PLEGRIDY 125 micrograms INJECTABLE SOLUTION IN PRE-FILLED SYRINGE

Introduction

Package Leaflet: Information for the User

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.

Contents of the pack

1. What is Plegridy and what is it used for
2. What you need to know before you use Plegridy

1. How to use Plegridy
2. Possible side effects

1. Storage of Plegridy
2. Contents of the pack and other information
3. Instructions for injecting the Plegridy pre-filled syringe

1. What is Plegridy and what is it used for

What is Plegridy

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

What is Plegridy used for

This medicine is used to treat relapsing-remitting multiple sclerosis (MS) in adults aged 18 years or over.

MS is a long-term disease that affects the central nervous system (CNS), including the brain and spinal cord. In MS, the body's immune system (its natural defences) damages the protective covering (myelin) that surrounds the nerves in the brain and spinal cord. This disrupts the messages between the brain and the rest of the body, causing the symptoms of MS.

Patients with relapsing-remitting MS have periods when the disease is not active (remission) between flare-ups of symptoms (relapses).

Each patient has specific MS symptoms.These may include:

• feeling unsteady or dizzy, problems with walking, muscle stiffness and spasms, tiredness, numbness in the face, arms or legs;
• sharp or ongoing pain, bladder or bowel problems, sexual problems and vision problems;
• difficulty thinking and concentrating, depression.

How does Plegridy work

Plegridy is thought to work by stopping the immune system from damaging the brain and spinal cord.This may help reduce the number of relapses you have and slow down the disabling effects of MS. Treatment with Plegridy may help prevent MS from getting worse, although it will not cure MS.

2. What you need to know before you use Plegridy

Do not use Plegridy

• to peginterferon beta-1a, interferon beta-1a or any of the other ingredients of this medicine (listed in section 6). See the symptoms of an allergic reaction in section 4;

• or thoughts of suicide.

Warnings and precautions

Tell your doctor if you have ever had:

• depressionor mood problems;
• thoughts of suicide.

1. Your doctor may still prescribe Plegridy for you, but it is important that they know if you have had depression or other mood problems in the past.

Tell your doctor, pharmacist or nursebefore injecting Plegridy if you have any of the following conditionsas they may get worse while using Plegridy:

1. severe kidney or liver problems;

1. injection site irritation,which can cause skin and tissue damage

(injection site necrosis). When you are ready to administer, carefully follow the instructions described in section 7 "Instructions for injecting the Plegridy pre-filled syringe", at the end of this leaflet. This reduces the risk of injection site reactions;

1. epilepsyor other seizure disorders, not controlled with medication;
2. heart problemsthat can cause symptoms such as chest pain (angina),especially after any activity; swelling of ankles, difficulty breathing (congestive heart failure)or an irregular heartbeat (arrhythmias);

1. thyroid problems;
2. low white blood cell or platelet counts,which can increase the risk of infection or bleeding.

Other things to consider when using Plegridy

• You will need blood tests to check your blood cell counts, blood chemistry and liver enzyme levels. These tests will be done before you start using Plegridy, at regular intervals after starting treatment with Plegridy and then periodically during treatment, even if you have no specific symptoms. These blood tests will be in addition to the tests that are normally done to monitor your MS.
• Your thyroid function will be checked regularly or at any time your doctor thinks it is necessary.
• Blood clots can form in small blood vessels during treatment. These blood clots could affect your kidneys. This can happen after several weeks or several years after starting treatment with Plegridy. Your doctor may want to check your blood pressure, blood (platelet count) and kidney function.

If you accidentally prick yourself or someone else with the Plegridy needle, wash the affected area immediatelywith soap and water and contact a doctor or nurse as soon as possible.

Children and adolescents

Plegridy must not be usedin children and adolescents under 18 years. The safety and efficacy of Plegridy in this age group have not been established.

Other medicines and Plegridy

Plegridy should be used with caution when given with other medicines that are processed 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 using, have recently used or might use any other medicines, especially those used to treat epilepsy or depression. This includes any medicines obtained without a prescription.

On occasion, you may need to remind other healthcare professionals that you are being treated with Plegridy, for example if they prescribe you other medicines or if they do a blood test. Plegridy may interact with other medicines or with the test results.

Pregnancy and breast-feeding

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

No harmful effects on the breast-fed child are expected. Plegridy can be used during breast-feeding.

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) per dose, i.e. it is essentially "sodium-free".

3. How to use Plegridy

Follow the instructions for administration of this medicine exactly as told by your doctor or pharmacist. If you are unsure, ask your doctor or pharmacist again.

Usual dose

One injection of Plegridy 125 micrograms every 14 days (every 2 weeks). Try to use Plegridy at the same time on the same day each time you inject.

Starting Plegridy by intramuscular injection

If you are using Plegridy for the first time, your doctor may advise you to gradually increase the doseduring the first month of treatment so that you can get used to the effects of Plegridy before using the full dose.

The full dose with the Plegridy pre-filled syringe is 125 micrograms. Dose adjustment clips can be attached to the syringe so that you can gradually increase the dose:

Dose 1 on Day 0:

1/2 dose (63 micrograms) with a YELLOW dose adjustment clip

Dose 2 on Day 14:

3/4 dose (94 micrograms) with a PURPLE dose adjustment clip

Dose 3 on Day 28 and every 2 weeks thereafter:

full dose (125 micrograms), NO dose adjustment clip needed

The Plegridy medicine supplied in this pack is designed to be injected into the muscle of the thigh.

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

If you have any doubts about how to inject the medicine, ask your doctor, pharmacist or nurse.

Intramuscular is abbreviated as IM on the syringe label.

Self-injection

Plegridy is injected into the muscle of the thigh (intramuscular injection). Alternate the injection site. Do not always use the same injection site for the other injections

You can inject Plegridy without the help of your doctor if you have been taught how to do it.

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

• If you have problemshandling the syringe, talk to your doctor or nurse who can help you.

Duration of treatment with Plegridy

Your doctor will tell you how long you should use Plegridy. It is important that you use Plegridy regularly. Do not make any changes without talking to your doctor.

If you use more Plegridy than you should

You should only inject Plegridy once every 2 weeks.

• If you have injected more than one dose of Plegridy within a 7-day period, contact your doctor or nurse immediately.

If you forget to use Plegridy

You should inject Plegridy once every 2 weeks. This regular schedule helps to keep the treatment as consistent as possible.

If you miss a dose, inject a dose as soon as possible and continue as usual. However, do not inject more than one dose in a 7-day period. Do not give yourself two injections to make up for a missed injection.

If you have any other 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 the following symptoms:

• yellowing of the skin or the white of the eyes;
• widespread itching;
• feeling sick (nausea and vomiting);
• bruises that appear easily on the skin.
• • Contact a doctor immediatelyas these may be signs of a possible liver problem.

• Depression

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

If you get:

• unusual feelings of sadness, anxiety or hopelessness; or
• thoughts of suicide.

• Contact a doctor immediately.

• Severe allergic reactions

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

If you get any of the following:

• difficulty breathing;
• swelling around the face (lips, tongue or throat);
• skin rash or redness.
• Contact a doctor immediately.

• Seizures

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

If you have a seizure or fit.

• Contact a doctor immediately.

• Injection site damage

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

If you get any of the following symptoms:

• any open sores on the skin along with swelling, inflammation or fluid leakage around the injection site.

• Contact a doctor for advice.

• Kidney problems including scarring that can reduce kidney function

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

If you get any of the following symptoms:

• foamy urine;
• fatigue;
• swelling, especially of ankles and eyelids, and weight gain.
• • Contact a doctor as these may be signs of a possible kidney problem.

• Blood problems

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

The following can occur: blood clots in small blood vessels that can affect your kidneys (thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome). The symptoms can include increased bruising, bleeding, fever, extreme weakness, headache, dizziness or fainting. Your doctor may find changes in your blood and kidney function.

If you get any of the following symptoms:

• increased bruising or bleeding;
• extreme weakness;
• headache, dizziness or fainting.

• 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 actually flu, see below. You cannot pass them on to anyone;
• headache;
• muscle pain (myalgia);
• joint pain, arms, legs or neck (arthralgia);
• chills;
• fever;
• weakness and tiredness (asthenia);
• redness, itching or pain around the injection site.
• If you are concerned about any of these effects, contact a doctor.

Flu-like symptoms

Flu-like symptoms are more common when you first start using Plegridy. As you continue to use the injections, the symptoms will gradually disappear. See below for some simple ways to help reduce the impact of flu-like symptoms if you experience them.

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

1. Be aware of the time you inject Plegridy. The start and end of flu-like symptoms are different for each patient. On average, flu-like symptoms start about 10 hours after injection and last for 12 to 24 hours.

1. Take paracetamol or ibuprofen 30 minutes before injecting Plegridy and continue to take it for as long as the flu-like symptoms last. Ask your doctor or pharmacist how much to take and for how long.
2. If you have a fever, drink plenty of water to stay hydrated.

Common side effects

(may affect up to 1 in 10 people)

• feeling sick (nausea or vomiting);
• hair loss (alopecia);
• itching of the skin (pruritus);
• increased body temperature;
• changes around the injection site such as swelling, inflammation, bruising, warmth, rash or change in colour;
• changes in the blood that can cause tiredness or reduced ability to fight infections;
• increased liver enzymes in the blood (which will show up in blood tests).
• If you are concerned about any of these effects, contact a doctor.

Uncommon side effects

(may affect up to 1 in 100 people)

• hives;
• changes in the blood that can cause unexplained bruising or bleeding.

• If you are concerned about any of these effects, contact a doctor.

Frequency not known

(cannot be estimated from the available data)

• Pulmonary arterial hypertension: a disease in which there is a significant narrowing of the blood vessels in the lungs, which causes an increase in the pressure in the blood vessels that carry blood from the heart to the lungs. Pulmonary arterial hypertension was observed at different times, even several years after the start of treatment with interferon beta-containing medicines.

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 tracing of this medicine, your doctor or pharmacist should record the name and batch number of the medicine given to you in your medical records. You may also want to make a note of this information for future reference.

5. Storage of 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 label and carton after CAD/EXP. The expiry date is the last day of the month stated.

• Store in the original packaging to protect from light. Only open the pack when a new syringe is needed.

• Store in a refrigerator(2°C to 8°C).

• Do not freeze. Discard any Plegridy that has been frozen by accident.

• Plegridy can be stored at room temperature (up to 25°C) for a maximum of 30 days, but must be protected from light.
• • The packs can be taken out and put back in the refrigerator more than once if necessary.
  • Make sure the time the syringes spend outside the refrigerator does not exceed30 days in total.
  • Discard any syringe that has been out of the refrigerator for more than 30 days.

• If it is not known for certain how many days a syringe has been out of the refrigerator, discard the syringe.

• Do not use this medicine if you notice that:
• • the syringe is broken.

• the solution has changed color, is cloudy, or you can see particles in suspension.

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

6. Package Contents and Additional Information

Plegridy Composition

The active substance is peginterferon beta-1a.

Each 125 microgram pre-filled syringe contains 125 micrograms of peginterferon beta-1a in 0.5 ml of injectable solution.

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

Appearance and Package Contents of the Product

Plegridy is a clear and colorless injectable solution in a glass pre-filled syringe accompanied by a needle.

Package sizes:

• The syringes are supplied in a pack containing two or six pre-filled syringes with sterile needles of 23 gauge and 3.175 cm in length.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

Netherlands

Manufacturer

FUJIFILM Diosynth Biotechnologies Denmark ApS

Biotek Allé 1

DK-3400 Hillerød

Denmark

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

Netherlands

You can request more information about this medicine from the local representative of the marketing authorisation holder:

Date of the last revision of this leaflet:01/2025.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

• Instructions for injecting the Plegridy pre-filled syringe

How to inject Plegridy

Read the instructions for use before starting to use the Plegridy pre-filled syringe. There may be new information. This information does not replace any conversation with your healthcare professional about your medical condition or treatment.

Materials you will need for the injection of Plegridy:

• 1 pack containing the dose of Plegridy for administration, which includes:

1. 1 Plegridy pre-filled syringe
2. Sterile needle of 23 gauge and 3.175 cm in length

• A container for sharp objects to dispose of used syringes and needles
• Additional materials not included in the pack:
• 1. Alcohol swab

• Gauze

• Band-Aid

If you are using Plegridy for the first time, the dose can be adjusted in 2 injections using the syringe with the Plegridy dose adjustment kit.

o Dose 1:

½ dose (yellow dose adjustment clip) (not supplied within the pack)

o Dose 2:

¾ dose (purple dose adjustment clip) (not supplied within the pack)

o Dose 3:

full dose (no clip required)

• The Plegridy dose adjustment clips are for single use only with the Plegridy pre-filled syringe. Do not reuse the syringe or the dose adjustment clips.

• You must prepare the Plegridy pre-filled syringe and needle before placing them in the Plegridy dose adjustment clip.

Preparing the Plegridy dose:

• Use a flat, clean, and well-lit surface, such as a table. Gather all the materials needed to administer or have the injection administered.
• Take a Plegridy pre-filled syringe out of the refrigerator at least 30 minutes before the scheduled injection time to allow it to reach room temperature. Do notuse external heat sources, such as hot water, to warm the pre-filled syringe.
• Check the expiry date printed on the syringe label, the double cap, and the outside of the carton. Do notuse the pre-filled syringe after the expiry date.

• Wash your hands with water and soap.

Preparing the Plegridy injection:

Administering the Plegridy injection:

1. Your doctor or nurse will teach you or your caregiver how to prepare and inject the dose of Plegridy before using the syringe for the first time. Your doctor or nurse will observe you injecting the dose of Plegridy the first time you use the syringe.
2. Inject Plegridy as your doctor or nurse has taught you.

1. Plegridy is injected into the muscle (intramuscularly).
2. Plegridy must be injected into the thigh (see Figure G).

1. Change (alternate) the injection sites with each dose. Do notuse the same injection site for each injection.
2. Do notadminister the injection in an area of the body where the skin is irritated, red, bruised, infected, or scarred.

After the Plegridy injection:

• Do notput the protective cover back on the needle. If you put the protective cover back on the needle, you could prick yourself with the needle.

• Discard used syringes and needles in a puncture-resistant container or a hard plastic container; for example, a detergent bottle or a coffee can. Check with your healthcare professional for the proper way to dispose of the container. There may be local or state requirements for disposing of used syringes and needles. Do notthrow away used syringes and needles in household trash or recycling containers.

• Plegridy can frequently cause redness, pain, or swelling of the skin at the injection site.
• Contact your healthcare professional immediately if the injection site becomes inflamed and painful or if the area appears to be infected and does not heal in a few days.

General information on the safety and efficacy of Plegridy

• Always use a new syringe and needle for each injection. Do notreuse the Plegridy syringe or needles.

• Do notshare the syringe or needles.