PALYNZIQ

1 Dosing Considerations • Treatment with Palynziq should be directed by physicians experienced in the management of PKU. • Use of Palynziq during pregnancy may cause fetal harm; its use is not recommended during pregnancy unless the clinical condition of the woman requires treatment with Palynziq and alternative strategies to lower phenylalanine levels have been considered and exhausted or ruled out.

Before initiating treatment in women of reproductive potential, determine pregnancy status. 1 Pregnant women). ca. • Before initiating treatment, blood phenylalanine level must be measured. Monitoring of blood phenylalanine levels once a month is recommended until the maintenance dosage of Palynziq is established.

After a maintenance dosage is established, periodic blood phenylalanine monitoring is recommended to assess blood phenylalanine control. • Dietary phenylalanine intake should remain consistent until a maintenance dose of Palynziq is established.

See Dose Adjustment for Low Phenylalanine Levels for management of phenylalanine. 4 Administration). ca. 4 Administration). 5 mg administered once per week for 4 weeks (see Table 1). Titration The dose should be escalated gradually based on tolerability to the daily maintenance dose required to achieve clinically determined target blood phenylalanine level (see Table 1).

, a phenylalanine level ≤ 600 micromol/L) taking into account patient tolerability to Palynziq and dietary protein intake (see Table 1). The maintenance dose can be titrated up or down as required to achieve the lowest effective and tolerated dose of Palynziq.

5 mg twice weekly 1 week1 10 mg once weekly 1 week1 10 mg twice weekly 1 week1 10 mg four times a week 1 week1 10 mg daily 1 week1 Maintenance2 20 mg daily 12 weeks to 24 weeks1 40 mg daily (2 consecutive injections of 20 mg pre-filled syringe)2 16 weeks1 60 mg daily (3 consecutive injections of 20 mg pre-filled syringe)2 Maximum recommended dose 1 Additional time may be required prior to each dose escalation based on patient tolerability with Palynziq.

2 The maintenance dose is individualized to achieve target blood phenylalanine levels. In clinical trials with Palynziq, the target blood phenylalanine level to determine maintenance dose was ≤ 600 micromol/L. 1 Pediatrics). No dose adjustment is required for pediatric patients 16 to under 18 years of age.

For management of a suspected drug overdose, contact your regional poison control centre. 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING To help ensure the traceability of biologic products, including biosimilars, health professionals should recognize the importance of recording both the brand name and the non-proprietary (active ingredient) name as well as other product-specific identifiers such as the Drug Identification Number (DIN) and the batch/lot number of the product supplied.

5-inch needle, a needle safety device, polypropylene plunger rod, and bromobutyl or chlorobutyl rubber syringe stopper with fluoropolymer coating. The automatic needle guard is composed of a polycarbonate transparent needle guard and a stainless- steel spring inside the needle guard.

After injection, the spring expands causing the needle to be covered by the needle guard. 7 WARNINGS AND PRECAUTIONS Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX. Driving and Operating Machinery Hypersensitivity reactions to Palynziq can include symptoms such as dizziness or syncope and may affect the ability to drive and use machines.

Exercise caution when driving or operating a vehicle or potentially dangerous machinery. 0 mL (pre-filled syringe 20 mg) Sodium chloride, trans-cinnamic acid, trometamol, trometamol hydrochloride, water for injection PALYNZIQ® (pegvaliase injection) Page 10 of 38 Hypophenylalaninemia In clinical trials, 132 (46%) patients reported at least one episode of hypophenylalaninemia (defined as two consecutive measurements ≤ 30 micromol/L).

4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data). Monitoring of blood phenylalanine level is recommended once a month during Palynziq treatment. 2 Recommended Dose and Dosage Adjustment). 15 events/treatment year] and can occur at any time during treatment.

). Palynziq is contraindicated in patients who have experienced severe systemic hypersensitivity reaction(s) or recurrent mild or moderate acute systemic hypersensitivity (anaphylactic) reactions. Re-Administration Following Hypersensitivity Reaction The prescribing physician should consider the risks and benefits of re-administering the medicinal product following resolution of the first mild to moderate acute systemic hypersensitivity (anaphylactic) reaction (see 2 CONTRAINDICATIONS and 7 WARNINGS AND PRECAUTIONS).

The first dose upon restarting after such a reaction must be done with premedication under supervision of a health professional with the ability to manage an acute systemic hypersensitivity (anaphylactic) reaction. Dose level at re-administration after a mild to moderate acute systemic hypersensitivity reaction (anaphylaxis) should be at the previous or a lower dose as listed in Table 1.

If the reaction occurs after 6 months of therapy and use of pre-medication has been discontinued, reintroduction of pre-medication use is advised. Administration Instructions The recommended injection sites on the body are the front middle of the thighs and the lower part of the abdomen except for within 5 cm of the navel.

If a caregiver is giving the injection, the top of the buttocks and the back of the upper arms are also appropriate injection sites. Palynziq should not be injected into moles, scars, birthmarks, bruises, rashes, or areas where the skin is hard, tender, red, damaged, burned, inflamed, or tattooed.

The injection site should be checked for redness, swelling, or tenderness. Patients or the caregiver should be advised to rotate sites for subcutaneous injections. If more than one injection is needed for a single dose, each injection site should be at least 5 cm away from another injection site.

5 Missed Dose If a dose is missed, instruct patients to take their next dose as scheduled and not to take two doses of Palynziq to make up for the missed dose. 5 OVERDOSAGE In clinical trials, doses of pegvaliase up to 150 mg/day were administered.

, severe serum sickness, severe angioedema, severe anaphylactic reaction) or a recurrence of a mild to moderate anaphylactic reaction to Palynziq or to any ingredient in the formulation, including any non- medicinal ingredient or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • in patients who have had an anaphylactic reaction to a product containing polyethylene glycol (PEG) or to another product containing a PEGylated ingredient.