Avonex

Avonex is used to treat relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. Avonex (interferon beta-1a) is given as an intramuscular injection into a muscle once a week.

Avonex is a disease-modifying therapy (DMT). It is a laboratory-made form of interferon beta, one of a family of proteins the body produces naturally that help regulate the immune response and fight viral infections.

• The way Avonex works in multiple sclerosis is not known. Interferon beta binds to specific receptors on the surface of human cells, which sets off a chain of events inside the cell and changes the levels of several immune-related proteins. How these changes translate into a benefit in MS has not been established.
• Avonex belongs to the drug class called interferons.

Avonex will not cure MS. In clinical trials it reduced the number of relapses and slowed the accumulation of disability compared with placebo.

Avonex (interferon beta-1a) gained FDA approval in 1996. There is no Avonex generic, more correctly called a biosimilar. Approval was supported by a two-year placebo-controlled trial in 301 people with relapsing MS, in which Avonex reduced the risk of sustained disability progression by 37% and lowered the annual relapse rate from 0.82 to 0.67 compared with placebo. A second trial, CHAMPS, studied 383 people who had experienced a first demyelinating event and found that Avonex delayed the development of a second relapse.

• Another form of interferon beta-1a, called Rebif, also used for MS, is given 3 times a week by subcutaneous (under the skin) injection.

Multiple sclerosis (MS) is an autoimmune disease that occurs when the immune system attacks the myelin sheath protecting nerve fibers, disrupting brain-body communication and causing MS symptoms like vision problems, muscle weakness, and coordination difficulties.

Avonex is used to modify the course of relapsing MS rather than to treat symptoms. In the two placebo-controlled trials that supported its approval, people taking Avonex had fewer relapses, slower accumulation of disability, and fewer new areas of inflammation on MRI than people taking placebo. The biological steps that produce these effects are not fully understood.

Avonex was studied in two randomized, double-blind, placebo-controlled trials. Study 1 enrolled 301 adults with relapsing MS and ran for up to two years. Study 2, known as CHAMPS, enrolled 383 adults who had just had a first demyelinating event, with MRI lesions typical of MS, and followed them for up to three years. The safety and effectiveness of Avonex beyond three years is not known.

In Study 1, the 22% versus 35% difference in disability progression represents a 37% reduction in the risk of accumulating disability. In Study 2, people taking Avonex were about half as likely to go on to a second relapse, which is the point at which clinically definite MS is diagnosed.

Liver Damage: Avonex injection can harm your liver, which can lead to liver failure and death. Call your doctor if you have symptoms such as nausea, loss of appetite, tiredness, sleepiness, confusion, easy bruising or bleeding, dark urine, pale or clay-colored stools, or yellowing of your skin or eyes.

Mental Health: Some MS patients using interferon beta-1a develop mood or behavior problems, including depression, suicidal thoughts, hallucinations (hearing or seeing things that others do not), irritability, nervousness, anxiety, or aggressive behavior. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

Latex: The tip cap of the Avonex prefilled syringe and the Avonex Pen contain natural rubber latex, which may cause an allergic reaction. Tell your healthcare provider if you have a latex allergy.

Before using Avonex injection, tell your doctor if you are allergic to any drugs, or if you have liver disease, a thyroid disorder, epilepsy or other seizure disorder, heart disease, chest pain (angina), congestive heart failure, a heart rhythm disorder, or a history of depression or suicidal behavior.

Do not use Avonex if you have ever had a hypersensitivity reaction to natural or recombinant interferon beta, or to any other ingredient in Avonex.

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

• depression, mental illness, or suicidal thoughts or actions;
• liver disease;
• bleeding problems or a blood clot;
• low blood cell counts;
• heart disease;
• a thyroid disorder;
• a latex allergy;
• an autoimmune disorder such as rheumatoid arthritis, lupus, or psoriasis;
• a seizure; or
• if you drink alcohol.

Tell your doctor if you are pregnant or plan to become pregnant, or if you are breastfeeding.

The safety and effectiveness of Avonex in children have not been established.

Use Avonex exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Avonex is given by intramuscular injection, typically in the thigh (vastus lateralis muscle) or upper arm (deltoid muscle). Rotate between different sites to prevent tissue damage and injection site reactions.

For thigh injections, alternate between left and right thighs, and vary the exact location within each thigh. If using the upper arm, you may need assistance from someone else for proper injection technique.

Keep a record of injection sites to ensure proper rotation. Never inject into areas that are red, bruised, infected, or have scar tissue.

Avonex Injection Guidelines:

• Frequency: Once weekly at bedtime, on the same day each week (such as every Monday)
• Method: Intramuscular injection into a muscle
• Injection devices: Available as a prefilled syringe or a prefilled autoinjector pen
• Site rotation: Use a different place each time you give an injection.

Avonex Injection Site Safety:

• Injection site reactions can occur with Avonex injections, including injection site necrosis
• About 2 hours after the Avonex injection, check for skin redness, swelling, or pain
• Report immediately: Any break in the skin with blue-black discoloration, swelling, or drainage
• Call your doctor if the injection site reaction doesn't go away within a few days.

Blood tests and monitoring during Avonex treatment

Alongside the tests normally used to monitor MS, the following are recommended during Avonex treatment:

• complete blood count and differential white cell count
• platelet count
• blood chemistry tests, including liver function tests
• thyroid function tests periodically, and at any point if you develop symptoms of an underactive or overactive thyroid.

People with low blood cell counts may need their blood counts checked more often. Your healthcare provider will decide how frequently you need testing.

Storage Instructions:

• Keep Avonex prefilled syringes and Pens in the refrigerator at 2°C to 8°C (36°F to 46°F), in the original carton to protect them from light.
• Do not freeze Avonex, and do not use it if it has been frozen.
• Take it out of the refrigerator about 30 minutes before injecting so it reaches room temperature. Do not warm it with hot water or any other heat source.
• If you cannot refrigerate it, Avonex can be kept at room temperature up to 25°C (77°F) for up to 7 days. Once it has been out of the refrigerator, it must not be stored above 25°C (77°F). If it has been kept in any other conditions, discard it and do not use it.
• Do not use Avonex after the expiration date. Dispose of used syringes and pens in an FDA-cleared sharps container.

Get emergency medical help if you have signs of an allergic reaction to Avonex (hives, itching, anxiety, feeling faint, difficult breathing, swelling in your face, eyes, lips, tongue, or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling, or sores in your mouth).

Life-threatening blood clots: Interferon beta-1a can cause life-threatening blood clots in the small blood vessels inside your organs, such as your brain or kidneys. Seek medical help right away if you have symptoms of this condition, such as a fever, tiredness, decreased urination, bruising, or nosebleeds.

Call your doctor at once if you have:

• pain, swelling, bruising, redness, oozing, or skin changes where the injection was given;
• a light-headed feeling, like you might pass out;
• unusual changes in mood or behavior (feeling hopeless, anxious, nervous, irritable, or depressed);
• thoughts about suicide or hurting yourself;
• easy bruising, unusual bleeding;
• a seizure;
• heart problems - swelling, rapid weight gain, feeling short of breath, rapid heartbeats, chest pain spreading to your jaw or shoulder, nausea, sweating;
• liver problems - nausea, loss of appetite, tiredness, confusion, easy bruising or bleeding, dark urine, clay-colored stools, or jaundice (yellowing of your skin or eyes);
• signs of infection - fever, chills, cough with mucus, bloody diarrhea, pain or burning when you urinate;
• thyroid problems - mood swings, trouble sleeping, tiredness, hunger, diarrhea, pounding heartbeats, muscle weakness, sweating, dry skin, thinning hair, menstrual changes, weight changes, puffiness in your face, feeling more sensitive to hot or cold temperatures; or
• breathing difficulties. Pulmonary arterial hypertension can occur with interferon beta products,including Avonex. Symptoms may include new or increasing fatigue or shortness of breath.

Common Avonex side effects may include:

• low blood cell counts;
• skin changes where the injection was given;
• depression;
• abnormal liver function tests;
• stomach pain; or
• flu symptoms: headache, fever, chills, chest pain, back pain, tiredness, weakness, muscle aches.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How common are Avonex side effects?

The figures below come from the placebo-controlled trials, in which 351 people received Avonex 30 micrograms and 333 received placebo. Placebo rates are shown alongside because many symptoms reported during treatment are also common in MS itself.

Other findings from the trials:

• Flu-like symptoms are the most common reason people need treatment for a side effect or stop Avonex. They usually last about a day after the injection, occur mainly early in treatment, and lessen or go away over time for many people.
• Injection site reactions of any kind occurred in 18% of people taking Avonex and 13% taking placebo.
• Suicidal tendency was reported in 4% of people taking Avonex in Study 1, compared with 1% taking placebo. In Study 2, depression was reported in 20% of the Avonex group and 13% of the placebo group.
• Four people taking Avonex in the two trials had a seizure, compared with none taking placebo. Three of the four had no previous history of seizures.

Reactions reported after Avonex came on the market, for which a frequency cannot be calculated, include hemolytic anemia, heavy or irregular menstrual bleeding, pulmonary arterial hypertension, rash including vesicular rash, and rare injection site abscess or cellulitis needing surgery.

Adult dose of Avonex for multiple sclerosis

The recommended dose is 30 micrograms given by intramuscular injection once a week.

To reduce how often flu-like symptoms occur and how severe they are, Avonex may be started at a lower dose and built up over three weeks:

• Week 1: 7.5 micrograms once weekly (one quarter of the dose)
• Week 2: 15 micrograms once weekly (half the dose)
• Week 3: 22.5 micrograms once weekly (three quarters of the dose)
• Week 4 onward: 30 micrograms once weekly (the full dose)

An AVOSTARTGRIP titration kit containing three titration devices can be used for this build-up. It is for use with Avonex prefilled syringes only, not with the Avonex Pen. Any product left in the syringe after a titrated dose is discarded.

Avonex is supplied as a single-dose prefilled syringe and a single-dose prefilled autoinjector (Avonex Pen). The first injection should be given under the supervision of an appropriately qualified healthcare professional.

Missed Dose

Use the medicine as soon as you can, and contact your prescriber for instructions.

Overdose

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

After an intramuscular injection, Avonex levels in the blood peak at about 15 hours, with a range of 6 to 36 hours. Levels then fall with an elimination half-life of about 19 hours, with a range of 8 to 54 hours, so most of the drug has cleared within a few days.

The biological effects last longer than the drug itself. Markers of interferon activity in the blood rise within 12 hours of a dose, peak at around 48 hours, and stay raised for at least four days. This is why Avonex is given once a week even though it clears from the blood much faster than that.

Neutralizing antibodies to Avonex

Some people develop antibodies that can reduce how well interferon beta works. In studies of people who took Avonex for at least a year, 5% (21 out of 390) had neutralizing antibodies detected on at least one occasion. Antibody test results vary between assays, so results for Avonex cannot be compared directly with results for other interferon beta products.

Other drugs may interact with interferon beta-1a, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Active ingredient: interferon beta-1aInactive ingredients: Avonex Single-Dose Prefilled Syringe: arginine hydrochloride, glacial acetic acid, polysorbate 20, sodium acetate trihydrate in water for injection.

Inactive ingredients: Avonex Single-Dose Prefilled Autoinjector Pen: arginine hydrochloride, glacial acetic acid, polysorbate 20, sodium acetate trihydrate in water for injection.