Extavia

Included as part of the PRECAUTIONS section.

• Novartis Pharmaceuticals Corporation

Extavia is part of the drug class:

• interferon

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your age

The recommended dose range of Extavia for the treatment of relapsing-form multiple sclerosis is 0.0625 mg to 0.25 mg injected subcutaneously every other day.

• It is used to treat MS (multiple sclerosis).

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

     Mechanism of Action

The mechanism of action of Extavia (interferon beta-1b) in patients with multiple sclerosis is unknown.

     Pharmacodynamics

Interferons (IFNs) 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 1 (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 bioactivities 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-1b receptor binding induces the expression of proteins that are responsible for the pleiotropic bioactivities of interferon beta-1b. A number of these proteins (including neopterin, β2-microglobulin, MxA protein, and IL-10) have been measured in blood fractions from interferon beta-1b-treated patients and interferon beta-1b-treated healthy volunteers. Immunomodulatory effects of interferon beta-1b include the enhancement of suppressor T cell activity, reduction of pro-inflammatory cytokine production, down-regulation of antigen presentation, and inhibition of lymphocyte trafficking into the central nervous system. It is not known if these effects play an important role in the observed clinical activity of interferon beta-1b in multiple sclerosis (MS).

     Pharmacokinetics

Because serum concentrations of interferon beta-1b are low or not detectable following subcutaneous administration of 0.25 mg or less of interferon beta-1b, pharmacokinetic information in patients with MS receiving the recommended dose of interferon beta-1b is not available.

Following single and multiple daily subcutaneous administrations of 0.5 mg interferon beta-1b to healthy volunteers (N=12), serum interferon beta-1b concentrations were generally below 100 IU/mL. Peak serum interferon beta-1b concentrations occurred between one to eight hours, with a mean peak serum interferon concentration of 40 IU/mL. Bioavailability, based on a total dose of 0.5 mg interferon beta-1b given as two subcutaneous injections at different sites, was approximately 50%.

After intravenous administration of interferon beta-1b (0.006 mg to 2 mg), similar pharmacokinetic profiles were obtained from healthy volunteers (N=12) and from patients with diseases other than MS (N=142). In patients receiving single intravenous doses up to 2 mg, increases in serum concentrations were dose proportional. Mean serum clearance values ranged from 9.4 mL/min•kg-1 to 28.9 mL/min•kg-1 and were independent of dose. Mean terminal elimination half-life values ranged from 8 minutes to 4.3 hours and mean steady-state volume of distribution values ranged from 0.25 L/kg to 2.88 L/kg. Three-times-a-week intravenous dosing for two weeks resulted in no accumulation of interferon beta-1b in sera of patients. Pharmacokinetic parameters after single and multiple intravenous doses of interferon beta-1b were comparable.

Following every other day subcutaneous administration of 0.25 mg interferon beta-1b in healthy volunteers, biologic response marker levels (neopterin, β2-microglobulin, MxA protein, and the immunosuppressive cytokine, IL-10) increased significantly above baseline six-twelve hours after the first interferon beta-1b dose. Biologic response marker levels peaked between 40 and 124 hours and remained elevated above baseline throughout the seven-day (168-hour) study. The relationship between serum interferon beta-1b levels or induced biologic response marker levels and the clinical effects of interferon beta-1b in multiple sclerosis is unknown.

Drug Interaction Studies

No formal drug interaction studies have been conducted with interferon beta-1b.

How Supplied

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

Stability and Storage

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.

You should not use Extavia if you are allergic to interferon beta, albumin, or mannitol.

To make sure Extavia is safe for you, tell your doctor if you have:

• liver disease;

• congestive heart failure;

• epilepsy or other seizure disorder;

• a bleeding or blood-clotting disorder, such as hemophilia;

• a history of low white blood cell (WBC) counts;

• anemia (lack of red blood cells);

• a history of depression or suicidal behavior; or

• if you are allergic to latex.

A small number of pregnant women have had miscarriages while using Extavia. Do not use Extavia if you are pregnant. Tell your doctor if you become pregnant during treatment.

It is not known whether interferon beta-1b passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Interferon beta-1b is made 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 Extavia.

Avoid injecting Extavia into skin that is sore, red, or infected.

Drinking alcohol with this medicine can cause serious side effects.

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