Interferon Beta-1b Kit

EXTAVIA (interferon beta-1b) is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.

Dosage Forms And Strengths

For injection: 0.3 mg lyophilized powder in a single-use vial for reconstitution.

Storage And Handling

EXTAVIA is supplied as a lyophilized powder in a clear glass, single-use vial (3 mL capacity). Each carton contains 15 blister units: NDC 0078-0569-12.

Each blister unit contains:

A single-use vial containing 0.3 mg EXTAVIA (interferon beta-1b)
A pre-filled single-use syringe containing 1.2 mL diluent (Sodium Chloride, 0.54% solution). The rubber cap of the pre-filled syringe contains natural rubber latex.
A vial adapter with a 27-gauge needle attached
2 alcohol prep pads

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

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. Revised: May 2016

This medication may be harmful to an unborn baby, or may cause a miscarriage. Do not use interferon beta-1b if you are pregnant. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Before using interferon beta-1b, tell your doctor if you are allergic to any drugs, or if you have liver disease, a thyroid disorder, epilepsy or other seizure disorder, a bleeding or blood-clotting disorder, anemia (low red blood cells), or a history of depression or suicidal behavior.

Some patients using interferon medications have become very depressed or had thoughts of suicide. Stop using interferon beta-1b if you have symptoms of depression (sadness, crying, loss of interest in things you once liked) or if you have any thoughts of hurting yourself.

Interferon beta-1b is given as an injection under the skin, usually at bedtime every 48 hours (2 days). You may be given instructions on how to use your injections at home. You may be shown how to inject your medicine at home.

Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

To be sure this medication is not causing harmful effects, your blood and liver function will need to be tested on a regular basis. Your thyroid function may also need to be tested. Do not miss any scheduled appointments.

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using interferon beta-1b.

Interferons can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Avoid being near people who have colds, the flu, or other contagious illnesses. Contact your doctor at once if you develop signs of infection.

Your pharmacist can provide more information about interferon beta-1b.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 3.03. Revision date: 12/15/2010.

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

• Hepatic Injury [see WARNINGS AND PRECAUTIONS]
• Anaphylaxis and Other Allergic Reactions [see WARNINGS AND PRECAUTIONS]
• Depression and Suicide [see WARNINGS AND PRECAUTIONS]
• Congestive Heart Failure [see WARNINGS AND PRECAUTIONS]
• Injection Site Necrosis and Reactions [see WARNINGS AND PRECAUTIONS]
• Leukopenia [see WARNINGS AND PRECAUTIONS]
• Thrombotic microangiopathy [see WARNINGS AND PRECAUTIONS]
• Flu-like Symptom Complex [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Drug Induced Lupus Erythematosus [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions and over varying lengths of time, adverse reaction rates observed in the clinical trials of interferon beta-1b cannot be directly compared to rates in clinical trials of other drugs, and may not reflect the rates observed in practice.

Among 1407 patients with MS treated with interferon beta-1b 0.25 mg every other day (including 1261 patients treated for greater than one year), the most commonly reported adverse reactions (at least 5% more frequent on interferon beta-1b than on placebo) were injection site reaction, lymphopenia, flu-like symptoms, myalgia leukopenia, neutropenia, increased liver enzymes, headache, hypertonia, pain, rash, insomnia, abdominal pain, and asthenia. The most frequently reported adverse reactions resulting in clinical intervention (for example, discontinuation of interferon beta-1b, adjustment in dosage, or the need for concomitant medication to treat an adverse reaction symptom) were depression, flu-like symptom complex, injection site reactions, leukopenia, increased liver enzymes, asthenia, hypertonia, and myasthenia.

Table 2 enumerates adverse reactions and laboratory abnormalities that occurred among patients treated with 0.25 mg of interferon beta-1b every other day by subcutaneous injection in the pooled placebo-controlled trials (Study 1-4) at an incidence that was at least 2% more than that observed in the placebo-treated patients [see Clinical Studies].

Table 2: Adverse Reactions and Laboratory Abnormalities in Patients with MS in Pooled Studies 1, 2, 3, and 4

In addition to the adverse reactions listed in Table 2, the following adverse reactions occurred more frequently on interferon beta-1b than on placebo, but with a difference smaller than 2%: alopecia, anxiety, arthralgia, constipation, diarrhea, dizziness, dyspepsia, dysmenorrhea, leg cramps, menorrhagia, myasthenia, nausea, nervousness, palpitations, peripheral vascular disorder, prostatic disorder, tachycardia, urinary frequency, vasodilatation, and weight increase.

In the four clinical trials (Studies 1, 2, 3, and 4), leukopenia was reported in 18% and 6% of patients in interferon beta-1band placebo-treated groups, respectively. No patients were withdrawn or dose reduced for neutropenia in Study 1. Three percent (3%) of patients in Studies 2 and 3 experienced leukopenia and were dose-reduced. Other abnormalities included increase of SGPT to greater than five times baseline value (12%), and increase of SGOT to greater than five times baseline value (4%). In Study 1, two patients were dose reduced for increased hepatic enzymes; one continued on treatment and one was ultimately withdrawn. In Studies 2 and 3, 1.5% of interferon beta-1b patients were dose-reduced or interrupted treatment for increased hepatic enzymes. In Study 4, 1.7% of patients were withdrawn from treatment due to increased hepatic enzymes, two of them after a dose reduction. In Studies 1-4, nine (0.6%) patients were withdrawn from treatment with interferon beta-1b for any laboratory abnormality, including four (0.3%) patients following dose reduction.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. Serum samples were monitored for the development of antibodies to interferon beta-1b during Study 1. In patients receiving 0.25 mg every other day 56/124 (45%) were found to have serum neutralizing activity at one or more of the time points tested. In Study 4, neutralizing activity was measured every 6 months and at end of study. At individual visits after start of therapy, activity was observed in 17% up to 25% of the interferon beta-1b-treated patients. Such neutralizing activity was measured at least once in 75 (30%) out of 251 interferon beta-1b patients who provided samples during treatment phase; of these, 17 (23%) converted to negative status later in the study. Based on all the available evidence, the relationship between antibody formation and clinical safety or efficacy is not known.

These data reflect the percentage of patients whose test results were considered positive for antibodies to interferon beta1b using a biological neutralization assay that measures the ability of immune sera to inhibit the production of the interferon-inducible protein, MxA. Neutralization assays 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-1b with the incidence of antibodies to other products may be misleading.

Anaphylactic reactions have been reported with the use of interferon beta-1b [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of interferon beta-1b. 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.

Blood and lymphatic system disorders: Anemia, Thrombocytopenia

Endocrine disorders: Hypothyroidism, Hyperthyroidism, Thyroid dysfunction

Metabolism and nutrition disorders: Triglyceride increased, Anorexia, Weight decrease, Weight increase

Psychiatric disorders: Anxiety, Confusion, Emotional lability

Nervous system disorders: Convulsion, Dizziness, Psychotic symptoms

Cardiac disorders: Cardiomyopathy, Palpitations, Tachycardia

Vascular disorders: Vasodilatation

Respiratory, thoracic and mediastinal disorders: Bronchospasm

Gastrointestinal disorders: Diarrhea, Nausea, Pancreatitis, Vomiting

Hepatobiliary disorders: Hepatitis, Gamma GT increased

Skin and subcutaneous tissue disorders: Alopecia, Pruritus, Skin discoloration, Urticaria

Musculoskeletal and connective tissue disorders: Arthralgia; drug-induced lupus erythematosus

Reproductive system and breast disorder: Menorrhagia

General disorders and administration site conditions: Fatal capillary leak syndrome*

*The administration of cytokines to patients with a preexisting monoclonal gammopathy has been associated with the development of this syndrome.

Read the entire FDA prescribing information for Extavia (Interferon Beta-1b Kit)