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PALYNZIQ Safety Information

Adverse reactions in clinical trials1*

Adverse reactions by exposure-adjusted rate1

  • The majority of adverse reactions were mild to moderate in severity; injection site reactions and arthralgia occurred most frequently2
  • In clinical trials, the rate of adverse reactions decreased over time1

The exposure-adjusted rate represents the number of episodes divided by patient-years (the number of patients multiplied by the years patients were exposed to treatment).1

Non–IgE-mediated anaphylaxis observed
in phase 3 clinical trials1

 
  • In clinical trials with an induction/titration/maintenance regimen, 9% of patients (26 of 285) experienced a total of 37 anaphylaxis episodes1
    • No drug-specific IgE was detected at or near the time of the episodes1†
  • 18 of 26 (69%) patients who experienced anaphylaxis were rechallenged. 13 of 18 (72%) were able to continue therapy without experiencing recurrence, and 5 of 18 (28%) patients who were rechallenged had recurrence of anaphylaxis1
  • Most episodes occurred within 1 hour after injection (76%; 28 of 37 episodes), though delayed episodes also occurred up to 48 hours after administration of PALYNZIQ™ (pegvaliase-pqpz) Injection1
  • Most episodes occurred within the first year of dosing (78%; 29 of 37 episodes), but cases also occurred after 1 year of dosing and up to 834 days (2.3 years) of total follow-up1

Management of anaphylaxis in clinical trials1

  • 54% of anaphylaxis episodes (20 of 37) were managed with administration of auto-injectable epinephrine

All anaphylaxis episodes resolved without sequelae1

25 of 26 patients who had anaphylaxis were tested for anti–pegvaliase-pqpz IgE antibodies, which recognize the PEGylated protein product. Of those 25 patients, 24 tested negative. The 1 patient who screened positive for anti–pegvaliase-pqpz IgE had insufficient sample to confirm IgE positivity. This patient tested negative for anti–pegvaliase-pqpz IgE at routine visits before and after the anaphylaxis episode (not at times of anaphylaxis).1

Type III immune complex–mediated hypersensitivity reactions

  • Since PALYNZIQ is a nonhuman enzyme, it elicits an immune response and may cause hypersensitivity reactions1
  • Hypersensitivity reactions, other than anaphylaxis, occurred in 69% of patients (196 of 285) treated with PALYNZIQ1
  • The rate of hypersensitivity reactions was highest during the induction/titration phases and decreased during the maintenance phase, but reactions can occur at any time1
  • Management of hypersensitivity reactions should be based on severity and recurrence of the reaction and clinical judgment of the healthcare provider, and may include treatment with antihistamines, antipyretics, and/or corticosteroids, as well as dosage adjustment, temporary drug interruption, or drug discontinuation1

Strategies for managing potential anaphylaxis episodes

Requirements

 
  • Prescribe auto-injectable epinephrine to all patients treated with PALYNZIQ. Prior to the first dose, instruct the patient and adult 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 use1
    • Instruct patients to carry auto-injectable epinephrine with them at all times during treatment with PALYNZIQ1
 

Considerations

  • Having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis or for other patients during treatment with PALYNZIQ1
    • If an adult observer is needed, the observer should be present during and for at least 1 hour after administration of PALYNZIQ, and should be able to administer auto-injectable epinephrine and call for emergency medical support upon its use1
 
  • Premedication with the following, based on individual patient tolerability, prior to each dose of PALYNZIQ1:
    • H1 antagonist
    • H2 antagonist
    • Antipyretic
 

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.

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.

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.