The following serious adverse reactions are discussed in more detail in other sections of labeling:
- Depression, Suicide, and Psychotic Disorders [see WARNINGS AND PRECAUTIONS]
- Hepatic Injury [see WARNINGS AND PRECAUTIONS]
- Anaphylaxis and Other Allergic-Reactions [see WARNINGS AND PRECAUTIONS]
- Congestive Heart Failure [see WARNINGS AND PRECAUTIONS]
- Decreased Peripheral Blood Counts [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
- Autoimmune Disorders [see WARNINGS AND PRECAUTIONS]
- Laboratory Tests [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of AVONEX cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice.
Among 351 patients with relapsing forms of MS treated with AVONEX 30 micrograms (including 319 patients treated for 6 months and 288 patients treated for greater than one year) the most commonly reported adverse reactions (at least 5% more frequent on AVONEX than on placebo) were flu-like symptoms. Symptoms can include chills, fever, myalgia and asthenia occurring within hours to days following an injection. Most people who take AVONEX have flu-like symptoms early during the course of therapy. Usually, these symptoms last for a day after the injection. For many people, these symptoms lessen or go away over time. The most frequently reported adverse reactions resulting in clinical intervention (for example, discontinuation of AVONEX or the need for concomitant medication to treat an adverse reaction symptom) were flu-like symptoms and depression.
Table 2 enumerates adverse reactions that occurred with AVONEX-treated patients at an incidence of at least 2% more than that observed in the placebo-treated patients in the pooled placebo-controlled studies in patients with relapsing forms of MS [see Clinical Studies].
Table 2: Adverse Reactions in the Placebo-Controlled Studies
(N = 333)
(N = 351)
|Body as a Whole|
|Flu-like symptoms (otherwise unspecified)||29%||49%|
|Injection site pain||6%||8%|
|Injection site inflammation||2%||6%|
|Injection site reaction||1%||3%|
|Depression||1 4%||1 8%|
|Dizziness||1 2%||1 4%|
|Upper respiratory tract infection||12%||14%|
|Sinusitis||1 2%||1 4%|
|Urinary tract infection||15%||17%|
|Urine constituents abnormal||0%||3%|
|Skin and Appendages|
|Hemic and Lymphatic System|
|Injection site ecchymosis||4%||6%|
Anaphylaxis and other allergic reactions have occurred in AVONEX-treated patients [see WARNINGS AND PRECAUTIONS]. As with all therapeutic proteins, there is a potential for immunogenicity. In studies assessing immunogenicity in multiple sclerosis patients administered AVONEX for at least 1 year, 5% (21 of 390 patients) showed the presence of neutralizing antibodies at one or more times.
These data reflect the percentage of patients whose test results were considered positive for antibodies to AVONEX using a two-tiered assay (ELISA binding assay followed by an antiviral cytopathic effect assay), and 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 AVONEX with the incidence of antibodies to other products may be misleading.
The following additional adverse reactions have been identified during post-approval use of AVONEX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Menorrhagia and metrorrhagia
- Rash (including vesicular rash)
- Rare cases of injection site abscess or cellulitis requiring surgical intervention