Avonex 30 micrograms/0.5 ml solution for injection in pre-filled pen

Patient Information Leaflet

Introduction

Patient Information Leaflet

AVONEX 30 micrograms/0.5 ml solution for injection in a pre-filled pen

(interferon beta-1a)

Pre-filled pen

Read this entire leaflet carefully before you start using this medicine, as it contains important information for you.

Even if you have previously used Avonex, some of the information may have changed.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

(Informational notes) This leaflet is updated from time to time. Please check whether this leaflet has been updated each time you renew your prescription.

(Informational notes) If you have any questions, consult your doctor or pharmacist.

Package leaflet contents

1. What AVONEX is and what it is used for
2. What you need to know before using AVONEX
3. How to use AVONEX PEN
4. Possible side effects
5. Storage of AVONEX PEN
6. Contents of the pack and other information
7. How to inject yourself using AVONEX PEN

1. What AVONEX is and what it is used for

AVONEX is a medicine that contains the active substance interferon beta-1, which belongs to a group of natural proteins produced by the body called interferons. AVONEX is used to treat:

• Patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of flare-ups and delay the progression of physical disability.

Multiple sclerosis is a disease that affects the central nervous system (brain and spinal cord). In MS, the immune system attacks the protective covering of nerve fibers, called myelin, leading to inflammation and damage. This disrupts communication between the brain and other parts of the body, causing symptoms such as muscle weakness, vision problems, and difficulty with coordination and balance.

AVONEX works by modifying the immune processes involved in MS, helping to reduce inflammation and the frequency of relapses. It is not a cure for multiple sclerosis, but it can help manage the disease over time.

The active substance in AVONEX is interferon beta-1a, produced by recombinant DNA technology using genetically modified mammalian cells (Chinese hamster ovary cells).

AVONEX is available as a solution for injection in prefilled syringes or vials. It is administered by intramuscular injection once weekly.

(Informational notes) Avonex works best when you use it: at the same time once a week regularly Do not stop your treatment with Avonex without first talking to your doctor.

What is AVONEX?

Avonex Pen is used to inject Avonex. The active substance in Avonex is a protein called interferon beta-1a. Interferons are natural substances produced by your body to protect you from infections and diseases. The protein in Avonex is made from exactly the same components as the interferon beta found naturally in the human body.

What is AVONEX used for?

Avonex is used to treat multiple sclerosis (MS). Treatment with Avonex may help prevent the disease from worsening, although it will not cure MS.

Each patient has specific MS symptoms. These may include:

• A feeling of unsteadiness or dizziness, difficulty walking, muscle stiffness and spasms, fatigue, tingling in the face, arms, or legs
• Sharp or chronic pain, bladder and bowel problems, sexual problems, and vision problems
• Difficulty thinking and concentrating, depression.

MS also tends to flare up periodically—these episodes are known as relapses.

Avonex can help reduce the number of relapses you may experience and slow the progression of disabling effects caused by MS. Your doctor will explain how long you can use Avonex or when to stop treatment.

How does AVONEX work?

Multiple sclerosis is associated with nerve damage (in the brain or spinal cord). In MS, your body's immune system reacts against its own myelin—the protective sheath surrounding nerve fibers. When myelin is damaged, the transmission of signals between the brain and other parts of the body is disrupted. This disruption causes the symptoms of MS. Avonex appears to work by preventing your body's immune system from attacking the myelin.

2. What you need to know before starting to use AVONEX

(Informational notes) Avonex and allergic reactions Since Avonex is made with a protein, there is a small chance of developing an allergic reaction. Additional information about depression You should not use Avonex if you have severe depression or suicidal thoughts. If you have depression, your doctor may still prescribe Avonex, but it is important to let your doctor know if you have had depression or any other mood-related condition.

Do not use AVONEX

• if you are allergic to interferon beta or to any of the other components of this medicine (listed in section 6);
• if you have severe depression or suicidal thoughts.

Contact your doctor immediately in any of these cases.

Warnings and precautions

Talk to your doctor before starting to use Avonex if you have or have previously had:

• Depression or problems affecting your mood
• Suicidal thoughts.

You must inform your doctor immediately about any changes in mood, suicidal thoughts, or unusual feelings of sadness, anxiety, or hopelessness.

• Epilepsy or other seizure disorders not controlled by medication
• Severe kidney or liver problems
• Low white blood cell or platelet counts, which may increase the risk of infection, bleeding, or anemia
• Heart problems that may cause symptoms such as chest pain (angina), especially after any activity; ankle swelling, shortness of breath (congestive heart failure), or an irregular heartbeat (arrhythmias).
• Irritation at the injection site that may cause skin and tissue damage (necrosis at the injection site). When you are ready to administer the injection, carefully follow the instructions in section 7 “How to inject AVONEX PEN” at the end of this leaflet. This reduces the risk of injection site reactions.

Talk to your doctor if you have any of these conditions or if they worsen while using Avonex.

During treatment, blood clots may form in small blood vessels. These clots could affect your kidneys. This may occur several weeks or years after starting treatment with Avonex.

Your doctor may want to monitor your blood pressure, blood (platelet count), and kidney function.

Inform your doctor that you are using Avonex:

• if you are going to have a blood test. Avonex may interfere with test results.

(Informational notes) You may occasionally need to remind other healthcare professionals that you are being treated with Avonex. For example, if other medications are prescribed for you or if you undergo a blood test, Avonex may interact with other drugs or affect the test result.

Pediatric population

The use of Avonex in children and adolescents is not recommended, as data on the use of Avonex in this population are limited. Avonex must not be used in children under 10 years of age, since its efficacy and safety have not yet been established in this age group.

Other medicines and AVONEX

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines, especially those used to treat epilepsy or depression. Avonex may affect other medicines or may be affected by them. This also includes any medicines obtained without a prescription.

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Harmful effects in the breastfed infant are not expected. Avonex may be used during breastfeeding.

Driving and use of machines

If you feel dizzy, do not drive. Avonex may cause dizziness in some people. If this occurs, or if you experience any other side effects that could impair your ability, do not drive or operate machinery.

Important information about some of the components of Avonex:

This medicine is essentially sodium-free. It contains less than 23 mg (1 mmol) of sodium per weekly dose.

3. How to use AVONEX PEN

(Informational notes) There is more information on how to inject yourself using the Avonex Pen on the back of this leaflet.

Recommended weekly dose

One injection using Avonex Pen, once a week.

Try to use Avonex at the same time on the same day each week.

Self-injection

You may self-inject using Avonex Pen without the help of your doctor, if you have been trained to do so. See the self-injection instructions at the end of this leaflet (see section 7, How to inject yourself using AVONEX PEN).

If you have difficulty handling Avonex Pen, consult your doctor, who can assist you.

Duration of treatment with AVONEX

Your doctor will inform you how long you should use Avonex. It is important that you use Avonex regularly. Do not make any changes not specifically instructed by your doctor.

If you inject more AVONEX than you should

The injection should be administered using only one Avonex Pen, once a week. If you have used more than one Avonex Pen within a three-day period, contact your doctor or pharmacist immediately for advice.

If you forget an injection

If you miss your usual weekly dose, inject a dose as soon as possible. Then wait one week before using Avonex Pen again. Continue injecting on that day each week. If you have a preferred day for using Avonex, talk to your doctor about adjusting the dose to return to your preferred day. Do not administer two injections to make up for a missed injection.

4. Possible adverse effects

(Informational notes) Although the list of possible adverse effects may seem concerning, it is possible that you may not experience any of them.

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

Serious side effects: seek medical help.

Severe allergic reactions

If you experience any of the following symptoms:

• Swelling of the face, lips, or tongue
• Difficulty breathing
• Rash

Call a doctor immediately. Do not use Avonex again until you have spoken with a doctor.

Depression

If you experience any symptoms of depression:

• Unusual feelings of sadness, anxiety, or hopelessness

Call a doctor immediately.

Liver problems

If you experience any of the following symptoms:

• Yellowing of the skin or of the whites of the eyes (jaundice)
• Widespread itching
• Feeling unwell (nausea and vomiting)
• Easy bruising on the skin

Call a doctor immediately, as these may be signs of a possible liver problem.

Side effects observed in clinical trials.

(Informational notes) Adverse effects observed in clinical trials. These are adverse effects reported by individuals during the evaluation of Avonex. The figures are based on the number of individuals who experienced them. They provide an indication of the likelihood that you may develop similar adverse effects.

Very common adverse effects (may affect more than 1 in 10 people)

• Flu-like symptoms: headache, muscle pain, chills, or fever: see Flu-like symptoms below
• Headache

Common adverse effects (may affect up to 1 in 10 people)

• Loss of appetite

• Feeling weak and tired

• Difficulty sleeping

• Depression

• Facial flushing

• Nasal congestion

• Diarrhea (loose stools)

• Feeling unwell (nausea or vomiting)

• Numbness or tingling of the skin

• Rash, skin bruising

• Increased sweating, night sweats

• Pain in muscles, joints, arms, legs, or neck

• Muscle cramps, stiffness in muscles and joints

• Pain, bruising, and redness at the injection site

• Changes in blood tests. Symptoms you may experience include fatigue, repeated infections, bruising, or bleeding without apparent cause.

Uncommon adverse effects (may affect up to 1 in 100 people)

• Hair loss

• Changes in menstruation

• Burning sensation at the injection site.

Rare adverse effects (may affect up to 1 in 1,000 people)

• Difficulty breathing
• Kidney problems including scarring that may reduce kidney function

If you experience any or all of the following symptoms:

• Foamy urine
• Fatigue
• Swelling, especially in ankles and eyelids, and weight gain

Tell your doctor, as these may be signs of a possible kidney problem.

• Blood clots in small blood vessels that can affect your kidneys (thrombotic thrombocytopenic purpura or hemolytic uremic syndrome). Symptoms may include increased bruising, bleeding, fever, extreme weakness, headache, dizziness, or lightheadedness. Your doctor may detect abnormalities in your blood tests and kidney function.

If you are concerned about any of these effects, talk to your doctor.

Other adverse effects

(Informational notes) These effects have been observed in individuals using Avonex, but the frequency with which they occur is unknown. If you feel dizzy, do not drive.

• Hypothyroidism or hyperthyroidism

• Nervousness or anxiety, emotional instability, irrational thoughts or hallucinations (seeing or hearing things that are not real), confusion, or suicidal behavior

• Numbness, dizziness, seizures or epileptic fits, and migraines

• Awareness of your heartbeat (palpitations), rapid or irregular heart rate, or heart problems accompanied by the following symptoms: reduced exercise capacity, inability to lie flat, shortness of breath, or ankle swelling

• Liver problems as previously described

• Hives or pseudovesicular rash, itching, worsening of pre-existing psoriasis

• Swelling or bleeding at the injection site, tissue destruction (necrosis), or chest pain after injection

• Weight gain or weight loss

• Changes in laboratory test results, such as abnormal liver function tests

• Pulmonary arterial hypertension: A disease characterized by marked narrowing of the blood vessels in the lungs, leading to increased pressure in the blood vessels carrying blood from the heart to the lungs. Pulmonary arterial hypertension has been observed at various times, even several years after starting treatment with medications containing interferon beta.

If you are concerned about any of these effects, speak with your doctor.

Injection-related effects

• Feeling faint: Your first Avonex injection may be administered by your doctor. You may feel dizzy or even faint. It is unlikely to happen again.
• Immediately after injection, you may experience muscle tightness or extreme weakness, as if reliving the experience. This is rare, occurs only with self-injection, and the effects pass quickly. These may occur at any time after starting Avonex treatment.
• If you notice skin irritation or any other skin problem after an injection, speak with your doctor.

Flu-like symptoms

(Informational notes) Three simple ways to reduce the impact of flu-like symptoms: Administer the Avonex Pen injection just before going to bed. This way, symptoms may occur while you sleep. Take paracetamol or ibuprofen half an hour before the Avonex Pen injection and continue taking it for one day. Speak with your doctor or pharmacist about the appropriate dosage. If you have a fever, drink plenty of water to stay hydrated.

Some people report feeling as though they have the flu after using Avonex Pen.

The symptoms are:

• Headache
• Muscle aches
• Chills or fever.

These symptoms are not actually due to influenza.

You cannot transmit them to anyone else. They are more common when you first start using Avonex. Flu-like symptoms gradually decrease with continued injections.

Children (10 years of age or older) and adolescents

In clinical trials, some adverse reactions were reported more frequently in children and adolescents than in adults, e.g., muscle pain, limb pain, fatigue, and joint pain.

Reporting of adverse reactions

If you experience any type of adverse reaction, talk to your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

To improve the traceability of this medicine, your doctor or pharmacist should record the name and batch number of the medicine you have been given in your medical record. You may also wish to note down this information in case you are asked for it in the future.

5. Storage of AVONEX PEN

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

Do not use this medicine after the expiry date stated on the label.

Avonex Pen contains a pre-filled syringe of Avonex. Keep in the original packaging to protect it from light.

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

Avonex Pen may also be stored at room temperature (between 15°C and 30°C) for a maximum of one week.

Do not use Avonex Pen if:

• The pen is damaged.
• The solution is discolored or you can see particles floating in it.
• The tamper-evident seal is broken.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of AVONEX PEN

The active substance is: interferon beta-1a 30 micrograms/0.5 ml.

The other components are: sodium acetate trihydrate, glacial acetic acid, arginine hydrochloride, polysorbate 20, and water for injections.

Appearance of AVONEX PEN and contents of the pack

Each individual pack contains one Avonex Pen, one needle, and a pen protector. The Avonex Pen contains a pre-filled syringe of Avonex and should only be used after receiving appropriate training. Avonex Pen is available in packs of four or twelve, providing one month or three months of injections.

Marketing Authorization Holder and Manufacturer

The Marketing Authorization Holder is:

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

The Netherlands

Avonex is manufactured by:

FUJIFILM Diosynth Biotechnologies Denmark ApS

Biotek Allé 1,

DK-3400 Hillerød,

Denmark

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

The Netherlands

Contact local representatives if you require a large-print version of this leaflet.

You may request further information about this medicinal product by contacting the local representative of the Marketing Authorization Holder.

Belgium/Belgium/Belgium Biogen Belgium NV/SA Tel: +32 2 2191218	Lithuania Biogen Lithuania UAB Tel: +370 5 259 6176
	Luxembourg/Luxembourg Biogen Belgium NV/SA Tel: +32 2 2191218
Czech Republic Biogen (Czech Republic) s.r.o. Tel: +420 255 706 200	Hungary Biogen Hungary Kft. Tel.: +36 1 899 9880
Denmark Biogen Denmark A/S Tlf.: +45 77 41 57 57	Malta Pharma. MT Ltd. Tel: +356 21337008
Germany Biogen GmbH Tel: +49 (0) 89 99 6170	Netherlands Biogen Netherlands B.V. Tel: +31 20 542 2000
Estonia Biogen Estonia OÜ Tel: +372 618 9551	Norway Biogen Norway AS Tlf: +47 23 40 01 00
Greece Genesis Pharma SA Tel: +30 210 8771500	Austria Biogen Austria GmbH Tel: +43 1 484 46 13
Spain Biogen Spain S.L. Tel: +34 91 310 7110	Poland Biogen Poland Sp. z o.o. Tel: +48 22 351 51 00
France Biogen France SAS Tél: +33 (0)1 41 37 9595	Portugal Biogen Portugal Sociedade Farmacêutica, Unipessoal Lda. Tel: +351 21 318 8450
Croatia Biogen Pharma d.o.o. Tel: +385 1 775 73 22	Romania Johnson & Johnson Romania S.R.L. Tel: +40 21 207 18 00
Ireland Biogen Idec (Ireland) Ltd. Tel: +353 (0)1 463 7799	Slovenia Biogen Pharma d.o.o. Tel: +386 1 511 02 90
Iceland Icepharma hf Sími: +354 540 8000	Slovakia Biogen Slovakia s.r.o. Tel: +421 2 323 34008
Italy Biogen Italia s.r.l. Tel: +39 02 584 9901	Finland Biogen Finland Oy Puh/Tel: +358 207 401 200
Cyprus Genesis Pharma Cyprus Ltd Tel: +357 22 76 57 15	Sweden Biogen Sweden AB Tel: +46 8 594 113 60
Latvia Biogen Latvia SIA Tel: +371 68 688 158

Date of the most recent review of this leaflet:

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

This leaflet can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.

1. How to inject yourself using AVONEX PEN

Avonex Pen (single-use)

Package contents – Avonex Pen, needle, and Avonex Pen protector

Avonex Pen – ready for injection

Avonex Pen – after injection (ready for disposal)

You should have received training on how to use the Avonex Pen.

These notes are a reminder. If you have any doubts or problems, consult your doctor or pharmacist.

Where to inject

Use a different injection site each week The best area is the outer side of the upper thigh muscle. Alternate between the left and right thigh. Record the injection site used each week.

• Avonex is injected into a muscle; the best area is the outer upper region of the thigh muscle, as shown in the diagram above. Injection into the buttocks is not recommended.

• Use a different injection site each week. This reduces the risk of skin or muscle irritation.

• Do not use areas of skin that are bruised, tender, infected, or have an open wound.

1. Preparation

2. Remove an Avonex Pen from the refrigerator.

Check that the package contains an Avonex Pen, a needle, and a pen cap.

Do not shake the Avonex Pen.

Check the expiration date shown on the label of the Avonex Pen.

Do not use if expired.

1. Allow the Avonex Pen to warm up.

Leave it at room temperature for half an hour.

This makes the injection more comfortable than when using it directly from the refrigerator.

Tip: Do not use external heat sources such as hot water to warm the Avonex Pen.

1. Wash your hands thoroughly with soap and water, and dry them.

2. Prepare alcohol wipes and adhesive bandages (not supplied), if needed.

3. Identify a clean, flat surface on which to place the materials required for the injection.

• Preparation of the Avonex Pen

1 Remove the tamper-evident seal cap Make sure the closure cap is intact and has not been opened. If it appears to have been opened, do not use that Avonex Pen. Hold the Avonex Pen with the closure cap facing upward. Bend the closure cap at a right angle to detach it. Do not touch the exposed glass tip. Tip: Place the pen on the table before proceeding to step 2.

2 Attach the needle The Avonex Pen is designed to work only with the provided needle Remove the packaging from the base of the needle shield. Attach the needle by pressing it onto the glass tip of the pen. Hold the pen vertically upright. Do not remove the needle shield. Carefully screw the needle on clockwise until firmly attached; otherwise, leakage may occur. You may not receive a complete dose if leakage occurs. Tip: The needle shield will detach automatically during the next step 3.

3 Extend the injector shield Firmly hold the body of the pen with one hand. Point the needle cap away from you and from anyone else. With the other hand and with a quick motion, lift the injector shield (slotted area) over the needle until the needle is completely covered. The plastic needle cap will detach. Tip: Do not press the blue activation button at the same time.

4 Check that the injector display screen is fully extended Check that the injector display screen is completely extended. A small rectangular area next to the oval viewing window will become visible. This is the safety lock.

5 Check the liquid Look through the oval viewing window. The liquid should be clear and colorless. If the solution is cloudy, colored, or contains floating particles, do not use this pen. Air bubbles are normal.

1. Use of Avonx Pen

	1 Clean the injection site If needed, use an alcohol wipe to clean the skin at the chosen injection site. Allow the skin to dry. Tip: The best area is the outer upper thigh.
	2 Place Avonex Pen on the skin Hold the pen body in one hand at a right angle to the injection site. Make sure the windows on the pen are visible. Tip: Be careful not to press the blue activation button too early. Firmly press the body of the pen against the skin to release the safety lock. Check that the safety lock has been released. The small rectangular window will disappear. Avonex Pen is ready to inject. Tip: Continue to hold the pen firmly against the skin.
	3 Administer the injection Press the blue activation button with your thumb to start the injection. You will hear a "click" indicating that the injection process has started. Do not remove the pen from the skin. Continue holding the pen against the skin and count slowly to 10 seconds. After 10 seconds, pull the pen away to remove the needle from the injection site. Press on the injection site for a few seconds. If there is any bleeding, clean it.
	Confirm administration of the injection Check the circular viewing window. When the full dose has been delivered, the window will appear yellow. Do not reuse Avonex Pen. It is for single use only.
	5 Disposal Place the pen cap on a flat, sturdy surface. Tip: Do not hold the pen cap. You could get a needle-stick injury. Insert the needle directly into the pen cap. Press firmly until you hear a "click" to seal the needle. You may need to use both hands. Once the pen is sealed, there is no risk of injury. Dispose of waste properly. Your doctor, nurse, or pharmacist will provide instructions on how to dispose of used Avonex Pen, for example, in a sharps container.