Rebif - patient leaflet, side effects, dosage

- 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 Rebif is and what it is used for

• 2. What you need to know before you use Rebif

• 3. How to use Rebif

• 4. Possible side effects

• 5. How to store Rebif

• 6. Contents of the pack and other information

1. What Rebif is and what it is used for

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.

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

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.

2. What you need to know before you use Rebif

Do not use Rebif

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

Warnings and precautions

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

• Rebif should only be used under the supervision of your doctor.
• Before treatment with Rebif, read carefully 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 Rebif if you have an allergy (hypersensitivity) to any other medicines.
• 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 Rebif. Your doctor may want to check your blood pressure, blood (platelet count) and the function of your kidney.

Inform your doctor if you have a disease of

• the bone marrow,
• kidney,
• liver,
• heart,
• thyroid,
• or if you have experienced depression,
• or if you have any history of epileptic seizures,

so that he/she can closely monitor your treatment and any worsening of these conditions.

Other medicines and Rebif

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. In particular you should tell your doctor if you are using antiepileptics or antidepressants.

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. Rebif can be used during breastfeeding.

Driving and using machines

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.

Rebif contains sodium and benzyl alcohol

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say it is 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.

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”).

3. How to use Rebif

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

Dose

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.

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

• on the same three days every week (at least 48 hours apart, e.g. Monday, Wednesday, Friday) at the same time of day (preferably in the evening).

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

No formal clinical studies have been conducted in children or teenagers. However there is some clinical data available suggesting that the safety profile in children and teenagers receiving Rebif 22 micrograms or Rebif 44 micrograms three times per week is similar to that seen in adults.

Use in children (below 2 years of age)

Rebif is not recommended for use in children below 2 years of age.

Method of administration

Rebif is intended for subcutaneous (under the skin) injection.

The first injection(s) must be performed under the supervision of an appropriately qualified healthcare professional. After receiving adequate training, you, a family member, friend or carer can use Rebif syringes to administer the medicine at home. It may also be administered with a suitable auto-injector.

For administration of Rebif, please read the following instructions carefully:

This medicine is for single use. Only clear to opalescent solution without particles and without visible signs of deterioration should be used.

How to inject Rebif

Choose an injection site. Your doctor will advise you on the possible injection sites (good sites include the upper thighs and the lower abdomen). Hold the syringe like a pencil or dart. It is recommended that you keep track of and rotate your injection sites, so that one area is not injected too frequently in order to minimise the risk of injection site necrosis.

NOTE: do not use any areas in which you feel lumps, firm knots, or pain; talk to your doctor or healthcare professional about anything you find.

Wash your hands thoroughly with soap and water.

Remove the Rebif syringe from the blister pack by peeling back the plastic covering.

Before the injection, use an alcohol wipe to clean the skin at the injection site. Let the skin dry. If a bit of alcohol is left on the skin, you may get a stinging sensation.

Gently pinch the skin together around the site (to lift it up a bit).

Resting your wrist on the skin near the site, stick the needle at a right angle straight into the skin with a quick, firm motion.

Inject the medicine by using a slow, steady push (push the plunger all the way in until the syringe is empty).

Hold a swab on the injection site. Remove the needle from the skin.

• Gently massage the injection site with a dry cotton ball or gauze.
• Dispose of all used items: once you have finished your injection, immediately discard the syringe in an appropriate disposal unit.

If you use more Rebif than you should

In case of overdose, contact your doctor immediately.

If you forget to use 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.

If you stop using Rebif

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.

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

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.

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

• Serious allergic (hypersensitivity) reactions. If, immediately following Rebif administration you experience a sudden difficulty breathing, which may appear in association with swelling of face, lips, tongue or throat, nettle rash, itching all over the body, and a feeling of weakness or faintness, contact your doctor immediately or seek urgent medical attention. These reactions are rare (may affect up to 1 in 1,000 people).
• Inform your doctor immediately if you experience any of the following possible symptoms of a liver problem: jaundice (yellowing of the skin or of the whites of the eyes), widespread itching, loss of appetite accompanied by nausea and vomiting and easy bruising of the skin. Severe liver problems can be associated with additional signs, e.g. difficulty concentrating, sleepiness and confusion.
• Depression is common (may affect up to 1 in 10 people) in treated patients with multiple sclerosis. If you feel depressed or develop thoughts of suicide, report it immediately to your doctor.

Talk to your doctor if you experience any of the following side effects:

• Flu-like symptoms, such as headache, fever, chills, muscle and joint pains, fatigue and nausea

are very common (may affect more than 1 in 10 people).

These symptoms are usually mild, are more common at the start of the treatment and decrease with continued use.

To help reduce these symptoms your doctor may advise you to take a fever reducing painkiller before a dose of Rebif and then for 24 hours after each injection.

• Injection site reactions including redness, swelling, discoloration, inflammation, pain and skin breakdown are very common.

The occurrence of injection site reactions usually decreases over time.

Tissue destruction (necrosis), abscess and mass at injection site are uncommon (may affect up to 1 in 100 people).

See recommendations in section “Warnings and precautions” to minimise the risk of injection site reactions.

The injection site can become infected (uncommon) ; the skin may become swollen tender and hard and the whole area could be very painful. If you experience any of these symptoms, contact your doctor for advice.

• Certain laboratory tests may change. These changes are generally not noticed by the patient (no symptoms), are usually reversible and mild, and most often do not require particular treatment.

The number of red blood cells, white blood cells or platelets may decrease either individually (very common) or all at one time (rare). Possible symptoms resulting from these changes could include tiredness, reduced ability to fight infection, bruising or unexplained bleeding.

Liver function tests may be disturbed (very common). Inflammation of the liver has also been reported (uncommon). If you experience symptoms suggesting a liver disorder, such as loss of appetite accompanied by other symptoms such as nausea, vomiting, jaundice, please contact your doctor immediately (see above “Tell your doctor immediately…”).

• Thyroid dysfunction is uncommon. The thyroid 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.
• MS pseudo-relapse (frequency not known): 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.

Other possible side effects include:

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

• Headache

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

• Insomnia (sleeping difficulty)
• Diarrhoea, nausea, vomiting
• Itching, rash (skin eruptions)
• Muscle and joints pain
• Fatigue, fever, chills
• Hair loss

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

• Hives
• Epileptic seizures
• Liver inflammation (hepatitis)
• Breathing difficulties
• Blood clots such as deep venous thrombosis
• Disorders of the retina (back of the eye) such as inflammation or blood clots with consequent vision disorders (vision disturbances, loss of vision)
• Increased sweating

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

• Suicide attempt
• Serious skin reactions – some with mucosal lesions
• 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.
• 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.

• 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 the national reporting system listed inBy 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).

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 syringe contains 22 micrograms, corresponding to 6 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

Rebif is available as a solution for injection in a pre-filled syringe with a fixed needle for self-administration. Rebif solution is clear to opalescent. The pre-filled syringe is ready for use and contains 0.5 mL of solution.

Rebif is available in packs of 1, 3, 12 and 36 pre-filled syringes. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Merck Europe B.V.

Gustav Mahlerplein 102

1082 MA Amsterdam

The Netherlands

Manufacturer

Merck Serono S.p.A.

Via delle Magnolie 15

I-70026 Modugno (Bari)

Italy

This leaflet was last revised in

Other sources of information

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