PALYNZIQ Dosing & Administration

PALYNZIQ® (pegvaliase-pqpz) Injection is a daily at-home subcutaneous injection available in 3 dosage strengths1

PALYNZIQ is available in 3 different dosage strengths1:

  • 2.5 mg/0.5 mL single-dose prefilled syringe (white)
  • 10 mg/0.5 mL single-dose prefilled syringe (green)
  • 20 mg/mL single-dose prefilled syringe (blue)
 
  • PALYNZIQ is supplied in a prefilled syringe intended for use as a single at-home subcutaneous injection1
  • PALYNZIQ should be refrigerated at 36ºF (2ºC) to 46ºF (8ºC) in the original carton to protect from light1
  • PALYNZIQ can be safely stored at room temperature in the original carton for up to 30 days1
    • On the carton, patients should record the date that they remove PALYNZIQ from the refrigerator
    • Do not re-refrigerate once stored at room temperature

Recommended dosing regimen

  • There are 3 phases to the recommended dosing regimen for PALYNZIQ: induction, titration, and maintenance1

The first injection must be performed under the supervision of a healthcare provider equipped to manage anaphylaxis; patients must be closely observed for at least 1 hour following injection. Prior to self-injection, the patient's competency with self-administration must be confirmed.1

Additional time may be required between dose escalations based on patient tolerability.1

Individualize treatment to the lowest effective and tolerated dosage. Consider increasing to a maximum of 40 mg subcutaneously once daily in patients who have not achieved a response after at least 24 weeks of continuous treatment with 20 mg subcutaneously once daily.1

Discontinue PALYNZIQ if either a ≥20% reduction from baseline or a blood Phe concentration ≤600 µmol/L (10 mg/dL) is not achieved after at least 16 weeks of continuous treatment with 40 mg subcutaneously once daily.1

Therapeutic dosage is based on patient tolerability, blood Phe concentrations, and dietary Phe intake1

In clinical trials, consistent dietary Phe intake was recommended until therapeutic dosage was achieved2

  • Obtain baseline blood Phe concentration prior to treatment initiation and assess blood Phe levels every 4 weeks until therapeutic dosage is achieved1
    • After therapeutic dosage is achieved, periodic blood Phe monitoring is recommended1
  • Monitor patients’ dietary Phe intake throughout treatment with PALYNZIQ and counsel them on how to adjust their intake, as needed, based on blood Phe concentrations1
  • Most patients were not on a Phe-restricted diet prior to and during the trials2
    • Patients’ total protein intake remained relatively stable throughout treatment, while dietary Phe intake increased2
  • If patients experience blood Phe levels ≤30 µmol/L (0.5 mg/dL), reduce dosage of PALYNZIQ and/or modify dietary Phe intake to keep levels within a clinically acceptable range and above 30 µmol/L (0.5 mg/dL)1

A 20% reduction in blood Phe levels or blood Phe concentration was defined as the first sign of response in clinical trials1

  • Treatment may be continued to reach individualized Phe targets once this threshold is met, based on patient tolerability

References: 1. PALYNZIQ [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2018. 2. Thomas J, Levy H, Amato S, et al, for the PRISM investigators. Pegvaliase for the treatment of phenylketonuria: results of a long-term phase 3 clinical trial program (PRISM). Mol Genet Metab. 2108;124(1):27-38.

Important Safety Information
WARNING: RISK OF ANAPHYLAXIS
 

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
  • Prescribe auto-injectable epinephrine to all patients treated with PALYNZIQ. 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 treatment with PALYNZIQ
  • PALYNZIQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALYNZIQ REMS. 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 treatment with PALYNZIQ. If an adult observer is needed, the observer should be present during and for at least 60 minutes after administration of PALYNZIQ, and 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 treatment with PALYNZIQ. Prior to the first dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, on 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 dose titration of PALYNZIQ should be based on patient tolerability and therapeutic response
  • Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to administration of PALYNZIQ based upon individual patient tolerability

Other Hypersensitivity Reactions

  • Hypersensitivity reactions other than anaphylaxis have been reported in 196 of 285 (69%) patients treated with PALYNZIQ
  • Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to PALYNZIQ administration based upon individual patient tolerability
  • 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, drug discontinuation, 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 reaction lasting at least 14 days, pruritus, nausea, abdominal pain, oropharyngeal pain, vomiting, cough, diarrhea, and fatigue
  • Of the 285 patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 31 (11%) 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) and 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 (14% 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 arthralgia (13% of patients), hypersensitivity reactions (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients)

Blood Phenylalanine Monitoring and Diet

  • Obtain blood phenylalanine concentrations every 4 weeks until a maintenance dosage is established
  • After a maintenance dosage is established, periodically monitor blood phenylalanine concentrations
  • Counsel patients to monitor dietary protein and phenylalanine 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, 2 patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced hypersensitivity reactions, and 1 of the 2 patients also experienced anaphylaxis
  • The clinical effects of concomitant treatment with different PEGylated products is unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions

USE IN SPECIFIC POPULATIONS

Pregnancy and Lactation

  • PALYNZIQ may cause fetal harm when administered to a pregnant woman
  • If PALYNZIQ is administered during pregnancy, or if a patient becomes pregnant while receiving PALYNZIQ or within 1 month following the last dose of PALYNZIQ, healthcare providers should report PALYNZIQ exposure by calling 1-866-906-6100
  • Monitor blood phenylalanine concentrations in breastfeeding women treated with PALYNZIQ

Pediatric Use

  • The safety and efficacy 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 and the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information, including Boxed Warning, at PALYNZIQ.com/hcp.

US/PAL/0314 0319

US/PAL/0442 0619

INDICATION

PALYNZIQ® (pegvaliase-pqpz) Injection is a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 µmol/L on existing management.

Important Safety Information
WARNING: RISK OF ANAPHYLAXIS
 

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
  • Prescribe auto-injectable epinephrine to all patients treated with PALYNZIQ. 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 treatment with PALYNZIQ
  • PALYNZIQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALYNZIQ REMS. 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 treatment with PALYNZIQ. If an adult observer is needed, the observer should be present during and for at least 60 minutes after administration of PALYNZIQ, and 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 treatment with PALYNZIQ. Prior to the first dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, on 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 dose titration of PALYNZIQ should be based on patient tolerability and therapeutic response
  • Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to administration of PALYNZIQ based upon individual patient tolerability

Other Hypersensitivity Reactions

  • Hypersensitivity reactions other than anaphylaxis have been reported in 196 of 285 (69%) patients treated with PALYNZIQ
  • Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to PALYNZIQ administration based upon individual patient tolerability
  • 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, drug discontinuation, 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 reaction lasting at least 14 days, pruritus, nausea, abdominal pain, oropharyngeal pain, vomiting, cough, diarrhea, and fatigue
  • Of the 285 patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 31 (11%) 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) and 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 (14% 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 arthralgia (13% of patients), hypersensitivity reactions (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients)

Blood Phenylalanine Monitoring and Diet

  • Obtain blood phenylalanine concentrations every 4 weeks until a maintenance dosage is established
  • After a maintenance dosage is established, periodically monitor blood phenylalanine concentrations
  • Counsel patients to monitor dietary protein and phenylalanine 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, 2 patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced hypersensitivity reactions, and 1 of the 2 patients also experienced anaphylaxis
  • The clinical effects of concomitant treatment with different PEGylated products is unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions

USE IN SPECIFIC POPULATIONS

Pregnancy and Lactation

  • PALYNZIQ may cause fetal harm when administered to a pregnant woman
  • If PALYNZIQ is administered during pregnancy, or if a patient becomes pregnant while receiving PALYNZIQ or within 1 month following the last dose of PALYNZIQ, healthcare providers should report PALYNZIQ exposure by calling 1-866-906-6100
  • Monitor blood phenylalanine concentrations in breastfeeding women treated with PALYNZIQ

Pediatric Use

  • The safety and efficacy 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 and the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information, including Boxed Warning, at PALYNZIQ.com/hcp.

US/PAL/0314 0319

US/PAL/0442 0619

INDICATION

PALYNZIQ® (pegvaliase-pqpz) Injection is a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 µmol/L on existing management.