PALYNZIQ 2.5 MG Injectable solution

Зміст інструкції

1. Palynziq 2.5 mg injectable solution in pre-filled syringe, 10 mg injectable solution in pre-filled syringe, 20 mg injectable solution in pre-filled syringe
   1. What is Palynziq and what is it used for
   2. What you need to know before you use Palynziq
   3. How to use Palynziq
   4. Possible side effects
   5. How to store Palynziq
   6. Contents of the pack and other information
   7. Instructions for Use

Palynziq 2.5 mg injectable solution in pre-filled syringe, 10 mg injectable solution in pre-filled syringe, 20 mg injectable solution in pre-filled syringe

Pegvaliase
(pegvaliasum)
Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

• 1. What Palynziq is and what it is used for
• 2. What you need to know before you use Palynziq
• 3. How to use Palynziq
• 4. Possible side effects
• 5. How to store Palynziq
• 6. Contents of the pack and other information

1. What is Palynziq and what is it used for

Palynziq contains the active substance pegvaliase, an enzyme that can break down a substance called phenylalanine in the body. Palynziq is a treatment for patients aged 16 years and older with phenylketonuria (PKU), a rare inherited disorder that causes a build-up of phenylalanine from proteins in food in the body. People who suffer from PKU have high levels of phenylalanine and this can cause serious health problems. Palynziq reduces the levels of phenylalanine in the blood of patients with PKU whose phenylalanine levels in the blood cannot be maintained below 600 micromol/L with other means, for example with diet.

2. What you need to know before you use Palynziq

Do not use Palynziq

• if you are severely allergic to pegvaliase or any of the other ingredients of this medicine (listed in section 6) or to another medicine that contains polyethylene glycol (PEG).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you use Palynziq.
Allergic reactions
You may have allergic reactions during treatment with Palynziq. Your doctor will tell you how
to manage allergic reactions based on their severity and will prescribe additional medicines to
treat them.
Before using Palynziq, tell your doctor if you cannot or do not want to use an epinephrine auto-injector to treat a severe allergic reaction to Palynziq.

Palynziq can cause severe allergic reactions that can be life-threateningand can
occur at any time after an injection of Palynziq.

• Stop injecting Palynziq if you experience any of the following symptoms.
• Swelling of the face, eyes, lips, mouth, throat, tongue, hands and/or feet
• Difficulty breathing or wheezing
• Tightness of the throat or feeling of suffocation
• Difficulty swallowing or speaking
• Feeling dizzy or faint
• Loss of bladder or bowel control
• Rapid heartbeat
• Hives (like an itchy, raised rash) that spreads quickly
• Flushing
• Severe stomach cramps or pain, vomiting or diarrhea
• Use the epinephrine auto-injector according to your doctor’s instructions and seekurgent medical attention.

Your doctor will prescribe an epinephrine auto-injector for you to use in case of a severe allergic
reaction. Your doctor will instruct you, and someone assisting you, on how to use the epinephrine and understand when
to use it. Keep the epinephrine auto-injector with you at all times.

For at least the first 6 months of treatment, someone should stay with youwhen you self-inject
Palynziq. This person should stay with you for at least 1 hour after the injection to check for signs and symptoms of a severe allergic reaction and, if necessary, administer
an epinephrine injection and call emergency medical assistance.

If you have a severe allergic reaction, do not continue to use Palynziquntil you have spoken with
the doctor who prescribes the medicine. Tell your doctor if you have had a severe allergic reaction. Your
doctor will tell you if you can continue treatment with Palynziq.
Time it takes to lower blood phenylalanine levels
Your doctor will initially prescribe Palynziq at a low dose, which will be slowly increased. It will
take some time to establish the best dose to lower your blood phenylalanine levels. Most people respond within 18 months, but it may sometimes
take up to 30 months.
Injection of other medicines that contain PEG, during the use of Palynziq
Palynziq contains a component called polyethylene glycol (PEG). If you inject Palynziq with a
another injectable medicine containing PEG, such as medroxyprogesterone acetate PEGilate, you could
have an allergic reaction. Tell your doctor or pharmacist if you are injecting, have recently
injected, or may inject any other medicine.
Excessively low blood phenylalanine levels
During the use of Palynziq, you may have excessively low levels of phenylalanine in your blood. Your
doctor will check your blood phenylalanine levels monthly. If your blood phenylalanine levels are excessively low, your doctor may ask you to change
your diet and/or reduce your 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 whether Palynziq is safe and effective in children and adolescents with PKU under the age of
16 years, 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 taking, have recently taken or might take
any other medicines.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding ask your doctor for advice before using this medicine.
Palynziq is not recommended during pregnancy unless your clinical condition requires
treatment with Palynziq and other methods to control blood phenylalanine levels have not
worked. During pregnancy, excessively high or excessively low levels of phenylalanine could cause harm to you or the baby. You and your doctor will decide on the best way to
manage your blood phenylalanine levels. It is very important to keep phenylalanine levels under
control before and during pregnancy.
It is not known whether Palynziq passes into breast milk or has effects on the baby. If you use Palynziq, speak to
your healthcare professional about the best way to feed your baby.
It is not known whether Palynziq has effects on fertility. Studies in animals suggest that women
may have difficulty becoming pregnant if their phenylalanine levels are abnormally
low.

Driving and using machines
Palynziq can impair your ability to drive and use machines if you develop a severe
allergic reaction.

Palynziq contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per pre-filled syringe, that is to say it is
essentially ‘sodium-free’.

3. How to use Palynziq

Use this medicine following the doctor’s instructions exactly. If you have any doubts, consult your
doctor.
Palynziq is administered as an injection under the skin (subcutaneous injection).

Dose

• You will start Palynziq at the minimum 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.
• The doctor will then slowly increase your dose and/or the frequency of Palynziq injections. The doctor will tell you how long to use each dose. Slowly increasing the dose over time allows the body to adjust to the medicine.
• The goal is to reach a daily dose that reduces phenylalanine levels in the blood to the desired range of 120 - 600 micromol/L and does not cause excessive side effects. Patients generally need a daily dose of 20 mg, 40 mg, or 60 mg to reach the desired phenylalanine level in the blood.

Examples of increments to reach the target phenylalanine level in the blood
If more than one injection is needed to administer the
daily dose, all injections must be given at the
same time of day and the injection sites must be at
least 5 cm apart. Do not divide the daily
dose throughout the day.

• During treatment, the doctor will continue to monitor phenylalanine levels in the blood and may adjust the dose of Palynziq or ask you to modify your diet.
• The doctor will need to check phenylalanine levels in the blood monthly to verify that the medicine is effective for you.

Starting Palynziq

• The healthcare professional will administer the Palynziq injection to you until you (or someone assisting you) are able to do it independently.
• The doctor will prescribe medicines to take before the Palynziq injection, such as paracetamol, fexofenadine and/or ranitidine. These medicines help reduce the symptoms of an allergic reaction.
• A healthcare professional will observe you for at least 1 hour after the administration of Palynziq to check for signs or symptoms of an allergic reaction.
• The doctor will also prescribe an epinephrine auto-injector to be used in case of severe allergic reactions. The healthcare professional will also tell you which signs and symptoms to watch for and what to do in case of a severe allergic reaction.
• The doctor will show you how and when to use the epinephrine auto-injector. Keep it with you at all times.

Continuing Palynziq

• This medicine is supplied in prefilled syringes with 3 different dosages (2.5 mg with a white plunger, 10 mg with a green plunger, or 20 mg with a blue plunger). More than one prefilled syringe may be needed for the prescribed dose. The healthcare professional will tell you which syringe or combination of syringes to use and will show you (or show someone assisting you) how to inject Palynziq.

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

• The doctor will tell you how long to continue taking medicines such as paracetamol, fexofenadine and/or ranitidine, before using Palynziq.

• For at least the first 6 months of treatment with Palynziq, you should have someone with you when you self-inject Palynziq and for at least 1 hour after the injection, to check for signs and symptoms of a severe allergic reaction and, if necessary, administer an epinephrine injection and call emergency medical assistance. o The doctor will instruct this person to recognize signs and symptoms of a severe allergic reaction and to administer an epinephrine injection. o The doctor will tell you if you will 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, inform your doctor. See section 4 for information on how to
act based on the symptoms.

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

If you stop treatment with Palynziq
If you stop treatment with Palynziq, phenylalanine levels in the blood are likely to
increase. Contact your doctor before stopping treatment with Palynziq.
If you have any questions about using this medicine, contact 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. Symptoms of an allergic reaction may include skin rash, itching, swelling of the head or face, itchy or watery eyes,
cough, difficulty breathing, wheezing and feeling dizzy. Your doctor will tell you how to manage allergic reactions based on their severity and will prescribe additional medicines to treat them. Some
of these allergic reactions may be more serious and require immediate attention, as
described below.
Serious side effects include:

• Sudden severe allergic reactions: (common, may affect up to 1 in 10 people).Stop injecting Palynziq if you notice any sudden severe signs of allergy or a combination of the signs listed below. o Swelling of the face, eyes, lips, mouth, throat, tongue, hands and/or feet o Difficulty breathing or wheezing o Tightness of the throat or feeling of suffocation o Difficulty swallowing or speaking o Feeling dizzy or faint o Loss of bladder or bowel control o Rapid heartbeat o Hives (like an itchy, raised rash) that spreads quickly o Flushing o Severe stomach cramps or pain, vomiting or diarrhea

Use your epinephrine injection device as instructed by your doctor and seek urgent
medical attention.Your doctor will prescribe an epinephrine injection device to use in case of
a severe allergic reaction. Your doctor will instruct you, and instruct someone who helps care for you, on how to use epinephrine and
understand when to use it. Keep your epinephrine injection device with you at all times.
Contact your doctor immediatelyif you have:

• A type of allergic reaction called serum sickness disease, which includes a combination of fever (high temperature), rash, muscle and joint pain (common, mayaffect up to 1 in 10 people)

Other side effects

Very common: may affect more than 1 in 10 people)

• Redness, swelling, bruising, tenderness or pain where Palynziq was injected
• joint pain
• decreased levels of complement factor C3 and C4 proteins (which are part of the immune system), shown by blood tests
• allergic reaction
• excessively low levels of phenylalanine shown by blood tests
• headache
• skin rash
• stomach pain
• feeling unwell, also known as nausea
• vomiting
• hives (itchy, raised bumps on the skin)
• itching
• thinning or loss of hair
• cough
• increased C-reactive protein (CRP) levels, shown by blood tests (CRP is a protein that indicates the presence of inflammation)
• swollen glands in the neck, armpits or groin
• skin flushing
• muscle pain
• diarrhea
• fatigue

Common: may affect up to 1 in 10 people

• difficulty breathing
• joint stiffness
• joint swelling
• muscle stiffness
• skin rash with small blisters
• blisters or peeling of the outer layer of skin

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Palynziq

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date that is reported on the syringe label, on the
tray cover and on the carton after “Scad.”/“EXP”. The expiry date refers to the last
day of that month.
Store in a refrigerator (2 °C - 8 °C). Do not freeze.
If necessary, Palynziq can be stored in its sealed tray outside the refrigerator (at a
temperature below 25 °C) for a single time for a maximum period of 30 days, away from sources
of heat. Note the date of removal from the refrigerator on the closed tray of the product. After being
stored outside the refrigerator, the product must not be returned to the refrigerator.
Do not use this medicine if the pre-filled syringe is damaged or if you notice that the solution is of a
different colour, is cloudy or contains particles.
Use safe disposal procedures for syringes. Do not dispose of any medicine in the wastewater and
household waste. Ask your pharmacist how to dispose of medicines you no longer use. This
will help protect the environment.

6. Contents of the pack and other information

What Palynziq contains

• The active ingredient is pegvaliase. Each 2.5 mg pre-filled syringe contains 2.5 mg of pegvaliase in 0.5 mL of solution. Each 10 mg pre-filled syringe contains 10 mg of pegvaliase in 0.5 mL of solution. Each 20 mg pre-filled syringe contains 20 mg of pegvaliase in 1 mL of solution.
• The other ingredients are trometamol, trometamol hydrochloride, sodium chloride (see section 2 for further information), trans-cinnamic acid, water for injections.

Description of Palynziq and contents of the pack
Palynziq injectable solution (injectable) is a clear to slightly opalescent, from
colorless to pale yellow solution. The pre-filled syringe includes an automatic needle protection.
2.5 mg pre-filled syringe (white plunger)
Each 2.5 mg pack contains 1 pre-filled syringe.
10 mg pre-filled syringe (green plunger)
Each 10 mg pack contains 1 pre-filled syringe.
20 mg pre-filled syringe (blue plunger)
Each 20 mg pack contains 1 or 10 pre-filled syringes.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
BioMarin International Limited
Shanbally, Ringaskiddy
County Cork
Ireland
P43 R298

Other sources of information
More detailed information on this medicine is available on the European Medicines Agency website, https://www.ema.europa.eu. Links to other websites on rare diseases
and related therapeutic treatments are also provided.

7. Instructions for Use

BEFORE YOU START
Before you start using the prefilled syringe of Palynziq, read these instructions for use and every time you receive a new prescription. There may be new information. Also, contact your healthcare provider for information about your medical condition or your treatment.
Follow these instructions carefully while using Palynziq. If your healthcare provider decides that you or the person providing care for you can administer Palynziq injections at home, they will show you or show the person providing care for you how to inject Palynziq before you inject it for the first time. Donot inject Palynziq until your healthcare provider has shown you or has shown the person providing care for you how to perform the injection.
Contact your healthcare provider if you have any questions about how to inject Palynziq correctly.
Do not share the prefilled syringes with anyone else.
For storage instructions, see section 5 “How to store Palynziq” of this leaflet.

Important things to know about using the Palynziq prefilled syringe:

• Use each Palynziq prefilled syringe only once. Donot use a Palynziq syringe more than once.
• Donot pull back the plunger.
• Donot remove the needle cap until you are ready to perform the injection.

Figure A below shows what the prefilled syringe looks like before use.

Figure A

Selecting the correct Palynziq prefilled syringe(s) for the prescribed dose:
When you receive the Palynziq prefilled syringe(s), check that the packaging or packages state the name “Palynziq”.

• Palynziq prefilled syringes are available in 3 different dosages: 2.5 mg, 10 mg, and 20 mg.
• More than one prefilled syringe may be needed for the prescribed dose. Your healthcare provider will tell you which syringe or combination of syringes to use. If you have any questions, contact your healthcare provider.
• Before injecting Palynziq, check each package and syringe to make sure you have the correct prefilled syringe for the prescribed dose.

Figure B

PREPARING THE INJECTION
Step 1: Prepare the supplies:
Gather the supplies for the injection and place them on a flat, clean surface. Remove from the refrigerator the number of packages needed for the prescribed dose.
Supplies needed for injecting Palynziq:

• Palynziq prefilled syringe(s) in the tray(s) or sealed trays. Each tray contains 1 syringe.
• Gauze pad or cotton ball
• 1 alcohol swab
• 1 bandage
• 1 sharps container for disposal of sharp objects

Step 2: Remove the tray(s) of Palynziq from the packaging and check the expiration date:

• Remove the necessary packages from the refrigerator for the prescribed dose. Check the expiration date on the packaging. If the expiration date has passed, do not use the prefilled syringe contained in that package.
• Open each package and remove the sealed tray needed for the dose.
• Place each sealed tray on a flat, clean surface, out of the reach of children and pets.
• Return the package with the other trays to the refrigerator. If a refrigerator is not available,

Step 3: Before opening, allow the tray(s) of Palynziq to reach room temperature for 30 minutes:
Leave the sealed tray(s) at room temperature for at least 30 minutes. Injecting cold Palynziq can be uncomfortable.

• Donot heat the prefilled syringe in any other way. Donot put it in the microwave or hot water.

Step 4: Remove the syringe from the tray:
Peel back the cover of the tray. Grasp the middle part of the body of the prefilled syringe and remove it from the tray (see Figure C).

Figure C

• Donot use the prefilled syringe if it appears damaged or used. Use a new prefilled syringe for the injection.
• Donot remove the needle cap from the prefilled syringe.
• Donot shake the syringe or roll it between your hands.

Step 5: Check the syringe dosage and check for particles:
Check the syringe label to make sure you have the correct dosage for the prescribed dose.
Examine the liquid through the inspection window (see Figure D). The liquid should be clear and from colorless to light yellow. It is normal to see an air bubble.

Figure D

• Donot tap the syringe or try to remove the air bubble.
• Donot use the prefilled syringe if the liquid is cloudy, is a different color, or contains clumps or particles. Use a new prefilled syringe for the injection.

INJECTING PALYNZIQ
Step 6: Choose the injection site.
The recommended injection sites are:

Figure E

• The front center of the thighs.
• The lower abdomen, except for the area within 5 centimeters around the navel.

If the injection is administered by a person providing care, the upper buttocks and the upper back of the arms can also be used (see Figure E).

Note:

• Donot inject into scars, moles, birthmarks, bruises, rashes, or areas where the skin is hardened, painful, red, damaged, burned, inflamed, or tattooed.
• If more than 1 injection is needed for the daily dose, the injection sites must be at least 5 centimeters apart (see Figures E and F).
• Change (alternate) the injection sites every day. Choose an injection site that is at least 5 centimeters away from the site(s) used the previous day. The site can be on the same side or on a different part of the body (see Figures E and F). Figure FInject at least 5 cm apart

Step 7: Wash your hands thoroughly with soap and water (see Figure G).

Figure G

Step 8: Clean the chosen site with an alcohol swab. Allow the skin to dry for at least 10 seconds before performing the injection (see Figure H).

Figure H

• Donot touch the cleaned injection site.
• Donot remove the needle cap until you are ready to inject Palynziq.
• Before injecting, make sure the needle is not damaged or bent.

Injecting Palynziq
Step 9: Hold the body of the prefilled syringe with one hand, with the needle pointing away from you (see Figure I).

Figure I

• Donot use the prefilled syringe if it has been dropped. Use a new prefilled syringe for the injection.

Step 10: Pull off the needle cap by pulling it straight off the needle (see Figure J).

Figure J

• Donot rotate the needle cap while removing it.
• Donot hold the prefilled syringe by the plunger or plunger head while removing the needle cap.

You may see a drop of liquid on the tip of the needle. This is normal. Donot wipe it off. Dispose of the needle cap in a sharps container.

Step 11: Hold the body of the prefilled syringe in one hand between your thumb and forefinger. Use your other hand to form a fold in the skin around the injection site. Hold the skin firmly (see Figure K).

Figure K

• Donot touch the plunger head while inserting the needle into the skin.

Step 12: With a quick motion, insert the needle completely into the skin fold at a 45- to 90-degree angle (see Figure L). Release the skin fold. Use the same hand to hold the lower part of the syringe firmly. Place your thumb on the plunger head (see Figure L).

Figure L

Step 13: Using your thumb, slowly and steadily push the plunger all the way in to inject all the medicine (see Figure M). For 10 mg and 20 mg dosages, you may need to apply more pressure to inject all the medicine.

Figure M

Step 14: Slowly lift your thumb to release the plunger, allowing the needle to be automatically covered by the body of the syringe (see Figure N).

Figure N

Treating the injection site
Step 15: Treat the injection site (if needed).
If you see drops of blood at the injection site, press a sterile gauze pad or cotton ball on it for about 10 seconds. If needed, you can cover the injection site with an adhesive bandage.

If more than one syringe is needed:
Step 16: If your healthcare provider indicates that more than one syringe is needed for the prescribed dose, repeat steps 4 through 15 above for each syringe to be used.

If more than one syringe is needed for the prescribed dose, immediately repeat, for each syringe to be used, the

• Note: Donot inject more than one injection into the same site. Injection sites must be at least 5 centimeters apart. See Step 6 for choosing an injection site.
• If more than one syringe is needed for a single dose, all injections must be given at the same time of day. Doses should not be divided throughout the day. steps 4 to 15.

AFTER THE INJECTION
Disposal of used syringes
Immediately after use, place used needles and syringes in a sharps container. Ask your doctor, pharmacist, or nurse what is the proper way to dispose of the container. Use safe disposal procedures for syringes.