Betaseron Side Effects
Generic Name: interferon beta-1b
Please note - some side effects for Betaseron may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Side Effects of Betaseron - for the Consumer
Betaseron Solution
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Betaseron Solution:
Seek medical attention right away if any of these SEVERE side effects occur when using Betaseron Solution:Decreased sexual ability; flu-like symptoms (eg, low-grade fever, chills, general body discomfort; unusual sweating); frequent urination; headache; joint pain; mild pain, swelling, or redness at the injection site; muscle pain or weakness; nausea; stomach upset; trouble sleeping; unusual spotting or menstrual bleeding; weakness.
Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blue-black discoloration, skin breakdown, oozing, or persistent pain or swelling around the injection site; chest pain; decreased coordination; feeling cold or hot all the time; mood or mental changes (eg, depression, anxiety, nervousness, severe or persistent trouble sleeping); muscle stiffness; seizures; severe or persistent headache or dizziness; shortness of breath; suicidal thoughts or behaviors; swelling of the hands, ankles, or feet; swollen lymph nodes; symptoms of infection (eg, severe or persistent fever, chills, sore throat); symptoms of liver problems (eg, yellowing of the skin or eyes, dark urine, pale stools, right-sided stomach pain); unusual bruising or bleeding; unusual weight gain or loss.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
TopBetaseron Side Effects - for the Professional
Betaseron
In all studies, the most serious adverse reactions with Betaseron were depression, suicidal ideation and injection site necrosis. 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. In postmarketing experience, Betaseron administration has been rarely associated with severe liver dysfunction, including hepatic failure requiring liver transplantation.
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).
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System Organ Class MedDRA v. 8.0* Adverse Reaction |
Placebo (N=965) |
Betaseron (N=1407) |
| Blood and lymphatic system disorders | ||
| Lymphocytes count decreased (<1500/mm3) † | 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 ‡ | 7% | 9% |
| Impotence § | 6% | 8% |
| General disorders and administration site conditions | ||
| Injection site reaction (various kinds ) ¶ | 26% | 78% |
| Asthenia | 48% | 53% |
| Flu-like symptoms (complex) # | 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% |
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. 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..
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.
TopSide Effects by Body System - for Healthcare Professionals
General
The most serious side effects reported in all studies were depression, suicidal ideation, and injection site necrosis. The most frequently reported side effects were lymphopenia (lymphocytes less than 1500/mm3), injection site reaction, asthenia, flu-like symptom complex, headache, and pain. The most commonly reported side effects resulting in clinical intervention (e.g., discontinuation of interferon beta-1b, dosage adjustment, or the need for treatment of side effect symptom with concomitant medication) were depression, flu-like symptom complex, injection site reactions, leukopenia, elevated liver enzymes, asthenia, hypertonia, and myasthenia.
Local
Local side effects have included injection site reaction (various kinds; 78%) and injection site necrosis (4%). Injection site reaction (various kinds) includes injection site inflammation (42%), injection site pain (16%), injection site hypersensitivity (4%), injection site mass (2%), injection site edema (2%), injection site reaction, injection site hemorrhage, injection site atrophy, and nonspecific reactions. Severe necrotic lesions have occurred.
About 69% of patients experienced injection site reactions during the first 3 months of therapy with the incidence decreasing to about 40% at the end of the trials.
Other
Flu-like symptom complex appears to occur most frequently during the first 3 months of therapy, and abates with continued treatment.
Other side effects have included flu-like symptom complex (denotes flu syndrome and/or a combination of at least 2 side effects from fever, chills, myalgia, malaise, sweating; 57%), asthenia (53%), pain (42%), fever (31%), chills (21%), peripheral edema (12%), chest pain (9%), and malaise (6%).
Hematologic
Hematologic side effects have included decreased lymphocyte count (less than 1500/mm3; 86%), decreased white blood cell count (less than 3000/mm3; 13% to 18%), decreased absolute neutrophil count (less than 1500/mm3; 13%), and lymphadenopathy (6%). Anemia and thrombocytopenia have been reported during postmarketing experience.
Psychiatric
One suicide and four suicide attempts were reported in 372 patients treated with 1.6 or 8 million international units every other day, while none were reported in patients on placebo.
Psychiatric side effects have included depression (any severity; about 30%), suicidal ideation, suicide attempts, and suicide. Anxiety, confusion, depersonalization, emotional lability, and psychotic symptoms have been reported during postmarketing experience.
Nervous system
Nervous system side effects have included headache (50%), insomnia (21%), incoordination (17%), somnolence, and myasthenia. Sudden hearing loss, which was reversible within 7 to 14 days of drug discontinuation, has been reported. Ataxia, convulsion, dizziness, and paresthesia have been reported during postmarketing experience.
Musculoskeletal
Musculoskeletal side effects have included hypertonia (40%) and myalgia (23%). In a study of 124 multiple sclerosis patients, myalgia (44%) and myasthenia (13%) were reported. A study of 19 patients with primary progressive multiple sclerosis reported frequent and clinically significant increase in spasticity that appeared approximately 2 months after start of interferon beta-1b. Arthralgia has been reported during postmarketing experience.
Dermatologic
Dermatologic side effects have included rash (21%) and skin disorder (10%). Contact dermatitis, erythema nodosum, exfoliative dermatitis, furunculosis, hirsutism, leukoderma, lichenoid dermatitis, maculopapular rash, psoriasis, seborrhea, benign skin neoplasm, skin carcinoma, skin hypertrophy, skin necrosis, skin ulcer, vesiculobullous lesions, sarcoid-like dermatitis, and septal panniculitis have been reported. Alopecia, pruritus, skin discoloration, and urticaria have been reported during postmarketing experience.
A case of sarcoid-like dermatitis is reported in a 57-year-old white man diagnosed with multiple sclerosis. The cutaneous eruption that developed 2 months after initiation of interferon beta-1b therapy histologically resembled sarcoidal granulomas, but without distinctive features of true sarcoidosis.
A case of cutaneous necrosis in a 38-year-old woman diagnosed with relapsing-remitting multiple sclerosis is believed to be a result of an immunological response to the improperly dissolved lyophilized drug. The patient was rechallenged with the drug, after introducing changes to the way she reconstituted the drug, without any reports of scars.
Hepatic
Hepatic side effects have included elevated liver enzymes, including elevated alanine aminotransferase (SGPT greater than 5 times baseline; 12%) and aspartate aminotransferase (SGOT greater than 5 times baseline; 4%). Hepatitis and elevated gamma-glutamyltransferase have been reported during postmarketing experience.
Gastrointestinal
Gastrointestinal side effects have included abdominal pain (16%). Diarrhea, nausea, pancreatitis, and vomiting have been reported during postmarketing experience.
Genitourinary
Genitourinary side effects have included menstrual disorders/irregularities (12%) and metrorrhagia (9%) in premenopausal women, urinary urgency (11%), and male impotence (8%). Severe vaginal bleeding has been reported. Menorrhagia, urinary tract infection, and urosepsis have been reported during postmarketing experience.
A 19-year-old white woman diagnosed with multiple sclerosis experienced severe vaginal bleeding when her dose of interferon beta-1b was increased, 1 month from the start of therapy, from 4 to 8 million international units.
Cardiovascular
Development of fatal capillary leak syndrome has been associated with the administration of cytokines to patients with a preexisting monoclonal gammopathy.
Cardiovascular side effects have included hypertension (6%). Cardiomyopathy, palpitations, tachycardia, deep vein thrombosis, pulmonary embolism, vasodilatation, and fatal capillary leak syndrome have been reported during postmarketing experience.
Hypersensitivity
Hypersensitivity side effects have included anaphylaxis and other allergic reactions.
Respiratory
Respiratory side effects have included dyspnea (6%). Bronchospasm and pneumonia have been reported during postmarketing experience.
Metabolic
Metabolic side effects have included hypocalcemia, hyperuricemia, increased triglycerides, anorexia, decreased weight, and increased weight during postmarketing experience.
Immunologic
Immunologic side effects have included the development of antibodies against interferon beta, often as early as 3 months after the start of treatment. The antibodies may bind to and block the beneficial effect of interferon beta in multiple sclerosis. The overall clinical significance is unknown.
Results of a prospective study suggest that several autoimmune events may occur during interferon beta treatment of multiple sclerosis and recommends the close monitoring of thyroid, liver function, and autoantibodies.
Neutralizing antibodies formation occurred after the 24-week treatment in 95% of patients treated with natural interferon beta compared to 27% of patients treated with recombinant interferon beta.
Endocrine
Endocrine side effects have included hypothyroidism, hyperthyroidism, and thyroid dysfunction during postmarketing experience.
Renal
Renal side effects have included hemolytic uremic syndrome and nephrotic syndrome with minimal histologic changes of the glomerulus during postmarketing experience. Upon withdrawal of interferon beta therapy these side effects subsided.
TopMore Betaseron resources
- Betaseron Prescribing Information (FDA)
- Betaseron Consumer Overview
- Betaseron Advanced Consumer (Micromedex) - Includes Dosage Information
- Betaseron Solution MedFacts Consumer Leaflet (Wolters Kluwer)
- Interferon Beta-1b Professional Patient Advice (Wolters Kluwer)
- Extavia Prescribing Information (FDA)
- Extavia Consumer Overview
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