PALYNZIQ Solution for injection Ref.[10154] Active ingredients: Pegvaliase

2.1 Dosage

• Treatment with Palynziq should be managed by a healthcare provider experienced in the management of PKU.
• Obtain baseline blood phenylalanine concentration before initiating treatment.

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 (2.4)].

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 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 of 60 mg once daily [see Clinical Studies (14)].

Table 1. Recommended Dosing Regimen:

* Additional time may be required prior to each dosage escalation based on patient tolerability.
^† Individualize treatment to the lowest effective and tolerated dosage. Consider increasing to 40 mg once daily in patients who have not achieved a response with 20 mg once daily continuous treatment for at least 24 weeks. Consider increasing to a maximum of 60 mg once daily in patients who have not achieved a response with 40 mg once daily continuous treatment for at least 16 weeks [see Clinical Studies (14)].
^‡ Discontinue Palynziq in patients who have not achieved an adequate response after 16 weeks of continuous treatment at the maximum dosage of 60 mg once daily.

Dose Reduction for Low Phenylalanine Concentrations

During titration and maintenance of Palynziq treatment, patients may experience blood phenylalanine concentrations below 30 micromol/L. For blood phenylalanine concentrations below 30 micromol/L, the dosage of Palynziq may be reduced and/or dietary protein and phenylalanine intake may be modified to maintain blood phenylalanine concentrations within a clinically acceptable range and above 30 micromol/L [see Dosage and Administration (2.2)].

Readministration Following Anaphylaxis

If the decision is made to readminister Palynziq after an anaphylaxis episode, administer the first dose following the anaphylaxis episode 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 should be based on patient tolerability and therapeutic response [see Warnings and Precautions (5.1)].

Missed Dose

If a dose is missed, instruct patients to take their next dose as scheduled and to not take two doses of Palynziq to make up for the missed dose.

2.2 Blood Phenylalanine Monitoring and Diet

After initiating treatment with Palynziq, obtain blood phenylalanine concentrations every 4 weeks until a maintenance dosage is established. After a maintenance dosage is established, periodic blood phenylalanine monitoring is recommended to assess blood phenylalanine control.

Monitor patients' dietary protein and phenylalanine intake throughout treatment with Palynziq and counsel them on how to adjust their dietary intake, as needed, based on blood phenylalanine concentrations.

2.3 Premedication

For hypersensitivity reactions, consider premedication with an H₁‑receptor antagonist, H₂‑receptor antagonist, and/or antipyretic prior to Palynziq administration based upon individual patient tolerability [see Warnings and Precautions (5.1, 5.3)].

2.4 Administration Instructions

• Each prefilled syringe of Palynziq is intended for use as a single subcutaneous injection.
• Inspect Palynziq visually for particulate matter and discoloration prior to administration. Palynziq is a clear to slightly opalescent, colorless to pale yellow solution. Discard if discolored, cloudy, or if particulate matter is present.
• Prior to first dose of Palynziq, prescribe auto-injectable epinephrine, and 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.
• Perform initial administration(s) and/or readministration after an anaphylaxis episode under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection [see Warnings and Precautions (5.1)]. Prior to self-injection, confirm patient competency with self‑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 each Palynziq administration, should be able to administer auto-injectable epinephrine, and to call for emergency medical support upon its use [see Warnings and Precautions (5.1)].
• The recommended injection sites for Palynziq are: the front middle of thighs and the abdomen at least 2 inches (five centimeters) away from the navel. If a caregiver is giving the injection, the top of buttocks and the back of the upper arms are also appropriate injection sites.
• Do not inject Palynziq into moles, scars, birthmarks, bruises, rashes, or areas where the skin is hard, tender, red, damaged, burned, inflamed, or tattooed. Check the injection site for redness, swelling, or tenderness.
• Rotate sites for subcutaneous injections of Palynziq. If more than one injection is needed for a single dose of Palynziq, the injection sites should be at least 2 inches away from each other. The second injection site can be on the same part of the body or a different part of the body.

• 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.