BETASERON (interferon beta-1b) for injection

BETASERON (interferon beta-1b) for injection

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BETASERON (interferon beta-1b) for injection

BETASERON (interferon beta-1b) is a purified, sterile, lyophilized protein product produced by recombinant DNA techniques. Interferon beta-1b is manufactured by bacterial fermentation of a strain of Escherichia coli that bears a genetically engineered plasmid containing the gene for human interferon betaser17. The native gene was obtained from human fibroblasts and altered in a way that substitutes serine for the cysteine residue found at position 17. Interferon beta1b has 165 amino acids and an approximate molecular weight of 18,500 daltons. It does not include the carbohydrate side chains found in the natural material.

The specific activity of BETASERON is approximately 32 million international units (IU)/mg interferon beta-1b. Each vial contains 0.3 mg of interferon beta-1b. The unit measurement is derived by comparing the antiviral activity of the product to the World Health Organization (WHO) reference standard of recombinant human interferon beta. Mannitol, USP and Albumin (Human), USP (15 mg each/vial) are added as stabilizers.

Lyophilized BETASERON is a sterile, white to off-white powder, for subcutaneous injection after reconstitution with the diluent supplied (Sodium Chloride, 0.54% Solution). Albumin (Human) USP and Mannitol, USP (15 mg each/vial) are added as stabilizers.

Indications and usage

BETASERON is an interferon beta indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.

Mechanism of Action

The mechanism of action of BETASERON (interferon beta-1b) in patients with multiple sclerosis is unknown.

Dosage and administration

  • For subcutaneous use only
  • The recommended dose is 0.25 mg every other day. Generally, start at 0.0625 mg (0.25 mL) every other day, and increase over a six-week period to 0.25 mg (1 mL) every other day.
  • Reconstitute lyophilized powder with supplied diluent
  • Concurrent use of analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with BETASERON use

Contraindications

History of hypersensitivity to natural or recombinant interferon beta, albumin or mannitol

Adverse reactions

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

Warnings and precautions

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.

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. Discontinue BETASERON if anaphylaxis occurs.

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.

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.

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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. 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.

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. Discontinue BETASERON if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.

Flu-like Symptom Complex: In controlled clinical trials, the rate of flu-like symptom complex for patients on BETASERON was 57%. 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. Analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with BETASERON use.

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.

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.

Use in specific populations

Pregnancy: Although there have been no well-controlled studies in pregnant women, available data, which includes prospective observational studies, have not generally indicated a drug-associated risk of major birth defects with interferon beta-1b during pregnancy. Administration of BETASERON to monkeys during gestation resulted in increased embryo-fetal death at or above exposures greater than 3 times the human therapeutic dose.

Lactation: There are no data on the presence of BETASERON in human milk, the effects on the breastfed infant, or the effects of the drug on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BETASERON and any potential adverse effects on the breastfed child from BETASERON or from the underlying maternal condition.

Pediatric Use: Safety and efficacy in pediatric patients have not been established.

Geriatric Use: Clinical studies of BETASERON did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.

Stability and Storage

BETASERON and the diluent are for single-use only. Discard unused portions. The reconstituted product contains no preservative. Store BETASERON vials at room temperature 68°F to 77°F (20°C to 25°C). Excursions of 59°F to 86°F (15°C to 30°C) are permitted for up to 3 months. After reconstitution, if not used immediately, refrigerate the reconstituted solution and use within three hours. Do not freeze.

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