Rebif

REBIF (interferon beta-1a) is indicated for the treatment of patients with relapsing forms of multiple sclerosis to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability.

This medication may be harmful to an unborn baby, or may cause a miscarriage. Do not use interferon beta-1a if you are pregnant. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Before using interferon beta-1a, tell your doctor if you are allergic to any drugs, or if you have liver disease, a thyroid disorder, epilepsy or other seizure disorder, heart disease, chest pain (angina), congestive heart failure, a heart rhythm disorder, or a history of depression or suicidal behavior.

Some patients using interferon medications have become very depressed or had thoughts of suicide. Stop using interferon beta-1a if you have symptoms of depression (sadness, crying, loss of interest in things you once liked) or if you have any thoughts of hurting yourself.

Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your liver or thyroid function may also need to be tested. Visit your doctor regularly.

Before receiving Rebif, tell your doctor about all of your medical conditions including if you have, or have had:

• mental illness or had treatment in the past for any mental illness, including depression and suicidal behavior
• problems with your thyroid gland
• blood problems such as bleeding or bruising easily and anemia (low red blood cells) or low white blood cells
• seizures (epilepsy)
• heart problems
• liver disease
• autoimmune disease (psoriasis, lupus, rheumatoid arthritis)

You should also tell your doctor if you:

• drink alcohol
• are pregnant or are planning to become pregnant 
• are breastfeeding or plan to breastfeed

You should tell your doctor if you are taking any other prescription or nonprescription medicines, vitamins or mineral supplements, or herbal products.

It is not known if Rebif crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Rebif.

INTRAMUSCULAR, ONCE-WEEKLY FORM

To get the most benefit from this medicine, it is important that you use Rebif exactly as your doctor tells you.

• This form of Rebif is given by injection into the muscle (intramuscular injection) once a week, on the same day (for example, every Monday right before bedtime).
• If you miss a dose, you should take your next dose as soon as you remember. You should continue your regular schedule the following week.
• Do not inject intramuscular Rebif on two consecutive days. Take only the dose your doctor has prescribed for you.
• Do not change your dose unless you are told to by your doctor. If you take more than your prescribed dose, call your healthcare provider right away. Your doctor may want to monitor you more closely. You should always follow your doctor's instructions and advice about how to take this medication.
• If your doctor feels that you, or a family member or friend, may give you the injections, then you and/or the other person should be instructed by your doctor or other healthcare provider in how to prepare and inject your dose of Rebif.
• Do not try to give yourself injections at home until you are sure that you (or the person who will be giving you the injections) fully understands and is comfortable with how to prepare and inject the product.
• Always use a new, unopened Rebif vial or prefilled syringe for each injection. Never reuse the vials or syringes. It is important to keep your work area, your hands, and your injection site clean to minimize risk of infection. You should wash your hands prior to handling the syringe.
• It is important that you change your injection site each week. Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way. Use the alcohol wipe to thoroughly clean the skin at the injection site you have chosen. Using a circular motion, and starting at the injection site and moving outward, clean the injection site with an alcohol wipe.
• Let the skin area dry before you inject the Rebif.

SUBCUTANEOUS, 3X/WEEK FORM

This form of Rebif is given by injection under the skin (subcutaneous injection) on the same three days a week (for example, Monday, Wednesday and Friday). Your injections should be at least 48 hours apart so it is best to take them the same time each day. Your doctor will tell you what dose to use, and may change the dose based on how your body responds. You should not change the dose without talking with your doctor.

If you miss a dose, you should take your next dose as soon as you remember or are able to take it, then skip the following day. Do not take doses on two consecutive days. You should return to your regular schedule the following week. If you accidentally take more than your prescribed dose, or take it on two consecutive days, call your doctor right away.

You should always follow your doctor's instructions and advice about how to take this medication. If your doctor feels that you, or a family member or friend may give you the injections then you and/or the other person should be trained by your doctor or health care provider in how to give an injection. Do not try to give yourself (or have another person give you) injections at home until you (or both of you) understand and are comfortable with how to prepare your dose and give the injections.

Always use a new, unopened, pre-filled syringe or autoinjector for each injection. Do not reuse pre-filled syringes or autoinjectors.

It is important that you change your injection site each time Rebif is injected. This will lessen the chance of your having a serious skin reaction at the spot where you inject it. You should always avoid injecting this medication into an area of skin that is sore, reddened, infected or otherwise damaged.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

This medicine may cause some people to be anxious, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you or your caregiver notice any of these side effects, tell your doctor right away.

Check with your doctor right away if you have dark urine, persistent loss of appetite, flu-like symptoms, headache, continuing vomiting, general feeling of tiredness or weakness, light-colored stools, right upper stomach pain or tenderness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may cause serious allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

This medicine may lower the number of white blood cells in the blood. This will increase your chance of getting an infection. It can also lower the number of platelets in the blood. Platelets are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects, such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

This medicine may cause redness, pain, or swelling at the injection site. Some patients have developed skin infections or a permanent depression (necrosis) under the skin at the injection site. Contact your doctor right away if you notice depressed or indented skin, blue-green to black skin discoloration, or pain, redness, or sloughing (peeling) of the skin.

This medicine commonly causes a flu-like reaction, with aching muscles, chills, fever, headaches, joint pain, and nausea. Using your shot at bedtime may allow you to sleep through the symptoms. Your doctor may want you to take a medicine to help control the pain or fever (eg, acetaminophen or ibuprofen). Carefully follow your doctor's instructions about how to prevent or treat these symptoms.

This medicine contains albumin, which comes from human blood. Some human blood products have transmitted certain viruses to people who have received them, although the risk is low. Human donors and donated blood are both tested for viruses to keep the transmission risk low. Talk with your doctor about this risk if you are concerned. The Avonex® prefilled autoinjector pen and prefilled syringe do not contain albumin which comes from donated human blood.

The tip cap of the Avonex® prefilled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions in people who are sensitive to latex. Tell your doctor if you have a latex allergy before you start using this medicine.

Rebif (interferon beta-1a) is indicated for the treatment of patients with relapsing forms of multiple sclerosis to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability.

Rebif is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, human albumin, or any other component of the formulation.

The following adverse reactions are discussed in more detail in the Warnings and Precautions section of the label:

• Depression and Suicide [see Warnings and Precautions (5.1)]
• Hepatic Injury [see Warnings and Precautions (5.2)]
• Anaphylaxis and Other Allergic Reactions [see Warnings and Precautions (5.3)]
• Injection Site Reactions including Necrosis [see Warnings and Precautions (5.4)]
• Decreased Peripheral Blood Counts [see Warnings and Precautions (5.5)]
• Thrombotic Microangiopathy [see Warnings and Precautions (5.6) ]
• Seizures [see Warnings and Precautions (5.7)]
• Laboratory Tests [see Warnings and Precautions (5.8)]

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Rebif cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.

A total of 712 patients with relapsing-remitting multiple sclerosis (RRMS) in two controlled clinical trials took Rebif (22 mcg or 44 mcg given three times per week) [see Clinical Studies (14)]. Ages ranged from 18 to 55 years. Nearly three-fourths of the patients were female, and more than 90% were Caucasian, largely reflecting the general demographics of the population of patients with multiple sclerosis.

The most commonly reported adverse reactions were injection site disorders, influenza-like symptoms (headache, fatigue, fever, rigors, chest pain, back pain, myalgia), abdominal pain, depression, elevation of liver enzymes and hematologic abnormalities. The most frequently reported adverse reactions resulting in clinical intervention (e.g., discontinuation of Rebif, adjustment in dosage, or the need for concomitant medication to treat an adverse reaction were injection site disorders, influenza-like symptoms, depression, and elevation of liver enzymes [see Warnings and Precautions (5)].

Study 1 was a 2-year placebo-controlled study in RRMS patients treated with Rebif 22 mcg (n=189), 44 mcg (n=184), or placebo (n=187). Table 3 enumerates adverse reactions and laboratory abnormalities that occurred at an incidence that was at least 2% more in either Rebif-treated group than was observed in the placebo group.

Adverse reactions in Study 2, a 1-year active-controlled (vs. interferon beta-1a, 30 mcg once weekly intramuscular injection, n=338) study including 339 patients with MS treated with Rebif were generally similar to those in Study 1, taking into account the disparity in study durations.

Immunogenicity

Anaphylaxis and other allergic reactions have been observed with the use of Rebif [see Warnings and Precautions (5.3)]. As with all therapeutic proteins, there is a potential for immunogenicity. In Study 1, the presence of neutralizing antibodies (NAb) to Rebif was determined by collecting and analyzing serum pre-study and at 6 month time intervals during the 2 years of the clinical trial. Serum NAb were detected in 59/189 (31%) and 45/184 (24%) of Rebif-treated patients at the 22 mcg and 44 mcg three times per week doses, respectively, at one or more times during the study. The data reflect the percentage of patients whose test results were considered positive for antibodies to Rebif using an antiviral cytopathic effect assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of NAb positivity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to Rebif with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Rebif. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Autoimmune Disorders: Drug-induced lupus erythematosus, autoimmune hepatitis

Eye Disorders: Retinal vascular disorders (i.e. retinopathy, cotton wool spots or obstruction of retinal artery or vein)

Skin and Subcutaneous Tissue Disorders: Erythema multiforme, Stevens-Johnson syndrome

Rebif (interferon beta-1a) is made from human proteins. Interferons help the body fight viral infections.

Rebif is used to treat relapsing multiple sclerosis (MS). This medication will not cure MS, it will only decrease the frequency of relapse symptoms.

Rebif may also be used for purposes not listed in this medication guide.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.