PLEGRIDY 125 MICROGRAMS SOLUTION FOR INJECTION IN PRE FILLED SYRINGE - patient leaflet, side effects, dosage

Package leaflet: Information for the user

Plegridy 63 micrograms solution for injection in pre-filled syringe Plegridy 94 micrograms solution for injection in pre-filled syringe Plegridy 125 micrograms solution for injection in pre-filled syringe peginterferon beta-1a

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

- if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. see section 4.

What is in this leaflet

1. what plegridy is and what it is used for1. what plegridy is and what it is used for

What Plegridy is

The active substance in Plegridy is peginterferon beta-1a. Peginterferon beta-1a is a modified long-acting form of interferon. Interferons are natural substances made in the body to help protect from infections and diseases.

What Plegridy is used for

This medicine is used to treat relapsing-remitting multiple sclerosis (MS) in adults aged 18 or over. MS is a long term illness that affects the central nervous system (CNS), including the brain and spinal cord, in which the body’s immune system (its natural defences) damages the protective layer (myelin) that surrounds the nerves in the brain and spinal cord. This disrupts the messages between the brain and other parts of the body, causing the symptoms of MS. Patients with relapsing-remitting MS have periods when the disease is not active (remission) in between flare-ups of symptoms (relapses).

Everyone has their own set of MS symptoms. These can include:

• – Feeling off-balance or light headed, walking problems, stiffness and muscle spasms, tiredness, numbness in the face, arms or legs

• – Acute or chronic pain, bladder and bowel problems, sexual problems and problems with vision

• – Difficulty thinking and concentrating, depression.

How Plegridy works

Plegridy seems to work by stopping the body’s immune system from damaging your brain and spinal cord. This can help to reduce the number of relapses that you have and slow down the disabling effects of MS. Treatment with Plegridy can help to prevent you from getting worse, although it will not cure MS.

2. what you need to know before you use plegridy- if you are allergic to peginterferon beta-1a, interferon beta-1a or any of the ingredients of this medicine (listed in section 6). see section 4 for the symptoms of an allergic reaction.

• - If you have severe depression or think about committing suicide.

Warnings and precautions

Talk to your doctor if you have ever had:

• - Depression or problems affecting your mood

• - Thoughts about committing suicide

– Your doctor may still prescribe Plegridy for you, but it’s important to let your doctor know if you have had depression or any similar problems affecting your mood in the past.

Talk to your doctor, pharmacist or nurse before injecting Plegridy if you have any of the conditions listed below. They may get worse while using Plegridy:

• - Serious liver or kidney problems

• - Irritation at an injection site, which can lead to skin and tissue damage (injection site necrosis ). When you are ready to inject, carefully follow the instructions in section 7 “Instructions for injecting Plegridy pre-filled syringe ”, at the end of this leaflet. This is to reduce the risk of injection site reactions.

• - Epilepsy or other seizure disorders, not controlled by medicine

• - Heart problems , which can cause symptoms such as chest pain (angina ), particularly after any

activity; swollen ankles, shortness of breath (congestive heart failure ); or an irregular heartbeat (arrhythmia ).

• - Thyroid problems

• - A low number of white blood cells or platelets , which can cause an increased risk of infection, or bleeding

Other things to consider when using Plegridy

• – You will need blood tests to determine your numbers of blood cells, blood chemistry and your levels of liver enzymes. These will be performed before you start using Plegridy, regularly after treatment with Plegridy has been initiated and then periodically during treatment, even if you have no particular symptoms. These blood tests will be in addition to the tests which are normally done to monitor your MS.

• – The functioning of your thyroid gland will be checked regularly or whenever thought necessary by your doctor.

• – Blood clots in the small blood vessels may occur during your treatment. These blood clots could affect your kidneys. This might happen several weeks to several years after starting Plegridy. Your doctor may want to check your blood pressure, blood (platelet count) and the function of your kidneys.

If you accidentally prick yourself or someone else with the needle in Plegridy, the area affected should be washed immediately with soap and water and a doctor or nurse should be contacted as soon as possible.

Children and adolescents

Plegridy is not to be used in children and adolescents below 18 years old. The safety and effectiveness of Plegridy in this age group are not known.

Other medicines and Plegridy

Plegridy should be used carefully with medicines that are broken down in the body by a group of proteins called “cytochrome P450” (e.g. some medicines used for epilepsy or depression).

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, especially those used to treat epilepsy or depression. This includes any medicines obtained without a prescription.

Sometimes you will need to remind other healthcare professionals that you are being treated with Plegridy. For example, if you are prescribed other medicines, or if you have a blood test. Plegridy may affect the other medicines or the test result.

Pregnancy and breast-feeding

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

No harmful effects on the breastfed newborn/infant are anticipated. Plegridy can be used during breastfeeding.

Driving and using machines

Plegridy has no or negligible influence on the ability to drive and use machines.

Plegridy contains sodium

This medicine contains less than 1 mmol sodium (23 mg), that is to say it is essentially “sodium-free”.

3. how to use plegridy

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The usual dose

One injection of Plegridy 125 micrograms every 14 days (every two weeks). Try to use Plegridy at the same time on the same day, every time you inject.

Starting Plegridy

If you are new to Plegridy, your doctor may advise you to gradually increase your dose so that you can adjust to the effects of Plegridy before taking the full dose. You will be provided with an Initiation Pack containing your first 2 injections: one orange syringe with Plegridy 63 micrograms (for day 0) and one blue syringe with Plegridy 94 micrograms (for day 14).

After that you will be provided with a maintenance pack containing grey syringes with Plegridy 125 micrograms (for day 28 and then every two weeks).

Read the instructions in section 7 “Instructions for injecting Plegridy pre-filled syringe ” at the end of this leaflet before you start using Plegridy.

Use the record table printed on the inside of the lid of the Initiation Pack to keep a track of your injection dates.

Injecting yourself

Plegridy is to be injected under the skin (subcutaneous injection ). Alternate the sites you use for injections. Do not use the same injection site for consecutive injections.

You can inject Plegridy yourself without the help of your doctor, if you have been trained how to do this.

• – Read and follow the advice given in the instructions in section 7 “Instructions for injecting Plegridy pre-filled syringe ” before you start.

• - If you have trouble handling the syringe, ask your doctor or nurse who may be able to help.

How long to use Plegridy

Your doctor will tell you how long you need to keep using Plegridy. It is important to continue using Plegridy regularly. Do not make changes unless your doctor tells you.

If you use more Plegridy than you should

You must only inject Plegridy once every 2 weeks.

• – If you have used more than one injection of Plegridy in a 7-day period, contact your doctor or nurse straight away.

If you forget to use Plegridy

You need to inject Plegridy once every 2 weeks. This regular schedule helps to deliver the treatment as evenly as possible.

If you do miss your usual day, inject as soon as you can and carry on as usual. However, do not inject more than once in a 7-day period. Do not use two injections to make up for a missed injection.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. possible side effects

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

Serious side effects

• - Liver problems

(common – may affect up to 1 in 10 people)

If you get any of these symptoms:

• – Yellowing of your skin or the whites of your eyes

• – Itching all over

• – Feeling sick, being sick (nausea and vomiting)

• – Easy bruising of the skin

– Contact a doctor immediately. They may be signs of a possible liver problem.

• - Depression

(common – may affect up to 1 in 10 people)

If you:

• – Feel unusually sad, anxious or worthless or

• – Have thoughts about suicide

– Contact a doctor immediately.

• - Serious allergic reaction

(uncommon – may affect up to 1 in 100 people)

If you get any of these:

• – Difficulty breathing

• – Swelling around the face (lips, tongue or throat)

• – Skin rashes or redness

– Contact a doctor immediately.

– Seizures

(uncommon – may affect up to 1 in 100 people)

If you have a seizure or a fit

– Contact a doctor immediately.

• - Injection site damage

(rare – may affect up to 1 in 1,000 people)

If you get any of these symptoms:

• – Any break in the skin together with swelling, inflammation or fluid leaking around the injection site

– Contact a doctor for advice.

• - Kidney problems including scarring that may reduce your kidney function

(rare – may affect up to 1 in 1,000 people)

If you get some or all of these symptoms:

• – Foamy urine

• – Fatigue

• – Swelling, particularly in the ankles and eyelids, and weight gain.

– Contact a doctor as they may be signs of a possible kidney problem.

• - Blood problems

(rare – may affect up to 1 in 1,000 people)

The following may occur: Blood clots in the small blood vessels that can affect your kidneys (thrombotic thrombocytopenic purpura or haemolytic uremic syndrome). Symptoms may include increased bruising, bleeding, fever, extreme weakness, headache, dizziness or light-headedness. Your doctor may find changes in your blood and the function of your kidneys.

If you get some or all of these symptoms:

• – Increased bruising or bleeding

• – Extreme weakness

• – Headache, dizziness or light-headedness

– Contact a doctor immediately.

Other side effects

Very common side effects

(may affect more than 1 in 10 people)

• – Flu-like symptoms. These symptoms are not really flu, see below. You can’t pass it on to anyone else.

• – Headache

• – Muscle pain (myalgia )

• – Pain in your joints, arms, legs or neck (arthralgia )

• – Chills

• – Fever

• – Feeling weak and tired (asthenia )

• – Redness, itching or pain around the place you have injected

– If any of these effects trouble you, contact a doctor.

Flu-like symptoms

Flu-like symptoms are more common when you first start using Plegridy. They gradually get less as you keep using your injections. See below for simple ways to manage these flu-like symptoms if you get them.

Three simple ways to help reduce the impact of flu-like symptoms:

• 1. Consider the timing of your Plegridy injection. The start and end of flu-like symptoms are different for every patient. On average, flu-like symptoms begin approximately 10 hours after injection and last between 12 and 24 hours.

• 2. Take paracetamol or ibuprofen half an hour before your Plegridy injection and continue to take paracetamol or ibuprofen for the duration of your flu-like symptoms. Speak to your doctor or pharmacist about how much to take and how long to take it.

• 3. If you have a fever, drink plenty of water to keep you hydrated.

Common side effects

(may affect up to 1 in 10 people)

• – Feeling or being sick (nausea or vomiting)

• – Hair loss (alopecia )

• – Itchy skin (pruritus )

• – Increase in body temperature

• – Changes around the place you have injected such as swelling, inflammation, bruising, warmth, rash or colour change

• – Changes in your blood which might cause tiredness or reduced ability to fight infection

• – Increases in liver enzymes in the blood (will show up in blood tests)

– If any of these effects trouble you, contact a doctor.

Uncommon side effects

(may affect up to 1 in 100 people)

• – Hives

• – Changes in your blood which might cause unexplained bruising or bleeding.

– If any of these effects trouble you, contact a doctor.

Frequency not known

(frequency cannot be estimated from the available data)

• – Pulmonary arterial hypertension: A disease of severe narrowing of the blood vessels in the lungs resulting in high blood pressure in the blood vessels that carry blood from the heart to the lungs. Pulmonary arterial hypertension has been seen at various time points during treatment, including several years after starting treatment with interferon beta-products.

Reporting of side effects

If you get 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 via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

In order to improve the traceability of this medicine, your doctor or pharmacist should record the name and the lot number of the product you have been given in your patient file. You may also wish to make a note of these details in case you are asked for this information in the future.

5. how to store plegridy

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

Do not use this medicine after the expiry date which is stated on the carton and the label after “EXP”. The expiry date refers to the last day of that month.

• – Store in the original package in order to protect from light. Only open the pack when you need a new syringe.

• - Store in a refrigerator (fridge) 2° –8 °C.

– Do not freeze. Throw away any Plegridy that is accidentally frozen.

– Plegridy can be kept outside a fridge at room temperature (up to 25 °C) for up to 30 days but it must be kept away from light.

• – Packs can be taken out of the fridge and then put back in a fridge more than once if you need to.

• – Make sure the time the syringes spend out of a fridge is no more than 30 days in total.

• – Throw away any syringe that is kept out of the fridge for more than 30 days.

• – If you are unsure of the number of days you have kept a syringe out of the fridge, throw the

syringe away.

– Do not use this medicine if you notice any of the following:

• – If the syringe is broken.

• – If the solution is coloured, cloudy or you can see particles floating in it.

• – Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other informationthe active ingredient is peginterferon beta-1a.

Each 63 microgram pre-filled syringe contains 63 micrograms of peginterferon beta-1a in 0.5 mL solution for injection.

Each 94 microgram pre-filled syringe contains 94 micrograms of peginterferon beta-1a in 0.5 mL solution for injection.

Each 125 microgram pre-filled syringe contains 125 micrograms of peginterferon beta-1a in 0.5 mL solution for injection.

The other ingredients are: Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20 and water for injections (see Section 2 “Plegridy contains sodium”).

What Plegridy looks like and contents of the pack

Plegridy is a clear and colourless solution for injection in a glass pre-filled syringe with an attached needle.

Pack sizes:

• – The Plegridy Initiation Pack contains one orange pre-filled syringe of 63 micrograms and one blue pre-filled syringe of 94 micrograms.

• – The 125 micrograms grey syringes are provided in a pack containing either two or six pre-filled syringes.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

The Netherlands

Manufacturer

FUJIFILM Diosynth Biotechnologies Denmark ApS

Biotek Alle 1

DK-3400 Hillerod

Denmark

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

The Netherlands

Espana Biogen Spain S.L. © +34 91 310 7110	Polska Biogen Poland Sp. z o.o. © +48 22 351 51 00
France Biogen France SAS © +33 (0)1 41 37 9595	Portugal Biogen Portugal Sociedade Farmaceutica, Unipessoal Lda. © +351 21 318 8450
Hrvatska Biogen Pharma d.o.o. © +385 1 775 73 22	Romania Johnson & Johnson Romania S.R.L. © +40 21 207 18 00
Ireland Biogen Idec (Ireland) Ltd. © +353 (0)1 463 7799	Slovenija Biogen Pharma d.o.o. © +386 1 511 02 90
Island Icepharma hf © +354 540 8000	Slovenska republika Biogen Slovakia s.r.o. © +421 2 323 34008
Italia Biogen Italia s.r.l. © +39 02 584 9901	Suomi/Finland Biogen Finland Oy © +358 207 401 200
Knnpog Genesis Pharma Cyprus Ltd © +357 22 76 57 40	Sverige Biogen Sweden AB © +46 8 594 113 60
Latvija Biogen Latvia SIA © +371 68 688 158	United Kingdom (Northern Ireland) Biogen Idec (Ireland) Limited © +44 (0) 1628 50 1000

This leaflet was last revised in < {MM/YYYY }> <{month YYYY }>.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:.

7. Instructions for injecting Plegridy pre-filled syringe

BEFORE YOU START

How to inject Plegridy

Read the instructions for use before you start using Plegridy and each time you get a refill of your prescription. There may be new information. This information does not take the place of talking to your doctor or nurse about your medical condition or your treatment.

Note:

• Before you use the Plegridy pre-filled syringe for the first time, your doctor or nurse should show you or your carer how to prepare and inject the Plegridy pre-filled syringe.
• Plegridy pre-filled syringe is for injecting the medicine under the skin only (subcutaneous)
• Each Plegridy pre-filled syringe can be used once only.

d Do not share your Plegridy pre-filled syringe with anyone else to avoid giving an infection to them or getting an infection from them.

d Do not use more than one pre-filled syringe every 14 days (every 2 weeks).

d Do not use your syringe if it has been dropped or is visibly damaged.

Dosage schedule

The Initiation Pack contains your first two injections to gradually adjust your dose. Choose the correct syringe from a pack.

When	Which dose	Which pack
Day 0 (63 micrograms)	First injection: 63 micrograms, choose orange syringe	INITIATION PACK
Day 14 (94 micrograms)	Second injection: 94 micrograms, choose blue syringe
Day 28 and then every two weeks after that (125 micrograms)	Full dose injection: 125 micrograms, choose grey syringe	125 MICROGRAM PACK —■■11---w~ j» f

d Do not use more than one pre-filled syringe per 14-day period (every 2 weeks).

Supplies needed for your Plegridy injection

Plegridy pre-filled syringe (see Figure A)

Before Use – Parts of your Plegridy pre-filled syringe (Figure A)

Figure A

Additional supplies which are not included in the pack (See Figure B):

• Alcohol wipe
• Gauze pad

Adhesive bandage

Ask your doctor, pharmacist, or nurse for instructions on throwing away used syringes.

Preparing for your injection

Step 1: Remove your pre-filled syringe from the fridge

• Remove one Plegridy pack out of the fridge and select the appropriate pre-filled syringe from the

pack.

• Close the pack and put pack back in the fridge after removing one pre-filled syringe.
• Let the Plegridy pre-filled syringe warm to room temperature for at least 30 minutes.

A Do not use external heat sources such as hot water to warm the Plegridy pre-filled syringe.

Step 2: Collect your supplies and wash your hands

• Find a well-lit, clean, flat surface to work on, like a table. Collect all the supplies you will need to give yourself or to receive an injection.
• Wash your hands with soap and water.

Step 3: Check the Plegridy pre-filled syringe

• Check the expiry date on the Plegridy pre-filled syringe (See Figure C).

A Do not use Plegridy pre-filled syringe past the expiry date.

• Check that your Plegridy medicine is clear and colourless (See Figure D).

D Do not use the Plegridy pre-filled syringe if the liquid is coloured, cloudy, or has floating particles in it.

o You might see air bubbles in the Plegridy medicine. This is normal and does not need to be expelled before your injection.

Giving your injection
Step 4: Choose and clean your injection site
Plegridy pre-filled syringe is for subcutaneous injection (injection into skin). Plegridy pre-filled syringe should be injected into the abdomen, thigh, or the back of the upper arm. (See Figure E). d Do not inject directly into your belly button. d Do not inject into an area of the body where the skin is irritated, tender, red, bruised, tattooed, infected, or scarred. Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose. d Do not touch or blow this area again before giving the injection.	h.' WV Back of Upper Arm Figure E
Step 5: Firmly remove the needle cover
Using one hand, hold the syringe by the glass barrel. With your other hand, firmly grasp needle cover and pull it straight off the needle (See Figure F). A Use caution when removing the needle cover to avoid getting a needle stick injury. A Do not touch the needle. c Caution – Do not recap the Plegridy pre-filled syringe. You could get a needle injury.	tv Figure F

Step 6: Gently pinch the injection site
Gently pinch the skin around the cleaned injection site using thumb and forefinger to create a slight bulge (See Figure G).

	Figure G
Step 7: Inject medicine
Hold the Plegridy pre-filled syringe at a 90° angle to the injection site. Quickly insert the needle straight into the skin fold until the needle is fully under the skin. (See Figure H). After the needle is in, let go of your skin. d Do not pull back on the plunger.	▼ 1 ■ 4 v \90° bbERP Figure H
Slowly push the plunger all the way down until syringe is empty (See Figure I). A Do not take your Plegridy pre-filled syringe out of the injection site until you have pushed the plunger all the way down.	Figure 1

	Keep the needle inserted in for 5 seconds (see Figure J).	GO
		Figure J

After your injection

Step 9: Disposing of the used Plegridy pre-filled syringe

• Check with your doctor, pharmacist or nurse about the right way to throw away the used syringe.

Step 10: Care for your injection site

• If needed, apply a gauze pad or adhesive bandage to the injection site.

Step 11: Check your injection site

• After 2 hours, check the injection site for redness, swelling, or tenderness.
• If you have a skin reaction and it does not clear up in a few days, contact your doctor or nurse.

Record date and location

• Record the date and location of each injection.
• For the first injections, you can use the record table printed on the inside of the lid of the Initiation Pack.

General warnings

A Do not reuse your Plegridy pre-filled syringe.

D Do not share your Plegridy pre-filled syringe.

• Keep Plegridy pre-filled syringe and all medicines out of reach of children.

Storage

• Recommended storage is controlled refrigeration 2°C to 8°C in the closed original carton to protect from light.
• If needed, Plegridy may be stored in the closed original carton without refrigeration up to 25°C for

up to 30 days.

• Plegridy can be removed from and returned to, a refrigerator if necessary. The total combined time out of refrigeration at a temperature up to 25°C, should not exceed 30 days.