Betaseron Side Effects

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in more details in other sections of labeling: • Hepatic Injury [see Warnings and Precautions ( 5.1 )] • Anaphylaxis and Other Allergic Reactions [see Warnings and Precautions ( 5.2 )] • Depression and Suicide [see Warnings and Precautions ( 5.3 )] • Congestive Heart Failure [see Warnings and Precautions ( 5.4 )] • Injection Site Reactions Including Necrosis [see Warnings and Precautions ( 5.5 )] • Leukopenia [see Warnings and Precautions ( 5.6 )] • Thrombotic Microangiopathy [see Warnings and Precautions ( 5.7 )] • Pulmonary Arterial Hypertension [see Warnings and Precautions ( 5.8 )] • Flu-like Symptom Complex [see Warnings and Precautions ( 5.9 )] • Seizures [see Warnings and Precautions ( 5.10 )] • Drug Induced Lupus Erythematosus [see Warnings and Precautions ( 5.11 )] In controlled clinical trials, the most common adverse reactions (at least 5% more frequent on BETASERON than on placebo) were: injection site reaction, lymphopenia, flu-like symptoms, myalgia, leukopenia, neutropenia, increased liver enzymes, headache, hypertonia, pain, rash, insomnia, abdominal pain, and asthenia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience 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.

Among 1407 patients with MS treated with BETASERON 0.25 mg every other day (including 1261 patients treated for greater than one year), the most commonly reported adverse reactions (at least 5% more frequent on BETASERON than on placebo) were injection site reaction, lymphopenia, flu-like symptoms, myalgia leukopenia, neutropenia, increased liver enzymes, headache, hypertonia, pain, rash, insomnia, abdominal pain, and asthenia.

The most frequently reported adverse reactions resulting in clinical intervention (for example, 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.

Table 2 enumerates adverse reactions and laboratory abnormalities that occurred among patients treated with 0.25 mg of BETASERON every other day by subcutaneous injection in the pooled placebo-controlled trials (Study 1-4) at an incidence that was at least 2% more than that observed in the placebo-treated patients [see Clinical Studies ( 14 )] .

Table 2: Adverse Reactions and Laboratory Abnormalities in Patients with MS in Pooled Studies 1, 2, 3, and 4 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 "Injection site reaction" comprises all adverse reactions occurring at the injection site (except injection site necrosis), that is, 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.

26% 78% Asthenia 48% 53% Flu-like symptoms (complex) "Flu-like symptom (complex)" denotes flu syndrome and/or a combination of at least two adverse reactions from fever, chills, myalgia, malaise, sweating.

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% In addition to the Adverse Reactions listed in Table 2 , the following adverse reactions occurred more frequently on BETASERON than on placebo, but with a difference smaller than 2%: alopecia, anxiety, arthralgia, constipation, diarrhea, dizziness, dyspepsia, dysmenorrhea, leg cramps, menorrhagia, myasthenia, nausea, nervousness, palpitations, peripheral vascular disorder, prostatic disorder, tachycardia, urinary frequency, vasodilatation, and weight increase.

Laboratory Abnormalities In the four clinical trials (Studies 1, 2, 3, and 4), leukopenia was reported in 18% and 6% of patients in BETASERON- and placebo-treated groups, respectively.