Rebif Solution for Injection in Pre-Filled Cartridges - Consumer Medicine Information
|Manufacture:||EMD Serono, Inc|
|Condition:||Multiple Sclerosis Fatigue (Fatigue)|
|Form:||Liquid solution, Subcutaneous (SC)|
|Ingredients:||interferon beta-1a, mannitol, benzyl alcohol, poloxamer-188, methionine|
Solution for injection in pre-filled cartridges
About This Medication
What the Medication is Used For
REBIF is used for the treatment of relapsing forms of Multiple Sclerosis (MS) to reduce the number and the severity of clinical exacerbation and to slow the progression of disability (prolonging the time physical ability is maintained).
REBIF is also approved for use in patients who have symptoms which are likely to be a first sign of multiple sclerosis (single clinical event suggestive of multiple sclerosis. Any other reasons which could explain the symptoms have to be ruled out. Your doctor will perform a test using an imaging machine (magnetic resonance imaging [MRI]). This test has to show at least two signs of inflammation in the central nervous system suggestive of multiple sclerosis.
What it Does
Multiple sclerosis is a life-long disease the affects your nervous system (i.e., brain and spinal cord) by destroying the protective covering (myelin) that surrounds your nerve fibers. An abnormal response by the body’s immune system is thought to play an important part in the process which damages the nervous system.
REBIF is a form of protein called interferon beta that occurs naturally in the body. Interferon beta has been shown to modify the immune system response, but the exact way that REBIF works in MS is unknown. REBIF will not cure MS but it has been shown to decrease the number of flare-ups and slow the occurrence of some of the physical disabilities that are common in people with MS.
When it Should not be Used
REBIF should not be used if:
- You have a known hypersensitivity to any component of the formulation,
- You are pregnant,
- You have severe liver disease.
What the Medicinal Ingredient Is
What the Important Nonmedicinal Ingredients Are
Mannitol, benzyl alcohol, poloxamer-188, methionine
For a full listing of nonmedicinal ingredients see Product Information.
What Dosage Forms it Comes In
REBIF is available as a solution (liquid) in a pre-filled multi-dose cartridge, for subcutaneous injection.
REBIF in pre-filled cartridge is available as:
- 3 doses of 22 g/0.5 mL in one cartridge (66 g/1.5 mL). One box, light green packaging, contains 4 cartridges)
- 3 doses of 44 g/0.5 mL in one cartridge (132 g /1.5mL). One box, dark green packaging, contains 4 cartridges
Warnings and Precautions
BEFORE you use REBIF talk to your doctor or pharmacist if:
- You are pregnant, are thinking of becoming pregnant or if you are breast-feeding
- You have cardiac disease, severe renal failure or severe decrease in the development of blood cells
- You have a pre-existing seizure disorder
- You have depression or suicidal thoughts
- You have liver problems
- You have problems with your thyroid gland
Pregnancy and Breastfeeding
You must not start treatment with REBIF if you are pregnant. While taking REBIF, you must use effective methods of contraception if you are a woman of child-bearing potential. If you become pregnant or plan to become pregnant while using REBIF ask your doctor for advice.
Prior to taking the medicine, please inform your doctor if you are breast-feeding. The use of REBIF is not recommended if you are breast-feeding.
Your liver may be affected by taking REBIF and a few patients have developed severe liver injury. Your healthcare provider may ask you to have regular blood tests to make sure that your liver is working properly. If your skin or the whites of your eyes become yellow or if you are bruising easily you should call your doctor right away.
Some patients treated with interferons, including REBIF, have become seriously depressed (feeling sad). Some patients have thought about killing themselves and a few have committed suicide. Depression (a sinking of spirits or sadness) is not uncommon in people with multiple sclerosis. However, if you are feeling noticeably sadder or helpless, or feel like hurting yourself or others, you should tell a family member or friend right away and call your doctor as soon as possible. Your doctor may ask that you stop using REBIF. You should also tell your doctor if you have ever had any mental illness, including depression, and if you take any medications for depression.
Symptoms of the flu-like syndrome associated with REBIF may prove stressful to patients with cardiac conditions, such as angina, congestive heart failure or arrhythmia. If you experience symptoms like irregular heart beat, fluid retention (swelling) in the lower parts of your body (eg, ankles, legs), or shortness of breath, call your doctor immediately.
Some patients have had seizures while taking interferons. It is not known whether the seizures are related to the effects of MS, to interferons, or to a combination of both. If you have a seizure while taking REBIF, you should call your doctor right away.
Some people taking REBIF may develop changes in the function of their thyroid. Symptoms of these changes include difficulty concentrating, feeling abnormally cold or hot, gaining or losing weight without a change in your diet or the amount of exercise you are getting, feeling unusually tired or nervous and unusual very dry skin. If you experience these symptoms, you should call your doctor right away.
As with other interferon products, in rare cases, blood clots in the small blood vessels may occur during your treatment. These blood clots could affect your kidney (thrombotic thrombocytopenic purpura or haemolytic uremic syndrome) . This might happen several weeks to several years after starting and may cause death. Talk to your doctor if you experience the following symptoms: increased bruising, bleeding, extreme weakness, headache, dizziness or light-headedness. Your doctor may want to check your blood pressure, blood (platelet count) and the function of your kidney.
Interactions With This Medication
With the exception of steroids or ACTH (anti-inflammatory medicines) that MS patients can receive during relapses, the use of REBIF was not studied together with other substances that modify the immune system response. Caution should be exercised when interferons are given in combination with other drugs which need a certain liver enzyme system (the cytochrome P450 system) for their metabolism. These drugs include some commonly used drugs against fever and pain. You should tell your doctor if you are taking any other prescription or nonprescription medicines, including vitamin and mineral supplements and herbal products.
Proper use of This Medication
Patients with Relapsing-Remitting MS
The recommended dose is 44 g given three times per week by subcutaneous injection. Your physician may reduce your dose to 22 g three times per week if you are not able to tolerate the higher dose.
Patients who Have Experienced a Single Clinical Event
The recommended dose is 44 g given three times per week by subcutaneous injection.
Treatment is initiated by a gradual increase of dose in order to reduce some of the side effects.
Patients with Relapsing-Remitting MS
- During weeks one and two, REBIF 8.8 µg/0.2 mL should be injected three times per week.
- During weeks three and four, REBIF 22 µg/0.5 mL should be injected three times per week.
- From the fifth week onwards, please see section entitled ‘Usual Dose- Patients with Relapsing-Remitting MS ’.
Patients who have experienced a single clinical event
- During weeks one and two, REBIF 8.8 µg/0.2 mL should be injected three times per week, as per your physician’s recommendations.
- During weeks three and four, REBIF 22 µg/0.5 mL should be injected three times per week, as per your physician’s recommendations.
- From the fifth week onwards, please see section entitled ‘Usual Dose-Patients who have experienced a single clinical event ’
Two alternative devices, the RebiSmart autoinjector device and the RebiSlide re-usable pen injector are available for administration of REBIF.
The RebiSmart autoinjector electronic device is programmed for the three times per week dosing frequency. The RebiSlide re-usable manual pen injector can be used with the three times per week and once per week dosing frequency. Please discuss with your physician which device is adequate for you.
If you missed one dose of REBIF, continue to inject from the day of the next scheduled dose. You should not take a double dose to make up for the missed dose.
|If you have accidentally injected too much REBIF, do not panic. Simply contact your physician or healthcare professional for further instructions.|
When using REBIF always follow the basic principles of injection:
- Maintain sterile conditions
- Check medication
- Check expiry date
- Check dosage and instructions
- Rotate injection sites
Important: Store all injection materials and your REBIF out of the reach of children at all times.
STEP 1: Cleanse
Before you start, wash your hands well with soap and water. It is important that your hands and the items you use be as clean as possible. Needles should not touch any surface except alcohol-cleaned skin; keep them capped prior to use.
STEP 2: Assembly of injection materials
Find a clean area and lay out everything you will need (alcohol swabs, pre-filled cartridge, RebiSmart autoinjector device or RebiSlideTM re-usable pen injector, disposal container). The injection can be given anywhere you feel comfortable. If you use your kitchen, ensure that all medicines and needles are kept well away from food.
|The REBIF pre-filled cartridge is ready to be used with the RebiSmart autoinjection device and the RebiSlidere-usable pen injector. For instructions on how to load the cartridge into the RebiSmartautoinjection device or the RebiSlidere-usable pen injector, please read the instructions provided with each device.|
STEP 3: Selecting and preparing the injection site
REBIF is injected just under the skin, in the layer of subcutaneous tissue. For your own comfort, you should avoid injecting into the same area too often. There are many possible injection sites on your body (e.g., arms, thighs, buttocks, abdomen) - refer to the diagram following these instruction or in your patient diary. It is difficult to self-inject into the back of the arm, you will likely require assistance if you choose this site. It is a good idea to plan an injection site rotation schedule and note it in a diary.
Note: Do not inject in any area in which you feel lumps, firm knots or pain. Consult your doctor or healthcare professional about any such abnormalities you find.
Use an alcohol swab to clean the skin at the selected injection site. Let the skin dry completely (15 to 20 seconds) to avoid possible burning, then discard the alcohol swab.
Carefully inspect the contents of the cartridge. The liquid should be clear to slightly yellow. Do not use if the liquid is cloudy, discoloured, or contains particles.
STEP 4: Injecting REBIF subcutaneously
Your doctor or nurse will have already advised you where to inject (e.g., abdomen, front of thigh, back of arm, buttock). Refer to the injection sites diagram (keeping a diary of injection sites as they are used is recommended). Follow the detailed instructions below each time you inject REBIF pre-filled cartridges. If you have questions about injecting REBIF, contact your healthcare professional or call Multiple Support Program at 1-888-MS-REBIF (1-888-677-3243).
Note: Your first REBIF injection should be done under the supervision of your doctor or an appropriately qualified healthcare professional. After receiving adequate training, you, a family member, friend or caregiver can use REBIF cartridges with the RebiSmartautoinjector device or RebiSlideTM re-usable pen injector to administer the medicine at home.
Possible Sites for Injection of 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). 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 minimize 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 cartridge from the blister pack by peeling back the plastic covering.
- To place the cartridge in the device and perform the injection, follow the instructions in the instruction manual provided with your RebiSmart or RebiSlide. The manufacturer’s instructions for using the device must be followed carefully for loading the cartridge, attaching the injection needle and administering REBIF.
- Ensure that the injection settings always correspond to the dose in the cartridge inserted in the RebiSmart
Full instructions for use are provided with the RebiSmart autoinjector device and the RebiSlideTM re-usable pen injector.
STEP 5: Disposal of used items
Once you have finished your injection, immediately discard the needle in the disposal container provided. When the disposal container is full, consult your clinic for the safe disposal of its contents. They should not be disposed of in household garbage.
It is important that you are familiar with the correct injection technique as outlined in the instructions before beginning your treatment with REBIF. If the injection site bleeds afterwards, firmly press a cotton ball or gauze over the injection site immediately after removing the needle. This usually stops any further bleeding.
Local skin reactions are less likely to occur if you vary the injection site. If they do occur, they usually will disappear within a few days. In the meantime, icing the area may help reduce irritation. Swelling and irritation at the injection site may also be reduced by gently massaging the area for five minutes after the injection has been given. If a generalized rash develops, you should always report it to your doctor or nurse. Bruises may also occasionally occur at the injection site - even when the injection has been given correctly - but they will disappear.
Finally, remember that every treatment is individualized. REBIF has been carefully selected for you by your doctor according to your own specific needs. It is very important that you keep your appointments and follow your doctor's instructions, particularly with regard to the amount and frequency of the medication you are taking.
Side Effects and What to do About Them
Like all medicines, REBIF can have side effects. The most common side effects are flu-like symptoms (headache, fever, chills, muscle and joint pains, fatigue and nausea) and injection site reactions (redness, swelling, discolouration, inflammation, pain and skin breakdown). These symptoms are generally mild, are more common at the start of the treatment, and decrease with continued use. If any of these undesirable effects are severe or persist, you should contact your health care team.
In some cases, your physician may prescribe you a pain reliever (acetaminophen or ibuprofen) or may temporarily change your dose. You should not stop or alter the medication without your doctor’s advice.
Should you develop multiple lesions and/or experience any break in the skin, which may be associated with swelling or drainage of fluid from the injection site, you should consult your physician, as a decision may be required to discontinue REBIF until healing has occurred.
Other less common adverse events reported in association with interferon beta include diarrhea, loss of appetite, vomiting, inflammation of the liver, sleeping difficulty, dizziness, nervousness, itching, rash, nettle-rash, hair loss, dilatation of the blood vessels and palpitation.
Certain laboratory tests may change: the number of white blood cells or platelets may decrease and liver function tests may be disturbed. These changes are generally not noticed by the patient (no symptoms), are usually reversible and mild, and most often do not require particular treatment. Possible symptoms resulting from these changes could include tiredness, reduced ability to fight infection, bruising or unexplained bleeding.
Interferons may cause your thyroid gland to 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.
Although uncommon, there is a potential risk of liver injury. As a safety precaution, your doctors will monitor your liver function with regular laboratory testing. If you notice any symptoms such as loss of appetite with malaise, fatigue, nausea, vomiting, abdominal pain, dark urine, please contact your doctor.
As with all interferons, female patients are recommended to take adequate contraception, as it is not known if interferons interfere with oral contraceptives, or if it interferes with the fetus. Please speak to your doctor if you are pregnant or are planning on becoming pregnant.
Depression, thoughts or attempt of suicide may occur in patients with multiple sclerosis. If you have any of these feelings, please contact your physician immediately. If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.
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 noticed any of these side effects, talk to your doctor.
Serious Side Effects, How Often They Happen and What to do About Them
|Symptom/effect||Talk with your doctor or pharmacist||Stop taking
|Common||Flu-like symptoms (headache, fever, chills, muscle aches, fatigue, nausea)||✓|
|Injection site reactions [redness, swelling, discolouration, inflammation, pain, skin breakdown, and tissue destruction (necrosis)||✓|
|Uncommon||Liver injury (symptoms: loss of appetite, nausea, vomiting, fatigue, abdominal pain, dark urine)||✓|
This is not a complete list of side effects. For any unexpected effects while taking REBIF, contact your doctor or pharmacist.
How to Store It
REBIF cartridges should be stored refrigerated at 2°-8°C. REBIF cartridges may be stored for a limited period of time at room temperature (up to 25°C), for up to 1 month. Do not freeze.
Refer to the storage information for REBIF cartridges as RebiSmart can be stored containing a cartridge of REBIF. Always store RebiSmart in its storage box. Do not freeze.
Refer to the storage information for REBIF cartridges as RebiSlide can be stored containing a cartridge of REBIF. Always store RebiSlideTM in the supplied storage case. Keep away from direct sources of light and heat. Do not freeze.
Reporting suspected side effects
You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:
- Report online at www.healthcanada.gc.ca/medeffect
- Call toll-free at 1-866-234-2345
- Complete a Canada Vigilance Reporting Form and:
- Fax toll-free to 1-866-678-6789, or
- Mail to: Canada Vigilance Program
Postal Locator 0701E
Ottawa, ON K1A 0K9
Postage paid labels, Canada Vigilance Reporting Forms and the adverse reaction reporting guidelines are available on the MedEffect™ Canada Web site at www.healthcanada.gc.ca/medeffect.
NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.
This document plus the full product monograph, prepared for health professionals can be obtained by contacting the sponsor, EMD Serono, A Division of EMD Inc., Canada.
If you have any questions, call the Multiple Support Program at 1-888-MS-REBIF (1-888-677-3243).