Generic Name
Beta-1A
Brand Names
Rebif, Rebif REBIDOSE, Avonex
FDA approval date: March 07, 2002
Classification: Interferon beta
Form: Injection, Kit
What is Rebif (Beta-1A)?
AVONEX is indicated for the treatment of relapsing forms of multiple sclerosis , to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. AVONEX is for the treatment of relapsing forms of multiple sclerosis , to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
Approved To Treat
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Brand Information
Rebif (interferon beta-1a)
1INDICATIONS AND USAGE
REBIF is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
2DOSAGE FORMS AND STRENGTHS
- Injection: 8.8 mcg per 0.2 mL in a graduated, single-dose REBIF prefilled syringe
- Injection: 22 mcg per 0.5 mL in a graduated, single-dose REBIF prefilled syringe
- Injection: 44 mcg per 0.5 mL in a graduated, single-dose REBIF prefilled syringe
- Injection: 8.8 mcg per 0.2 mL in a single-dose prefilled REBIF Rebidose autoinjector
- Injection: 22 mcg per 0.5 mL in a single-dose prefilled REBIF Rebidose autoinjector
- Injection: 44 mcg per 0.5 mL in a single-dose prefilled REBIF Rebidose autoinjector
3CONTRAINDICATIONS
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.
4ADVERSE REACTIONS
The following adverse reactions are discussed in more detail in the
- Depression and Suicide [see
- Hepatic Injury [see
- Anaphylaxis and Other Allergic Reactions [see
- Injection Site Reactions including Necrosis [see
- Decreased Peripheral Blood Counts [see
- Thrombotic Microangiopathy
- Pulmonary Arterial Hypertension
- Seizures [see
- Laboratory Tests [see
4.1Clinical 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)
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
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.
4.2Immunogenicity
Anaphylaxis and other allergic reactions have been observed with the use of REBIF
4.3Postmarketing 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)
Respiratory, Thoracic and mediastinal disorders: Pulmonary Arterial Hypertension
Skin and Subcutaneous Tissue Disorders: Erythema multiforme, Stevens-Johnson syndrome
Blood and Lymphatic System Disorders: Hemolytic anemia
5DESCRIPTION
REBIF (interferon beta-1a) is a purified 166 amino acid glycoprotein with a molecular weight of approximately 22,500 daltons. It is produced by recombinant DNA technology using genetically engineered Chinese Hamster Ovary cells into which the human interferon beta gene has been introduced. The amino acid sequence of REBIF is identical to that of natural fibroblast derived human interferon beta. Natural interferon beta and interferon beta-1a (REBIF) are glycosylated with each containing a single N-linked complex carbohydrate moiety.
Using a reference standard calibrated against the World Health Organization natural interferon beta standard (Second International Standard for Interferon, Human Fibroblast GB 23 902 531), REBIF has a specific activity of approximately 270 million international units (MIU) of antiviral activity per mg of interferon beta-1a determined specifically by an
REBIF (interferon beta-1a) is formulated as a sterile solution in a prefilled syringe or REBIF Rebidose autoinjector intended for subcutaneous (sc) injection. Each 0.5 mL (0.5 cc) of REBIF contains either 22 mcg or 44 mcg of interferon beta-1a, 2 mg or 4 mg albumin (human), 27.3 mg mannitol, 0.4 mg sodium acetate, and water for injection. Each 0.2 mL (0.2 cc) of REBIF contains 8.8 mcg of interferon beta-1a, 0.8 mg albumin (human), 10.9 mg mannitol, 0.16 mg sodium acetate, and water for injection.
6CLINICAL STUDIES
Two multicenter studies evaluated the safety and efficacy of REBIF in patients with relapsing-remitting multiple sclerosis.
Study 1 was a randomized, double-blind, placebo controlled study in patients with multiple sclerosis for at least one year, Kurtzke Expanded Disability Status Scale (EDSS) scores ranging from 0 to 5, and at least 2 acute exacerbations in the previous 2 years. Patients with chronic progressive forms of multiple sclerosis were excluded from the study. Patients received subcutaneous injections of either placebo (n = 187), REBIF 22 mcg (n = 189), or REBIF 44 mcg (n = 184) administered three times per week for two years. Doses of study agents were progressively increased to their target doses during the first 4 to 8 weeks for each patient in the study
The primary efficacy endpoint was the number of clinical exacerbations. Numerous secondary efficacy endpoints were also evaluated and included exacerbation-related parameters, effects of treatment on progression of disability and magnetic resonance imaging (MRI)-related parameters. Progression of disability was defined as an increase in the EDSS score of at least one point sustained for at least 3 months. Neurological examinations were completed every 3 months, during suspected exacerbations, and coincident with MRI scans. All patients underwent proton density T2-weighted (PD/T2) MRI scans at baseline and every 6 months. A subset of 198 patients underwent PD/T2 and T1-weighted gadolinium-enhanced (Gd)-MRI scans monthly for the first 9 months. Of the 560 patients enrolled, 533 (95%) provided 2 years of data and 502 (90%) received 2 years of study agent.
Study results are shown in Table 4 and Figure 1. REBIF at doses of 22 mcg and 44 mcg administered three times per week significantly reduced the number of exacerbations per patient as compared to placebo. Differences between the 22 mcg and 44 mcg groups were not significant (p >0.05).
The time to onset of progression in disability sustained for three months was significantly longer in patients treated with REBIF than in placebo-treated patients. The Kaplan-Meier estimates of the proportions of patients with sustained disability are depicted in Figure 1.
Figure 1: Proportions of Patients with Sustained Disability Progression
Study 2 was a randomized, open-label, evaluator-blinded, active comparator study. Patients with relapsing-remitting multiple sclerosis with EDSS scores ranging from 0 to 5.5, and at least 2 exacerbations in the previous 2 years were eligible for inclusion. Patients with chronic progressive forms of multiple sclerosis were excluded from the study. Patients were randomized to treatment with three times per week subcutaneous injections of REBIF 44 mcg (n=339) or once weekly intramuscular injections of 30 mcg AVONEX (n=338). Study duration was 48 weeks.
The primary efficacy endpoint was the proportion of patients who remained exacerbation-free at 24 weeks. The principal secondary endpoint was the mean number per patient per scan of combined unique active MRI lesions through 24 weeks, defined as any lesion that was T1 active or T2 active. Neurological examinations were performed every three months by a neurologist blinded to treatment assignment. Patient visits were conducted monthly, and mid-month telephone contacts were made to inquire about potential exacerbations. If an exacerbation was suspected, the patient was evaluated with a neurological examination. MRI scans were performed monthly and analyzed in a treatment-blinded manner.
Patients treated with REBIF 44 mcg three times per week were more likely to remain relapse-free at 24 and 48 weeks than were patients treated with AVONEX 30 mcg once per week (Table 5). This study does not support any conclusion regarding effects on the accumulation of physical disability.
7HOW SUPPLIED/STORAGE AND HANDLING
REBIF is supplied as a sterile solution containing no preservative available in the following package presentations:
8PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide).
Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking REBIF. Instruct patients to take REBIF only as prescribed.
9MEDICATION GUIDE REBIF (interferon beta-1a) Injection for subcutaneous use
Read this Medication Guide before you start using REBIF and each time you get a refill. There may be new information. The information does not take the place of talking with your healthcare provider about your medical condition or your treatment.
What is the most important information I should know about REBIF?
REBIF can cause serious side effects. Tell your healthcare provider right away if you have any of the symptoms listed below while taking REBIF.
- Behavioral health problems including depression and suicidal thoughts. You may have mood problems including:
- depression (feeling hopeless or feeling bad about yourself)
- thoughts of hurting yourself or suicide
- Liver problems or worsening of liver problems including liver failure. Symptoms may include:
- nausea
- loss of appetite
- tiredness
- dark colored urine and pale stools
- yellowing of your skin or the white part of your eye
- bleeding more easily than normal
- confusion
- sleepiness
During your treatment with REBIF you will need to see your healthcare provider regularly and have regular blood tests to check for side effects.
- Serious allergic and skin reactions. Symptoms may include:
- itching
- swelling of your face, eyes, lips, tongue or throat
- trouble breathing
- anxiousness
- feeling faint
- skin rash, hives, sores in your mouth, or skin blisters and peels
- Injection site problems. REBIF may cause redness, pain, itching or swelling at the place where your injection was given. Call your healthcare provider right away if an injection site becomes swollen and painful or the area looks infected. You may have a skin infection or an area of severe skin damage (necrosis) requiring treatment by a healthcare provider.
What is REBIF?
REBIF is a prescription medicine used to treat relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. It is a form of protein called beta interferon that is produced in the body.
It is not known if REBIF is safe and effective in children.
Who should not take REBIF?
Do not take REBIF if you:
- are allergic to interferon beta, human albumin, or any of the ingredients in REBIF. See the end of this Medication Guide for a complete list of ingredients in REBIF.
What should I tell my healthcare provider before taking REBIF?
Before you take REBIF, tell your healthcare provider if you have or have had any of the following conditions:
- mental illness, including depression and suicidal behavior
- liver problems
- bleeding problems or blood clots
- low blood cell counts
- seizures (epilepsy)
- thyroid problems
- drink alcohol
- you are pregnant or plan to become pregnant. It is not known if REBIF can harm your unborn baby.
- you are breastfeeding or plan to breastfeed. REBIF may pass into your breastmilk. Talk with your healthcare provider about the best way to feed your baby if you take REBIF.
Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
REBIF and other medicines may affect each other causing side effects.
Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I use REBIF?
- See the Instructions for Use at the end of this Medication Guide on how to prepare and give an injection of REBIF using a prefilled syringe. For the REBIF Rebidose autoinjector, read the Instructions for Use that comes with the REBIF Rebidose autoinjector.
- Your healthcare provider should show you how to prepare and measure your dose of REBIF and how to inject your REBIF before you use it for the first time.
- REBIF is given by injection under the skin (subcutaneous injection) on the same 3 days a week, for example, Monday, Wednesday and Friday.
- Your injections should be at least 48 hours apart. Take them the same time each day.
- Inject REBIF exactly as your healthcare provider tells you.
- Your healthcare provider will tell you how much REBIF to inject, and may change the dose based on how your body responds. Do not inject more than your healthcare provider tells you to.
- Do not change your dose unless your healthcare provider tells you to.
- Change (rotate) your injection site you choose with each injection. This will help decrease the chance that you will have an injection site reaction.
- Do not inject REBIF into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.
- REBIF comes as a:
What are the possible side effects of REBIF?
REBIF may cause serious side effects, including:
- See "
- Blood problems. REBIF can affect your bone marrow and cause low red and white blood cell, and platelet counts. In some people, these blood cell counts may fall to dangerously low levels. If your blood cell counts become very low, you can get infections and problems with bleeding and bruising. Your healthcare provider may ask you to have regular blood tests to check for blood problems.
- Pulmonary arterial hypertension. Pulmonary arterial hypertension can occur with interferon beta products, including REBIF. Symptoms may include new fatigue or shortness of breath. Contact your healthcare provider right away if you develop these symptoms.
- Seizures. Some people have had seizures while taking REBIF.
The most common side effects of REBIF include:
- flu-like symptoms. You may have flu-like symptoms when you first start taking REBIF. You may be able to manage these flu-like symptoms by taking over-the-counter pain and fever reducers. For many people, these symptoms lessen or go away over time. Symptoms may include:
- stomach pain
- change in liver blood tests
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of REBIF. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
How should I store REBIF?
- Store REBIF in the refrigerator between 36°F to 46°F (2°C to 8°C).
- Do not freeze REBIF.
- If you cannot refrigerate your REBIF, you can store your REBIF at temperatures above 36°F and below 77°F (2°C to 25°C) for up to 30 days.
- Keep REBIF away from heat and light.
Keep REBIF and all medicines out of the reach of children.
General information about the safe and effective use of REBIF
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use REBIF for a condition for which it was not prescribed. Do not give REBIF to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about REBIF. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about REBIF that is written for healthcare professionals.
For more information, go to www.REBIF.com or call toll-free 1-877-447- 3243.
What are the ingredients in REBIF?
Active ingredient: interferon beta-1a
Inactive ingredients: albumin (human), mannitol, sodium acetate, water for injection
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Revised 7/2023
10Instructions for Use REBIF (Re-bif) (interferon beta-1a) (in-ter-feer-on beta-one-â) Injection for subcutaneous use Prefilled Syringe
Read and follow the Instructions for Use that come with your REBIF prefilled syringe before you start using it and each time you get a refill. Before you use a REBIF prefilled syringe for the first time, make sure your healthcare provider shows you the right way to use it.
Important: For the REBIF Rebidose autoinjector, read the Instructions for Use that come with the REBIF Rebidose autoinjector.
Parts of your REBIF Prefilled Syringe
Supplies needed for a REBIF Injection (See
- REBIF prefilled syringe
- alcohol pad or cotton balls and rubbing alcohol
- small adhesive bandage strip if desired
- puncture resistant safety container for disposal of used syringes. See "
- antibacterial soap
- an over-the-counter pain or fever reducing medicine, if your healthcare provider has recommended that you take this before, at the same time, or after you give yourself REBIF to help decrease the fever, chills, sweating and muscle aches (flu-like symptoms) that may happen.
Titration (Dosing) Schedule
- When first starting treatment with REBIF, your healthcare provider may prescribe either the 22 mcg or 44 mcg dose of REBIF. You should gradually increase the dose over 4 weeks, starting at 20% of the prescribed dose for the first 2 weeks, half-dose for the second 2 weeks (weeks 3 and 4), and then the full dose prescribed by your healthcare provider.
If your prescribed dose is 22 mcg of REBIF, a REBIF Titration Pack containing 6 prefilled syringes with 8.8 mcg and 6 prefilled syringes with 22 mcg should be prescribed to you for use during the 4-week starting period. Table 1 explains the amount to inject using the REBIF Titration Pack syringes to gradually increase to 22 mcg.
If your prescribed dose is 44 mcg, you may be prescribed either a REBIF Titration Pack (described above) or REBIF Rebidose Titration Pack containing 6 autoinjectors with 8.8 mcg and 6 autoinjectors with 22 mcg for use during the 4 week titration period. Table 2 explains the amount to inject using the REBIF Titration Pack or REBIF Rebidose Titration Pack to gradually increase to 44 mcg.
Step 1. Preparing for your REBIF Injection
- Check the expiration date
- Remove your REBIF syringe from the refrigerator at least 30 minutes before you plan to use it so it can warm to room temperature.
- Be sure that the dose, either, 8.8 mcg, 22 mcg or 44 mcg, described on the carton is the same as the dose prescribed by your healthcare provider.
- Remove the REBIF syringe from the plastic packaging. Keep the needle capped.
- Look at the contents of the syringe carefully. The liquid should be clear to slightly yellow.
Step 2. Choose and Prepare your Injection Site
- The best sites for giving yourself an injection are those areas with a layer of fat between the skin and muscle, like your thigh, the outer surface of your upper arm, your stomach or buttocks.
- Do not use the area near your waistline or within 2 inches of your navel. If you are very thin, use only the thigh or outer surface of the arm for injection.
- Use a different site each time you inject such as the thigh, hip, stomach or upper arm
- Do not inject REBIF into an area of your body where the skin is irritated, reddened, bruised, infected or abnormal in any way.
- Wash your hands thoroughly with antibacterial soap before preparing to inject the medicine.
- Clean the injection site with an alcohol pad or cotton ball with rubbing alcohol using a circular motion. To avoid stinging, you should let your skin dry before you inject REBIF.
Step 3. Inject your REBIF
- Remove the needle cap from the syringe needle.
- If your healthcare provider has told you to use less than the full 0.5 mL dose, slowly push the plunger in until the amount of medicine left in the syringe is the amount healthcare provider told you to use.
- Use your thumb and forefinger to pinch a pad of skin surrounding the cleaned injection site (
- While still pinching the skin, quickly insert the needle like a dart at about a 90 degree angle (just under the skin) into the pad of tissue as shown
- After the needle is in, remove the hand that you used to pinch your skin and inject the medicine using a slow, steady push on the plunger until all the medicine is injected and the syringe is empty
- Withdraw the needle and apply gentle pressure to the injection site with a dry cotton ball or sterile gauze. Applying a cold compress or ice pack to the injection site after injection may help reduce local skin reactions.
- Put a small adhesive bandage strip over the injection site, if desired.
- Keep a record of the date and location of each injection.
- After 2 hours, check the injection site for redness, swelling, or tenderness. If you have a skin reaction and it does not clear up in a few days, call your healthcare provider.
Step 4. Disposing of your Needles and Syringes
- Put your used needles, syringes, and autoinjectors, including REBIF, in an FDA-cleared sharps container right away after use.
- When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used autoinjectors and syringe needles. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
- Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
Manufactured by:
Marketed by:
Revised 11/2021
11PRINCIPAL DISPLAY PANEL - Kit Carton - 8822
Rebif
NDC 44087-8822-1
8.8 mcg/0.2 mL
For subcutaneous injection
6 single-dose 8.8 mcg/0.2 mL prefilled syringes
EMD
12PRINCIPAL DISPLAY PANEL - Kit Carton - 0188
Rebif
NDC 44087-0188-1
6 single-use 8.8 mcg / 0.2 mL autoinjectors
Rx only
8.8 mcg / 0.2 mL
Titration Pack
Attention pharmacist:
EMD
13PRINCIPAL DISPLAY PANEL - 12 Syringe Carton - 0022
Rebif
NDC 44087-0022-3
For subcutaneous injection
12 single-dose prefilled syringes
EMD
14PRINCIPAL DISPLAY PANEL - 12 Syringe Carton - 0044
Rebif
NDC 44087-0044-3
For subcutaneous injection
12 single-dose prefilled syringes
EMD
15PRINCIPAL DISPLAY PANEL - 12 Autoinjector Carton - 3322
NDC 44087-3322-1
Rebif
12 single-use autoinjectors
22 mcg / 0.5 mL
Rx only
For subcutaneous injection
Attention pharmacist: Each patient is required
EMD
16PRINCIPAL DISPLAY PANEL - 12 Autoinjector Carton - 3344
NDC 44087-3344-1
Rebif
12 single-use autoinjectors
44 mcg / 0.5 mL
Rx only
For subcutaneous injection
Attention pharmacist: Each patient is required
EMD
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