AVONEX 30 micrograms/0.5 ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

AVONEX 30 micrograms/0.5 ml solution for injection

(interferon beta-1a)

Pre-filled syringe

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

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is AVONEX and what is it used for

What is AVONEX?

The active substance of 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 produced with exactly the same ingredients as the interferon beta present in the human body.

What is AVONEX used for?

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

Each patient has specific symptoms of MS.These can be:

• Feeling of instability or dizziness, walking problems, muscle stiffness and spasms, fatigue, tingling in the face, arms or legs
• Acute or chronic pain, bladder and bowel problems, sexual problems and vision problems
• Difficulty thinking and concentrating, depression.

MS also tends to flare up from time to time: this is what is known as a relapse.

Avonex may help reduce the number of relapses you may have and slow down the disabling effects of 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 defense system reacts to your own myelin, i.e. the insulation that surrounds nerve fibers. When myelin is damaged, messages between the brain and other parts of the body are disrupted. This is what causes the symptoms of MS. Avonex appears to work by preventing your body's defense system from attacking myelin.

2. What you need to know before you use AVONEX

Do not use AVONEX

• if you are allergicto interferon beta or any of the other ingredients of this medicine (listed in section 6);
• if you have severe depressionor have had thoughts of suicide.

Talk to your doctor immediately in any of these cases.

Warnings and precautions

Talk to your doctor before you start using Avonex if you have or have had in the past:

• Depressionor mood problems
• Suicidal thoughts.

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

• Epilepsyor other uncontrolled seizure disorders

• Severe kidney or liver problems
• Low white blood cell or platelet counts, which may increase the risk of infection, bleeding or anemia
• Heart problemsthat may cause symptoms such as chest pain (angina),especially after any activity; swelling of ankles, difficulty breathing (congestive heart failure)or an irregular heartbeat (arrhythmias).
• Irritation at the injection site that can cause skin and tissue damage (injection site necrosis). When you are ready to administer the injection, carefully follow the instructions in section 7, "How to inject AVONEX" at the end of this leaflet. This reduces the risk of injection site reactions.

Talk to your doctor if you have any of these conditionsor if they get worse while using Avonex.

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

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

Tell your doctor that you are using Avonex:

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

Pediatric population

Avonex is not recommended for use in children and adolescents because the data on the use of Avonex in this population are limited. Avonex must not be used in children under 10 years of age because it has not been established whether it would work for them and whether it would be safe.

Other medicines and AVONEX

Tell your doctorif you are using, have recently used, or might use any other medicines, especially for the treatment of epilepsy or depression. Avonex may affect other medicines or be affected by them. This includes any other medicine, including medicines obtained without a prescription.

Pregnancy and breastfeeding

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

No harmful effects on the baby are expected. Avonex can be used during breastfeeding.

Driving and using machines

If you feel dizzy, do not drive.Avonex can make some people feel dizzy. If this happens to you or if you have any other side effect that may affect your ability, do not drive or use machines.

Important information about some of the ingredients 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 Dosage

Recommended weekly dose

One Avonex injection once a week.

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

If you have decided to start treatment with Avonex, your doctor may provide you with a dose adjustment device called Avostartclip. The Avostartclip attaches to the syringe and allows you to gradually increase the dose of Avonex when you start treatment. This is to limit the flu-like symptoms that some patients experience when they start using Avonex. Your doctor or nurse will help you use the Avostartclip dose adjustment device.

Self-injection

You can inject Avonex without your doctor's help if you have been taught how to do it. See the self-injection instructions at the end of this leaflet (see section 7, How to inject AVONEX).

If you have problemshandling the syringe, talk to your doctor. You may receive help.

Duration of treatment with AVONEX

Your doctor will tell you how long you should use Avonex. It is essential that you use Avonex regularly. Do not make any changes that your doctor has not told you to make.

If you inject more AVONEX than you should

You should only have one Avonex injection once a week. If you have had more than one Avonex injection within three days, contact your doctor or pharmacist immediately.

If you miss an injection

If you miss your usual weekly dose, inject a dose as soon as possible. Then skip the treatment for one week. Continue with the injection on that day of each week. If you have a preferred day for using Avonex, talk to your doctor to adjust the dose and get back to your preferred day. Do not give yourself two injections to make up for the missed injection.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe Adverse 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 until you have spoken with a doctor.

Depression

If you experience any symptoms of depression:

• Unusual feeling of sadness, anxiety, or hopelessness.

Call a doctor immediately.

Liver Problems

If you experience any of the following symptoms:

• Yellowing of the skin or the white part of the eyes (jaundice)

• Generalized itching
• Feeling of discomfort (nausea and vomiting)
• Bruises that appear easily on the skin.

Call a doctor immediatelyas they may be manifestations of a possible liver problem.

Adverse Effects Observed in Clinical Trials

Very Common Adverse Effects

(may affect more than 1 in 10 people)

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

Common Adverse Effects

(may affect up to 1 in 10 people)

• Loss of appetite
• Feeling of weakness and fatigue
• Difficulty sleeping

• Depression
• Facial flushing

• Nasal discharge

• Diarrhea (soft stools)

• Feeling of discomfort (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. The symptoms you may experience are 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 can reduce kidney function. If you experience any of the following symptoms:
• • Foamy urine
  • Fatigue

• Swelling, especially of ankles and eyelids, and weight gain.

Report to your doctor as they may be manifestations of a possible kidney problem.

• Blood clots in small blood vessels that can affect your kidneys (thrombotic thrombocytopenic purpura or hemolytic uremic syndrome). The symptoms may include an increase in bruising, bleeding, fever, extreme weakness, headache, dizziness, or fainting. Your doctor may find changes in your blood and kidney function.

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

Other Adverse Effects

• Thyroid dysfunction or excess activity

• Nervousness or anxiety, emotional instability, irrational thoughts or hallucinations (seeing or hearing things that are not real), confusion, or suicide
• Numbness, dizziness, seizures, or epileptic fits and migraines
• Perception of your heartbeat (palpitations), rapid or irregular heartbeat, or heart problems accompanied by the following symptoms: reduced exercise capacity, inability to stay lying down, difficulty breathing, or swelling of ankles
• Liver problems as described previously

• Hives or pseudovesicular rash, itching, worsening of existing psoriasis
• Swelling or bleeding at the injection site, tissue destruction (necrosis), or chest pain after an injection

• Weight gain or loss
• Changes in test results, such as variations in liver function tests
• Pulmonary arterial hypertension: a disease in which there is a significant narrowing of the blood vessels in the lungs, causing an increase in 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 starting treatment with interferon beta-containing medications.

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

Injection Site Effects

• Fainting sensation:The first injection of Avonex may be administered by your doctor. You may feel dizzy. You may even faint. It is unlikely to happen again.

• Immediately after the injection, you may notice your muscles are tense or very weak,as if you were going to repeat the experience. It is rare. It only occurs when self-injecting, and the effects pass quickly. They can occur at any time after starting treatment with Avonex.
• If you notice any skin irritation or other skin problemsafter an injection, talk to your doctor.

Pseudoflu-like Symptoms

Some people report that after injecting Avonex, they experience a pseudoflu-like sensation.

The signs are:

• Headache
• Muscle pain

• Chills or fever.

These symptoms do not actually correspond to the flu

You cannot transmit them to anyone. They are more frequent when using Avonex for the first time. Your doctor may provide you with a dose adjustment device, Avostartclip, which will allow you to gradually increase the dose when starting treatment to help limit pseudoflu-like symptoms. Pseudoflu-like symptoms gradually decrease as more injections are administered.

Children (10 years of age or older) and adolescents

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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Medicines Monitoring System: www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

In order to improve the traceability of this medicine, your doctor or pharmacist must record the name and batch number of the medicine administered to you in your medical history. You may also want to take note of this information in case you are asked for it in the future.

5. Storage of AVONEX

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

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

Store in the original packaging (sealed plastic tray) to protect it from light.

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

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

DO NOT use Avonexif you notice:

• The pre-filled syringe is broken.

• The sealed plastic tray is damaged or open.
• The solution is colored or you notice particles in suspension.

• The tamper-evident cap is damaged.

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

6. Container Contents and Additional Information

AVONEX Composition

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

The other componentsare: sodium acetate trihydrate, glacial acetic acid, arginine hydrochloride, polysorbate 20, and water for injectables.

Product Appearance and Container Contents

Avonex injectable is presented as a ready-to-use injection

A box of Avonex contains four or twelve pre-filled syringes, each with 0.5 ml of a clear and colorless liquid inside. Only certain package sizes may be marketed. Each syringe is packaged in a sealed plastic tray. The tray also includes a needle for administering the injection.

Marketing Authorization Holder and Manufacturer

The marketing authorization holder is:

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

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

Netherlands

Contact your local representative if you want a version of this leaflet with larger text.

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

Date of Last Revision of this Leaflet:08/2024.

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

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

1. How to Inject AVONEX

You should receive training on how to inject Avonex

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

Where to Inject

• Avonex is injected into a muscle, for example, into the muscles of the upper thigh. It is not recommended to inject Avonex into the buttocks.

• Inject at a different site each week. This involves less risk of skin or muscle irritation.

• Do not useareas of skin with bruises, ulcers, or infections, or if there is an open wound.

• Preparation
  1. Remove a sealed plastic tray from the refrigerator

• Check the expiration date on the tray lid. Do not use if it is expired.
• Completely remove the paper lid. Check that the blister tray contains a pre-filled syringe and an injection needle (see the image "Contents of the Plastic Tray").

1. Allow the syringe to warm up

• Let it sit at room temperature for half an hour. This makes the injection more comfortable than if it were injected directly from the refrigerator.

Tip:do not use external heat sources, such as hot water, to warm up the syringe.

1. Wash your handswith water and soap and dry them.

1. Prepare alcohol-soaked cotton balls and adhesive bandages(not provided) if you need them.

Locate a clean and stable surface to place the necessary materialsfor the injection. Place the tray on it.