Rebif

Interferon beta-1a · Injection, Solution · Subcutaneous

Prescription (Rx) Interferon beta

Uses

1 INDICATIONS 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. Rebif is an interferon beta 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. ( 1 )

Dosage and administration

For subcutaneous injection only ( 2.1 ) The recommended dose is either 22 mcg or 44 mcg injected subcutaneously three times per week ( 2.1 ) Titration: Generally, the starting dose should be 20% of the prescribed dose three times per week, and increased over a 4 week period to the targeted recommended dose of either 22 mcg or 44 mcg injected subcutaneously three times per week ( 2.1 ) Analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms ( 2.3 ) 2.1 Dosing Information The recommended dose of REBIF is either 22 mcg or 44 mcg injected subcutaneously three times per week. REBIF should be administered, if possible, at the same time (preferably in the late afternoon or evening) on the same three days (e.g., Monday, Wednesday, and Friday) at least 48 hours apart each week. Generally, patients should be started at 20% of the prescribed dose three times per week and increased over a 4-week period to the targeted dose, either 22 mcg three times per week (see Table 1 ) or 44 mcg three times per week (see Table 2 ). Patients prescribed a targeted dose of 22 mcg three times per week should use the prefilled syringes for titration. A Titration Pack containing 6 doses of 8.8 mcg (0.2 mL) and 6 doses of 22 mcg (0.5 mL) is available for use during the titration period in both REBIF prefilled syringes and REBIF Rebidose autoinjectors. Table 1: Titration Schedule for a 22 mcg Prescribed Dose Use only prefilled syringes, not autoinjectors, to titrate to the 22 mcg Prescribed Dose Week of Use Dose Syringe to Use Amount of syringe Week 1 Titration 4.4 mcg 8.8 mcg syringe Use half of syringe Week 2 Titration 4.4 mcg 8.8 mcg syringe Use half of syringe Week 3 Titration 11 mcg 22 mcg syringe Use half of syringe Week 4 Titration 11 mcg 22 mcg syringe Use half of syringe Week 5 and after 22 mcg 22 mcg syringe or autoinjector Use full syringe or autoinjector Table 2: Titration Schedule for a 44 mcg Prescribed Dose Prefilled syringes or autoinjectors can be used to titrate to the 44 mcg Prescribed Dose Week of Use Dose Syringe or Autoinjector to Use Amount of syringe or autoinjector Week 1 Titration 8.8 mcg 8.8 mcg syringe or autoinjector Use full syringe or autoinjector Week 2 Titration 8.8 mcg 8.8 mcg syringe or autoinjector Use full syringe or autoinjector Week 3 Titration 22 mcg 22 mcg syringe or autoinjector Use full syringe or autoinjector Week 4 Titration 22 mcg 22 mcg syringe or autoinjector Use full syringe or autoinjector Week 5 and after 44 mcg 44 mcg syringe or autoinjector Use full syringe or autoinjector Decreased peripheral blood counts or elevated liver function tests may necessitate dose reduction or discontinuation of REBIF administration until toxicity is resolved [see Warnings and Precautions (5.2 , 5.5) and Adverse Reactions (6) ]. 2.2 Important Administration Instructions REBIF is intended for use under the guidance and supervision of a physician. It is recommended that physicians or qualified medical personnel train patients in the proper technique for self-administering subcutaneous injections using the prefilled syringe or injection device approved for use with REBIF. Injection depth of the REBIF Rebidose autoinjector is fixed at 8 mm; the healthcare provider should determine the injection technique. The initial injection should be performed under the supervision of an appropriately qualified healthcare provider. Appropriate instruction for self-injection or injection by another person should be provided to the patient or their caregiver, including careful review of the REBIF Medication Guide and the REBIF Rebidose autoinjector Instructions for Use that accompanies the product. Users should demonstrate competency in all aspects of the injection prior to independent use. If a patient is to self-administer REBIF, the physical and cognitive ability of that patient to self-administer and properly dispose of prefilled syringes or the REBIF Rebidose autoinjectors should be assessed. Patients with severe neurological deficits should not self-administer injections without assistance from a trained caregiver. Advise patients and caregivers to: visually inspect REBIF for particulate matter and discoloration prior to administration use aseptic technique when administering REBIF rotate site of injection with each dose to minimize the likelihood of severe injection site reactions, including necrosis or localized infection [see Warnings and Precautions (5.4) ] use a puncture-resistant container for safe disposal of used needles, prefilled syringes and REBIF Rebidose autoinjectors do not re-use needles, syringes or REBIF Rebidose autoinjectors 2.3 Premedication for Flu-like Symptoms Concurrent use of analgesics and/or antipyretics may help ameliorate flu-like symptoms associated with REBIF use on treatment days.

Dosage 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 Injection: 8.8 mcg in 0.2 mL, and 22 mcg or 44 mcg in 0.5 mL in single-dose prefilled syringe ( 3 ) Injection: 8.8 mcg in 0.2 mL, and 22 mcg or 44 mcg in 0.5 mL in single-dose autoinjector ( 3 )

Contraindications

4 CONTRAINDICATIONS 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. History of hypersensitivity to natural or recombinant interferon beta, human albumin, or any other component of the formulation ( 4 )

Warnings and precautions

Depression and Suicide: Advise patients to immediately report any symptoms of depression and/or suicidal ideation; consider discontinuation of REBIF if depression occurs ( 5.1 ) Hepatic Injury: Monitor liver function tests; monitor patients for signs and symptoms of hepatic injury; consider discontinuing REBIF if hepatic injury occurs ( 5.2 ) Anaphylaxis and Other Allergic Reactions: Discontinue REBIF if anaphylaxis occurs ( 5.3 ) Injection Site Reactions Including Necrosis: Do not administer REBIF into affected area until fully healed; if multiple lesions occur, change injections sites or discontinue REBIF until healing of skin lesions ( 5.4 ) Decreased Peripheral Blood Counts: Monitor complete blood counts ( 5.5 ) Thrombotic Microangiopathy: Cases of thrombotic microangiopathy have been reported. Discontinue REBIF if clinical symptoms and laboratory findings consistent with TMA occur ( 5.6 ). Pulmonary Arterial Hypertension: Cases of pulmonary arterial hypertension (PAH) have been reported in patients treated with interferon beta products, including REBIF. Discontinue REBIF if PAH is diagnosed ( 5.7 ) Seizures: Monitor for seizures when administering REBIF to patients, particularly those with pre-existing seizure disorders ( 5.8 ) 5.1 Depression and Suicide REBIF (interferon beta-1a) should be used with caution in patients with depression, a condition that is common in people with multiple sclerosis. Depression, suicidal ideation, and suicide attempts have been reported to occur with increased frequency in patients receiving interferon compounds, including REBIF. In addition, there have been postmarketing reports of suicide in patients treated with REBIF. Patients should be advised to report immediately any symptoms of depression and/or suicidal ideation to the prescribing physician. If a patient develops depression, cessation of treatment with REBIF should be considered. 5.2 Hepatic Injury Severe liver injury, including some cases of hepatic failure requiring liver transplantation, has been reported rarely in patients taking REBIF. Symptoms of liver dysfunction began from one to six months following the initiation of REBIF. If jaundice or other symptoms of liver dysfunction appear, treatment with REBIF should be discontinued immediately due to the potential for rapid progression to liver failure. Asymptomatic elevation of hepatic transaminases (particularly SGPT) is common with interferon therapy [see Adverse Reactions (6.1) ] . REBIF should be initiated with caution in patients with active liver disease, alcohol abuse, increased serum SGPT (> 2.5 times ULN), or a history of significant liver disease. Also, the potential risk of REBIF used in combination with known hepatotoxic products should be considered prior to REBIF administration, or when adding new agents to the regimen of patients already on REBIF. Reduction of REBIF dose should be considered if SGPT rises above 5 times the upper limit of normal. The dose may be gradually re-escalated when enzyme levels have normalized [see Warnings and Precautions (5.9) and Dosage and Administration (2.1) ]. 5.3 Anaphylaxis and Other Allergic Reactions Anaphylaxis has been reported as a rare complication of REBIF use. Other allergic reactions have included skin rash and urticaria, and have ranged from mild to severe without a clear relationship to dose or duration of exposure. Several allergic reactions, some severe, have occurred after prolonged use. Discontinue REBIF if anaphylaxis occurs. 5.4 Injection Site Reactions Including Necrosis Injection site reactions, including injection site necrosis, can occur with the use of interferon beta products, including REBIF. In controlled clinical trials, injection site reactions occurred more frequently in REBIF-treated patients (92% in the 44 mcg group and 89% in the 22 mcg group) than in placebo-treated patients (39%) and at a higher frequency in REBIF treated patients (83%) than in AVONEX-treated patients (28%). Injection site necrosis also occurred more frequently in REBIF-treated patients (3% in the 44 mcg group and 1% in the 22 mcg group) than in placebo- treated patients (0) during the two years of therapy. Injection site reactions including injection site pain, erythema, edema, cellulitis, abscess, and necrosis have been reported in the postmarketing setting. Some occurred more than 2 years after initiation of REBIF. Necrosis occurred at single and at multiple injection sites. Some cases of injection site necrosis required treatment with intravenous antibiotics and surgical intervention (debridement and skin grafting). Some cases of injection site abscesses and cellulitis required treatment with hospitalization for surgical drainage and intravenous antibiotics. Patient understanding and use of aseptic self-injection techniques and procedures should be periodically evaluated, particularly if injection site necrosis has occurred. Patients should be advised of the importance of rotating sites of injection with each dose and not reusing syringes. Patients should be advised against injecting an area which is inflamed, edematous, erythematous, ecchymotic, or has any other signs of infection. These signs should be reported to a healthcare professional immediately. If multiple lesions occur, change injection site or discontinue therapy until healing occurs. 5.5 Decreased Peripheral Blood Counts Decreased peripheral blood counts in all cell lines, including pancytopenia, have been reported in REBIF-treated patients. In controlled clinical trials, leukopenia occurred at a higher frequency in REBIF-treated patients (36% in 44 mcg group and 28% in 22 mcg group) than in placebo-treated patients (14%) and at a higher frequency in REBIF-treated patients (6%) compared to the AVONEX-treated patients (<1%). Thrombocytopenia and anemia occurred more frequently in 44 mcg REBIF-treated patients (8% and 5%, respectively) than in placebo-treated patients (2% and 3%, respectively).

Side effects

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) ] Pulmonary Arterial Hypertension [ see Warnings and Precautions (5.7) ] Seizures [see Warnings and Precautions (5.8) ] Laboratory Tests [see Warnings and Precautions (5.9) ] The most common adverse reactions in controlled clinical trials were injection site disorders, influenza-like symptoms, abdominal pain, depression, elevation of liver enzymes and hematologic abnormalities ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono at 1-800-283-8088 ext. 5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 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. Table 3. Adverse Reactions and Laboratory Abnormalities in Study 1 Body System Placebo tiw (n=187) REBIF 22 mcg tiw (n=189) REBIF 44 mcg tiw (n=184) Preferred Term % % % BODY AS A WHOLE Influenza-like symptoms 51 56 59 Headache 63 65 70 Fatigue 36 33 41 Fever 16 25 28 Rigors 5 6 13 Chest pain 5 6 8 Malaise 1 4 5 INJECTION SITE DISORDERS Injection Site Reaction 39 89 92 Injection Site Necrosis 0 1 3 NERVOUS SYSTEM DISORDERS Hypertonia 5 7 6 Coordination Abnormal 2 5 4 Convulsions 2 5 4 Somnolence 1 4 5 ENDOCRINE DISORDERS Thyroid Disorder 3 4 6 GASTROINTESTINAL SYSTEM DISORDERS Abdominal Pain 17 22 20 Dry Mouth 1 1 5 LIVER AND BILIARY SYSTEM DISORDERS SGPT Increased 4 20 27 SGOT Increased 4 10 17 Bilirubinemia 1 3 2 MUSCULO-SKELETAL SYSTEM DISORDERS Myalgia 20 25 25 Back Pain 20 23 25 Skeletal Pain 10 15 10 HEMATOLOGIC DISORDERS Leukopenia 14 28 36 Lymphadenopathy 8 11 12 Thrombocytopenia 2 2 8 Anemia 3 3 5 SKIN DISORDERS Rash Erythematous 3 7 5 Rash Maculo-Papular 2 5 4 Hyperhidrosis 2 4 4 URINARY SYSTEM DISORDERS Micturition Frequency 4 2 7 Urinary Incontinence 2 4 2 VISION DISORDERS Vision Abnormal 7 7 13 Xerophthalmia 0 3 1 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. 6.2 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. 6.3 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.

Use in specific populations

Pregnancy: Epidemiological data do not suggest a clear relationship between interferon beta use and major congenital malformations, but interferon beta may cause fetal harm based on animal data ( 8.1 ). 8.1 Pregnancy Risk Summary Data from a large population-based cohort study, as well as other published studies over several decades, have not identified a drug-associated risk of major birth defects with the use of interferon beta during early pregnancy. Findings regarding a potential risk for low birth weight or miscarriage with the use of interferon beta in pregnancy have been inconsistent (see Data ) . It is unclear whether, as a class of products, administration of interferon beta therapies to pregnant animals at doses greater than those used clinically results in an increased rate of abortion. The potential for REBIF to have adverse effects on embryofetal development has not been fully assessed in animals [ see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Human data The majority of observational studies reporting on pregnancies exposed to interferon beta products did not identify an association between the use of interferon beta products during early pregnancy and an increased risk of major birth defects. In a population-based cohort study conducted in Finland and Sweden, data were collected from 1996—2014 in Finland and from 2005—2014 in Sweden on 2,831 pregnancy outcomes from women with MS. 797 pregnancies were in women exposed to interferon beta only. No evidence was found of an increased risk of major birth defects among women with MS exposed to interferon beta products compared to women with MS that were unexposed to any non-steroid therapy for MS (n=1,647) within the study. No increased risks were observed for miscarriages and ectopic pregnancies, though there were limitations in obtaining complete data capture for these outcomes, making the interpretation of the findings more difficult. Two small cohort studies that examined pregnancies exposed to interferon beta products (without differentiating between subtypes of interferon beta products) suggested that a decrease in mean birth weight may be associated with interferon beta exposure during pregnancy, but this finding was not confirmed in larger observational studies. Two small studies observed an increased prevalence of miscarriage, although the finding was only statistically significant in one study. Most studies enrolled patients later in pregnancy, which made it difficult to ascertain the true percentage of miscarriages. In one small cohort study, a significantly increased risk of preterm birth following interferon beta exposure during pregnancy was observed. Animal data In a study in pregnant cynomolgus monkeys, interferon beta was administered daily (intramuscular doses approximately 1, 2, and 7 times the maximum recommended cumulative weekly human dose, based on body surface area) either throughout the period of organogenesis or later in pregnancy (gestation day 90 to term). No adverse effects on embryofetal development were observed; however, the possibility of adverse effects cannot be ruled out because of the small number of animals tested (six per dose group at each developmental period). 8.2 Lactation Risk Summary Limited published literature has described the presence of interferon beta-1a products in human milk at low levels. There are no data on the effects of interferon beta-1a on milk production. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for REBIF and any potential adverse effects on the breastfed child from REBIF or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of REBIF did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Pregnancy

8.1 Pregnancy Risk Summary Data from a large population-based cohort study, as well as other published studies over several decades, have not identified a drug-associated risk of major birth defects with the use of interferon beta during early pregnancy. Findings regarding a potential risk for low birth weight or miscarriage with the use of interferon beta in pregnancy have been inconsistent (see Data ) . It is unclear whether, as a class of products, administration of interferon beta therapies to pregnant animals at doses greater than those used clinically results in an increased rate of abortion. The potential for REBIF to have adverse effects on embryofetal development has not been fully assessed in animals [ see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Human data The majority of observational studies reporting on pregnancies exposed to interferon beta products did not identify an association between the use of interferon beta products during early pregnancy and an increased risk of major birth defects. In a population-based cohort study conducted in Finland and Sweden, data were collected from 1996—2014 in Finland and from 2005—2014 in Sweden on 2,831 pregnancy outcomes from women with MS. 797 pregnancies were in women exposed to interferon beta only. No evidence was found of an increased risk of major birth defects among women with MS exposed to interferon beta products compared to women with MS that were unexposed to any non-steroid therapy for MS (n=1,647) within the study. No increased risks were observed for miscarriages and ectopic pregnancies, though there were limitations in obtaining complete data capture for these outcomes, making the interpretation of the findings more difficult. Two small cohort studies that examined pregnancies exposed to interferon beta products (without differentiating between subtypes of interferon beta products) suggested that a decrease in mean birth weight may be associated with interferon beta exposure during pregnancy, but this finding was not confirmed in larger observational studies. Two small studies observed an increased prevalence of miscarriage, although the finding was only statistically significant in one study. Most studies enrolled patients later in pregnancy, which made it difficult to ascertain the true percentage of miscarriages. In one small cohort study, a significantly increased risk of preterm birth following interferon beta exposure during pregnancy was observed. Animal data In a study in pregnant cynomolgus monkeys, interferon beta was administered daily (intramuscular doses approximately 1, 2, and 7 times the maximum recommended cumulative weekly human dose, based on body surface area) either throughout the period of organogenesis or later in pregnancy (gestation day 90 to term). No adverse effects on embryofetal development were observed; however, the possibility of adverse effects cannot be ruled out because of the small number of animals tested (six per dose group at each developmental period).

Pediatric use

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Clinical studies of REBIF did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Description

(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 in vitro cytopathic effect bioassay using WISH cells and Vesicular Stomatitis virus. REBIF 8.8 mcg, 22 mcg and 44 mcg contains approximately 2.4 million international units, 6 million international units or 12 million international units, respectively, of antiviral activity using this method. 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.

Mechanism of action

12.1 Mechanism of Action The mechanism(s) by which REBIF (interferon beta-1a) exerts its therapeutic effects in patients with multiple sclerosis is unknown.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING REBIF is supplied as a sterile solution containing no preservative available in the following package presentations: Prefilled Syringes : REBIF (interferon beta -1a) Titration Pack, NDC 44087-8822-1 - Six REBIF 8.8 mcg prefilled syringes and Six REBIF 22 mcg prefilled syringes REBIF (interferon beta -1a) 22 mcg Prefilled syringe - Twelve REBIF 22 mcg prefilled syringes, NDC 44087-0022 - 3 REBIF (interferon beta -1a) 44 mcg Prefilled syringe - Twelve REBIF 44 mcg prefilled syringes, NDC 44087-0044-3 REBIF Rebidose Autoinjectors : REBIF Rebidose (interferon beta-1a) Titration Pack, NDC 44087-0188-1 - Six REBIF Rebidose 8.8 mcg autoinjectors with lime-green injector buttons and Six REBIF Rebidose 22 mcg with yellow injector buttons. REBIF Rebidose (interferon beta-1a) 22 mcg Autoinjector - Twelve REBIF Rebidose 22 mcg autoinjectors with yellow injector buttons, NDC 44087-3322-1 REBIF Rebidose (interferon beta-1a) 44 mcg Autoinjector - Twelve REBIF Rebidose 44 mcg autoinjectors with teal-green injector buttons, NDC 44087-3344-1 REBIF should be stored refrigerated between 36°F to 46°F (2°C to 8°C). DO NOT FREEZE. If needed, REBIF may be stored between 36°F to 77°F (2°C to 25°C) for up to 30 days and away from heat and light, but refrigeration is preferred. Do not use beyond the expiration date printed on packages. REBIF contains no preservatives. Each prefilled syringe and REBIF Rebidose autoinjector is intended for a single dose. Unused portions should be discarded.

Storage

REBIF should be stored refrigerated between 36°F to 46°F (2°C to 8°C). DO NOT FREEZE. If needed, REBIF may be stored between 36°F to 77°F (2°C to 25°C) for up to 30 days and away from heat and light, but refrigeration is preferred. Do not use beyond the expiration date printed on packages. REBIF contains no preservatives. Each prefilled syringe and REBIF Rebidose autoinjector is intended for a single dose. Unused portions should be discarded.

Patient 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. Depression and Suicide Advise patients that depression, suicidal ideation, and suicide have been reported during the use of REBIF. Inform patients of the symptoms of depression and suicidal ideation and instruct patients to immediately report any of these symptoms to their healthcare provider [see Warnings and Precautions (5.1) ] . Hepatic Injury Advise patients that severe liver injury, including hepatic failure, has been reported with the use of REBIF. Educate patients about the symptoms of hepatic injury and instruct patients to report them immediately to their healthcare provider [see Warnings and Precautions (5.2) ]. Anaphylaxis and Other Allergic Reactions Advise patients of the symptoms of allergic reactions and anaphylaxis, and instruct patients to seek immediate medical attention if these symptoms occur [see Warnings and Precautions (5.3) ]. Injection Site Reactions Including Necrosis Advise patients that injection site reactions occur in most patients treated with REBIF and that injection site necrosis may occur [see Warnings and Precautions (5.4) ] . Instruct patients to promptly report any break in the skin, which may be associated with blue-black discoloration, swelling, or drainage of fluid from the injection site, prior to continuing their REBIF therapy. To minimize the likelihood of injection site reactions, inform patients of the importance of rotating injection sites with each dose and the use of aseptic injection technique [see Dosage and Administration (2.2) ]. Advise patients not to re-use needles or syringes and instruct patients on safe disposal procedures. Provide appropriate instruction for self-injection of REBIF and REBIF Rebidose, including careful review of the REBIF Medication Guide. Decreased Peripheral Blood Counts Advise patients that they may develop a lowering of their peripheral blood counts, including their white blood counts, red blood counts, and platelets, and that their blood counts will be checked during therapy with REBIF. Inform patients that they may be more likely to get infections, anemia, or be at risk for bleeding, and that they should contact their healthcare provider if they develop symptoms of these adverse reactions [see Warnings and Precautions (5.5) ] . Pulmonary Arterial Hypertension Inform patients that PAH has occurred in patients treated with interferon beta products, including REBIF. Instruct patients to promptly report any new symptoms such as new or increasing fatigue or shortness of breath to their healthcare provider [see Warnings and Precautions (5.7) ] . Seizures Instruct patients to report seizures immediately to their healthcare provider [see Warnings and Precautions (5.8) ]. Flu-like Symptoms Inform patients that flu-like symptoms are common following initiation of therapy with REBIF . Advise patients that concurrent use of analgesics and/or antipyretics may help reduce flu-like symptoms on treatment days [see Dosage and Administration (2.3) ]. Pregnancy Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant [see Use in Specific Populations (8.1) ] .

Label text from the FDA structured product label by EMD Serono, Inc. (revised Sep 22, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Rebif NDC products (3)

NDCStrength & formLabelerType
44087-0022Interferon Beta-1a 22 ug/.5mL
Injection, Solution		EMD Serono, Inc.BLA
44087-0044Interferon Beta-1a 44 ug/.5mL
Injection, Solution		EMD Serono, Inc.BLA
44087-8822
Kit		EMD Serono, Inc.BLA

Frequently asked questions

What is Rebif used for?

1 INDICATIONS 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. Rebif is an interferon beta indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting…

What are the side effects of Rebif?

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… See the full label for the complete list.

Who makes Rebif?

Rebif is listed by 1 labeler in the FDA NDC directory, including EMD Serono, Inc..