Pegvaliase

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.

Pegvaliase-pqpz is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine to ammonia and trans -cinnamic acid. It substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme activity in patients with PKU and reduces blood phenylalanine concentrations.

Obtain baseline blood Phe concentration before initiating treatment. Consider premedication for hypersensitivity reactions. The recommended initial dosage for PALYNZIQ is 2.5 mg subcutaneously once weekly for 4 weeks. See the Full Prescribing Information for titration, maintenance, discontinuation, and dose reduction. See Full Prescribing Information for dosage and administration modifications due to anaphylaxis. Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe concentrations during maintenance therapy and monitor dietary protein and phenylalanine intake throughout treatment. 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.

None. None.

Boxed warning (anaphylaxis): Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment. 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. Hypersensitivity Reactions, Other than Anaphylaxis: Management should be based on the severity of the reaction, recurrence, and clinical judgement. Injection Site Infections: Serious injection site infections, including abscess, cellulitis, necrosis, and ulcer have been reported. Instruct patients to contact their healthcare provider if signs or symptoms of an infection develop, persist, or worsen. Hypophenylalaninemia: Some PKU patients treated with PALYNZIQ have experienced hypophenylalaninemia, monitor blood Phe levels periodically during treatment.

The following serious adverse reactions are discussed below and in other sections of labeling: Anaphylaxis Other Hypersensitivity Reactions Injection Site Infections Hypophenylalaninemia 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. 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.

Effect of PALYNZIQ on Other PEGylated Products: Monitor for hypersensitivity reactions, including anaphylaxis, with concomitant treatment. 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.

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.