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In all studies, the most serious adverse reactions with Betaseron (interferon beta-1b) were depression, suicidal ideation and injection site necrosis (see WARNINGS). The incidence of depression of any severity was approximately 30% in both Betaseron (interferon beta-1b) -treated patients and placebo-treated patients. Anaphylaxis and other allergic reactions have been reported in patients using Betaseron (see WARNINGS). The most commonly reported adverse reactions were lym-phopenia (lymphocytes < 1500/mm³), injection site reaction, asthenia, flu-like symptom complex, headache, and pain. The most frequently reported adverse reactions resulting in clinical intervention (e.g., discontinuation of Betaseron (interferon beta-1b) , adjustment in dosage, or the need for concomitant medication to treat an adverse reaction symptom) were depression, flu-like symptom complex, injection site reactions, leukopenia, increased liver enzymes, asthenia, hypertonia, and myasthenia.

Because clinical trials are conducted under widely varying conditions and over varying lengths of time, adverse reaction rates observed in the clinical trials of Betaseron (interferon beta-1b) cannot be directly compared to rates in clinical trials of other drugs, and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

The data described below reflect exposure to Betaseron (interferon beta-1b) in the four placebo controlled trials of 1407 patients with MS treated with 0.25 mg or 0.16 mg/m², including 1261 exposed for greater than one year. The population encompassed an age range from 18-65 years. Sixty-four percent (64%) of the patients were female. The percentages of Caucasian, Black, Asian, and Hispanic patients were 94.8%, 3.5%, 0.1%, and 0.7%, respectively.

The safety profiles for Betaseron (interferon beta-1b) -treated patients with SPMS and RRMS were similar. Clinical experience with Betaseron (interferon beta-1b) in other populations (patients with cancer, HIV positive patients, etc.) provides additional data regarding adverse reactions; however, experience in non-MS populations may not be fully applicable to the MS population.

Table 2 enumerates adverse events and laboratory abnormalities that occurred among all patients treated with 0.25 mg or 0.16 mg/m²Betaseron (interferon beta-1b) every other day for periods of up to three years in the four placebo controlled trials (Study 1-4) at an incidence that was at least 2.0% more than that observed in the placebo patients (System Organ Class, MedDRA v. 8.0).

Table 2 Adverse Reactions and Laboratory Abnormalities

Injection Site Reactions

In four controlled clinical trials, injection site reactions occurred in 78% of patients receiving Betaseron (interferon beta-1b) with injection site necrosis in 4%. Injection site inflammation (42%), injection site pain (16%), injection site hypersensitivity (4%), injection site necrosis (4%), injection site mass (2%), injection site edema (2%) and non-specific reactions were significantly associated with Betaseron treatment (see WARNINGS and PRECAUTIONS). The incidence of injection site reactions tended to decrease over time. Approximately 69% of patients experienced the event during the first three months of treatment, compared to approximately 40% at the end of the studies.

Flu-Like Symptom Complex

The rate of flu-like symptom complex was approximately 57% in the four controlled clinical trials. The incidence decreased over time, with only 10% of patients reporting flu-like symptom complex at the end of the studies. For patients who experienced a flu-like symptom complex in Study 1, the median duration was 7.5 days.

Laboratory Abnormalities

In the four clinical trials, leukopenia was reported in 18% and 6% [of patients in Betaseron (interferon beta-1b) - and placebo-treated groups, respectively. No patients were withdrawn or dose reduced for neutropenia in Study 1. Three percent (3%) of patients in Studies 2 and 3 experienced leukopenia and were dose-reduced. Other abnormalities included increase of SGPT to greater than five times baseline value (12%), and increase of SGOT to greater than five times baseline value (4%). In Study 1, two patients were dose reduced for increased hepatic enzymes; one continued on treatment and one was ultimately withdrawn. In Studies 2 and 3, 1.5% of Betaseron (interferon beta-1b) patients were dose-reduced or interrupted treatment for increased hepat-ic enzymes. In Study 4, 1.7% of patients were withdrawn from treatment due to increased hepatic enzymes, two of them after a dose reduction. In Studies 1-4, nine (0.6%) patients were withdrawn from treatment with Betaseron (interferon beta-1b) for any laboratory abnormality, including four (0.3%) patients following dose reduction. (see PRECAUTIONS, Laboratory tests).

Menstrual Irregularities

In the four clinical trials, 97 (12%) of the 783 pre-menopausal females treated with Betaseron (interferon beta-1b) and 79 (15%) of the 528 pre-menopausal females treated with placebo reported menstrual disorders. One event was reported as severe, all other reports were mild to moderate severity. No patients withdrew from the studies due to menstrual irregularities.

Postmarketing Experience

The following adverse events have been observed during postmarketing experience with Betaseron (interferon beta-1b) and are classified within body system categories:

Blood and lymphatic system disorders: Anemia, Thrombocytopenia

Endocrine disorders: Hypothyroidism, Hyperthyroidism, Thyroid dysfunction

Metabolism and nutrition disorders: Hypocalcemia, Hyperuricemia, Triglyceride increased, Anorexia, Weight decrease

Psychiatric disorders: Confusion, Depersonalization, Emotional lability

Nervous system disorders: Ataxia, Convulsion, Paresthesia, Psychotic symptoms

Cardiac disorders: Cardiomyopathy

Vascular disorders: Deep vein thrombosis, Pulmonary embolism

Respiratory, thoracic and mediastinal disorders: Bronchospasm, Pneumonia

Gastrointestinal disorders: Pancreatitis,

Vomiting Hepatobiliary disorders: Hepatitis, Gamma GT increased

Skin and subcutaneous tissue disorders: Pruritus, Skin discoloration, Urticaria

Renal and urinary disorders: Urinary tract infection, Urosepsis

General disorders and administration site conditions: Fatal capillary leak syndrome*.

*The administration of cytokines to patients with a pre-existing monoclonal gammopathy has been associated with the development of this syndrome.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. Serum samples were monitored for the development of antibodies to Betaseron (interferon beta-1b) during Study 1. In patients receiving 0.25 mg every other day 56/124 (45%) were found to have serum neutralizing activity at one or more of the time points tested. In Study 4, neutralizing activity was measured every 6 months and at end of study. At individual visits after start of therapy, activity was observed in 16.5% up to 25.2% of the Betaseron (interferon beta-1b) treated patients. Such neutralizing activity was measured at least once in 75 (29.9%) out of 251 Betaseron (interferon beta-1b) patients who provided samples during treatment phase; of these, 17 (22.7%) converted to negative status later in the study.

Based on all the available evidence, the relationship between antibody formation and clinical safety or efficacy is not known.

These data reflect the percentage of patients whose test results were considered positive for antibodies to Betaseron (interferon beta-1b) using a biological neutralization assay that measures the ability of immune sera to inhibit the production of the interferon-inducible protein, MxA. Neutralization assays are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of neutralizing activity 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 Betaseron (interferon beta-1b) with the incidence of antibodies to other products may be misleading.

Anaphylactic reactions have rarely been reported with the use of Betaseron (interferon beta-1b) .

Drug Abuse And Dependence

No evidence or experience suggests that abuse or dependence occurs with Betaseron (interferon beta-1b) therapy; however, the risk of dependence has not been systematically evaluated.

No formal drug interaction studies have been conducted with Betaseron (interferon beta-1b) . In the placebo controlled studies in MS, corticosteroids or ACTH were administered for treatment of relapses for periods of up to 28 days in patients (N=664) receiving Betaseron (interferon beta-1b) .

Last reviewed on RxList: 6/26/2008
This monograph has been modified to include the generic and brand name in many instances.