PALYNZIQ Solution for injection Ref.[113789] Active ingredients: Pegvaliase

Treatment with Palynziq should be directed by physicians experienced in the management of PKU.

Posology

Before initiating treatment, blood phenylalanine level must be obtained. Monitoring of blood phenylalanine level is recommended once a month.

Dietary phenylalanine intake should remain consistent until a maintenance dose is established.

Dosing regimens

Induction

The recommended starting dose of Palynziq is 2.5 mg administered once per week for 4 weeks.

Titration

The dose should be escalated gradually based on tolerability to the daily maintenance dose required to achieve blood phenylalanine level of 120 to 600 micromol/l according to Table 1.

Maintenance

The maintenance dose is individualised to achieve patient’s blood phenylalanine control (i.e. a phenylalanine level between 120 to 600 micromol/l) taking into account patient tolerability to Palynziq and dietary protein intake (see Table 1).

Table 1. Recommended dosing regimen:

¹ If blood phenylalanine levels are below 30 micromol/l, dietary protein intake should be increased to appropriate levels, and then, if needed, the dose of Palynziq should be reduced (see section 4.4, Hypophenylalaninaemia).
² Additional time may be required prior to each dose escalation based on patient tolerability with Palynziq.
³ The maintenance dose is individualised to achieve blood phenylalanine levels between 120 to 600 micromol/l.
⁴ If multiple injections are needed for a single dose, injections should be administered at the same time of day and injection sites should be at least 5 cm away from each other. Doses should not be divided over the course of the day (see Method of administration).

Dose adjustments

During titration and maintenance of Palynziq treatment, patients may develop blood phenylalanine levels below 30 micromol/l. To manage hypophenylalaninaemia, dietary protein intake should be increased to appropriate levels, and then, if needed, the dose of Palynziq should be reduced. In patients experiencing hypophenylalaninaemia despite appropriate levels of protein intake, dose reductions are expected to be most effective in managing hypophenylalaninaemia (see section 5.2, Exposure-effect). Patients should be monitored every 2 weeks until blood phenylalanine levels are within a clinically acceptable range (see section 4.4, Hypophenylalaninaemia).

If hypophenylalaninaemia develops prior to reaching daily dosing, the dose may be reduced to the previous titration dose. If hypophenylalaninaemia develops once daily dosing is reached, the dose may be reduced by at least 10 mg decrements to achieve and maintain blood phenylalanine levels in the clinically acceptable range. In patients experiencing hypophenylalaninaemia on 10 mg/day, the dose may be reduced to 5 mg/day.

Special populations

Paediatric population

The safety and efficacy of Palynziq in paediatric patients from birth to less than 16 years have not been established. No data are available.

Currently available data on patients aged 16 up to 18 years are described in section 4.8 and 5.1. Posology is the same in these patients as in adults.

Method of administration

Subcutaneous use. Each pre-filled syringe is for single use only.

Due to the potential for an acute systemic hypersensitivity reaction, premedication prior to each dose is required during induction and titration (time prior to reaching blood phenylalanine levels less than 600 micromol/l while on a stable dose; see section 4.8). Patients should be instructed to pre-medicate with an H1-receptor antagonist, H2-receptor antagonist, and antipyretic. During maintenance, premedication may be reconsidered for subsequent injections based on patient tolerability to Palynziq.

Initial administration(s) should be performed under supervision of a healthcare professional and patients should be closely observed for at least 60 minutes following each of these initial injection(s) (see sections 4.4 and 4.8).

Prior to first dose of Palynziq, the patient should be trained on the signs and symptoms of an acute systemic hypersensitivity reaction and to seek immediate medical care if a reaction occurs, and how to properly administer adrenaline injection device (auto-injector or pre-filled syringe/pen).

Patients should be instructed to carry an adrenaline injection device with them at all times during Palynziq treatment.

For at least the first 6 months of treatment when the patient is self-injecting (i.e. when administration is not under healthcare professional supervision), an observer must be present during and for at least 60 minutes after each administration. An observer is someone who:

• would be present with the patient during and after Palynziq administration,
• is able to recognise the signs and symptoms of an acute systemic hypersensitivity reaction,
• can call for emergency medical support and administer adrenaline, if warranted.

After 6 months of Palynziq treatment, the need for an observer may be reconsidered.

Prior to independent self-injection, a healthcare professional should:

• train the patient and assess patient competency on proper self-administration of this medicinal product,
• train the observer to recognise signs and symptoms of an acute systemic hypersensitivity reaction and to seek immediate medical care if a reaction occurs, and how to properly administer adrenaline injection device (auto-injector or pre-filled syringe/pen).

Re-administration following mild to moderate acute systemic hypersensitivity reactions: 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 reaction (see sections 4.3 and 4.4). Re-administration for the first dose must be done under supervision of a healthcare professional with the ability to manage acute systemic hypersensitivity reactions.

The recommended injection sites on the body are: the front middle of the thighs and the lower part of the abdomen except for 5 cm directly around 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 a 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.

Palynziq is a clear to slightly opalescent, colourless to pale yellow solution. The solution should not be used if discoloured or cloudy or if visible particles are present.

In clinical trials, doses of pegvaliase were explored up to 150 mg/day and no specific signs or symptoms were identified following these higher doses. No differences in the safety profile were observed. For management of adverse reactions, see sections 4.4 and 4.8.

2 years.

Palynziq may be stored in its sealed tray outside the refrigerator (below 25°C) for a single period up to 30 days with protection from sources of heat. After removal from the refrigerator, the medicinal product must not be returned to the refrigerator.

Store in a refrigerator (2°C–8°C). Do not freeze.

See section 6.3 for additional information on storage outside the refrigerator (below 25°C).

1 ml pre-filled syringe made of Type I borosilicate glass, equipped with a stainless steel 26 gauge needle, needle safety device, polypropylene plunger rod, and chlorobutyl or bromobutyl 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.

Pre-filled syringe 2.5 mg (white plunger):

Each carton contains 1 pre-filled syringe.

Pre-filled syringe 10 mg (green plunger):

Each carton contains 1 pre-filled syringe.

Pre-filled syringe 20 mg (blue plunger):

Each carton contains 1 or 10 pre-filled syringes.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements. After injection, the needle automatically retracts into the needle guard safely covering the needle.

Instructions for the preparation and administration of Palynziq are given in the package leaflet.