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Active ingredient: Interferon Beta-1a

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Interferon Beta-1a uses


1 INDICATIONS AND USAGE

Interferon Beta-1a (interferon beta-1a) is indicated for the treatment of patients with relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease 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.

Interferon Beta-1a is an interferon beta indicated for the treatment of patients with relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease 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. (1)

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Information

Interferon Beta-1a is administered intramuscularly.

The recommended dose is 30 micrograms once a week. To reduce the incidence and severity of flu-like symptoms that may occur when initiating Interferon Beta-1a therapy at a dose of 30 micrograms, Interferon Beta-1a may be started at a dose of 7.5 micrograms and the dose may be increased by 7.5 micrograms each week for the next three weeks until the recommended dose of 30 micrograms is achieved. An AVOSTARTGRIP kit containing 3 titration devices can be used for titration and is to be used only with Interferon Beta-1a Prefilled Syringes.

1 Dosed once a week, intramuscularly
Interferon Beta-1a Dose1 Recommended Dose
Week 1 7.5 micrograms 1/4 dose
Week 2 15 micrograms 1/2 dose
Week 3 22.5 micrograms 3/4 dose
Week 4+ 30 micrograms full dose

2.2 Important Administration Instructions

All Interferon Beta-1a dosage forms are single-use (injection of reconstituted solution, prefilled syringe, and prefilled autoinjector). See Patient's Instructions for Use for complete administration instructions.

The first Interferon Beta-1a injection should be performed under the supervision of an appropriately qualified healthcare professional. If patients or caregivers are to administer Interferon Beta-1a, train them in the proper intramuscular injection technique and assess their ability to inject intramuscularly to ensure the proper administration of Interferon Beta-1a.

Advise patients and caregivers to:


A 25 gauge, 1” needle for intramuscular injection with Interferon Beta-1a prefilled syringe or injection of reconstituted solution may be substituted for the 23 gauge, 1 ¼” needle by the healthcare provider, if deemed appropriate. A 25 gauge, 5/8” needle specific to the prefilled autoinjector is supplied with the Interferon Beta-1a PEN® Administration Dose Pack. DO NOT use any other needle with the autoinjector.

Use safe disposal procedures for needles and syringes. Do not re-use needles, syringes, prefilled syringes, or autoinjectors. Following the administration of each titrated dose, discard any remaining product.

2.3 Premedication for Flu-like Symptoms

Concurrent use of analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with Interferon Beta-1a use.

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3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

Interferon Beta-1a is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, or any other component of the formulation [see Warnings and Precautions (5.3)].

The lyophilized vial formulation of Interferon Beta-1a is contraindicated in patients with a history of hypersensitivity to albumin (human).

5 WARNINGS AND PRECAUTIONS

5.1 Depression, Suicide, and Psychotic Disorders

Patients treated with Interferon Beta-1a 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 Interferon Beta-1a therapy should be considered.

Depression and suicide have been reported to occur with increased frequency in patients receiving Interferon Beta-1a. In Study 1, the incidence of depression was similar in placebo-treated and in AVONEX-treated patients, but suicidal tendency was seen more frequently in AVONEX-treated patients (4% in Interferon Beta-1a group vs. 1% in placebo group). In Study 2, there was a greater incidence of depression in AVONEX-treated patients than in placebo-treated patients (20% in Interferon Beta-1a group vs. 13% in placebo group) [see Clinical Studies (14)].

Additionally, there have been postmarketing reports of depression, suicidal ideation, and/or development of new or worsening of other pre-existing psychiatric disorders, including psychosis. For some of these patients, symptoms of depression improved upon cessation of Interferon Beta-1a.

5.2 Hepatic Injury

Severe hepatic injury, including cases of hepatic failure, has been reported rarely in patients taking Interferon Beta-1a. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with Interferon Beta-1a. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. The potential risk of Interferon Beta-1a used in combination with known hepatotoxic drugs or other products should be considered prior to starting Interferon Beta-1a, or before starting hepatotoxic drugs. Patients should be monitored for signs of hepatic injury [see Warnings and Precautions (5.9)].

5.3 Anaphylaxis and Other Allergic-Reactions

Anaphylaxis has been reported as a rare complication of Interferon Beta-1a use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria. Discontinue Interferon Beta-1a if anaphylaxis or other allergic reactions occur.

5.4 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 Interferon Beta-1a. 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. In some cases, these events have been temporally related to the administration of Interferon Beta-1a. In some of these instances recurrence upon rechallenge was observed.

5.5 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 [see Adverse Reactions ]. In some cases, platelet counts were below 10,000/microliter. Some cases recurred with rechallenge [see Adverse Reactions (6.2)]. Patients should be monitored for symptoms or signs of decreased blood counts.

5.6 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 Interferon Beta-1a. Cases have been reported several weeks to years after starting interferon beta products. Discontinue Interferon Beta-1a if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.

5.7 Seizures

Seizures have been temporally associated with the use of beta interferons in clinical trials and postmarketing safety surveillance. In the two placebo-controlled studies in multiple sclerosis, 4 patients receiving Interferon Beta-1a experienced seizures, while no seizures occurred in the placebo group [see Clinical Studies (14)]. Three of these 4 patients had no prior history of seizure [see Adverse Reactions (6.1)]. It is not known whether these events were related to the effects of multiple sclerosis alone, to Interferon Beta-1a, or to a combination of both.

5.8 Autoimmune Disorders

Postmarketing reports of autoimmune disorders of multiple target organs in AVONEX-treated patients included idiopathic thrombocytopenia, hyper- and hypothyroidism, and rare cases of autoimmune hepatitis. If AVONEX-treated patients develop a new autoimmune disorder, consider stopping the therapy.

5.9 Laboratory Tests

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 during Interferon Beta-1a therapy [see Warnings and Precautions (5.2, 5.5, 5.8)]. Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts. Thyroid function should be monitored periodically. If patients have or develop symptoms of thyroid dysfunction (hypo- or hyperthyroidism), thyroid function tests should be performed according to standard medical practice.

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6 ADVERSE REACTIONS

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


The most common adverse reactions (at least 5% more frequent on Interferon Beta-1a than on placebo) were flu-like symptoms including chills, fever, myalgia, and asthenia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1-800-456-2255 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, adverse reaction rates observed in the clinical trials of Interferon Beta-1a cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice.

Among 351 patients with relapsing forms of MS treated with Interferon Beta-1a 30 micrograms (including 319 patients treated for 6 months and 288 patients treated for greater than one year) the most commonly reported adverse reactions (at least 5% more frequent on Interferon Beta-1a than on placebo) were flu-like symptoms. Symptoms can include chills, fever, myalgia and asthenia occurring within hours to days following an injection. Most people who take Interferon Beta-1a have flu-like symptoms early during the course of therapy. Usually, these symptoms last for a day after the injection. For many people, these symptoms lessen or go away over time. The most frequently reported adverse reactions resulting in clinical intervention (for example, discontinuation of Interferon Beta-1a or the need for concomitant medication to treat an adverse reaction symptom) were flu-like symptoms and depression.

Table 2 enumerates adverse reactions that occurred with AVONEX-treated patients at an incidence of at least 2% more than that observed in the placebo-treated patients in the pooled placebo-controlled studies in patients with relapsing forms of MS [see Clinical Studies (14)].

Placebo Interferon Beta-1a
Adverse Reaction (N = 333) (N = 351)
Body as a Whole
Headache 55% 58%
Flu-like symptoms (otherwise unspecified) 29% 49%
Pain 21% 23%
Asthenia 18% 24%
Fever 9% 20%
Chills 5% 19%
Abdominal pain 6% 8%
Injection site pain 6% 8%
Infection 4% 7%
Injection site inflammation 2% 6%
Chest pain 2% 5%
Injection site reaction 1% 3%
Toothache 1% 3%
Nervous System
Depression 14% 18%
Dizziness 12% 14%
Respiratory System
Upper respiratory tract infection 12% 14%
Sinusitis 12% 14%
Bronchitis 5% 8%
Digestive System
Nausea 19% 23%
Musculoskeletal System
Myalgia 22% 29%
Arthralgia 6% 9%
Urogenital
Urinary tract infection 15% 17%
Urine constituents abnormal 0% 3%
Skin and Appendages
Alopecia 2% 4%
Special Senses
Eye disorder 2% 4%
Hemic and Lymphatic System
Injection site ecchymosis 4% 6%
Anemia 1% 4%
Cardiovascular System
Migraine 3% 5%
Vasodilation 0% 2%

Immunogenicity

Anaphylaxis and other allergic reactions have occurred in AVONEX-treated patients [see Warnings and Precautions (5.3)]. As with all therapeutic proteins, there is a potential for immunogenicity. In studies assessing immunogenicity in multiple sclerosis patients administered Interferon Beta-1a for at least 1 year, 5% (21 of 390 patients) showed the presence of neutralizing antibodies at one or more times.

These data reflect the percentage of patients whose test results were considered positive for antibodies to Interferon Beta-1a using a two-tiered assay (ELISA binding assay followed by an antiviral cytopathic effect assay), and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of neutralizing activity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Interferon Beta-1a with the incidence of antibodies to other products may be misleading.

6.2 Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of Interferon Beta-1a. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

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8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Interferon Beta-1a should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In pregnant monkeys given interferon beta at 100 times the recommended weekly human dose (based upon a body surface area [mg/m2] comparison), no teratogenic or other adverse effects on fetal development were observed. Abortifacient activity was evident following 3 to 5 doses at this level. No abortifacient effects were observed in monkeys treated at 2 times the recommended weekly human dose (based upon mg/m2).

8.3 Nursing Mothers

It is not known whether Interferon Beta-1a is excreted in human milk.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of Interferon Beta-1a did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.

11 DESCRIPTION

Interferon Beta-1a 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 Interferon Beta-1a is identical to that of natural human interferon beta.

Using the World Health Organization International Standard for Interferon, Interferon Beta-1a 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). Interferon Beta-1a 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 Interferon Beta-1a with other interferon betas is not appropriate, because of differences in the reference standards and assays used to measure activity.

11.1 Interferon Beta-1a Lyophilized Powder Vial

A vial of Interferon Beta-1a 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 Interferon Beta-1a 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.

11.2 Interferon Beta-1a Single-Use Prefilled Syringe

A prefilled syringe of Interferon Beta-1a is a sterile liquid for intramuscular injection. Each 0.5 mL of Interferon Beta-1a 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.

11.3 Interferon Beta-1a PEN Single-Use Prefilled Autoinjector

Interferon Beta-1a 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 Interferon Beta-1a 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.

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action by which Interferon Beta-1a exerts its effects in patients with multiple sclerosis is unknown.

12.2 Pharmacodynamics

Interferons are a family of naturally occurring proteins, produced by eukaryotic cells in response to viral infection and other biologic agents. Three major types of interferons have been defined: type I (IFN-alpha, beta, epsilon, kappa and omega), type II (IFN–gamma) and type III (IFN-lambda). Interferon-beta is a member of the type I subset of interferons. The type I interferons have considerably overlapping but also distinct biologic activities. The bioactivities of all IFNs, including IFN-beta, are induced via their binding to specific receptors on the membranes of human cells. Differences in the bioactivites induced by the three major subtypes of IFNs likely reflect differences in the signal transduction pathways induced by signaling through their cognate receptors.

Interferon beta exerts its biological effects by binding to specific receptors on the surface of human cells. This binding initiates a complex cascade of intracellular events that leads to the expression of numerous interferon-induced gene products and markers. These include 2', 5'-oligoadenylate synthetase, β2-microglobulin, and neopterin. These products have been measured in the serum and cellular fractions of blood collected from patients treated with Interferon Beta-1a.

Clinical studies conducted in multiple sclerosis patients showed that interleukin 10 (IL-10) levels in cerebrospinal fluid were increased in patients treated with Interferon Beta-1a compared to placebo. Serum IL-10 levels maximally were increased by 48 hours after intramuscular injection of Interferon Beta-1a and remained elevated for 1 week. However, no relationship has been established between absolute levels of IL-10 and clinical outcome in multiple sclerosis.

12.3 Pharmacokinetics

Pharmacokinetics of Interferon Beta-1a in multiple sclerosis patients have not been evaluated. The pharmacokinetic and pharmacodynamic profiles of Interferon Beta-1a in healthy subjects following doses of 30 micrograms through 75 micrograms have been investigated. Serum levels of Interferon Beta-1a as measured by antiviral activity are slightly above detectable limits following a 30 microgram intramuscular dose, and increase with higher doses.

After an intramuscular dose, serum levels of Interferon Beta-1a generally peak at 15 hours post-dose (range: 6-36 hours) and then decline at a rate consistent with a 19 (range: 8-54) hour elimination half-life.

Subcutaneous administration of Interferon Beta-1a should not be substituted for intramuscular administration as there is no data establishing that subcutaneous and intramuscular administration of Interferon Beta-1a result in equivalent pharmacokinetic and pharmacodynamic parameters.

Biological response markers (e.g., neopterin and β2-microglobulin) are induced by Interferon Beta-1a following parenteral doses of 15 micrograms through 75 micrograms in healthy subjects and treated patients. Biological response marker levels increase within 12 hours of dosing and remain elevated for at least 4 days. Peak biological response marker levels are typically observed 48 hours after dosing. The relationship of serum Interferon Beta-1a levels or levels of these induced biological response markers to the mechanisms by which Interferon Beta-1a exerts its effects in multiple sclerosis is unknown.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

Carcinogenesis: The carcinogenic potential of Interferon Beta-1a has not been tested in animals.

Mutagenesis: Interferon beta was not mutagenic when tested in an in vitro bacterial reverse mutation (Ames) test or in an in vitro cytogenetic assay in human lymphocytes.

Impairment of Fertility: In monkeys administered interferon beta by subcutaneous injection (8 to 15 doses of 1.25 mcg/kg or 50 mcg/kg) over the course of one menstrual cycle, menstrual irregularities, anovulation, and decreased serum progesterone levels were observed at the higher dose. These effects were reversible after discontinuation of drug. The no-effect dose (1.25 mcg/kg) is approximately 2 times the recommended weekly dose in humans (30 mcg) on a mg/m2 basis.

14 CLINICAL STUDIES

The clinical effects of Interferon Beta-1a in patients with relapsing forms of multiple sclerosis (MS) were studied in two randomized, multicenter, double-blind, placebo-controlled studies in patients with MS (Studies 1 and 2). Safety and efficacy of treatment with Interferon Beta-1a beyond 3 years is not known.

In Study 1, 301 patients received either 30 micrograms of Interferon Beta-1a (n=158) or placebo (n=143) by intramuscular injection once weekly. Patients received injections for up to 2 years, and continued to be followed until study completion. Two hundred eighty-two patients completed 1 year on study, and 172 patients completed 2 years on study. There were 144 patients treated with Interferon Beta-1a for more than 1 year, 115 patients for more than 18 months and 82 patients for 2 years.

All patients had a definite diagnosis of multiple sclerosis of at least 1 year duration and had at least 2 exacerbations in the 3 years prior to study entry (or 1 per year if the duration of disease was less than 3 years). At entry, study participants were without exacerbation during the prior 2 months and had Kurtzke Expanded Disability Status Scale (EDSS3) scores ranging from 1.0 to 3.5. The EDSS is a scale that quantifies disability in patients with MS and ranges from 0 (normal neurologic exam) to 10 (death due to MS). Patients with chronic progressive multiple sclerosis were excluded from this study.

Disability

The primary outcome assessment was time to progression in disability, measured as an increase in the EDSS score of at least 1 point that was sustained for at least 6 months. An increase in EDSS score reflects accumulation of disability. This endpoint was used to help distinguish permanent increase in disability from a transient increase due to an exacerbation.

As shown in Figure 1, the time to onset of sustained progression in disability was significantly longer in AVONEX-treated patients than in placebo-treated patients in Study 1 (p = 0.02). The percentage of patients progressing by the end of 2 years was 35% for placebo-treated patients and 22% for AVONEX-treated patients. This represents a 37% relative reduction in the risk of accumulating disability in the AVONEX-treated group compared to the placebo-treated group.

1 Kaplan-Meier Methodology; Disability progression was defined as at least a 1 point increase in EDSS score sustained for at least 6 months.

The distribution of confirmed EDSS change from study entry (baseline) to the end of the study is shown in Figure 2. There was a statistically significant difference between the Interferon Beta-1a and placebo groups in confirmed change for patients with at least 2 scheduled visits (p = 0.006).

Figure 1 Figure 2

Exacerbations

The rate and frequency of MS exacerbations were secondary outcomes. For all patients included in the study, irrespective of time on study, the annual exacerbation rate was 0.67 per year in the AVONEX-treated group and 0.82 per year in the placebo-treated group (p = 0.04).

Interferon Beta-1a treatment significantly decreased the frequency of exacerbations in the subset of patients who were enrolled in the study for at least 2 years (87 placebo-treated patients and 85 AVONEX-treated patients; p = 0.03; see Table 3).

MRI Results

Gadolinium (Gd)-enhanced and T2-weighted magnetic resonance imaging (MRI) scans of the brain were obtained in most patients at baseline and at the end of 1 and 2 years of treatment. Secondary outcomes included Gd-enhanced lesion number and volume, and T2-weighted lesion volume. Gd-enhancing lesions seen on brain MRI scans represent areas of breakdown of the blood brain barrier thought to be secondary to inflammation. AVONEX-treated patients demonstrated significantly lower Gd-enhanced lesion number after 1 and 2 years of treatment than placebo-treated patients (p ≤ 0.05; see Table 3). The volume of Gd-enhanced lesions showed similar treatment effects in the Interferon Beta-1a and placebo groups (p ≤ 0.03). Percentage change in T2-weighted lesion volume from study entry to Year 1 was significantly lower in AVONEX-treated than placebo-treated patients (p = 0.02). A significant difference in T2-weighted lesion volume change was not seen between study entry and Year 2 in the Interferon Beta-1a and placebo groups.

The exact relationship between MRI findings and the clinical status of MS patients is unknown. The prognostic significance of MRI findings in these studies has not been evaluated.

Summary of Effects of Clinical and MRI Endpoints in Study 1

A summary of the effects of Interferon Beta-1a on the clinical and MRI endpoints of this study is presented in Table 3.

Note: (N:, ) denotes the number of evaluable placebo and Interferon Beta-1a patients, respectively.

1 Patient data included in this analysis represent variable periods of time on study.

2 Analyzed by Mantel-Cox (logrank) test.

3 Analyzed by Mann-Whitney rank-sum test.

4 Analyzed by Cochran-Mantel-Haenszel test.

5 Analyzed by likelihood ratio test.

Endpoint Placebo Interferon Beta-1a P-Value
PRIMARY ENDPOINT:
Time to sustained progression
in disability (N: 143, 158)1 --- See Figure 1 --- 0.022
Percentage of patients progressing
in disability at 2 years
(Kaplan-Meier estimate)1 35% 22%
SECONDARY ENDPOINTS:
DISABILITY
Mean confirmed change in EDSS
from study entry to end of study
(N: 136, 150)1 0.50 0.20 0.0063
EXACERBATIONS
Number of exacerbations in subset
completing 2 years (N: 87, 85)
0 26% 38% 0.033
1 30% 31%
2 11% 18%
3 14% 7%
≥ 4 18% 7%
Percentage of patients exacerbation-
free in subset completing 2 years
(N: 87, 85) 26% 38% 0.104
Annual exacerbation rate
(N: 143, 158)1 0.82 0.67 0.045
Table 3 (continued): Clinical and MRI Endpoints in Study 1
Endpoint Placebo Interferon Beta-1a P-Value
MRI
Number of Gd-enhanced lesions:
At study entry (N: 132, 141)
Mean (Median) 2.3 (1.0) 3.2 (1.0)
Range 0-23 0-56
Year 1 (N: 123, 134)
Mean (Median) 1.6 (0) 1.0 (0) 0.023
Range 0-22 0-28
Year 2 (N: 82, 83)
Mean (Median) 1.6 (0) 0.8 (0) 0.053
Range 0-34 0-13
T2 lesion volume:
Percentage change from study
entry to Year 1 (N: 116, 123)
Median -3.3% -13.1% 0.023
Percentage change from study
entry to Year 2 (N: 83, 81)
Median -6.5% -13.2% 0.363

In Study 2, 383 patients who had recently experienced an isolated demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and who had lesions typical of multiple sclerosis on brain MRI, received either 30 micrograms of Interferon Beta-1a (n = 193) or placebo (n = 190) by intramuscular injection once weekly. Patients were enrolled into the study over a two-year period and followed for up to three years or until they developed a second clinical exacerbation in an anatomically distinct region of the central nervous system.

Exacerbations

In Study 2, the primary outcome measure was time to development of a second exacerbation in an anatomically distinct region of the central nervous system. Time to development of a second exacerbation was significantly delayed in AVONEX-treated compared to placebo-treated patients (p = 0.002). The Kaplan-Meier estimates of the percentage of patients developing an exacerbation within 24 months were 39% in the placebo group and 21% in the Interferon Beta-1a group. The relative rate of developing a second exacerbation in the Interferon Beta-1a group was 0.56 of the rate in the placebo group (95% confidence interval 0.38 to 0.81).

1 Kaplan-Meier Methodology

Figure 3

MRI Findings

Secondary outcomes were brain MRI measures, including the cumulative increase in the number of new or enlarging T2 lesions, T2 lesion volume at baseline compared to results at 18 months, and the number of Gd-enhancing lesions at 6 months. See Table 4 for the MRI results.

1 P value <0.001
2 P value <0.03
* P value from a Mann-Whitney rank-sum test
Interferon Beta-1a Placebo
CHANGE FROM BASELINE IN T2 VOLUME OF LESIONS AT 18 MONTHS: N = 119 N = 109
Actual Change (mm3)1*

Median (25th%, 75th%)

28 (-576, 397)

313 (5, 1140)
Percentage Change1*

Median (25th%, 75th%)

1 (-24, 29)

16 (0, 53)
NUMBER OF NEW OR ENLARGING T2 LESIONS AT 18 MONTHS 1* : N = 132

N (%)

 N = 119

N (%)
0 62 (47) 22 (18)
1-3 41 (31) 47 (40)
≥4 29 (22) 50 (42)
Mean (SD) 2.13 (3.2) 4.97 (7.7)
NUMBER OF GD-ENHANCING LESIONS AT 6 MONTHS 2* : N = 165

N (%)

 N = 152

N (%)
0 115 (70) 93 (61)
1 27 (16) 16 (11)
>1 23 (14) 43 (28)
Mean (SD) 0.87 (2.3) 1.49 (3.1)

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 Interferon Beta-1a Lyophilized Powder Vial

A vial of Interferon Beta-1a is supplied as a lyophilized powder in a single-use vial containing 33 micrograms of Interferon Beta-1a; 16.5 mg Albumin (Human), USP; 6.4 mg Sodium Chloride, USP; 6.3 mg Dibasic Sodium Phosphate, USP; and 1.3 mg Monobasic Sodium Phosphate, USP, and is preservative-free. Diluent is supplied in a single-use vial (Sterile Water for Injection, USP).

Interferon Beta-1a lyophilized vials are available in the following package configuration (NDC 59627-111-03): A package containing four Administration Dose Packs (each containing one vial of Interferon Beta-1a, one 10 mL diluent vial, two alcohol wipes, one gauze pad, one 3 mL syringe, one MICRO PIN®* vial access pin, one 23 gauge, 1¼ inch needle, and one adhesive bandage).

Vials of Interferon Beta-1a should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Should refrigeration be unavailable, vials of Interferon Beta-1a 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 Interferon Beta-1a.

16.2 Interferon Beta-1a Single-Use Prefilled Syringe

A prefilled syringe of Interferon Beta-1a is supplied as a sterile liquid albumin-free formulation containing 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. Each prefilled glass syringe contains 0.5 mL for Intramuscular injection.

Interferon Beta-1a prefilled syringes are available in the following package configuration (NDC 59627-222-05): A package containing four Administration Dose Packs (each containing one single-use syringe of Interferon Beta-1a and one 23 gauge, 1¼ inch needle), and a recloseable accessory pouch containing 4 alcohol wipes, 4 gauze pads, and 4 adhesive bandages.

Interferon Beta-1a in prefilled syringes should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Once removed from the refrigerator, Interferon Beta-1a 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 Interferon Beta-1a in a prefilled syringe. Should refrigeration be unavailable, Interferon Beta-1a 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.

16.3 Interferon Beta-1a PEN Single-Use Prefilled Autoinjector

Interferon Beta-1a PEN is supplied as a sterile liquid albumin-free formulation containing 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. Each single-use prefilled autoinjector contains 0.5 mL for intramuscular injection.

Interferon Beta-1a PEN single-use prefilled autoinjectors are available in the following package configuration (NDC 59627-333-04): A package containing four Interferon Beta-1a PEN Administration Dose Packs (each containing one Interferon Beta-1a PEN autoinjector, one 25 gauge, 5/8 inch needle and an Interferon Beta-1a PEN cover), and a recloseable accessory pouch containing 4 alcohol wipes, 4 gauze pads, and 4 adhesive bandages.

Interferon Beta-1a PEN should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Once removed from the refrigerator, Interferon Beta-1a PEN should be allowed to warm to room temperature (about 30 minutes). Do not use external heat sources such as hot water to warm Interferon Beta-1a. Should refrigeration be unavailable, Interferon Beta-1a 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.

17 PATIENT COUNSELING INFORMATION

Instruct patients to carefully read the supplied Interferon Beta-1a Medication Guide and caution patients not to change the Interferon Beta-1a dose or schedule of administration without medical consultation.

Inform patients that the Prefilled Syringe tip cap of this product contains natural rubber latex which may cause allergic reactions.

Instruction on Self-injection Technique and Procedures

Provide appropriate instruction for reconstitution of Interferon Beta-1a and methods of self-injection, including careful review of the Interferon Beta-1a Medication Guide. Instruct patients in the use of aseptic technique when administering Interferon Beta-1a.

Inform patients that their healthcare provider should show them or their caregiver how to prepare and inject Interferon Beta-1a before administering the first dose. Their healthcare provider should watch the first Interferon Beta-1a injection given. Tell patients not to re-use needles or syringes and instruct patients on safe disposal procedures. Inform patients to dispose of used needles and syringes in a puncture-resistant container and instruct the patient regarding safe disposal of full containers.

Advise patients:


Pregnancy

Advise patients that Interferon Beta-1a should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use in Special Population (8.1)].

Depression

Advise patients of the symptoms of depression, suicidal ideation, or psychotic disorders as they have been reported with the use of Interferon Beta-1a and instruct patients to report them immediately to their physician [see Warnings and Precautions (5.1)].

Liver Disease

Advise patients that severe hepatic injury, including hepatic failure, has been reported during the use of Interferon Beta-1a. Advise patients of symptoms of hepatic dysfunction, and instruct patients to report them immediately to their physician [see Warnings and Precautions (5.2)].

Allergic Reactions and Anaphylaxis

Advise patients of the symptoms of allergic reactions and anaphylaxis, and instruct patients to seek immediate medical attention if these symptoms occur [see Warnings and Precautions (5.3)].

Congestive Heart Failure

Advise patients that worsening of pre-existing congestive heart failure has been reported in patients using Interferon Beta-1a. Advise patients of symptoms of worsening cardiac condition, and instruct patients to report them immediately to their physician [see Warnings and Precautions (5.4)].

Seizures

Advise patients that seizures have been reported in patients using Interferon Beta-1a. Instruct patients to report seizures immediately to their physician [see Warnings and Precautions (5.7)].

Flu-like Symptoms

Inform patients that flu-like symptoms are common following initiation of therapy with Interferon Beta-1a [see Dosage and Administration (2.3) and Adverse Reactions (6)]. Advise patients that starting with a lower dose than 30 micrograms and increasing the dose over 3 weeks reduces the incidence and severity of flu-like symptoms.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License #1697

© Biogen [1996-2016]. All rights reserved.

1-800-456-2255

*MICRO PIN ® is the trademark of B. Braun Medical Inc.

Medication Guide

Interferon Beta-1a ® (a-vuh-necks)

(interferon beta-1a)

Injection for intramuscular use

Read this Medication Guide before you start using Interferon Beta-1a, and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about Interferon Beta-1a?

Interferon Beta-1a can cause serious side effects. Tell your healthcare provider right away if you have any of the symptoms listed below while taking Interferon Beta-1a.


What is Interferon Beta-1a?

Interferon Beta-1a is a form of a protein called beta interferon that occurs naturally in the body. Interferon Beta-1a is a prescription medicine used to treat adults with relapsing forms of multiple sclerosis (MS). This includes people who have had their first symptoms of multiple sclerosis and have an MRI consistent with multiple sclerosis.

Interferon Beta-1a will not cure your MS but may decrease the number of flare-ups of the disease and slow the occurrence of some of the physical disability that is common in people with MS. MS is a life-long disease that affects your nervous system by destroying the protective covering (myelin) that surrounds your nerve fibers.

The way Interferon Beta-1a works in MS is not known.

It is not known if Interferon Beta-1a is safe and effective in children.

Who should not use Interferon Beta-1a?

Do not take Interferon Beta-1a if you:


What should I tell my healthcare provider before using Interferon Beta-1a?

Before taking Interferon Beta-1a, tell your healthcare provider if you:


Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

How should I use Interferon Beta-1a?


Your healthcare provider will decide which one is best for you. See the Instructions for Use at the end of this Medication Guide for detailed instructions for preparing and injecting your dose of Interferon Beta-1a.


What are the possible side effects of Interferon Beta-1a?

Interferon Beta-1a can cause serious side effects including:


Tell your healthcare provider right away if you have any of the symptoms listed above.

The most common side effects of Interferon Beta-1a include:


Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Interferon Beta-1a?


Keep Interferon Beta-1a vials, prefilled syringes, pens and all other medicines out of the reach of children.

General advice about the safe and effective use of Interferon Beta-1a

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Interferon Beta-1a for a condition for which it was not prescribed. Do not give Interferon Beta-1a to other people, even if they have the same symptoms that you have, it may harm them.

This Medication Guide summarizes the most important information about Interferon Beta-1a. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about Interferon Beta-1a that is written for healthcare professionals.

What are the ingredients in Interferon Beta-1a?

Active ingredient: Interferon Beta-1a

Inactive ingredients:


This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License #1697

© Biogen [1996-2016]. All rights reserved.

1-800-456-2255

Revised: 03/2016

Instructions for Use

Interferon Beta-1a PEN ® (a-vuh-necks) (pen)

(interferon beta-1a)

injection for intramuscular use

single-use prefilled autoinjector pen

Read the Instructions for Use before you start using Interferon Beta-1a and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Your healthcare provider should show you or your caregiver how to prepare the dose of Interferon Beta-1a and how to inject your Interferon Beta-1a PEN the right way before Interferon Beta-1a PEN is used for the first time. Your healthcare provider or nurse should watch you inject the dose of Interferon Beta-1a the first time Interferon Beta-1a PEN is used.

Preparing the Interferon Beta-1a PEN:


Supplies you will need to give the Interferon Beta-1a PEN injection:


Identifying parts of the Interferon Beta-1a PEN.

Single-Use Administration Dose Pack Contents – Interferon Beta-1a PEN, Supplied Needle and Interferon Beta-1a PEN Cover

(Figure A)

Preparing the Interferon Beta-1a PEN injection:

Step 1: Hold the Interferon Beta-1a PEN with the white tamper-evident cap (cap) pointing up.

  • Check that the cap is intact and has not been removed. If the cap has been removed or is not tightly attached, do not use it, throw it away and get a new Interferon Beta-1a PEN.

(Figure B)
Step 2: With your other hand, grasp the cap and bend it at a 90° angle until the cap snaps off.

  • After the cap comes off, you will see the glass tip of the syringe. Do not touch the glass tip of the syringe.

(Figure C)

(Figure D)
Step 3: Place the Interferon Beta-1a PEN down on a flat work surface.
Step 4: Pull off the sterile foil from the needle cover.

  • Only use the needle that comes with your Interferon Beta-1a PEN.

(Figure E)
Step 5: Hold the Interferon Beta-1a PEN with the glass syringe tip pointing up. Press the needle onto the Interferon Beta-1a PEN glass syringe tip.

(Figure F)
Step 6: Gently turn the needle clockwise until it is firmly attached.

  • If the needle is not firmly attached, it may leak, and you may not get your full dose of Interferon Beta-1a.

(Figure G)
  • Do not remove the plastic cover from the needle.

(Figure H)
Step 7: Hold the body of the Interferon Beta-1a PEN in 1 hand with the needle and needle cover pointing away from you and other people. Do not remove the plastic cover from the needle.

(Figure I)
Step 8: Using your other hand, hold onto the injector shield (grooved area) tightly and quickly pull up on the injector shield until the injector shield covers the needle all the way.

  • The plastic needle cover will “pop” off after the injector shield has been fully extended.

(Figure J)
  • When the injector shield is extended the right way, you will see a small blue rectangular area next to the oval medication display window.

(Figure K)
Step 9: Check the oval medication display window and make sure the Interferon Beta-1a is clear and colorless.

You might see air bubbles in the oval display window. This is normal and will not affect your dose.

  • Do not use Interferon Beta-1a PEN if the liquid is colored, cloudy, or contains any lumps or particles. Throw away the Interferon Beta-1a PEN and get a new one, then repeat steps 1 to 9.

(Figure L)

Giving the Interferon Beta-1a injection:


Figure M

Step 10: Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose.

  • Do not touch this area again before giving the injection.

(Figure N)
Step 11: Place the Interferon Beta-1a PEN on the injection site.

(Figure O)
Step 12: Hold the body of the Interferon Beta-1a PEN at a 90º angle to the injection site, and make sure you can see the windows.

(Figure P)
Step 13: Keeping your fingers away from the blue activation button, firmly push the body of the Interferon Beta-1a PEN down against the thigh to release the safety lock. Do not lift the Interferon Beta-1a PEN off of the injection site.

  • Check to make sure the safety lock has been released. You will know the safety lock is released when the small blue rectangular area above the oval medication display window is gone.

(Figure Q)

(Figure R)
Step 14: Continue to firmly maintain pressure and push down on the Interferon Beta-1a PEN against the injection site, then push down on the blue activation button with your thumb. Keep the Interferon Beta-1a PEN pushed down against the injection site and slowly count to 10.

  • You will hear a “click” when the injection starts. If you do not hear a “click”, your injection was not given the right way.
    • If this happens, make sure that the injector shield is extended, the safety lock is completely released, and that you are firmly maintaining pressure and pushing down against the injection site. Press the blue activation button with your thumb again. If you still do not hear a “click”, call Biogen Idec Inc. at 1-800-456-2255.

(Figure S)
Step 15: After you count to 10, pull the Interferon Beta-1a PEN straight out of the skin. Use the gauze pad to apply pressure to the injection site for a few seconds or rub gently in a circular motion.

  • If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.

(Figure T)
Step 16: Check the circular display window on the Interferon Beta-1a PEN to make sure that it is yellow. This is to be sure that you have been given your full dose.

  • If you did not receive your full dose of Interferon Beta-1a, throw away the Interferon Beta-1a PEN and call your doctor. Do not re-use the Interferon Beta-1a PEN.

(Figure U)
STEP 17: Do not hold the Interferon Beta-1a PEN cover with your hands. Place the Interferon Beta-1a PEN cover on a flat work surface. Line up the exposed needle with the hole of the Interferon Beta-1a PEN cover, and insert directly into the opening.

(Figure V)
STEP 18: Firmly press the Interferon Beta-1a PEN down until you hear a “click” to seal the needle. You may need to hold both hands around the Interferon Beta-1a PEN body to snap the Interferon Beta-1a PEN cover into place.

(Figure W)

After the Interferon Beta-1a injection:


General information about the safe and effective use of Interferon Beta-1a PEN


This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License # 1697©Biogen [1996-2015]. All rights reserved.

1-800-456-2255

Revised: 08/2015

41610-02

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Instructions for Use

Interferon Beta-1a ® (a-vuh-necks)

(interferon beta-1a)

injection for intramuscular use

single-use prefilled syringe

Read the Instructions for Use before you start using Interferon Beta-1a and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Supplies you will need for the Interferon Beta-1a injection:


Preparing the dose of Interferon Beta-1a:


Identifying parts of the Interferon Beta-1a prefilled syringe :

Preparing the Interferon Beta-1a injection:

Step 1: Hold the Interferon Beta-1a prefilled syringe with the cap pointing down and with the 0.5 mL mark at eye level.

  • Check the syringe:
    • The syringe should not have any cracks or damage.
    • Check that the cap is intact and has not been removed.
    • The amount of liquid in the syringe should be at or very close to the 0.5 mL mark.
    • Interferon Beta-1a should look clear, colorless, and should not have any particles in it.
  • Do not use the Interferon Beta-1a prefilled syringe if:
    • the syringe is cracked or damaged
    • the solution is cloudy, colored, or has lumps or particles in it
    • the cap has been removed or is not tightly attached or
    • there is not enough liquid in the syringe

Do not use that syringe. Get a new syringe. Contact MS ACTIVESOURCE at 1-800-456-2255.

(Figure A)
Step 2: With 1 hand, hold the Interferon Beta-1a prefilled syringe right under the cap and with the cap pointing up.

  • Make sure you are holding the Interferon Beta-1a prefilled syringe by the ridged part, directly under the cap.

(Figure B)
Step 3: With the other hand, grasp the cap and bend it at a 90º angle until the cap snaps off.

(Figure C)

(Figure D)
Step 4: Open the sterile needle package and take out the covered needle. Hold the Interferon Beta-1a prefilled syringe with the glass syringe tip pointing up. Press the needle on the Interferon Beta-1a prefilled syringe glass tip.

(Figure E)
Step 5: Gently turn the needle forward (clockwise) until it is tight and firmly attached.

  • If the needle is not firmly attached, it may leak and you may not get your full dose of Interferon Beta-1a.
  • Do not remove the plastic cover from the needle.

(Figure F)

Giving the Interferon Beta-1a injection:

Step 6: Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose.

  • Do not touch this area again before giving the injection.


(Figure G) (Figure H)
Step 7: Pull the protective cover straight off the needle. Do not twist the cover off.

(Figure I)
Step 8: With 1 hand, stretch the skin out around the injection site. With the other hand, hold the syringe like a pencil. Use a quick dart-like motion and insert the needle at a 90 degree angle, through the skin and into the muscle. Once the needle is in, let go of the skin.

(Figure J)

Step 9: Slowly push the plunger down until the syringe is empty.

(Figure K)
Step 10: Pull the needle out of the skin. Press down on the injection site with the gauze pad for a few seconds or rub gently in a circular motion.

  • If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.

(Figure L)

After the Interferon Beta-1a injection:


General information about the safe and effective use of Interferon Beta-1a


This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License # 1697

© Biogen [1996-2015]. All rights reserved.

1-800-456-2255

Revised: 08/2014

41611-02

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Instructions for Use

AVOSTARTGRIP ® Titration Kit

Use with Interferon Beta-1a ® (interferon beta-1a) Prefilled Syringe Only

Read the Instructions for Use before you start using Interferon Beta-1a and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Preparing the Interferon Beta-1a Prefilled Syringe:


Supplies you will need for the Interferon Beta-1a injection:


Identifying parts of the Interferon Beta-1a prefilled syringe :

Preparing the Interferon Beta-1a injection:

Step 1: Hold the Interferon Beta-1a prefilled syringe with the cap pointing down and with the 0.5 mL mark at eye level.

  • Check the syringe:
    • The syringe should not have any cracks or damage.
    • Check that the cap is intact and has not been removed.
    • The amount of liquid in the syringe should be at or very close to the 0.5 mL mark.
    • Interferon Beta-1a should look clear, colorless, and should not have any particles in it.
  • Do not use the Interferon Beta-1a prefilled syringe if:
    • the syringe is cracked or damaged
    • the solution is cloudy, colored, or has lumps or particles in it
    • the cap has been removed or is not tightly attached or
    • there is not enough liquid in the syringe

Do not use that syringe. Get a new syringe. Contact MS ACTIVESOURCE at 1-800-456-2255.

(Figure A)
Step 2: With 1 hand, hold the Interferon Beta-1a prefilled syringe right under the cap and with the cap pointing up.

  • Make sure you are holding the Interferon Beta-1a prefilled syringe by the ridged part, directly under the cap.

(Figure B)
Step 3: With the other hand, grasp the cap and bend it at a 90º angle until the cap snaps off.

(Figure C)

(Figure D)
Step 4: Open the sterile needle package and take out the covered needle. Hold the Interferon Beta-1a prefilled syringe with the glass syringe tip pointing up. Press the needle on the Interferon Beta-1a prefilled syringe glass tip.

(Figure E)
Step 5: Gently turn the needle forward (clockwise) until it is tight and firmly attached.

  • If the needle is not firmly attached, it may leak and you may not get your full dose of Interferon Beta-1a.
  • Do not remove the plastic cover from the needle.

(Figure F)

Using the Interferon Beta-1a prefilled syringe with the AVOSTARTGRIP titration kit:


Identifying the parts of AVOSTARTGRIP titration kit :

(Figure G)


(Figure H)

Attaching the AVOSTARTGRIP device:

Step 6: Choose the right AVOSTARTGRIP titration device for your weekly dose.

  • Week 1 Injection: Choose the white device to give ¼ dose.

(Figure I)
  • Week 2 Injection: Choose the yellow device to give ½ dose.

 (Figure J)
  • Week 3 Injection: Choose the purple device to give ¾ dose.
 (Figure K)
Step 7: Put the right AVOSTARTGRIP device on a flat surface with the door open.

(Figure L)
Step 8: Line up the Interferon Beta-1a prefilled syringe over the AVOSTARTGRIP device with the plunger pointing to the left and the needle pointing to the right.

(Figure M)
Step 9: Push the Interferon Beta-1a prefilled syringe down into the AVOSTARTGRIP device until both ends “snap” into place.

(Figure N)
Step 10: Using two fingers, push the door down until it closes over the Interferon Beta-1a prefilled syringe.

  • You will hear a “snap” when the door is closed the right way. Do not open door after it is closed.

(Figure O)
Step 11: Check to make sure that the Interferon Beta-1a prefilled syringe is in the AVOSTARTGRIP device the right way and that the door is tightly closed.

Giving the Interferon Beta-1a injection:

Step 12: Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose.

  • Do not touch this area again before giving the injection.

 (Figure P) (Figure Q)
Step 13: Pull the protective cover straight off the needle. Do not twist the cover off.

(Figure R)
Step 14: With 1 hand, stretch the skin out around the injection site. With the other hand, hold the syringe like a pencil. Use a quick dart-like motion and insert the needle at a 90º angle, through the skin and into the muscle. Once the needle is in, let go of the skin.

(Figure S)
Step 15: Make sure that you push the plunger all the way down until it touches the collar.

(Figure T)
Step 16: Pull the needle out of the skin. Press down on the injection site with the gauze pad for a few seconds or rub gently in a circular motion.

  • If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.

(Figure U)

After the Interferon Beta-1a injection:

Do not recap the needle. Recapping the needle can lead to a needle stick injury.


General information about the safe and effective use of Interferon Beta-1a


This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised 09/2016

Manufactured for:

Biogen Inc.

250 Binney Street

Cambridge, MA 02142 USA

©2012-2016 Biogen. All rights reserved.

1-800-456-2255

I11073-05

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Instructions for Use

Interferon Beta-1a ® (a-vuh-necks)

(interferon beta-1a)

lyophilized powder for intramuscular injection

single-use vial

Read the Instructions for Use before you start using Interferon Beta-1a and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

Supplies you will need for the Interferon Beta-1a injection :


Preparing the Interferon Beta-1a dose:


(Figure A)

Preparing the Interferon Beta-1a dose:

Step 1: Pull off the cap from the vial of Interferon Beta-1a and the vial of diluent.

(Figure B)
Step 2: Wipe the rubber stopper on each vial with an alcohol wipe.

(Figure C)
Step 3: Open the sterile package and take out the MICRO PIN. Hold the syringe with the tip pointing up. Push the MICRO PIN down onto the top of the syringe. Turn the MICRO PIN counterclockwise until it is tight and firmly attached.

  • Do not over-tighten the MICRO PIN, it can make it hard to remove.

(Figure D)
Step 4: Pull straight up on the MICRO PIN cover to remove it, and save the cover for later. Do not twist the MICRO PIN cover when you are removing it.

(Figure E)
Step 5: Pull down the syringe plunger until the rubber tip reaches the 1.1 mL mark.

(Figure F)
Step 6: Push the MICRO PIN down through the center of the rubber stopper of the diluent vial.

(Figure G)
Step 7: Push the plunger all the way in. This puts air into the diluent vial.

(Figure H)
Step 8: Keep the MICRO PIN in the vial. Turn the diluent vial and syringe upside down and slowly pull the plunger down until the rubber tip reaches the 1.1 mL mark on the syringe.

  • If there are air bubbles, tap the syringe gently a few times to let any air bubbles rise to the top. If you still see air bubbles, slowly push the plunger up until the bubbles come out through the needle. Check to make sure there is still 1.1 mL of diluent in the syringe.

(Figure I)

(Figure J)
Step 9: Slowly pull the MICRO PIN out of the diluent vial's rubber stopper.

(Figure K)
Step 10: Push the MICRO PIN through the center of the rubber stopper of the Interferon Beta-1a vial.

  • If the rubber stopper of the Interferon Beta-1a vial falls into the vial, do not use the Interferon Beta-1a. Throw away the Interferon Beta-1a vial and get a new one, then repeat steps 1 to 10.

(Figure L)
Step 11: Slowly push the plunger all the way in. This puts the diluent into the vial of Interferon Beta-1a. Do not remove the syringe.

  • Do not aim the stream of diluent directly on the Interferon Beta-1a powder or push the plunger down too fast. If you aim the stream of diluent directly on the Interferon Beta-1a powder or push the plunger down too fast, the Interferon Beta-1a may foam and make it hard to withdraw the Interferon Beta-1a into the syringe.

(Figure M)
Step 12: Gently swirl the Interferon Beta-1a vial until the powder in the vial is dissolved. Do not shake the Interferon Beta-1a vial.

  • Check the Interferon Beta-1a vial to make sure that all of the Interferon Beta-1a is dissolved.
  • Interferon Beta-1a should look clear to slightly yellow in color after mixing and should not have any particles in it. Do not use Interferon Beta-1a if it looks cloudy, is colored any color other than slightly yellow, or has any lumps or particles in it.

Do not use that vial. Get a new vial. Contact MS ACTIVESOURCE at 1-800-456-2255.

(Figure N)
Step 13: Turn the Interferon Beta-1a vial and syringe upside down and slowly pull the plunger down until the rubber tip reaches the 1 mL mark on the syringe.

  • If there are large bubbles in the syringe, slowly push the plunger all the way in to push the Interferon Beta-1a solution back into the vial, then repeat Step 13.
  • If there are small air bubbles, tap the syringe gently a few times to let any air bubbles rise to the top. If you still see air bubbles, slowly push the plunger up until the bubbles come out through the needle.

(Figure O)

(Figure P)
Step 14: Pull the MICRO PIN and syringe out of the Interferon Beta-1a vial's rubber stopper.

(Figure Q)
Step 15: Put the cover back on the MICRO PIN and turn it clockwise to remove the MICRO PIN from the syringe.

(Figure R)

(Figure S)
Step 16: Open the sterile needle package and take out the covered needle. Hold the syringe with the tip pointing up. Push the needle onto the syringe and turn it forward (clockwise) until it is tight and firmly attached.

  • If the needle is not firmly attached, it may leak and you may not get your full dose of Interferon Beta-1a.
  • Do not remove the plastic cover from the needle.

(Figure T)

Giving the Interferon Beta-1a injection:

Step 17: Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose.

  • Do not touch this area again before giving the injection.


(Figure U) (Figure V)
Step 18: Pull the protective cover straight off the needle. Do not twist the cover off.

(Figure W)
Step 19: With 1 hand, stretch the skin out around the injection site. With the other hand, hold the syringe like a pencil. Use a quick dart-like motion and insert the needle at a 90 degree angle, through the skin and into the muscle. Once the needle is in, let go of the skin.

(Figure X)
Step 20: Slowly push the plunger in until the syringe is empty.

(Figure Y)
Step 21: Pull the needle out of the skin. Press down on the injection site with the gauze pad for a few seconds or rub gently in a circular motion.

  • If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.

(Figure Z)

After the Interferon Beta-1a injection:


General information about the safe and effective use of Interferon Beta-1a


This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

© Biogen [1996-2015]. All rights reserved.

1-800-456-2255

MICRO PIN ® is the trademark of B. Braun Medical Inc.

Revised: 08/2015

41612-02

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Principal Display Panel - 30 mcg Carton Label

NDC 59627-333-04

Interferon Beta-1a Pen ®

(interferon beta-1a)

Injection

30 mcg/0.5 mL Single-Use Prefilled Autoinjector

For Intramuscular Injection

Once a Week

Principal Display Panel - 30 mcg Carton Label

NDC 59627-222-05

Interferon Beta-1a ®

(interferon beta-1a)

Injection

30 mcg/0.5 mL Single-Use Prefilled Syringe

For Intramuscular Injection

Once a Week

Principal Display Panel - 30 mcg Carton Label

NDC 59627-111-03

Interferon Beta-1a ®

(interferon beta-1a)

Injection

30 mcg Single-Use Lyophilized Powder Vial

For Intramuscular Injection

Once a Week

Principal Display Panel - 30 mcg Tray Lid Label

NDC 59627-111-04

Interferon Beta-1a ® (interferon beta-1a)

30 mcg Single-Use Lyophilized Powder Vial

For Intramuscular Injection

Principal Display Panel - Carton Label

NDC 59627-003-04

Interferon Beta-1a PEN®

(interferon beta-1a)

Injection

30 mcg/0.5 mL

Single-Use Prefilled Autoinjector

For Intramuscular Injection

Contents:

4 Interferon Beta-1a Pen Administration Dose Packs

Dispense with enclosed Medication Guide

Rx only

Biogen Idec ®

Principal Display Panel - Carton Label

NDC 59627-002-05

AVONEX® Prefilled Syringe

(interferon beta-1a)

Injection

30 mcg Prefilled Syringe

For intramuscular injection

Contents:

4 Interferon Beta-1a Administration Dose Packs

Dispense with enclosed Medication Guide

Rx only

Biogen Idec ®

Principal Display Panel - Carton Label

NDC 59627-001-03

AVONEX®

(interferon beta-1a)

Injection

30 mcg

For Intramuscular Injection

Contents:

4 Interferon Beta-1a Administration Dose Packs

Dispense with enclosed Medication Guide

Rx only

Biogen Idec ®

Interferon Beta-1a available forms, composition, doses:


Indications and Usages:

ATC codes:


ICD-10 codes:


Interferon Beta-1a destination | category:


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Drugs with same active ingredients (Pharmaceutical companies):


References

  1. Dailymed."AVONEX (INTERFERON BETA-1A) KIT AVONEX PEN (INTERFERON BETA-1A) INJECTION, SOLUTION AVONEX (INTERFERON BETA-1A) INJECTION, POWDER, LYOPHILIZED, FOR SOL". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Interferon Beta-1a?

Depending on the reaction of the Interferon Beta-1a after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Interferon Beta-1a not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Interferon Beta-1a addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Interferon Beta-1a, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Interferon Beta-1a consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology


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