8.8 micrograms / 0.1 ml and 22 micrograms / 0.25 ml solution for injection in a cartridge, cartridge. Interferon beta-1a. Initial packaging.
What Rebif is and what it is used for
Rebif belongs to a group of medicines called interferons. They are natural substances that transmit messages between cells. Interferon is produced by the body and plays an important role in the immune system. Through mechanisms that are not fully understood, interferon helps you to limit damage to the central nervous system associated with multiple sclerosis.
Rebif is a very pure, soluble protein that is similar to the natural interferon-beta produced in the body.
Rebif is used to treat multiple sclerosis. The drug has been shown to reduce the number and severity of relapses and delay the development of disability. It is also approved for use in patients who have had a single clinical episode that was probably the first sign of multiple sclerosis.
What you need to know before using 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.
Warnings and cautions
Talk to your doctor, pharmacist, or nurse before using Rebif.
- Rebif should only be used under the supervision of your doctor.
- Before starting treatment with Rebif, you should read carefully and then follow the instructions given under the heading “How to use Rebif”, this to reduce the risk of necrosis at the injection site (degradation of the skin and tissue death) which has been reported for patients treated with Rebif. Contact your doctor if you experience troublesome local reactions.
- Talk to your doctor or pharmacist before taking Rebif if you are allergic (hypersensitive) to any other medicine.
- During treatment, blood clots may form in the small blood vessels. Blood clots can affect your kidneys. This can happen several weeks or up to several years after you start Rebif. Your doctor may want to check your blood pressure, blood count ( platelet count ), and kidney function.
Tell your doctor if you have
- bone marrow disease
- kidney disease
- liver disease
- heart disease
- thyroid disease
- or if you have been depressed
- or if you have had epileptic seizures
so that the doctor can closely monitor the treatment and the possible worsening of these conditions.
Other medicines and Rebif
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, you should tell your doctor if you are taking medicines for epilepsy ( antiepileptics ) or depression (antidepressants).
Pregnancy and breastfeeding
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 breastfed newborns/infants are expected. Rebif can be used during breastfeeding.
Driving and using machines
Both the disease itself and the treatment can affect your ability to drive and use machines. Talk to your doctor if you have any concerns.
Rebif contains sodium and benzyl alcohol
This medicine contains less than 1 mmol (23 mg) sodium per dose, ie essentially ‘sodium-free’.
This medicine contains 0.5 mg benzyl alcohol per 0.1 ml dose and 1.25 mg benzyl alcohol per 0.25 ml dose. Benzyl alcohol can cause allergic reactions.
Benzyl alcohol is associated with the risk of serious side effects such as difficulty breathing in young children.
Do not use the medicine for more than 1 week in newborns (younger than 3 years) unless recommended by a doctor or pharmacist.
If you are pregnant or breastfeeding, or if you have impaired liver or kidney function, consult your doctor or pharmacist before using this medicine. Large amounts of benzyl alcohol can be stored in the body and cause side effects (metabolic acidosis ).
How to use Rebif
For multiple-dose use.
Always use this medicine exactly as your doctor has told you. Consult a doctor if you are unsure.
When treatment begins
Treatment begins with a gradual increase in dose one (so-called dose titration) over 4 weeks to reduce some of the side effects. Therefore, it is recommended that:
- During weeks one and two, Rebif injects 8.8 micrograms three times a week.
- During weeks three and four, Rebif injects 22 micrograms three times a week.
From the fifth week and for the rest of the treatment period after you have completed your initiation period, you will follow the usual dosage prescribed by your doctor.
Dose
The usual dose is 44 micrograms (12 million IU) given three times a week.
A lower dose of 22 micrograms (6 million IU) given three times a week is recommended for patients with multiple sclerosis who do not tolerate the higher dose.
Rebif should be taken three times a week, and if possible:
- on the same three weekdays each week (at least 48 hours between each time, eg Monday, Wednesday, Friday)
- at the same time of day (preferably in the evening).
Use for children and adolescents (2 to 17 years)
No formal clinical studies have been performed on children or adolescents. However, there are some clinical data available that suggest that the safety profile of children and adolescents receiving Rebif 22 micrograms or Rebif 44 micrograms three times a week is similar to that seen in adults.
Use for children (under 2 years)
Rebif is not recommended for use in children under 2 years of age.
Method of administration
- Rebif should be injected subcutaneously (under the skin).
- The first injection ( s) must be given in the presence of specially trained healthcare professionals. After receiving adequate training, you, a family member, friend, or caregiver can use Rebif cartridges, cartridges, with your injection aid to inject the medicine at home.
- The initial pack contains two identical cartridges, cassettes, with Rebif and you can start treatment with any cartridge, cartridge.
- The cartridge, and cassette, should be used with the RebiSmart electronic injection device.
- Complete instructions for use are included with your injection aid. Read this carefully.
- Brief instructions for using the Rebif cartridge are provided below.
Before you begin
- Wash your hands thoroughly with soap and water.
- Take cartridge one, the cartridge, with Rebif from the blister pack by tearing off the plastic film.
- Check (when removing the Rebif from the refrigerator) that the cartridge, the cartridge, has not been frozen in the package or the injection aid. Only a ready-to-opalescent solution without particles and visible signs of deterioration should be used.
- To place the cartridge one, the cartridge, in the injection aid and make the injection one, follow the instructions for use that come with your injection aid.
Where to inject Rebif
How to inject Rebif
- Your doctor will tell you how to choose the right dose. Also, read the instructions in the instruction manual that comes with your injection device (RebiSmart).
After injection of Rebif with RebiSmart
- Remove and discard the needle according to the instructions for use provided with your injection device.
- Gently massage the injection site with a dry cotton ball or gauze.
- Store your injection device containing a cartridge, or cassette, with Rebif according to the instructions in section 5 “How to store Rebif”.
If you have any further questions, ask your doctor, nurse, or pharmacist.
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 injecting on the next injection day. Do not take a double dose to make up for a forgotten dose.
If you stop using Rebif
The effect of Rebif may not be immediately noticeable. You should therefore not stop taking Rebif, but continue to use it regularly to achieve the desired result. If you are not sure about the benefits of treatment, you should consult your doctor.
You should not stop treatment without first consulting your doctor.
If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately and stop using Rebif if you experience any of the following serious side effects:
- Severe allergic (hypersensitivity) reaction. If shortly after Rebif injection you suddenly feel difficult to breathe, which can occur in connection with swelling of the face, lips, tongue, or throat, hives, itching all over the body, and a feeling of weakness or dullness, you should immediately contact your doctor or seek emergency medical attention. These reactions are rare (may affect up to 1 in 1,000 people).
- Tell your doctor immediately if you experience any of the following possible symptoms of liver problems: jaundice (yellowing of the skin or whites of the eyes), widespread itching, loss of appetite followed by nausea and vomiting, and bruising of the skin. Serious liver problems can be associated with additional signs, e.g. difficulty concentrating, drowsiness, and confusion.
- Depression is common (may affect up to 1 in 10 people) in patients with multiple sclerosis. If you feel depressed or have suicidal thoughts, report this to your doctor immediately.
Talk to your doctor if you experience any of the following side effects:
- Influenza-like symptoms, such as headache, fever, chills, muscle and joint pain, fatigue, and nausea are very common (may affect more than 1 in 10 people). These symptoms are usually mild, are more common at the beginning of treatment, and subside with continued use.
To reduce these symptoms, your doctor may advise you to take an antipyretic and painkiller before taking a dose of Rebif and then for 24 hours after each injection.
- Injection site reactions such as redness, swelling, discoloration, inflammation, pain, and breakdown of the skin are very common.
The incidence of injection site reactions usually decreases with time.
Tissue death ( necrosis ), abscesses, and lumps at the injection site are less common (may affect up to 1 in 100 people).
See the recommendations in the section “Warnings and precautions” to minimize the risk of injection site reactions.
The injection site may become infected (less common ); the skin may become swollen, sore, and hard and the whole area may be sore. Contact your doctor for advice if you experience any of these symptoms.
- Some laboratory tests may change. These changes are generally not noticed by the patient (no symptoms), are usually transient and mild, and usually do not require special treatment.
The number of red blood cells, white blood cells, or platelets can decrease either only one variety ( very common ) or all varieties at once ( rare ). These changes can result in possible symptoms such as fatigue, decreased resistance to infections, bruising, or unexplained bleeding. Liver function tests may be affected ( very common)). Hepatitis has also been reported (uncommon ). Contact a doctor immediately (see above “Contact your doctor immediately …”) if you experience symptoms that indicate liver disorder such as loss of appetite followed by other symptoms such as nausea, vomiting, or jaundice.
- Disrupted thyroid activity is less common. The thyroid gland can function either excessively or insufficiently. These changes in thyroid activity are rarely felt by the patient as a symptom, but your doctor may recommend laboratory testing.
- False MS relapse ( no known frequency ): It is possible that at the beginning of your treatment with Rebif you experience symptoms reminiscent of a multiple sclerosis relapse. For example, your muscles may feel sore or very weak, which prevents you from moving the way you want. In some cases, such symptoms are associated with fever or flu-like symptoms as described above. Talk to your doctor if you notice any of these side effects.
Other possible side effects are:
Very common (may affect more than 1 in 10 people):
- Headache
Common (may affect up to 1 in 10 people):
- Insomnia (difficulty sleeping)
- Diarrhea, nausea, vomiting
- Itching, exanthema (rash)
- Muscle and joint pain
- Fatigue, fever, chills
- Hair loss
Uncommon (may affect up to 1 in 100 people):
- Hives
- Epileptic seizures
- Hepatitis _ _
- Breathing difficulties
- Blood clots such as deep vein thrombosis
- Retinal disturbance (posterior part of the eye) such as inflammation or blood clots with visual disturbance as a result (visual disturbances, loss of vision)
- Increased sweating
Rare (may affect up to 1 in 1,000 people):
- Suicide attempt
- Severe skin reactions – sometimes with damage to mucous membranes
- Blood clots in the small blood vessels can affect the kidneys (thrombotic thrombocytopenic purpura or hemolytic uremic syndrome ). Symptoms may include bruising, bleeding, fever, extreme weakness, headache, dizziness, or fainting. Your doctor may notice changes in your blood and kidney function.
- Drug-induced lupus erythematosus: a side effect of long-term use of Rebif. Symptoms may include muscle aches, aching and swollen joints, and skin rash. You may also experience other signs such as fever, weight loss, and fatigue. Usually, the symptoms disappear within one or two weeks after the end of treatment.
- Kidney problems include scarring that can impair your kidney function.
If you get any or all of these symptoms:- frothy urine
- fatigue
- swelling, especially in the ankles and eyelids, and weight gain. Talk to your doctor as it may be a sign of a possible kidney problem.
The following side effects have been reported with interferon beta (no known frequency):
- Dizziness
- Nervousness
- Loss of appetite
- Dilated blood vessels and palpitations
- Irregular and/or altered menstruation
- Pulmonary arterial hypertension – a disease with severe narrowing of the blood vessels of the lungs that leads to high blood pressure in the blood vessels that transport blood from the heart to the lungs. Pulmonary arterial hypertension has been observed at various times during treatment, even up to several years after initiating treatment with Rebif.
- Inflammation of the adipose tissue under the skin (panniculitis), can make the skin feel hard, with the possible development of painful red bumps or spots.
You should not stop or change your medication without consulting your doctor.
Children and young people
Side effects in children and adolescents are similar to those observed in adults.
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 (2ºC-8ºC).
Do not freeze. (To prevent the medicine from freezing, avoid placing it near the cooling element).
After the first injection: use within 28 days.
The injection device (RebiSmart) containing a pre-filled cartridge, and cassette, with Rebif, must be stored in the product storage box in the refrigerator (2ºC-8ºC). At the end-user, Rebif can be removed from the refrigerator and stored at a maximum of 25 ° C for a single period of up to 14 days. Rebif must then be put back in the refrigerator and used before the expiry date.
Store in the original package. Sensitive to light.
Do not use this medicine if you notice any signs of deterioration, e.g. if the solution in cartridge one, the cartridge, is no longer clear and colorless or if it contains particles.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Contents of the pack and other information
Content declaration
- The active substance is interferon beta-1a. Each cartridge, cartridge, contains 132 micrograms equivalent to 36 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 the medicine looks like and the contents of the pack
Pre-filled cartridge, cartridge, (type I glass) with a flask, a stopper (rubber), and a shrinking cap (aluminum and halobutyl rubber), containing 1.5 ml solution. Pack size: 2 cartridges, cartridges.
The cartridge, and cassette, should be used with the RebiSmart electronic injection device. The injection aid is provided separately.
Marketing Authorisation Holder
Merck Europe BV
Gustav Mahlerplein 102
1082 MA Amsterdam
Netherlands
Manufacturer
Merck Serono SpA
Via Delle Magnolia 15
I-70026 Modugno (Bari)
Italy