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The following adverse reactions were reported in the PRISMS study for Rebif® 44 mcg and Rebif® 22 mcg vs placebo:
Adverse reactions in the EVIDENCE study were generally similar to those in the PRISMS study.
Compared with Avonex®, adverse events were similar over an average of 64 weeks, despite higher, more frequent dosing with Rebif®. Exceptions include (Rebif® vs Avonex®):
AE: adverse event; PML: progressive multifocal leukoencephalopathy; SGOT: serum glutamic oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase.
INDICATION AND IMPORTANT SAFETY INFORMATION
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.
Important Safety Information
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.
Use Rebif with caution in patients with depression, a common condition 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.
There have been rare reports of severe liver injury, including some cases of hepatic failure requiring liver transplantation, in patients taking Rebif. Consider the potential for hepatic injury when Rebif is used in combination with other products associated with hepatotoxicity. Monitor liver function tests and patients for signs and symptoms of hepatic injury. Consider discontinuing Rebif if hepatic injury occurs.
Anaphylaxis and other allergic reactions (some severe) have been reported. Discontinue Rebif if anaphylaxis occurs.
In controlled clinical trials, injection site reactions occurred more frequently in Rebif-treated patients than in placebo-treated and Avonex-treated patients. Injection site reactions including injection site pain, erythema, edema, cellulitis, abscess, and necrosis have been reported in the postmarketing setting with the use of Rebif. Do not administer Rebif into affected area until fully healed; if multiple lesions occur, change injection site or discontinue Rebif until skin lesions are healed. 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. Rotate site of injection with each dose to minimize likelihood of severe injection site reactions, including necrosis or localized infection.
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 than in placebo and Avonex-treated patients. Thrombocytopenia and anemia occurred more frequently in 44 mcg Rebif-treated patients than in placebo-treated patients. Monitor patients for symptoms or signs of decreased blood counts. Monitoring of complete blood and differential white blood cell counts is also recommended.
Cases of thrombotic microangiopathy (TMA), some fatal, have been reported with interferon beta products, including Rebif, up to several weeks or years after starting therapy. Discontinue Rebif if clinical symptoms and laboratory findings consistent with TMA occur and manage as clinically indicated.
Seizures have been temporally associated with the use of beta interferons, including Rebif, in clinical trials and in postmarketing reports. Monitor for seizures when administering Rebif to patients, particularly those with pre-existing seizure disorders.
New or worsening thyroid abnormalities have developed in some patients treated with Rebif. Thyroid function tests are recommended every 6 months in patients with history of thyroid dysfunction or as clinically indicated.
The most common side effects with Rebif are injection-site disorders, influenza-like symptoms, abdominal pain, depression, elevated liver enzymes, and hematologic abnormalities.
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 studies. Data from a large human population-based cohort study, as well as other published studies over several decades, have not identified an increased risk of major birth defects with exposure to interferon beta products during early pregnancy. Findings regarding a potential risk for low birth weight or miscarriage with the use of interferon beta products in pregnancy have been inconsistent.
References: 1. Data on file. EMD Serono, Inc. PRISMS study report. 2. Rebif® [Prescribing Information]. Rockland, MA: EMD Serono, Inc. 3. Data on file. EMD Serono, Inc. NS/RS patients through MS LifeLines®. 4. Panitch H, Goodin D, Francis G, et al; for EVIDENCE (EVidence of Interferon Dose-response-European North American Comparative Efficacy) Study Group and the University of British Columbia MS/MRI Research Group. Benefits of high-dose, high-frequency interferon beta-1a in relapsing-remitting multiple sclerosis are sustained to 16 months: final comparative results of the EVIDENCE trial. J Neurol Sci.2005;239(1):67-74.