Betaseron kit Kit

BETASERON is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

BETASERON is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, Albumin (Human), or any other component of the formulation.

The following serious adverse reactions are discussed in more details in other sections of labeling:

1. •Hepatic Injury [see Warnings and Precautions (5.1)]
2. •Anaphylaxis and Other Allergic Reactions [see Warnings and Precautions (5.2)]
3. •Depression and Suicide [see Warnings and Precautions (5.3)]
4. •Congestive Heart Failure [see Warnings and Precautions (5.4)]
5. •Injection Site Reactions Including Necrosis [see Warnings and Precautions (5.5)]
6. •Leukopenia [see Warnings and Precautions (5.6)]
7. •Thrombotic Microangiopathy [see Warnings and Precautions (5.7)]
8. •Pulmonary Arterial Hypertension [see Warnings and Precautions (5.8)]
9. •Flu-like Symptom Complex [see Warnings and Precautions (5.9)]
10. •Seizures [see Warnings and Precautions (5.10)]
11. •Drug Induced Lupus Erythematosus [see Warnings and Precautions (5.11)]

• Hepatic Injury: Monitor liver function tests and signs and symptoms of hepatic injury; consider discontinuing BETASERON if serious hepatic injury occurs. (5.1, 5.11)

• Anaphylaxis and Other Allergic Reactions: Discontinue if anaphylaxis occurs. (5.2)

• Depression and Suicide: Advise patients to immediately report any symptom of depression and/or suicidal ideation; consider discontinuation of BETASERON if depression occurs. (5.3)

• Congestive Heart Failure (CHF): Monitor patients with CHF for worsening of cardiac symptoms; consider discontinuation of BETASERON if worsening of CHF occurs. (5.4)

• Injection Site Reactions Including Necrosis: Do not administer BETASERON into affected area until fully healed; if multiple lesions occur, change injection site or discontinue BETASERON until healing of skin lesions. (5.5)

• Leukopenia: Monitor complete blood count. (5.6, 5.12)

• Thrombotic Microangiopathy: Cases of thrombotic microangiopathy (TMA) have been reported. Discontinue BETASERON if clinical symptoms and laboratory findings consistent with TMA occur and a relationship to BETASERON is suspected. (5.7)

• Pulmonary Arterial Hypertension: Cases of pulmonary arterial hypertension (PAH) have been reported in patients treated with interferon beta products, including BETASERON. Discontinue BETASERON if PAH is diagnosed. (5.8)

• Flu-like Symptom Complex: Consider analgesics and/or antipyretics on injection days. (5.9)

• Drug-induced Lupus Erythematosus: Cases of drug-induced lupus erythematosus have been reported. Discontinue BETASERON if patients develop new characteristic signs and symptoms. (5.11) 5.1 Hepatic Injury

Severe hepatic injury including cases of hepatic failure, some of which have been due to autoimmune hepatitis, has been rarely reported in patients taking BETASERON. In some cases, these events have occurred in the presence of other drugs or comorbid medical conditions that have been associated with hepatic injury. Consider the potential risk of BETASERON used in combination with known hepatotoxic drugs or other products (eg, alcohol) prior to BETASERON administration, or when adding new agents to the regimen of patients already on BETASERON. Monitor patients for signs and symptoms of hepatic injury. Consider discontinuing BETASERON if serum transaminase levels significantly increase, or if they are associated with clinical symptoms such as jaundice.

Asymptomatic elevation of serum transaminases is common in patients treated with BETASERON. In controlled clinical trials, elevations of SGPT to greater than five times baseline value were reported in 12% of patients receiving BETASERON (compared to 4% on placebo), and increases of SGOT to greater than five times baseline value were reported in 4% of patients receiving BETASERON (compared to 1% on placebo), leading to dose-reduction or discontinuation of treatment in some patients [see Adverse Reactions (6.1)]. Monitor liver function tests

[see Warnings and Precautions (5.12)]. 5.2 Anaphylaxis and Other Allergic Reactions

Anaphylaxis has been reported as a rare complication of BETASERON use. Other allergic reactions have included dyspnea, bronchospasm, tongue edema, skin rash and urticaria [see Adverse Reactions (6.1)]. Discontinue BETASERON if anaphylaxis occurs. 5.3 Depression and Suicide

Depression and suicide have been reported to occur with increased frequency in patients receiving interferon beta products, including BETASERON. Advise patients to report any symptom of depression and/or suicidal ideation to their healthcare provider. If a patient develops depression, discontinuation of BETASERON therapy should be considered.

In randomized controlled clinical trials, there were three suicides and eight suicide attempts among the 1532 patients on BETASERON compared to one suicide and four suicide attempts among 965 patients on placebo. 5.4 Congestive Heart Failure

Monitor patients with pre-existing congestive heart failure (CHF) for worsening of their cardiac condition during initiation of and continued treatment with BETASERON. While beta interferons do not have any known direct-acting cardiac toxicity, cases of CHF, cardiomyopathy, and cardiomyopathy with CHF have been reported in patients without known predisposition to these events, and without other known etiologies being established. In some cases, these events have been temporally related to the administration of BETASERON. Recurrence upon rechallenge was observed in some patients. Consider discontinuation of BETASERON if worsening of CHF occurs with no other etiology. 5.5 Injection Site Reactions Including Necrosis

Injection site reactions, including injection site necrosis, can occur with the use of interferon beta products, including BETASERON. Injection site necrosis (ISN) was reported in 4% of BETASERON-treated patients in controlled clinical trials (compared to 0% on placebo) [see Adverse Reactions (6.1)]. Typically, ISN occurs within the first four months of therapy, although postmarketing reports have been received of ISN occurring over one year after initiation of therapy. The necrotic lesions are typically 3 cm or less in diameter, but larger areas have been reported. Generally the necrosis has extended only to subcutaneous fat, but has extended to the fascia overlying muscle. In some lesions where biopsy results are available, vasculitis has been reported. For some lesions, debridement, and/or skin grafting have been required. In most cases healing was associated with scarring.

In 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 nonspecific reactions were significantly associated with BETASERON treatment. The incidence of injection site reactions tended to decrease over time. Approximately 69% of patients experienced injection site reactions during the first three months of treatment, compared to approximately 40% at the end of the studies.

Injection site abscesses and cellulitis have been reported in the postmarketing setting with use of interferon beta products including BETASERON. Some cases required treatment with hospitalization for surgical drainage and intravenous antibiotics. Periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures, particularly if injection site necrosis has occurred. Patients should be advised of the importance of rotating injection sites with each dose. Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis. For patients who continue therapy with BETASERON after injection site necrosis has occurred, avoid administration of BETASERON into the affected area until it is fully healed. If multiple lesions occur, change injection site or discontinue therapy until healing occurs. 5.6 Leukopenia

In controlled clinical trials, leukopenia was reported in 18% of patients receiving BETASERON (compared to 6% on placebo), leading to a reduction of the dose of BETASERON in some patients [see Adverse Reactions (6.1)]. Monitoring of complete blood and differential white blood cell counts is recommended. Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts. 5.7 Thrombotic Microangiopathy

Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported with interferon beta products, including BETASERON.

Cases have been reported several weeks to years after starting interferon beta products. If clinical symptoms and laboratory findings consistent with TMA occur and a relationship to BETASERON is suspected, discontinue treatment and manage as clinically indicated. 5.8 Pulmonary Arterial Hypertension

Cases of pulmonary arterial hypertension (PAH) have been reported with interferon beta products, including BETASERON. PAH has occurred in patients treated with interferon beta products in the absence of other contributory factors. Many of the reported cases required hospitalization, including one case with interferon beta in which the patient underwent a lung transplant. PAH has developed at various time points after initiating therapy with interferon beta products and may occur several years after starting treatment.

Patients who develop unexplained symptoms (e.g., dyspnea, new or increasing fatigue) should be assessed for PAH. If alternative etiologies have been ruled out and a diagnosis of PAH is confirmed, discontinue treatment and manage as clinically indicated. 5.9 Flu-like Symptom Complex

In controlled clinical trials, the rate of flu-like symptom complex for patients on BETASERON was 57% [see Adverse Reactions (6.1)]. The incidence decreased over time, with 10% of patients reporting flu-like symptom complex at the end of the studies. The median duration of flu-like symptom complex in Study 1 was 7.5 days [see Clinical Studies (14)]. Analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with BETASERON use. 5.10 Seizures

Seizures have been temporally associated with the use of beta interferons in clinical trials and postmarketing safety surveillance. It is not known whether these events were related to a primary seizure disorder, the effects of multiple sclerosis alone, the use of beta interferons, other potential precipitants of seizures (eg, fever), or to some combination of these. 5.11 Drug-induced Lupus Erythematosus

Cases of drug-induced lupus erythematosus have been reported with some interferon beta products, including BETASERON. Signs and symptoms of drug-induced lupus reported in BETASERON-treated patients have included rash, serositis, polyarthritis, nephritis, and Raynaud's phenomenon. Cases have occurred with positive serologic testing (including positive anti-nuclear and/or anti-double-stranded DNA antibody testing). If BETASERON-treated patients develop new signs and symptoms characteristic of this syndrome, BETASERON therapy should be stopped. 5.12 Monitoring for Laboratory Abnormalities

In addition to those laboratory tests normally required for monitoring patients with multiple sclerosis, complete blood and differential white blood cell counts, platelet counts and blood chemistries, including liver function tests, are recommended at regular intervals (one, three, and six months) following introduction of BETASERON therapy, and then periodically thereafter in the absence of clinical symptoms.

For injection: 0.3 mg lyophilized powder in a single-dose vial for reconstitution.