PALYNZIQ and instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment. Prior to the first dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, how to properly administer auto-injectable epinephrine, and to seek immediate medical care upon its use. Consider the risks associated with auto-injectable epinephrine use when prescribing PALYNZIQ. Refer to the auto-injectable epinephrine prescribing information for complete information
  • Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. Subsequent PALYNZIQ dose titration should be based on patient tolerability and therapeutic response
  • Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to PALYNZIQ administration based upon individual patient tolerability
Other Hypersensitivity Reactions
  • Hypersensitivity reactions other than anaphylaxis have been reported in 204 of 285 (72%) patients treated with PALYNZIQ in clinical trials
  • Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgment of the healthcare provider, and may include dosage adjustment, temporary drug interruption, or treatment with antihistamines, antipyretics, and/or corticosteroids
ADVERSE REACTIONS
  • The most common adverse reactions (at least 20% of patients in either treatment phase) were injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety
  • Of the 285 patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. The most common adverse reactions leading to treatment discontinuation were hypersensitivity reactions (6% of patients) including anaphylaxis (3% of patients), angioedema (1% of patients), arthralgia (4% of patients), generalized skin reactions lasting at least 14 days (2% of patients), and injection site reactions (1% of patients)
  • The most common adverse reactions leading to dosage reduction were arthralgia (15% of patients), hypersensitivity reactions (9% of patients), injection site reactions (4% of patients), alopecia (3% of patients), and generalized skin reactions lasting at least 14 days (2% of patients)
  • The most common adverse reactions leading to temporary drug interruption were hypersensitivity reactions (14% of patients), arthralgia (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients)
  • Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema, and face edema) occurring independent of anaphylaxis. In clinical trials, serum sickness was reported in 7 out of 285 (2%) patients
Blood Phenylalanine Monitoring and Diet
  • Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe concentrations during maintenance therapy
  • Counsel patients to monitor dietary protein and Phe intake, and adjust as directed by their healthcare provider
DRUG INTERACTIONS

Effect of PALYNZIQ on Other PEGylated Products

  • In a single-dose study of PALYNZIQ in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced a hypersensitivity reaction. One of the two patients experienced anaphylaxis
  • The clinical effects of concomitant treatment with different PEGylated products are unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis
USE IN SPECIFIC POPULATIONS

Pregnancy and Lactation

  • PALYNZIQ may cause fetal harm when administered to a pregnant woman
  • Advise women who are exposed to PALYNZIQ during pregnancy or who become pregnant within one month following the last dose of PALYNZIQ that there is a pregnancy surveillance program that monitors pregnancy outcomes. Healthcare providers should report PALYNZIQ exposure and encourage these patients to report their pregnancy to BioMarin (1-866-906-6100)
  • Monitor blood Phe levels in breastfeeding women treated with PALYNZIQ
Pediatric Use
  • The safety and effectiveness of PALYNZIQ in pediatric patients have not been established
Geriatric Use
  • Clinical studies of PALYNZIQ did not include patients aged 65 years and older

You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information, with Boxed Warning for risk of anaphylaxis, and Medication Guide here.

INDICATION

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.
Adverse Reactions
  • 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.