Pegvaliase-Pqpz
FDA Drug Information • Also known as: Palynziq
- Brand Names
- Palynziq
- Drug Class
- Phenylalanine Metabolizing Enzyme [EPC]
- Route
- SUBCUTANEOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: ANAPHYLAXIS Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment [see Warnings and Precautions (5.1) ] . 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 administer epinephrine, if needed [see Dosage and Administration (2.5) ] . 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 epinephrine, and call for emergency medical support upon its use [see Warnings and Precautions (5.1) ] . Prescribe epinephrine to all patients treated with PALYNZIQ. Prior to the first dose, instruct the patient and observer (if applicable) how to recognize the signs and symptoms of anaphylaxis, how to properly administer epinephrine, and to seek immediate medical care upon its use. Instruct patients to carry epinephrine with them at all times during treatment with PALYNZIQ [see Dosage and Administration (2.5) and Warnings and Precautions (5.1) ] . Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, readminister 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 [see Dosage and Administration (2.5) and Warnings and Precautions (5.1) ] . Because of the risk of anaphylaxis, PALYNZIQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALYNZIQ REMS [see Warnings and Precautions (5.2) ]. WARNING: ANAPHYLAXIS See full prescribing information for complete boxed warning. Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment. ( 5.1 ) 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 epinephrine, if needed. ( 2.5 ) Prescribe epinephrine. Prior to 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 epinephrine with them at all times during PALYNZIQ treatment. ( 2.5 , 5.1 ) PALYNZIQ is available only through a restricted program called the PALYNZIQ REMS. ( 5.2 )
Description
11 DESCRIPTION Pegvaliase-pqpz is a phenylalanine-metabolizing enzyme that is composed of recombinant phenylalanine ammonia lyase (rAvPAL) conjugated to N-hydroxysuccinimide (NHS)-methoxypolyethylene glycol (PEG). rAvPAL is manufactured in Escherichia coli bacteria transformed with a plasmid containing the phenylalanine ammonia lyase (PAL) gene derived from Anabaena variabilis . During the rAvPAL manufacturing process, fermentation is carried out in nutrient medium containing the antibiotic kanamycin. However, kanamycin is cleared in the manufacturing process and is not detectable in the final product. rAvPAL is a homotetrameric protein with a molecular weight of 62 kD per monomer. To produce pegvaliase-pqpz, an average of nine (9) 20 kD PEG molecules are covalently bound (or conjugated) to each monomer of rAvPAL. The total molecular weight of pegvaliase-pqpz (rAvPAL-PEG) is approximately 1000 kD. PALYNZIQ (pegvaliase-pqpz) injection, intended for subcutaneous injection, is a clear to slightly opalescent, colorless to pale yellow, sterile, preservative-free solution and is formulated at pH 6.6 to 7.4. PALYNZIQ is provided in a single-dose prefilled syringe and is available in three dosage strengths: 2.5 mg/0.5 mL, 10 mg/0.5 mL, and 20 mg/mL. PALYNZIQ contents for each dosage strength are summarized in Table 5. Table 5: Contents of PALYNZIQ Strength Total Contents per Prefilled Syringe PALYNZIQ 2.5 mg/0.5 mL prefilled syringe 2.5 mg pegvaliase-pqpz (expressed as the amount of rAvPAL conjugated to 7.25 mg of 20 kD PEG in 0.5 mL Water for Injection, USP) and contains the following inactive ingredients: sodium chloride (for tonicity adjustment), trans -cinnamic acid (0.07 mg), and tromethamine and tromethamine hydrochloride (for pH adjustment). PALYNZIQ 10 mg/0.5 mL prefilled syringe 10 mg pegvaliase-pqpz (expressed as the amount of rAvPAL conjugated to 29 mg of 20 kD PEG in 0.5 mL Water for Injection, USP) and contains the following inactive ingredients: sodium...
What Is Pegvaliase-Pqpz Used For?
1 INDICATIONS AND USAGE PALYNZIQ is indicated to reduce blood phenylalanine concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management. PALYNZIQ is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Obtain baseline blood Phe concentration before initiating treatment. ( 2.1 ) Consider premedication for hypersensitivity reactions. ( 2.1 , 5.1 , 5.3 ) The recommended initial dosage for PALYNZIQ is 2.5 mg subcutaneously once weekly for 4 weeks. ( 2.2 ) See the Full Prescribing Information for titration, maintenance, discontinuation, and dose reduction. ( 2.2 ) See Full Prescribing Information for dosage and administration modifications due to anaphylaxis. ( 2.3 ) Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. ( 2.4 ) Periodically monitor blood Phe concentrations during maintenance therapy and monitor dietary protein and phenylalanine intake throughout treatment. ( 2.4 ) Rotate injection sites. If more than one injection is needed for a single dose, the injection sites should be at least 2 inches away from each other. ( 2.5 ) 2.1 Important Recommendation Prior to PALYNZIQ Treatment Treatment with PALYNZIQ should be managed by a healthcare provider experienced in the management of PKU. Obtain baseline blood phenylalanine concentration before initiating treatment. Consider premedication with an H 1 -receptor antagonist, H 2 -receptor antagonist, and/or antipyretic based upon individual patient tolerability [see Warnings and Precautions (5.1 , 5.3) ] . 2.2 Recommended Dosage and Administration Induction The recommended initial induction dosage for PALYNZIQ is 2.5 mg subcutaneously once weekly for 4 weeks. Administer the initial dose under the supervision of a healthcare provider [see Dosage and Administration (2.5) ]. Titration Titrate the PALYNZIQ dosage in a step-wise manner, based on tolerability, over at least 5 weeks, to achieve a dosage of 20 mg subcutaneously once daily according to Table 1. Maintenance Therapeutic response may not be achieved until the patient is titrated to an effective maintenance dosage of PALYNZIQ. Use the lowest effective and tolerated dosage of PALYNZIQ. Assess patient tolerability, blood phenylalanine concentrations, and dietary protein and phenylalanine intake throughout treatment. Individualize the maintenance dosage to achieve blood phenylalanine control (blood phenylalanine concentrations less than or equal to 600 micromol/L), taking into account patient tolerability to PALYNZIQ and dietary protein and phenylalanine intake (see Table 1 ). Maintain the PALYNZIQ dosage at 20 mg once daily for at least 24 weeks. Consider increasing the PALYNZIQ dosage to 40 mg once daily in patients who have been on 20 mg once daily continuously for at least 24 weeks without achieving blood phenylalanine control. Consider increasing the PALYNZIQ dosage to a maximum of 60 mg once daily in patients who have been on 40 mg once daily continuously for at least 16 weeks without achieving blood phenylalanine control. Discontinuation Discontinue PALYNZIQ in patients who have not achieved an adequate response after 16 weeks of continuous treatment with the maximum dosage...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and in other sections of labeling: Anaphylaxis [see Warnings and Precautions (5.1) ] Other Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Injection Site Infections [see Warnings and Precautions (5.4) ] Hypophenylalaninemia [see Warnings and Precautions (5.5) ] Most common adverse reactions (at least 20% in either treatment phase) are: 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. ( 6.1 ) Most common adverse reactions in patients who are 12 to less than 18 years of age (at least 20% and greater than in control) are: injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue, and pain in extremity. ( 6.1 ) 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. 6.1 Clinical Trial 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 rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials With Induction/Titration/Maintenance Dosage Regimen in Patients With PKU (Study 1, Study 2, and Study 3) The data described below reflect a total treatment exposure of 789 patient-years in 285 patients who received PALYNZIQ in an induction/titration/maintenance regimen in a pooled safety analysis of a phase 2 study (Study 1), and 2 phase 3 studies (Studies 2 and 3, respectively) [see Clinical Studies (14) ] . Twelve patients aged 16-17 years at enrollment received PALYNZIQ as part of the overall induction/titration/maintenance population and are included in this analysis. Of the 285 patients, 229 patients were exposed to PALYNZIQ for 24 weeks, 209 patients were exposed for 1 year, 181 patients were exposed for 2 years, and 160 patients were exposed for 3 years or longer. The patient population was evenly distributed between male and female patients, the mean age was 29 years (range: 16 to 56 years), and 98% of patients were White. 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 from the pooled safety analysis, 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). Table 2 lists adverse reactions reported in at least 15% of patients treated with PALYNZIQ in an induction/titration/maintenance dosage regimen in clinical trials and illustrates the adverse reaction rates over time by treatment phase. Table 3 lists laboratory...
Drug Interactions
7 DRUG INTERACTIONS Effect of PALYNZIQ on Other PEGylated Products : Monitor for hypersensitivity reactions, including anaphylaxis, with concomitant treatment. ( 7.1 ) 7.1 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 a hypersensitivity reaction on day 15 after a single PALYNZIQ dosage of 0.67 mg within 15 minutes following medroxyprogesterone acetate injectable suspension, and subsequently experienced anaphylaxis on day 89 within 30 minutes after the next dose of medroxyprogesterone acetate injectable suspension. The other patient experienced a hypersensitivity reaction on day 40 after a single PALYNZIQ dosage of 0.08 mg within 10 minutes following medroxyprogesterone acetate injectable suspension. Both patients had high anti-PEG IgG antibody titers at or around the time of the hypersensitivity reactions. In PALYNZIQ clinical trials, the majority of patients developed anti-PEG IgM and IgG antibodies after treatment with PALYNZIQ [see Clinical Pharmacology (12.6) ] . 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 including anaphylaxis.
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data from pharmacovigilance and published literature with pegvaliase-pqpz use in pregnant women have not identified a clear association with major birth defects, miscarriage or other adverse maternal or fetal outcomes (see Data ) . There are risks to the fetus associated with poorly controlled phenylalanine concentrations in women with PKU during pregnancy including increased risk for miscarriage, major birth defects (including microcephaly and major cardiac malformations), intrauterine fetal growth retardation, and future intellectual disability with low IQ; therefore, phenylalanine concentrations should be closely monitored in women with PKU during pregnancy (see Clinical Considerations and Data ). Advise pregnant women of the potential risks to the fetus. A reproduction study in pregnant rabbits without PKU treated with pegvaliase-pqpz demonstrated a high incidence of fetal malformations throughout the skeletal system, and in kidneys, lungs, and eyes. Embryo-fetal toxicity (increased resorptions and reduced fetal weight) was also observed. These effects occurred at 5 times the maximum recommended daily dose and were associated with strong signs of maternal toxicity, including marked reductions in weight gain and food consumption, and death. A reproduction study in pregnant rats without PKU treated with pegvaliase-pqpz demonstrated an increase in skeletal variations with no malformations observed. The effects in rats occurred at 2.8 times the maximum recommended daily dose. In a pre-/post-natal development study in rats, pegvaliase-pqpz produced reduced survival of offspring during lactation, decreases in pup weight and litter size, and delayed sexual maturation of offspring when administered daily at 13 times the maximum recommended daily dose. Observed embryofetal and postnatal findings could be attributable to maternal toxicity. All pregnancies have a background risk of major birth defects, pregnancy loss, or other adverse...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied PALYNZIQ (pegvaliase-pqpz) injection is supplied as a preservative-free, sterile, clear to slightly opalescent, colorless to pale yellow solution. All dosage strengths of PALYNZIQ are provided in a 1 mL glass syringe with a 26-gauge, 0.5 inch needle. Each carton contains 1 or 10 trays with single-dose prefilled syringe(s), Prescribing Information, Medication Guide, and Instructions for Use. The following packaging configurations are available. Table 8: PALYNZIQ Packaging Configurations Pegvaliase-pqpz 2.5 mg/0.5 mL 1 syringe/carton NDC 68135-058-90 Pegvaliase-pqpz 10 mg/0.5 mL 1 syringe/carton NDC 68135-756-20 Pegvaliase-pqpz 20 mg/mL 1 syringe/carton 10 syringes/carton NDC 68135-673-40 NDC 68135-673-45 Storage and Handling Store in refrigerator at 36°F to 46°F (2°C to 8°C) in its original carton to protect from light. Do not freeze or shake. For patients : If needed, store PALYNZIQ in the original carton at room temperature between 68°F to 77°F (20°C to 25°C) for up to 30 days. Record the date removed from refrigeration on the carton. Once stored at room temperature, do not return the product to the refrigerator. The shelf-life expires after storage at room temperature for 30 days, or after the expiration date on the product carton, whichever is earlier.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.