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The most frequently reported serious adverse reactions with Rebif® (interferon beta-1a) were psychiatric disorders including depression and suicidal ideation or attempt (see WARNINGS: Depression). The incidence of depression of any severity in the Rebif® (interferon beta-1a) -treated groups and placebo-treated group was approximately 25%.

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® (interferon beta-1a) , adjustment in dosage, or the need for concomitant medication to treat an adverse reaction symptom) were injection site disorders, influenza-like symptoms, depression and elevation of liver enzymes (see WARNINGS).

In Study 1, 6 patients randomized to Rebif® (interferon beta-1a) 44 mcg tiw (3%), and 2 patients who received Rebif® (interferon beta-1a) 22 mcg tiw (1%) developed injection site necrosis during two years of therapy. Rebif® (interferon beta-1a) was continued in 7 patients and interrupted briefly in one patient. There was one report of injection site necrosis in Study 2 during 48 weeks of Rebif® (interferon beta-1a) treatment. All events resolved with conservative management.

The rates of adverse reactions and association with Rebif® (interferon beta-1a) in patients with relapsing-remitting multiple sclerosis are drawn from the placebo-controlled study (n = 560) and the active comparator-controlled study (n = 339).

The population encompassed an age range 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.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Rebif® (interferon beta-1a) cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.

Table 3 enumerates adverse events and laboratory abnormalities that occurred at an incidence that was at least 2% more in either Rebif® (interferon beta-1a) -treated group than was observed in the placebo group.

Table 3. Adverse Reactions and Laboratory Abnormalities in Study 1

The adverse reactions were generally similar in Studies 1 and 2, taking into account the disparity in study durations.

Postmarketing Experience

In addition to adverse events reported from clinical trials, the following events have been reported during postmarketing use of Rebif® (interferon beta-1a) . Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to Rebif (interferon beta-1a) can not be reliably determined.

Blood and Lymphatic System Disorders: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS).

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

Hepatobiliary Disorders: Rare cases of severe liver dysfunction, including hepatic failure requiring liver transplantation (see WARNINGS: Hepatic Injury).

Nervous System: Seizures (see PRECAUTIONS: General). Transient neurological symptoms (i.e., hypoesthesia, muscle spasm, paresthesia, difficulty walking, musculoskeletal stiffness) that mimic MS exacerbations of limited duration, temporally related to the injections and most prominent at the initiation of therapy. In some cases, these symptoms were associated with flu-like syndrome.

Psychiatric Disorders: suicide (see WARNINGS: Depression and Suicide)

Skin and Subcutaneous Tissue Disorders: Injection site abscesses, injecton site infections, including cellulitis and necrosis requiring debridement, systemic antibiotic treatment and/or grafting; erythema multiforme, and Stevens-Johnson syndrome.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. In study 1, the presence of neutralizing antibodies (NAb) to Rebif® (interferon beta-1a) 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® (interferon beta-1a) -treated patients at the 22 mcg and 44 mcg tiw doses, respectively, at one or more times during the study. The clinical significance of the presence of NAb to Rebif® (interferon beta-1a) is unknown.

The data reflect the percentage of patients whose test results were considered positive for antibodies to Rebif® (interferon beta-1a) 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® (interferon beta-1a) with the incidence of antibodies to other products may be misleading.

Anaphylaxis and other allergic reactions have been observed with the use of Rebif® (see WARNINGS: Anaphylaxis).

Drug Abuse And Dependence

There is no evidence that abuse or dependence occurs with Rebif® (interferon beta-1a) therapy. However, the risk of dependence has not been systematically evaluated.

No formal drug interaction studies have been conducted with Rebif® (interferon beta-1a) . Due to its potential to cause neutropenia and lymphopenia, proper monitoring of patients is required if Rebif® (interferon beta-1a) is given in combination with myelosuppressive agents.

Also, the potential for hepatic injury should be considered when Rebif® (interferon beta-1a) is used in combination with other products associated with hepatic injury, or when new agents are added to the regimen of patients already on Rebif® (see WARNINGS: Hepatic Injury).

Immunization

In a nonrandomized prospective clinical study, 86 multiple sclerosis (MS) patients on Rebif® (interferon beta-1a) 44 mcg tiw for at least 6 months and 77 patients not receiving interferon received influenza vaccination. The proportion of patients achieving a positive antibody

response (defined as a titer > 1:40 measured by a hemagglutination inhibition assay) was similar in the two groups (93% and 91% respectively). The exact relationship of antibody titers to vaccine efficacy was not studied and is not known in patients receiving Rebif® (interferon beta-1a) . Therefore, while patients receiving Rebif® (interferon beta-1a) may receive concomitant vaccination, the overall effectiveness of such vaccination is unknown.

Last reviewed on RxList: 1/15/2010
This monograph has been modified to include the generic and brand name in many instances.