Rebif 22 micrograms / 0.5 ml solution for injection in cartridge – patient leaflet, side effects, dosage

1. What Rebif is and what it is used for

RebiSmart

Rebif belongs to a class of medicines known as interferons. These are natural substances that transmit messages between cells. Interferons are produced by the body and play an essential role in the immune system. Through mechanisms that are not totally understood, interferons help to limit the damage of the central nervous system associated with multiple sclerosis.

• Please ensure that the dose displayed on

  the screen of the device corresponds to the prescribed dose of 22 micrograms before the injection.

Driving and using machines

• Place RebiSmart at a right angle (90°) to the

  gland may function either excessively, or insufficiently. These changes in the thyroid activity are almost always not felt by the patient as symptoms; however your doctor may recommend testing as appropriate.

  skin.

Effects of the disease itself or of its treatment might influence your ability to drive or to use machines. You should discuss this with your doctor if you are concerned.

• Press the injection button. During the injection,

  the button will flash.

Rebif is a highly purified soluble protein that is similar to the natural interferon beta that is produced in the human body.

• Wait until the light switches off. This tells you

  • MS pseudo-relapse (frequency not known):

that the injection is completed.

Rebif contains sodium and benzyl alcohol

There is a possibility that at the beginning of your treatment with Rebif you may experience symptoms that resemble those of a multiple sclerosis relapse. For example, your muscles may feel very tense or very weak, preventing you from moving as you want. In some cases such symptoms are associated with fever or flu-like symptoms described above. If you notice any of these side effects talk to your doctor.

• Remove RebiSmart from the injection site.

Rebif is used for the treatment of multiple sclerosis. It has been shown to reduce the number and the severity of relapses and to slow the progression of disability.

This medicine contains less than 1 mmol sodium (23mg) per dose, that is to say essentially ‘sodium free’. This medicine contains 2.5 mg benzyl alcohol per dose. Benzyl alcohol may cause allergic reactions. Benzyl alcohol has been linked with the risk of severe side effects including breathing problems (called “gasping syndrome”) in young children. Do not use for more than a week in young children (less than 3 years old), unless advised by your doctor or pharmacist.

After the injection of Rebif with RebiSmart • Remove and discard the needle according to the

instruction manual provided with your device. • Gently massage the injection site with a dry

2. What you need to know before you use Rebif

cotton ball or gauze.

• Store your device containing a cartridge of Rebif

  as instructed in section 5 “How to store Rebif”. If you have any further questions, please ask your doctor, nurse or pharmacist.

Do not use Rebif

Other possible side effects include:

• if you are allergic to natural or recombinant

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

  interferon beta or any of the other ingredients of this medicine (listed in section 6). • if you are severely depressed at present or are

  Ask your doctor or pharmacist for advice if you are pregnant or breast-feeding, or if you have a liver or kidney disease. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called “metabolic acidosis”).

  If you use more Rebif than you should

  Common (may affect up to 1 in 10 people): • Insomnia (sleeping difficulty)

  In case of overdose, contact your doctor immediately.

  developing thoughts of suicide.

  • Diarrhoea, nausea, vomiting

Warnings and precautions

If you forget to use Rebif

• Itching, rash (skin eruptions)

Talk to your doctor, pharmacist or nurse before using Rebif.

If you miss a dose, continue to inject from the day of the next scheduled dose. Do not use a double dose to make up for a forgotten dose.

3. How to use Rebif

• Muscle and joints pain

• Rebif should only be used under the supervision

  This medicine is for multidose use.

• Fatigue, fever, chills

of your doctor.

• Hair loss

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

If you stop using Rebif

• Before treatment with Rebif, read carefully

  Uncommon (may affect up to 1 in 100 people): • Hives

  The effects of Rebif may not be noticed immediately. Therefore you should not stop using Rebif but continue to use it regularly to achieve the desired result. If you are uncertain about the benefits, please consult your doctor.

  and follow the advice given under “How to use Rebif” in order to minimise the risk of injection site necrosis (skin breakdown and tissue destruction) that has been reported in patients treated with Rebif. If you experience troubling local reactions, contact your doctor. • Talk to your doctor or pharmacist before taking

  Dose

  • Epileptic seizures

The usual dose is 44 micrograms (12 million IU) given three times per week. Your doctor has prescribed you a lower dose of 22 micrograms (6 million IU) given three times per week. This lower dose is recommended for patients who cannot tolerate the higher dose

• Liver inflammation (hepatitis)
• Breathing difficulties

You should not discontinue the treatment without first contacting your doctor.

• Blood clots such as deep venous thrombosis • Disorders of the retina (back of the eye) such

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

Rebif if you have an allergy (hypersensitivity) to any other medicines.

as inflammation or blood clots with consequent vision disorders (vision disturbances, loss of vision)

Rebif should be administered three times per week, and if possible:

• Blood clots in the small blood vessels may occur

4. Possible side effects

during your treatment. These blood clots could affect your kidneys. This might happen several weeks to several years after starting Rebif. Your doctor may want to check your blood pressure, blood (platelet count) and the function of your kidney.

• on the same three days every week (at least

  • Increased sweating

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

48 hours apart, e.g., Monday, Wednesday, Friday) • at the same time of day (preferably in the

Rare (may affect up to 1 in 1,000 people): • Suicide attempt

evening).

Tell your doctor immediately and stop using Rebif if you experience any of the following serious side effects:

• Serious skin reactions - some with mucosal

Use in children and teenagers (2 to 17 years old)

lesions

Inform your doctor if you have a disease of • the bone marrow,

• Blood clots in the small blood vessels

No formal clinical studies have been conducted in children or teenagers. However there is some clinical data available suggesting that the safety

• Serious allergic (hypersensitivity) reactions. If,
• kidney,

TW4815876 N67Q0203J 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.

Manufacturer

Merck Serono S.p.A.

Via delle Magnolie 15

I-70026 Modugno (Bari)

Italy

• Drug-induced lupus erythematosus: a side-effect of long-term use of Rebif. Symptoms may include muscle pain, joint pain and swelling, and rash. You may also experience other signs such as fever, weight loss, and fatigue. Usually symptoms disappear within one or two weeks after treatment is stopped.

  This leaflet was last revised in 02/2025

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

  If you get some or all of these symptoms: - foamy urine

  • fatigue
  • swelling, particularly in the ankles and eyelids, and weight gain.

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

The following side effects were reported for interferon beta (frequency not known) • Dizziness

• Nervousness
• Loss of appetite
• Dilatation of the blood vessels and palpitation • Irregularities and/or changes in menstrual flow • 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 Rebif.

• Inflammation of the fatty tissue under the skin

  (panniculitis), which can make the skin feel hard and possibly develop painful red lumps or patches.

You should not stop or alter the medication without your doctor’s advice.

Children and teenagers

Side effects in children and teenagers are similar to those observed in adults.

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:

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Rebif

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 after EXP.

Store in a refrigerator (2°C – 8°C).

Do not freeze. (To prevent accidental freezing, avoid placing near the freezer compartment). After first injection use within 28 days. The device (RebiSmart) containing a pre-filled cartridge of Rebif must be stored in the device storage box in a refrigerator (2°C - 8°C). For the purpose of ambulatory use, you may remove Rebif from the refrigerator and store it not above 25°C for one single period of up to 14 days. Rebif must then be returned to the refrigerator and used before the expiry date.

Store in the original package in order to protect from light.

Do not use this medicine if you notice any visible signs of deterioration such as if the solution is no longer clear or if it contains particles.

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

6. Contents of the pack and other information

What Rebif contains

• The active substance is interferon beta-1a.

  Each cartridge contains 66 micrograms corresponding to 18 million International Units (IU) of interferon beta-1a.

• The other ingredients are mannitol, poloxamer 188, L-methionine, benzyl alcohol, sodium acetate, acetic acid, sodium hydroxide and water for injections.

What Rebif looks like and contents of the pack

Pre-filled cartridge (type 1 glass) with a plunger stopper (rubber) and a crimp cap (aluminium and halobutyl rubber), containing 1.5 mL solution for injection. Pack size of 4 or 12 cartridges. Not all pack sizes may be marketed.

The cartridge is to be used with the RebiSmart electronic injection device. The device is provided separately.

Marketing Authorisation Holder

Merck Serono Ltd. 5 New Square, Bedfont Lakes Business Park, Feltham, Middlesex, TW14 8HA