Interferon Beta-1B
FDA Drug Information • Also known as: Betaseron
- Brand Names
- Betaseron
- Dosage Form
- KIT
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION 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 beta-1b 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.
What Is Interferon Beta-1B Used For?
1 INDICATIONS AND USAGE 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 an interferon beta indicated for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION
For subcutaneous use only ( 2.1 ) 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. ( 2.1 ) Reconstitute lyophilized powder with supplied diluent ( 2.2 ) 2.1 Dosing Information The recommended starting dose is 0.0625 mg (0.25 mL) subcutaneously every other day, with dose increases over a six-week period to the recommended dose of 0.25 mg (1 mL) every other day (see Table 1 ). Table 1: Schedule for Dose Titration BETASERON Dose Dosed every other day, subcutaneously Percentage of recommended dose Volume Weeks 1-2 0.0625 mg 25% 0.25 mL Weeks 3-4 0.125 mg 50% 0.5 mL Weeks 5-6 0.1875 mg 75% 0.75 mL Week 7 and thereafter 0.25 mg 100% 1 mL If a dose of BETASERON is missed, then it should be taken as soon as the patient remembers or is able to take it. The patient should not take BETASERON on two consecutive days. The next injection should be taken about 48 hours (two days) after that dose. If the patient accidentally takes more than their prescribed dose, or takes it on two consecutive days, they should be instructed to call their healthcare provider immediately. 2.2 Reconstitution of the Lyophilized Powder (a) Prior to reconstitution, verify that the vial containing lyophilized BETASERON is not cracked or damaged. Do not use cracked or damaged vials. (b) To reconstitute lyophilized BETASERON for injection, attach the pre-filled syringe containing the diluent (Sodium Chloride, 0.54% Solution) to the BETASERON vial using the vial adapter. (c) Slowly inject 1.2 mL of diluent into the BETASERON vial. (d) Gently swirl the vial to dissolve the lyophilized powder completely; do not shake . Foaming may occur during reconstitution or if the vial is swirled or shaken too vigorously. If foaming occurs, allow the vial to sit undisturbed until the foam settles. (e) 1 mL of reconstituted BETASERON solution contains 0.25 mg of interferon beta-1b. (f) After reconstitution, if not used immediately, refrigerate the reconstituted BETASERON solution at 35°F to 46°F (2°C to 8°C) and use within three hours. Do not freeze . 2.3 Important Administration Instructions (a) BETASERON is intended for use under the guidance and supervision of a physician. If patients or caregivers are to administer BETASERON, train them in the proper technique for self‐administering subcutaneous injections using the prefilled syringe or the optional injection device. The BETACONNECT autoinjector has three adjustable injection depth settings; the healthcare provider should determine the proper depth setting and injection technique. Use only the syringes in the BETASERON packaging with the BETACONNECT autoinjector. The initial BETASERON injection should be performed under the supervision of an appropriately qualified healthcare provider. Users should demonstrate competency in all aspects of the BETASERON injection prior to independent use....Side Effects (Adverse Reactions)
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...Contraindications
4 CONTRAINDICATIONS 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. History of hypersensitivity to natural or recombinant interferon beta, albumin or mannitol ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary 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 ( see Animal Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Human Data The majority of the observational studies reporting on pregnancies exposed to interferon beta-1b did not identify an association between the use of interferon beta-1b during pregnancy and an increased risk of major birth defects Animal Data When BETASERON (doses ranging from 0.028 to 0.42 mg/kg/day) was administered to pregnant rhesus monkeys throughout the period of organogenesis (gestation days 20 to 70), a dose-related abortifacient effect was observed. The low-effect dose is approximately 3 times the recommended human dose of 0.25 mg on a body surface area (mg/m 2 ) basis. A no-effect dose for embryo-fetal developmental toxicity in rhesus monkeys was not established.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied BETASERON is supplied as a lyophilized powder in a clear glass, single-dose vial (3 mL capacity). Each carton contains 5 single-dose cartons (NDC 50419-524-05) or 14 single-dose cartons (NDC 50419-524-35). Each single-dose carton contains: A single-dose vial containing 0.3 mg BETASERON (interferon beta-1b) A pre-filled single-dose syringe containing 1.2 mL diluent (Sodium Chloride, 0.54% solution) A vial adapter with a 30-gauge needle attached 2 alcohol prep pads The optional BETACONNECT autoinjector is not supplied with BETASERON, but is available for patients with a prescription for BETASERON by calling the BETAPLUS patient support program toll-free number at 1-800-788-1467. 16.2 Stability and Storage BETASERON and the diluent are for single-dose only. Discard unused portions. The reconstituted product contains no preservative. Store BETASERON vials between 36°F to 86°F (2°C to 30°C). After reconstitution, if not used immediately, refrigerate the reconstituted solution and use within three hours. Do not freeze.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.