AVONEX (interferon beta-1a) injection
AVONEX is a 166 amino acid glycoprotein with a molecular weight of approximately
22,500 daltons. It is produced by recombinant DNA technology using genetically engineered Chinese Hamster Ovary cells into which the human interferon beta gene has been introduced. The amino acid sequence of AVONEX is identical to that of natural human interferon beta.
Using the World Health Organization (WHO) International Standard for Interferon, AVONEX has a specific activity of approximately 200 million international units of antiviral activity per mg of interferon beta-1a determined specifically by an in vitro cytopathic effect bioassay using lung carcinoma cells (A549) and Encephalomyocarditis virus (ECM). AVONEX 30 micrograms contains approximately 6 million international units of antiviral activity using this method. The activity against other standards is not known. Comparison of the activity of AVONEX with other interferon betas is not appropriate, because of differences in the reference standards and assays used to measure activity.
AVONEX Lyophilized Powder Vial
A vial of AVONEX is a sterile, white to off-white lyophilized powder for intramuscular injection after reconstitution with supplied diluent (Sterile Water for Injection, USP). Each vial of reconstituted AVONEX contains 30 micrograms of interferon beta-1a; 15 mg Albumin (Human), USP; 5.8 mg Sodium Chloride, USP; 5.7 mg Dibasic Sodium Phosphate, USP; and 1.2 mg Monobasic Sodium Phosphate, USP, in 1.0 mL at a pH of approximately 7.3.
AVONEX Single-Use Prefilled Syringe
A prefilled syringe of AVONEX is a sterile liquid for intramuscular injection. Each 0.5 mL (30 microgram dose) of AVONEX in a prefilled glass syringe contains 30 micrograms of interferon beta-1a, 0.79 mg Sodium Acetate Trihydrate, USP; 0.25 mg Glacial Acetic Acid, USP; 15.8 mg Arginine Hydrochloride, USP; and 0.025 mg Polysorbate 20 in Water for Injection, USP at a pH of approximately 4.8.
AVONEX PEN Single-Use Prefilled Autoinjector
AVONEX PEN is a sterile liquid for intramuscular injection in a prefilled glass syringe surrounded by an autoinjector. Each 0.5 mL (30 microgram dose) in the AVONEX PEN contains 30 micrograms of interferon beta-1a, 0.79 mg Sodium Acetate Trihydrate, USP; 0.25 mg Glacial Acetic Acid, USP; 15.8 mg Arginine Hydrochloride, USP; and 0.025 mg Polysorbate 20 in Water for Injection, USP at a pH of approximately 4.8.
Indications and usage
AVONEX is an interferon beta 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
Mechanism of action
The mechanism of action by which AVONEX exerts its effects in patients with multiple sclerosis is unknown.
Dosage and administration
- For intramuscular use only
- Recommended dose: 30 micrograms once a week
- AVONEX may be titrated, starting with 7.5 micrograms for first week, to reduce flu-like symptoms
- Increase dose by 7.5 micrograms each week for next 3 weeks until recommended dose of 30 micrograms
- Perform first injection under the supervision of an appropriately qualified health care professional
- Analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms
History of hypersensitivity to natural or recombinant interferon beta, albumin or any other component of the formulation
The most common adverse reactions (at least 5% more frequent on AVONEX than on placebo) were flu-like symptoms including chills, fever, myalgia, and asthenia.
Warnings and precautions
Depression, Suicide, and Psychotic Disorders: Patients treated with AVONEX and their caregivers should be advised to report immediately any symptoms of depression, suicidal ideation, and/or psychosis to their prescribing physicians. If a patient develops depression or other severe psychiatric symptoms, cessation of AVONEX therapy should be considered.
Hepatic Injury: Severe hepatic injury, including cases of hepatic failure, has been reported rarely in patients taking AVONEX. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with AVONEX. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. The potential risk of AVONEX used in combination with known hepatotoxic drugs or other products (e.g., alcohol) should be considered prior to starting AVONEX, or before starting hepatotoxic drugs.
Anaphylaxis and Other Allergic-Reactions: Anaphylaxis has been reported as a rare complication of AVONEX use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria. Discontinue AVONEX if anaphylaxis or other allergic reactions occur.
Congestive Heart Failure: Patients with pre-existing congestive heart failure should be monitored for worsening of their cardiac condition during initiation of and continued treatment with AVONEX. While beta interferons do not have any known direct cardiac toxicity, during the postmarketing period cases of congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure have been reported in patients without known predisposition to these events, and without other etiologies being established.
Decreased Peripheral Blood Counts: Decreased peripheral blood counts in all cell lines, including rare pancytopenia and thrombocytopenia, have been reported from postmarketing experience in AVONEX-treated patients.
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 AVONEX. Cases have been reported several weeks to years after starting interferon beta products. Discontinue AVONEX if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.
Use in specific populations
Pregnancy: Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. AVONEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: It is not known whether AVONEX is excreted in human milk.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Storage and handling
AVONEX Lyophilized Powder Vial: Vials of AVONEX should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Should refrigeration be unavailable, vials of AVONEX can be stored at 25°C (77°F) for a period of up to 30 days. DO NOT EXPOSE TO HIGH TEMPERATURES. DO NOT FREEZE. Protect from light. Do not use beyond the expiration date stamped on the vial. Following reconstitution, it is recommended the product be used as soon as possible within 6 hours stored at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE RECONSTITUTED AVONEX.
AVONEX Single-Use Prefilled Syringe: AVONEX in prefilled syringes should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Once removed from the refrigerator, AVONEX in a prefilled syringe should be allowed to warm to room temperature (about 30 minutes). Do not use external heat sources such as hot water to warm AVONEX in a prefilled syringe. Should refrigeration be unavailable, AVONEX in a prefilled syringe can be stored at ≤ 25°C (77°F) for a period up to 7 days. Once the product is removed from the refrigerator, it must not be stored above 25°C (77°F). If the product has been exposed to conditions other than those recommended, DISCARD THE PRODUCT and DO NOT USE. DO NOT EXPOSE TO HIGH TEMPERATURES. DO NOT FREEZE. Protect from light. Do not use beyond the expiration date stamped on the syringe.
AVONEX PEN Single-Use Prefilled Autoinjector: AVONEX PEN should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Once removed from the refrigerator, AVONEX PEN should be allowed to warm to room temperature (about 30 minutes). Do not use external heat sources such as hot water to warm AVONEX. Should refrigeration be unavailable, AVONEX PEN can be stored at ≤ 25°C (77°F) for a period up to 7 days. Once the product is removed from the refrigerator, it must not be stored above 25°C (77°F). If the product has been exposed to conditions other than those recommended, DISCARD THE PRODUCT and DO NOT USE. DO NOT EXPOSE TO HIGH TEMPERATURES. DO NOT FREEZE. Protect from light. Do not use beyond the expiration date stamped on the prefilled autoinjector.