Interferon Beta 1a

Avonex and Rebif are the brand names of the injectable medicine interferon beta-1a, which is used to treat symptoms of relapsing-remitting multiple sclerosis (RRMS).

MS is a neurological condition where the immune system attacks the protective covering of nerves. Relapsing-remitting MS occurs when symptoms come and go.

Avonex is in a class of drugs known as immunomodulators, which work by acting on the immune system.

The Food and Drug Administration (FDA) approved this medicine in 1996. Avonex is manufactured by Biogen.

Avonex Pen

Avonex is available in a "pen," which is a prefilled, single-use autoinjector that's designed to make administering your dose of Avonex easier.

It includes a covered needle that's half the length of the standard needle for a prefilled syringe of Avonex.

Talk to your doctor about whether it's right for you.

Avonex Warnings

Some people who take Avonex experience depression or suicidal thoughts.

Stop using this medicine and tell your doctor if you have symptoms such as:

• Sadness
• Crying
• Loss of interest in things you once liked
• Suicidal thoughts or actions

Avonex may cause harm to your liver. Tell your doctor right away if you experience any of the following symptoms:

• Loss of appetite
• Nausea
• Extreme tiredness
• Dark-colored urine or pale-colored stools
• Yellowing of the eyes or skin (jaundice)
• Unusual bleeding or bruising
• Confusion

This medicine may also increase your risk for heart failure, especially if you have a history of heart problems.

Before taking this drug, tell your doctor if you have or have ever had:

• Heart disease or chest pain
• Congestive heart failure or a heart rhythm disorder
• A bleeding disorder or a history of blood clots
• An allergic reaction to medications
• Liver disease
• Seizures
• A thyroid disorder
• Cancer
• Depression or suicidal behavior
• An autoimmune disease such as psoriasis, lupus, or rheumatoid arthritis
• Human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)

Also, tell your physician before taking Avonex if you've ever consumed large amounts of alcohol.

This drug may increase your risk of developing an infection. Avoid contact with people who are sick or have infections.

Tell your healthcare provider you're taking this medicine before having any type of surgery, including a dental procedure.

Avonex hasn't been shown to benefit people with chronic progressive forms of MS.

The medicine helps prevent symptoms of relapse in people with MS, but it won't cure the condition.

Continue to take Avonex even if you feel well. Don't stop taking the medicine without first talking to your doctor.

Pregnancy and Avonex

It's not known if Avonex will harm an unborn baby. Taking this medicine while pregnant may increase your risk of miscarriage.

Don't take this drug if you're pregnant or plan to become pregnant without first talking to your doctor.

It's also not known whether Avonex can pass into breastmilk or harm a breastfeeding baby.

Tell your doctor if you're breastfeeding before taking this medicine.

No information provided. Please refer to the WARNINGS AND PRECAUTIONS sections.

Included as part of the PRECAUTIONS section.

Avoid drinking alcohol. It may increase your risk of liver damage.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Interferon Beta-1a is part of the drug class:

• interferon

Use interferon beta-1a exactly as your doctor prescribes it.

Intramuscular Form - The usual dose is 30 mcg injected intramuscularly (into the muscle) once a week. Do not change your dose unless your doctor tells you to.

Subcutaneous Form - Dosages are started low and gradually increased to 22 mcg or 44 mcg injected subcutaneously three times per week.

Call your doctor for instructions if you miss a dose of this medication. Your injections should be at least 48 hours apart. Do not use interferon beta-1a injections 2 days in a row.

The following adverse reactions are discussed in more detail in the WARNINGS AND PRECAUTIONS section of the label:

• Depression and Suicide [see WARNINGS AND PRECAUTIONS]
• Hepatic Injury [see WARNINGS AND PRECAUTIONS]
• Anaphylaxis and Other Allergic Reactions [see WARNINGS AND PRECAUTIONS]
• Injection Site Reactions including Necrosis [see WARNINGS AND PRECAUTIONS]
• Decreased Peripheral Blood Counts [see WARNINGS AND PRECAUTIONS]
• Thrombotic Microangiopathy [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Laboratory Tests [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

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

A total of 712 patients with relapsing-remitting multiple sclerosis (RRMS) in two controlled clinical trials took REBIF (22 mcg or 44 mcg given three times per week) [see Clinical Studies]. Ages ranged from 18 to 55 years. Nearly three-fourths of the patients were female, and more than 90% were Caucasian, largely reflecting the general demographics of the population of patients with multiple sclerosis.

The most commonly reported adverse reactions were injection site disorders, influenza-like symptoms (headache, fatigue, fever, rigors, chest pain, back pain, myalgia), abdominal pain, depression, elevation of liver enzymes and hematologic abnormalities. The most frequently reported adverse reactions resulting in clinical intervention (e.g., discontinuation of REBIF, adjustment in dosage, or the need for concomitant medication to treat an adverse reaction were injection site disorders, influenza-like symptoms, depression, and elevation of liver enzymes [see WARNINGS AND PRECAUTIONS].

Study 1 was a 2-year placebo-controlled study in RRMS patients treated with REBIF 22 mcg(n=189), 44 mcg (n=184), or placebo (n=187). Table 3 enumerates adverse reactions and laboratory abnormalities that occurred at an incidence that was at least 2% more in either REBIF-treated group than was observed in the placebo group.

Table 3: Adverse Reactions and Laboratory Abnormalities in Study 1

Adverse reactions in Study 2, a 1-year active-controlled (vs. interferon beta-1a, 30 mcg once weekly intramuscular injection, n=338) study including 339 patients with MS treated with REBIF were generally similar to those in Study 1, taking into account the disparity in study durations.

Immunogenicity

Anaphylaxis and other allergic reactions have been observed with the use of REBIF [see WARNINGS AND PRECAUTIONS]. As with all therapeutic proteins, there is a potential for immunogenicity. In Study 1, the presence of neutralizing antibodies (NAb) to REBIF was determined by collecting and analyzing serum pre-study and at 6 month time intervals during the 2 years of the clinical trial. Serum NAb were detected in 59/189 (31%) and 45/184 (24%) of REBIF-treated patients at the 22 mcg and 44 mcg three times per week doses, respectively, at one or more times during the study. The data reflect the percentage of patients whose test results were considered positive for antibodies to REBIF using an antiviral cytopathic effect assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of NAb positivity 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 REBIF with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of REBIF. 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.

Autoimmune Disorders: Drug-induced lupus erythematosus, autoimmune hepatitis

Eye Disorders: Retinal vascular disorders (i.e. retinopathy, cotton wool spots or obstruction of retinal artery or vein)

Skin and Subcutaneous Tissue Disorders: Erythema multiforme, Stevens-Johnson syndrome

Read the entire FDA prescribing information for Rebif (Interferon beta-1a)

You should not use this medicine if you are allergic to interferons or human albumin.

To make sure interferon beta-1a is safe for you, tell your doctor if you have:

• liver disease;

• epilepsy or other seizure disorder;

• heart disease, chest pain (angina);

• a bleeding disorder or history of blood clots;

• a thyroid disorder; or

• a history of depression or suicidal behavior.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether interferon beta-1a passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Some brands of interferon beta-1a contain albumin. Albumin comes from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Avonex is injected into a muscle. It is usually given once weekly at bedtime, on the same day each week (such as every Monday). Follow your doctor's instructions.

Rebif is injected under the skin. It is usually given 3 times per week (such as Monday, Wednesday, and Friday) at the same time on each dosing day. Follow your doctor's instructions.

You may be shown how to use injections 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.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Use a different place on your body each time you give the injection. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row.

The powder form of Avonex must be mixed with a liquid (diluent) in the medicine vial. Gently swirl but do not shake the vial after mixing the medicine. The mixture should be clear or light yellow. Do not use the mixture if it has changed colors or has any particles in it. Mix a new dose or call your doctor for a new prescription.

Do not draw your dose into a syringe until you are ready to give yourself an injection.

Each prefilled syringe or single use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left after injecting your dose.

Use a disposable needle only once, then throw away in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Interferon beta-1a can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Your liver or thyroid function may also need to be tested.

Store interferon beta-1a in a refrigerator. Do not freeze. You may take the Avonex prefilled syringe out of the refrigerator and allow it to reach room temperature before giving the injection. Do not heat the medicine before using.

Interferon beta-1a may be kept at room temperature for short periods if protected from light. Avonex powder or Rebif prefilled syringes can be stored at room temperature for up to 30 days. Avonex prefilled syringes can be stored at room temperature for only 7 days.

After mixing Avonex powder with a diluent, store in the refrigerator and use it within 6 hours.

Throw away any interferon beta-1a that has become frozen or has been exposed to light or high heat.

Thyroid function tests, CBC with differential, transaminase levels, blood chemistries, symptoms of autoimmune disorders, signs/symptoms of psychiatric disorder (including depression and/or suicidal ideation), signs/symptoms of new onset/worsening cardiovascular disease, signs/symptoms of thrombotic microangiopathy (new-onset hypertension, thrombocytopenia, renal impairment)

Avonex: Frequency of monitoring for patients receiving Avonex® has not been specifically defined; in clinical trials, monitoring was at 6-month intervals. Canadian labeling recommends liver function testing monthly for first 6 months, then every 6 months thereafter or as clinically indicated.

Rebif: CBC and liver function testing at 1-, 3-, and 6 months, then periodically thereafter. Thyroid function every 6 months (in patients with pre-existing abnormalities and/or clinical indications). Canadian labeling recommends liver function testing monthly for first 6 months, then every 6 months thereafter or as clinically indicated.