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Betaseron (Interferon Beta-1B) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

In all studies, the most serious adverse reactions with Betaseron were depression, suicidal ideation and injection site necrosis (see WARNINGS). The incidence of depression of any severity was approximately 30% in both Betaseron-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 lymphopenia (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, 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 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 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-treated patients with SPMS and RRMS were similar. Clinical experience with Betaseron 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/m2 Betaseron 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

System Organ Class MedDRA v. 8.0 1  

Adverse Reaction

Placebo

(N=965)

Betaseron

(N=1407)

Blood and lymphatic system disorders
Lymphocytes count decreased (<1500/mm3) 2 66% 86%
Absolute neutrophil count decreased (< 1500/mm3) 5% 13%
White blood cell count decreased (<3000/mm3) 4% 13%
Lymphadenopathy 3% 6%
Nervous system disorders
Headache 43% 50%
Insomnia 16% 21%
Incoordination 15% 17%
Vascular disorders
Hypertension 4% 6%
Respiratory, thoracic and mediastinal disorders
Dyspnea 3% 6%
Gastrointestinal disorders
Abdominal pain 11% 16%
Hepatobiliary disorders
Alanine aminotransferase increased
(SGPT > 5 times baseline)
4% 12%
Aspartate aminotransferase increased
(SGOT > 5 times baseline)
1% 4%
Skin and subcutaneous tissue disorders
Rash 15% 21%
Skin disorder 8% 10%
Musculoskeletal and connective tissue disorders
Hypertonia 33% 40%
Myalgia 14% 23%
Renal and urinary disorders
Urinary urgency 8% 11%
Reproductive system and breast disorders
Metrorrhagia 3 7% 9%
Impotence 4 6% 8%
General disorders and administration site conditions
Injection site reaction (various kinds ) 5 26% 78%
Asthenia 48% 53%
Flu-like symptoms (complex) 6 37% 57%
Pain 35% 42%
Fever 19% 31%
Chills 9% 21%
Peripheral edema 10% 12%
Chest pain 6% 9%
Malaise 3% 6%
Injection site necrosis 0% 4%

1 except for "injection site reaction (various kinds)" and "flu-like symptom complex#"the most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.
2 laboratory abnormality
3 pre-menopausal women
4 men
5 "Injection site reaction (various kinds)" comprises all adverse events occurring at the injection site (except injection site necrosis), i.e. the following terms: injection site reaction, injection site hemorrhage, injection site hypersensitivity, injection site inflammation, injection site mass, injection site pain, injection site edema and injection site atrophy.
6 "Flu-like symptom complex" denotes flu syndrome and/or a combination of at least two AEs from fever, chills, myalgia, malaise, sweating.

Injection Site Reactions

In four controlled clinical trials, injection site reactions occurred in 78% of patients receiving Betaseron 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- 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 patients were dose-reduced or interrupted treatment for increased hepatic 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 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 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 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, Weight increase

Psychiatric disorders: Anxiety, Confusion, Depersonalization, Emotional lability

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

Cardiac disorders: Cardiomyopathy, Palpitations, Tachycardia

Vascular disorders: Deep vein thrombosis, Pulmonary embolism, Vasodilatation

Respiratory, thoracic and mediastinal disorders: Bronchospasm, Pneumonia

Gastrointestinal disorders: Diarrhea, Nausea, Pancreatitis, Vomiting

Hepatobiliary disorders: Hepatitis, Gamma GT increased

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

Musculoskeletal and connective tissue disorders: Arthralgia

Reproductive system and breast disorder: Menorrhagia

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 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 treated patients. Such neutralizing activity was measured at least once in 75 (29.9%) out of 251 Betaseron 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 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 with the incidence of antibodies to other products may be misleading.

Anaphylactic reactions have rarely been reported with the use of Betaseron.



REPORTS OF SUSPECTED BETASERON SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Betaseron. The information is not vetted and should not be considered as verified clinical evidence.

Possible Betaseron side effects / adverse reactions in 58 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-03

Patient: 58 year old female

Reactions: Autonomic Nervous System Imbalance, Urinary Tract Infection, Abasia, Fall, Renal Impairment, Palpitations, LIP Injury, Gait Disturbance, Blood Pressure Decreased, Blood Pressure Fluctuation, Asthenia

Adverse event resulted in: hospitalization, disablity

Suspect drug(s):
Betaseron



Possible Betaseron side effects / adverse reactions in 53 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-04

Patient: 53 year old female

Reactions: Pyrexia

Suspect drug(s):
Betaseron

Other drugs received by patient: Multi-Vitamin; Aspirin; Valium; Ascorbic Acid; Tizanidine HCL; Vitamin A; Effexor; Vitamin D; Bactrim; Calcium D; Provigil



Possible Betaseron side effects / adverse reactions in 56 year old male

Reported by a consumer/non-health professional from United States on 2011-10-06

Patient: 56 year old male

Reactions: Cellulitis, Bacillus Infection, Tremor

Adverse event resulted in: hospitalization

Suspect drug(s):
Betaseron



See index of all Betaseron side effect reports >>

Drug label data at the top of this Page last updated: 2009-05-29

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