当前位置：药品说明书与价格首页 >> 神经内科 >> 多发性硬化症 >> 药品目录 >> 干扰素β-1a干扰素注射剂Avonex (Interferon beta-1a Injections)

干扰素β-1a干扰素注射剂Avonex (Interferon beta-1a Injections)

2011-01-13 18:49:12 作者：新特药房来源：中国新特药网天津分站浏览次数：405 文字大小：【大】【中】【小】

简介： 药品名称通用名：干扰素β-1a品牌名称:Avonex的预充式注射器，利比β-1a是一种蛋白质，叫做β-1a干扰素,是天然存在于人体。它帮助人体抵抗病毒感染。生产厂家 Biogen Inc. 适应症用于治疗复发型多 ...

药品名称

通用名：干扰素β-1a
品牌名称:Avonex的预充式注射器，利比
β-1a是一种蛋白质，叫做β-1a干扰素,是天然存在于人体。它帮助人体抵抗病毒感染。
生产厂家

Biogen Inc.
适应症

用于治疗复发型多发性硬化症，以减缓病人的身体残疾。这种药物将不能治愈硬化症，只会降低复发的频率。β-1a干扰素也可用于治疗生殖器疣。
注意事项

在使用干扰素β-1a时，告诉医生，您对任何药物的过敏史，并且如果您有肝病，甲状腺疾病，癫痫或其他癫痫症，心脏病，胸痛（心绞痛），充血性心力衰竭，心脏节律紊乱，或抑郁症，自杀行为等等。
其它问题的存在，可能会影响使用干扰素β-1α.一定要告诉医生是否有任何其他的医疗问题，特别是：酗酒,较高的肝酶浓度称为谷丙转氨酶,肝病(比如黄疸),心脏病,精神抑郁,精神障碍,癫痫症等。
禁忌

停止使用干扰素β-1a，如果对干扰素或人血白蛋白过敏;如果你有抑郁症的症状（悲伤，哭泣，对你曾经喜欢的东西失去兴趣），或者如果您有伤害自己的想法。
妊娠和母乳喂养

可能对未出生的婴儿有害，或导致流产。如果你怀孕不要使用β-1a。目前还不知道是否β-1a干扰素传递到母乳或可能损害婴儿的资料。如果你是母乳喂养婴儿，不要使用这种药物。
药物相互作用

不建议同时使用干扰素β-1a与下列药物: 轮状病毒活疫苗
使用干扰素β-1a与下列药物可能导致某些副作用增加。如果这两个药物是开在一起的，医生可能会改变剂量或服用时间: 齐多夫定
副作用

可能带来的副作用也以不同方式影响个人:
类似流感，如疼痛，发烧，发冷，出汗，头痛，疲劳和恶心
疼痛注射部位的反应，炎症或脓肿
疼痛，肌肉和关节
皮疹或皮肤发痒的反应
腹泻
食欲不振
睡眠困难（失眠）
抑郁症
脱发（斑秃）
干扰血液的组成部分
不规律月经
头晕
甲状腺过度活跃
混乱
癫痫发作（抽搐）
肝脏炎症（肝炎）

英文药名: Avonex (Interferon beta-1a Injections)

中文药名: 干扰素β-1a干扰素注射剂

生产厂家: Biogen Inc.

Avonex

Drug Descriptionfont sizeAAAAVONEX®
(Interferon beta-1a) IM Injection

DRUG DESCRIPTION
AVONEX® (Interferon beta-1a) is a 166 amino acid glycoprotein with a predicted 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) natural interferon beta standard, Second International Standard for Interferon, Human Fibroblast (Gb-23-902-531), AVONEX® has a specific activity of approximately 200 million international units (IU) 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 mcg contains approximately 6 million IU 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.

30 mcg Lyophilized Powder Vial
A vial of AVONEX® is formulated as 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 mcg 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.

30 mcg Prefilled Syringe
A prefilled syringe of AVONEX® is formulated as a sterile liquid for intramuscular injection. Each 0.5 mL (30 mcg dose) of AVONEX® in a prefilled glass syringe contains 30 mcg 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
AVONEX® (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. Safety and efficacy in patients with chronic progressive multiple sclerosis have not been established.
DOSAGE AND ADMINISTRATION
The recommended dosage of AVONEX® (Interferon beta-1a) is 30 mcg injected intramuscularly once a week.

AVONEX® is intended for use under the guidance and supervision of a physician. Patients may self-inject only if their physician determines that it is appropriate and with medical follow-up, as necessary, after proper training in intramuscular injection technique. Sites for injection include the thigh or upper arm (see Medication Guide).

A 25 gauge, 1“ needle for intramuscular injection may be substituted for the 23 gauge, 1 ¼” needle by the prescribing physician, if deemed appropriate.

Reconstitution of AVONEX® Vials
Use appropriate aseptic technique during the preparation of AVONEX® . To reconstitute lyophilized AVONEX® , use a sterile syringe and MICRO PIN® to inject 1.1 mL of the supplied diluent, Sterile Water for Injection, USP, into the AVONEX® vial. Gently swirl the vial of AVONEX® to dissolve the drug completely. DO NOT SHAKE. The reconstituted solution should be clear to slightly yellow without particles. Inspect the reconstituted product visually prior to use. Discard the product if it contains particulate matter or is discolored. Each vial of reconstituted solution contains 30 mcg/1.0 mL Interferon beta-1a.

Withdraw 1.0 mL of reconstituted solution from the vial into a sterile syringe. Replace the cover on the MICRO PIN®, attach the sterile needle and inject the solution intramuscularly. The AVONEX® and diluent vials are for single-use only; unused portions should be discarded.

Using AVONEX® Prefilled Syringes
The AVONEX® prefilled syringe should be held upright (cap faces up). Remove the cap by bending it at a 90° angle until it snaps free. Attach the needle and inject the solution intramuscularly. The AVONEX® prefilled syringe is for single-use only.
HOW SUPPLIED
30 mcg Lyophilized Powder Vial
A vial of AVONEX® is supplied as a lyophilized powder in a single-use vial containing 33 mcg (6.6 million IU) 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).

AVONEX® lyophilized vials are available in the following package configuration (NDC 59627-001-03): A package containing four Administration Dose Packs (each containing one vial of AVONEX® , 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).

30 mcg Prefilled Syringe
A prefilled syringe of AVONEX® is supplied as a sterile liquid albumin-free formulation containing 30 mcg 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 IM injection.

AVONEX® prefilled syringes are available in the following package configuration (NDC 59627-002-05): A package containing four Administration Dose Packs (each containing one single-use syringe of AVONEX® and one 23 gauge, 1¼ inch needle), and a recloseable accessory pouch containing 4 alcohol wipes, 4 gauze pads, and 4 adhesive bandages.

Stability and Storage
30 mcg Lyophilized Powder Vial
Vials of AVONEX® should be stored in a 2-8°C (36-46°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 2-8°C (36-46°F). DO NOT FREEZE RECONSTITUTED AVONEX® .

30 mcg Prefilled Syringe
AVONEX® in prefilled syringes should be stored in a 2-8°C (36-46°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® (Interferon beta-1a), Manufactured by: BIOGEN IDEC INC. 14 Cambridge Center Cambridge, MA 02142 USA, ©2006 Biogen Idec Inc. All rights reserved. 1-800-456-2255, U.S. Patent Pending, I63005-9 (Issue Date XX/2006), Rx only, *Micro Pin® is the trademark of B. Braun Medical Inc. FDA revision date: 2/2/2007
SIDE EFFECTS
Depression, suicidal ideation, and new or worsening other psychiatric disorders have been observed to be increased in patients using interferon compounds including AVONEX® (see WARNINGS: Depression and Suicide). Anaphylaxis and other allergic reactions have been reported in patients using AVONEX® (see WARNINGS: Anaphylaxis). Decreased peripheral blood counts have been reported in patients using AVONEX® (see WARNINGS: Decreased Peripheral Blood Counts). Hepatic injury, including hepatic failure, hepatitis, and elevated serum hepatic enzyme levels, has been reported in post-marketing experience (see WARNINGS: Hepatic Injury). Seizures, cardiovascular adverse events, and autoimmune disorders also have been reported in association with the use of AVONEX® (see PRECAUTIONS).

The adverse reactions most commonly reported in patients associated with the use of AVONEX® were flu-like and other symptoms occurring within hours to days following an injection. Symptoms can include myalgia, fever, fatigue, headaches, chills, nausea, and vomiting. Some patients have experienced paresthesias, hypertonia and myasthenia.

The most frequently reported adverse reactions resulting in clinical intervention (e.g., discontinuation of AVONEX® , or the need for concomitant medication to treat an adverse reaction symptom) were flu-like symptoms and depression.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of AVONEX® cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice.

The data described below reflect exposure to AVONEX® in 351 patients, including 319 patients exposed for 6 months, and 288 patients exposed for greater than one year in placebo-controlled trials. The mean age of patients receiving AVONEX® was 35 years, 74% were women and 89% were Caucasian. Patients received either 30 mcg AVONEX® or placebo.

Table 3 enumerates adverse events and selected laboratory abnormalities that occurred at an incidence of at least 2% higher frequency in AVONEX® -treated subjects than was observed in the placebo group. Reported adverse events have been classified using standard COSTART terms.

Table 3 : Adverse Events and Selected Laboratory Abnormalities in the Placebo-Controlled Studies

Adverse Event Placebo
(N = 333) AVONEX®
(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%

No AVONEX® -treated patients attempted suicide in the two placebo-controlled studies. In Study 2, AVONEX® -treated patients were more likely to experience depression than placebo-treated patients (20% in AVONEX® group vs. 13% in placebo group). The incidences of depression in the placebo-treated and AVONEX® -treated patients in Study 1 were similar. In Study 1, suicidal tendency was seen more frequently in AVONEX® -treated patients (4% in AVONEX® group vs. 1% in placebo group) (see WARNINGS).

Seizures

Seizures have been reported in 4 of 351 AVONEX® -treated patients in the placebo-controlled studies, compared to none in the placebo-treated patients (see PRECAUTIONS: Seizures).

Post-Marketing Experience

The following adverse events have been identified and reported during post-approval use of AVONEX® : New or worsening other psychiatric disorders, and anaphylaxis (see WARNINGS). Autoimmune disorders including autoimmune hepatitis, idiopathic thrombocytopenia, hyper- and hypothyroidism, and seizures in patients without prior history (see PRECAUTIONS).

Infrequent reports of congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure with rare cases being temporally related to the administration of AVONEX® (see PRECAUTIONS: Cardiomyopathy and Congestive Heart Failure).

Decreased peripheral blood counts in all cell lines, including rare pancytopenia and thrombocytopenia (see WARNINGS: Decreased Peripheral Blood Counts). Some cases of thrombocytopenia have had nadirs below 10,000/μL. Some of these cases reoccur upon rechallenge.

Hepatic injury, including hepatic failure and elevated serum hepatic enzyme levels, some of which have been severe, has been reported post-marketing (see WARNINGS: Hepatic Injury).

Meno- and metrorrhagia, rash (including vesicular rash), and rare cases of injection site abscess or cellulitis that may require surgical intervention have also been reported in post-marketing experience.

Because reports of these reactions are voluntary and the population is of an uncertain size, it is not always possible to reliably estimate the frequency of the event or establish a causal relationship to drug exposure.

Adverse Reactions Associated with Subcutaneous Use

AVONEX® has also been evaluated in 290 patients with diseases other than multiple sclerosis, primarily chronic viral hepatitis B and C, in which the doses studied ranged from 15 mcg to 75 mcg, given SC, 3 times a week, for up to 6 months. Inflammation at the site of the subcutaneous injection was observed in 52% of treated patients in these studies. Subcutaneous injections were also associated with the following local reactions: injection site necrosis, injection site atrophy, injection site edema and injection site hemorrhage. None of the above was observed in the multiple sclerosis patients participating in Study 1. Injection site edema and injection site hemorrhage were observed in multiple sclerosis patients participating in Study 2.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. In recent studies assessing immunogenicity in multiple sclerosis patients administered AVONEX® for at least 1 year, 5% (21 of 390 patients) showed the presence of neutralizing antibodies at one or more times. The clinical significance of neutralizing antibodies to AVONEX® is unknown.

These data reflect the percentage of patients whose test results were considered positive for antibodies to AVONEX® 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 AVONEX® with the incidence of antibodies to other products may be misleading.

Anaphylaxis has been reported as a rare complication of AVONEX® use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria (see WARNINGS: Anaphylaxis).

Drug Abuse And Dependence

There is no evidence that abuse or dependence occurs with AVONEX® therapy. However, the risk of dependence has not been systematically evaluated.

DRUG INTERACTIONS

No formal drug interaction studies have been conducted with AVONEX® . In the placebo-controlled studies in multiple sclerosis, corticosteroids or ACTH were administered for treatment of exacerbations in some patients concurrently receiving AVONEX® . In addition, some patients receiving AVONEX® were also treated with anti-depressant therapy and/or oral contraceptive therapy. No unexpected adverse events were associated with these concomitant therapies. However, the potential for hepatic injury should be considered when AVONEX® is used in combination with other products associated with hepatic injury, or when new agents are added to the regimen of patients already on AVONEX® (see WARNINGS: Hepatic Injury).

WARNINGS

Depression and Suicide

AVONEX® should be used with caution in patients with depression or other mood disorders, conditions that are common with multiple sclerosis.Depression and suicide have been reported to occur with increased frequency in patients receiving interferon compounds, including AVONEX® . Patients treated with AVONEX® should be advised to report immediately any symptoms of depression and/or suicidal ideation to their prescribing physicians. If a patient develops depression or other severe psychiatric symptoms,cessation of AVONEX® therapy should be considered. In Study 2, AVONEX® -treated patients were more likely to experience depression than placebo-treated patients. An equal incidence of depression was seen in the placebo-treated and AVONEX® -treated patients in Study 1. Additionally, there have been post-marketing reports of depression, suicidal ideation and/or development of new or worsening of pre-existing other psychiatric disorders, including psychosis. Some of these patients improved upon cessation of AVONEX® dosing.

Anaphylaxis

Anaphylaxis has been reported as a rare complication of AVONEX® use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria (see ADVERSE REACTIONS).

Decreased Peripheral Blood Counts

Decreased peripheral blood counts in all cell lines, including rare pancytopenia and thrombocytopenia, have been reported from post-marketing experience (see ADVERSE REACTIONS). Some cases of thrombocytopenia have had nadirs below 10,000/μL. Some cases reoccur with rechallenge (see ADVERSE REACTIONS). Patients should be monitored for signs of these disorders (see Precautions: Laboratory Tests).

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 AVONEX® administration, or when adding new agents to the regimen of patients already on AVONEX® . Patients should be monitored for signs of hepatic injury (see PRECAUTIONS: Laboratory Tests).

Albumin (Human)

The lyophilized vial of AVONEX® contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have been identified for albumin. The prefilled syringe of AVONEX® does not contain albumin.

PRECAUTIONS

Seizures

Caution should be exercised when administering AVONEX® to patients with pre-existing seizure disorders. In the two placebo-controlled studies in multiple sclerosis, 4 patients receiving AVONEX® experienced seizures, while no seizures occurred in the placebo group. Three of these 4 patients had no prior history of seizure (see ADVERSE REACTIONS).It is not known whether these events were related to the effects of multiple sclerosis alone, to AVONEX® , or to a combination of both. The effect of AVONEX® administration on the medical management of patients with seizure disorder is unknown.

Cardiomyopathy and Congestive Heart Failure

Patients with cardiac disease, such as angina, congestive heart failure, or arrhythmia, should be closely monitored for worsening of their clinical condition during initiation and continued treatment with AVONEX® . While AVONEX® does not have any known direct-acting cardiac toxicity, during the post-marketing period infrequent 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 known etiologies being established. In rare cases, these events have been temporally related to the administration of AVONEX® . In some of these instances recurrence upon rechallenge was observed.

Autoimmune Disorders

Autoimmune disorders of multiple target organs have been reported post-marketing including idiopathic thrombocytopenia, hyper- and hypothyroidism, and rare cases of autoimmune hepatitis have also been reported. Patients should be monitored for signs of these disorders (see PRECAUTIONS: Laboratory Tests) and appropriate treatment implemented when observed.

Information for Patients

All patients should be instructed to read the AVONEX® Medication Guide supplied to them. Patients should be cautioned not to change the dosage or the schedule of administration without medical consultation.

Patients should be informed of the most serious (see WARNINGS) and the most common adverse events associated with AVONEX® administration, including symptoms associated with flu syndrome (see ADVERSE REACTIONS). Symptoms of flu syndrome are most prominent at the initiation of therapy and decrease in frequency with continued treatment. Concurrent use of analgesics and/or antipyretics may help ameliorate flu-like symptoms on treatment days.

Patients should be cautioned to report depression or suicidal ideation (see WARNINGS). Patients should be advised about the abortifacient potential of AVONEX® (see Precautions: Pregnancy - Teratogenic Effects). If a woman becomes pregnant while taking AVONEX® , she should be advised to consider enrolling in the AVONEX® Pregnancy Registry by calling 1-800-456-2255.

When a physician determines that AVONEX® can be used outside of the physician's office, persons who will be administering AVONEX® should receive instruction in reconstitution and injection, including the review of the injection procedures. If a patient is to self-administer, the physical ability of that patient to self-inject intramuscularly should be assessed. The first injection should be performed under the supervision of a qualified health care professional. A puncture-resistant container for disposal of needles and syringes should be used. Patients should be instructed in the technique and importance of proper syringe and needle disposal and be cautioned against reuse of these items.

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 AVONEX® therapy (see WARNINGS: Decreased Peripheral Blood Counts and PRECAUTIONS: Cardiomyopathy and Congestive Heart Failure, and Autoimmune Disorders). During the placebo-controlled studies in multiple sclerosis, these tests were performed at least every 6 months. There were no significant differences between the placebo and AVONEX® groups in the incidence of liver enzyme elevation, leukopenia, or thrombocytopenia. However, these are known to be dose-related laboratory abnormalities associated with the use of interferons. 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.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Carcinogenesis: No carcinogenicity data for AVONEX® are available in animals or humans.

Mutagenesis: AVONEX® was not mutagenic when tested in the Ames bacterial test and in an in vitro cytogenetic assay in human lymphocytes in the presence and absence of metabolic activation. These assays are designed to detect agents that interact directly with and cause damage to cellular DNA. AVONEX® is a glycosylated protein that does not directly bind to DNA.

Impairment of Fertility: No studies were conducted to evaluate the effects of AVONEX® on fertility in normal women or women with multiple sclerosis. It is not known whether AVONEX® can affect human reproductive capacity.

Menstrual irregularities were observed in monkeys administered AVONEX® at a dose 100 times the recommended weekly human dose (based upon a body surface area comparison). Anovulation and decreased serum progesterone levels were also noted transiently in some animals. These effects were reversible after discontinuation of drug.

Treatment of monkeys with AVONEX® at 2 times the recommended weekly human dose (based upon a body surface area comparison) had no effects on cycle duration or ovulation.

The accuracy of extrapolating animal doses to human doses is not known. In the placebo-controlled studies in multiple sclerosis, 5% of patients receiving placebo and 6% of patients receiving AVONEX® experienced menstrual disorder. If menstrual irregularities occur in humans, it is not known how long they will persist following treatment.

Pregnancy - Teratogenic Effects

Pregnancy Category C: The reproductive toxicity of AVONEX® has not been studied in animals or humans. In pregnant monkeys given AVONEX® at 100 times the recommended weekly human dose (based upon a body surface area 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 a body surface area comparison). Although no teratogenic effects were seen in these studies, it is not known if teratogenic effects would be observed in humans. There are no adequate and well-controlled studies with interferons in pregnant women. If a woman becomes pregnant or plans to become pregnant while taking AVONEX® , she should be informed of the potential hazards to the fetus, and discontinuation of AVONEX® therapy should be considered.

If a woman becomes pregnant while taking AVONEX® , consider enrolling her in the AVONEX® Pregnancy Registry by calling 1-800-456-2255.

Nursing Mothers

It is not known whether AVONEX® is excreted in human milk. Because of the potential of serious adverse reactions in nursing infants, a decision should be made to either discontinue nursing or to discontinue AVONEX® .

Pediatric Use

Safety and effectiveness of AVONEX® in pediatric patients below the age of 18 years have not been evaluated.

Geriatric Use

Clinical studies of AVONEX® did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients

OVERDOSE

Safety of doses higher than 60 mcg once a week have not been adequately evaluated. The maximum amount of AVONEX® that can be safely administered has not been determined.

CONTRAINDICATIONS

AVONEX® is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, or any other component of the formulation.

The lyophilized vial formulation of AVONEX® is contraindicated in patients with a history of hypersensitivity to albumin (human).