PALYNZIQ 20 mg Injectable Solution in Pre-filled Syringe

2. What you need to know before you use Palynziq

Do not use Palynziq

• if you are allergic to pegvaliase or any of the other ingredients of this medicine, or to other medicines that contain polyethylene glycol (PEG) (including those listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Palynziq.

Allergic reactions

You may have allergic reactions during treatment with Palynziq. Your doctor will explain how to manage allergic reactions according to their severity and will prescribe other medicines to treat the reaction.

Before using Palynziq, tell your doctor if you cannot or do not want to use an adrenaline injection device to treat severe allergic reactions to Palynziq.

Palynziq may cause severe, life-threatening allergic reactionsat any time after receiving the injection.

• Stop injecting Palynziq if you experience any of the following symptoms:

• swelling of the face, eyes, lips, mouth, throat, tongue, hands, or feet;
• breathing problems or wheezing;
• feeling of compression in the throat or feeling of choking;
• difficulty swallowing or speaking;
• feeling of dizziness or fainting;
• loss of control of urine or feces;
• rapid heartbeat;
• urticarial rash (a raised, itchy skin rash) that spreads rapidly;
• redness of the skin;
• severe stomach pain, vomiting, or diarrhea.

• Use the adrenaline injection device according to the doctor's instructions and seek urgent medical attention.

Your doctor will prescribe an adrenaline injection device to treat severe allergic reactions and will explain to you and your caregiver when and how to administer adrenaline. Always carry the adrenaline injection device with you.

For at least the first 6 months of treatment, someone should be with youwhen you self-inject Palynziq. Your companion should stay with you for at least 1 hour after the injection to observe for any signs or symptoms of a severe allergic reaction and, if necessary, administer an adrenaline injection and seek urgent medical attention.

If you have a severe allergic reaction, do not continue using Palynziquntil you have talked to the doctor who prescribed Palynziq. Inform the doctor that you have had a severe allergic reaction. The doctor will indicate whether you can continue treatment with Palynziq.

Time needed to lower blood phenylalanine levels

When starting treatment with Palynziq, your doctor will prescribe a low dose, which will be gradually increased. It will take some time to find the most effective dose to reduce your blood phenylalanine levels. Most people respond within 18 months, but it may take up to 30 months.

Injection of other PEG-containing medicines while using Palynziq

Palynziq contains an ingredient called polyethylene glycol (PEG). If you inject Palynziq with another injectable medicine that contains PEG, such as pegylated medroxyprogesterone acetate, you may have an allergic reaction. Tell your doctor or pharmacist if you are injecting, have recently injected, or may need to inject any other medicine.

Low blood phenylalanine levels

When using Palynziq, you may have low blood phenylalanine levels. Your doctor will check your blood phenylalanine levels monthly. If they are too low, you may be asked to make changes to your diet and/or reduce the dose of Palynziq. Your doctor will check your blood phenylalanine levels every 2 weeks until they return to normal.

Children and adolescents

It is not known if Palynziq is safe in children and adolescents under 16 years of age who have PKU, and therefore, it should not be used in people under 16 years of age.

Other medicines and Palynziq

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Palynziq should not be used during pregnancy unless necessary to treat your condition and other methods to control blood phenylalanine levels are not effective. If your blood phenylalanine levels are too high or too low during pregnancy, it may be harmful to you or your baby. You and your doctor will decide the best way to control your blood phenylalanine levels. It is very important to keep your blood phenylalanine levels under control before and during pregnancy.

It is not known if Palynziq passes into breast milk or if it affects your baby. Ask your healthcare professional for advice on the best way to feed your baby if you use Palynziq.

It is not known if Palynziq affects fertility. Animal studies suggest that women may have difficulty getting pregnant if their blood phenylalanine levels are too low.

Driving and using machines

Palynziq may affect your ability to drive and use machines if you have a severe allergic reaction.

Palynziq contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe; this is essentially “sodium-free”.

3. How to use Palynziq

Follow the doctor's instructions for administering this medicine exactly.

In case of doubt, consult your doctor again.

Palynziq is administered by subcutaneous injection.

Dose

• You will start injecting Palynziq at the lowest dose. You will use the 2.5 mg syringe once a week for at least the first 4 weeks. The 2.5 mg syringe has a white plunger.

• Your doctor will gradually increase the dose or frequency of Palynziq injections and will indicate how long you should inject each dose. The gradual increase in dose over time allows your body to adapt to the medicine.
• The goal is to reach a daily dose that reduces blood phenylalanine levels within the target range of 120 to 600 micromol/l and does not cause too many side effects. Normally, patients need a daily dose of 20 mg, 40 mg, or 60 mg to reach their target blood phenylalanine level.

Example of steps to reach target blood phenylalanine level

1If you need multiple injections to complete your daily dose, all injections will be administered at the same time of day, leaving a distance of at least 5 centimeters between each injection site. Do not divide your daily dose throughout the day.

• Your doctor will continue to check your blood phenylalanine levels during treatment and may adjust your Palynziq dose or ask you to make changes to your diet.
• Your doctor will check your blood phenylalanine levels monthly to see if the medicine is effective.

Starting Palynziq treatment

• Your healthcare professional will administer the Palynziq injection until you (or your caregiver) are able to do so.
• Your doctor will prescribe medicines that you should take before injecting Palynziq, such as paracetamol, fexofenadine, or ranitidine. These medicines help reduce the symptoms of an allergic reaction.
• A healthcare professional will observe you for at least 1 hour after you inject Palynziq to detect any signs or symptoms of a severe allergic reaction.
• Your doctor will also prescribe an adrenaline injection device to treat severe allergic reactions and will explain to you and your caregiver when and how to administer adrenaline.
• Your doctor will teach you how and when to use the adrenaline injection device. Always carry it with you.

Continuing treatment with Palynziq

• This medicine comes in pre-filled syringes with 3 different doses (2.5 mg: white plunger; 10 mg: green plunger or 20 mg: blue plunger). You may need more than one pre-filled syringe to complete the prescribed dose. Your healthcare professional will indicate which syringe, or which combination of syringes, you should use and will teach you (or your caregiver) how to inject Palynziq.
• In the “Instructions for use” (section 7 of this leaflet), you will find:

• how to prepare and inject Palynziq, and
• how to properly dispose of Palynziq syringes after use.

• Your doctor will indicate how long you should continue using medicines, such as paracetamol, fexofenadine, and/or ranitidine, before injecting Palynziq.

• For at least the first 6 months of treatment with Palynziq, you should be accompanied when you self-inject Palynziq and for at least 1 hour after the injection. Your companion will observe for any signs or symptoms of a severe allergic reaction and, if necessary, administer an adrenaline injection and seek urgent medical attention.

• Your doctor will inform your companion of the signs and symptoms of a severe allergic reaction and how to administer an adrenaline injection.
• Your doctor will indicate whether you need an observer for more than 6 months.

• Do not change your protein intake unless your doctor tells you to.

If you use more Palynziq than you should

If you use more Palynziq than you should, talk to your doctor. See more details on how to proceed according to your symptoms in section 4.

If you forget to use Palynziq

If you forget a dose, inject the next dose at the usual time. Do not inject two doses of Palynziq to make up for forgotten doses.

If you stop treatment with Palynziq

If you stop treatment with Palynziq, your blood phenylalanine levels may increase. Talk to your doctor before stopping treatment with Palynziq.

If you have any other questions about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions are very common (may affect more than 1 in 10 people)and vary in severity. The symptoms of an allergic reaction may include skin rash, itching, swelling of the head or face, itching or tearing of the eyes, coughing, and wheezing. Your doctor will indicate how to treat allergic reactions according to their severity and will prescribe other medicines to treat the reaction. Some of these allergic reactions can be more serious, as described below, and require immediate attention.

Serious side effects include:

• Severe allergic reactions: (Common – may affect up to 1 in 10 people).Stop injecting Palynziq if you observe any severe signs of allergy or a combination of the signs listed below:

• swelling of the face, eyes, lips, mouth, throat, tongue, hands, or feet;
• breathing problems or wheezing;
• feeling of compression in the throat or feeling of choking;
• difficulty swallowing or speaking;
• feeling of dizziness or fainting;
• loss of control of urine or feces;
• rapid heartbeat;
• urticarial rash (a raised, itchy skin rash) that spreads rapidly;
• redness of the skin;
• severe stomach pain, vomiting, or diarrhea.

Use the adrenaline injection device according to the doctor's instructions and seek urgent medical attention.Your doctor will prescribe an adrenaline injection device to treat severe allergic reactions and will explain to you and your caregiver when and how to administer adrenaline. Always carry the adrenaline injection device with you.

Contact your doctor immediatelyif you have:

• a type of allergic reaction called serum sickness, which includes a combination of fever (high temperature), rash, muscle and joint pain (Common – may affect up to 1 in 10 people).

Other side effects

Very common: may affect more than 1 in 10 people

• redness of the skin, swelling, bruising, pain, or tenderness at the injection site;
• joint pain;
• reduction of proteins C3 and C4 of the complement factor C4 (which are parts of the immune system) in blood tests;
• allergic reaction;
• low blood phenylalanine levels in blood tests;
• headache;
• skin rash;
• stomach pain;
• feeling sick or nausea;
• vomiting;
• urticarial rash (itchy skin rash);
• itching;
• hair loss or thinning;
• coughing;
• increase in C-reactive protein (CRP) in blood tests (CRP is a protein that indicates inflammation);
• swollen glands in the neck, armpits, or groin;
• redness of the skin;
• muscle pain.

Common: may affect up to 1 in 10 people

• joint stiffness;
• joint swelling;
• muscle stiffness;
• skin rash with small bumps;
• blistering or peeling of the outer layer of the skin.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Palynziq

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label of the syringe, the cover of the tray, and the carton after “EXP”. The expiry date is the last day of the month stated.

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

If necessary, Palynziq can be stored outside the refrigerator (below 25 °C), in its sealed tray, for a single period of up to 30 days, away from any heat source. Write the date you removed it from the refrigerator on the product tray. Once you have removed it from the refrigerator, the medicine should not be put back in the refrigerator.

Do not use this medicine if the pre-filled syringe is damaged or if you notice that the solution has lost color, is cloudy, or has particles.

Dispose of syringes safely. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Palynziq

• The active ingredient is pegvaliasa.

Each 2.5 mg prefilled syringe contains 2.5 mg of pegvaliasa in 0.5 ml of solution. Each 10 mg prefilled syringe contains 10 mg of pegvaliasa in 0.5 ml of solution. Each 20 mg prefilled syringe contains 20 mg of pegvaliasa in 1 ml of solution.

• The other components are trometamol, trometamol hydrochloride, sodium chloride (see section 2 for more information), trans-cinnamic acid, and water for injectable preparations.

Appearance of Palynziq and Container Contents

Palynziq injectable solution is a clear to slightly opalescent and colorless to pale yellow solution. The prefilled syringe includes an automatic needle protector.

2.5 mg prefilled syringe (white plunger):

Each 2.5 mg carton contains 1 prefilled syringe.

10 mg prefilled syringe (green plunger):

Each 10 mg carton contains 1 prefilled syringe.

20 mg prefilled syringe (blue plunger):

Each 20 mg carton contains 1 or 10 prefilled syringes.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

BioMarin International Limited

Shanbally, Ringaskiddy

County Cork

Ireland

P43 R298

Date of Last Revision of this Leaflet: MM/YYYY.

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

1. Instructions for Use

BEFORE YOU START

Read these instructions for use before starting to use the Palynziq prefilled syringe and each time you are prescribed something new. There may be new information. Also, consult your healthcare professional about your medical condition or treatment.

Follow these instructions carefully when using Palynziq. If your healthcare professional decides that you or your caregiver can administer the Palynziq injections at home, you will be trained on how to do it before giving the first injection. Do notinject Palynziq until your healthcare professional has taught you or your caregiver how to do it.

Consult your healthcare professional if you have any questions about how to inject Palynziq correctly.

Do not share prefilled syringes with anyone.

To see the storage instructions, refer to section 5 "Storage of Palynziq" of this leaflet.

Important Things to Know About Using the Palynziq Prefilled Syringe:

• Use each Palynziq prefilled syringe only once. Do notuse a Palynziq syringe more than once.
• Neverpull back the plunger.
• Do notremove the needle protector until you are ready to administer the injection.

The figure A below shows the appearance of the prefilled syringe before use.

Figure A

Select the Correct Palynziq Prefilled Syringes for Your Dose:

When you receive your Palynziq prefilled syringes, check that the name "Palynziq" appears on the cartons.

• The Palynziq prefilled syringes come in 3 different doses: 2.5 mg, 10 mg, and 20 mg.
• You may need more than one prefilled syringe to complete the prescribed dose. Your healthcare professional will tell you which syringe, or which combination of syringes, to use. If you are unsure, consult your healthcare professional.
• Before injecting Palynziq, check each carton and syringe to make sure you have the correct prefilled syringe for the prescribed dose.

Figure B

PREPARATION FOR INJECTION

Step 1: Gather Everything You Need:

Gather everything you need for the injection and place it on a flat and clean surface. Remove the required number of cartons from the refrigerator.

This is what you will need for the Palynziq injection:

• Prefilled Palynziq syringe(s) in sealed tray(s); each tray contains 1 syringe;
• Cotton balls or swabs;
• 1 alcohol swab;
• 1 band-aid;
• 1 container for disposing of sharp objects or a puncture-resistant container.

Step 2: Remove the Palynziq Tray(s) from the Carton and Check the Expiration Date:

• Remove the required number of cartons from the refrigerator. Check the expiration date on the carton. If the expiration date has passed, do not use the prefilled syringe from that carton.
• Open each carton and remove the sealed tray you need for your dose.
• Place each sealed tray on a flat and clean surface, out of the reach of children and pets.
• Store the carton with the remaining trays in the refrigerator. If you do not have a refrigerator, refer to section 5 "Storage of Palynziq" of this leaflet.

Step 3: Before Opening the Palynziq Tray(s), Let it Sit at Room Temperature for 30 Minutes:

Let the sealed tray(s) sit at room temperature for at least 30 minutes. If you inject Palynziq when it is still cold, it may be uncomfortable.

• Do notheat the prefilled syringe in any other way. Do notheat it in the microwave or in hot water.

Step 5: Check the Dose on the Syringe and for Particles:

INJECTION OF PALYNZIQ

Inject Palynziq

Treat the Injection Site

AFTER THE INJECTION

Dispose of Used Syringes.

Place used needles and syringes in a puncture-resistant container or a sharps container immediately after use. Consult your doctor, pharmacist, or nurse about the proper way to dispose of the container. Dispose of the syringes safely.