Avonex

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially:

• Acetaminophen (Tylenol, others)
• Antidepressants
• Azathioprine (Imuran)
• Chemotherapy medications
• Cholesterol-lowering medications (statins)
• Cyclosporine (Neoral, Sandimmune)
• Iron products
• Isoniazid (INH, Nydrazid)
• Medications for AIDS or HIV
• Methotrexate (Rheumatrex)
• Niacin (nicotinic acid)
• Rifampin (Rifadin, Rimactane)
• Salicylate pain relievers such as aspirin, choline magnesium trisalicylate, choline salicylate (Arthropan), diflunisal (Dolobid), magnesium salicylate (Doan's, others), and salsalate (Argesic, Disalcid, Salgesic)
• Sirolimus (Rapamune)
• Tacrolimus (Prograf)

Avonex and Alcohol

Consuming alcohol while taking Avonex may increase your risk of liver damage.

You should avoid alcoholic beverages while taking this medicine.

AVONEX is a 166 amino acid glycoprotein with a 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) International Standard for Interferon, AVONEX has a specific activity of approximately 200 million international units 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 micrograms contains approximately 6 million international units 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.

AVONEX Lyophilized Powder Vial

A vial of AVONEX is 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 micrograms 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.

AVONEX Single-Use Prefilled Syringe

A prefilled syringe of AVONEX is a sterile liquid for intramuscular injection. Each 0.5 Ml (30 microgram dose) of AVONEX in a prefilled glass syringe contains 30 micrograms 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.

AVONEX PEN Single-Use Prefilled Autoinjector

AVONEX PEN is a sterile liquid for intramuscular injection in a prefilled glass syringe surrounded by an autoinjector. Each 0.5 mL (30 microgram dose) in the AVONEX PEN contains 30 micrograms 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.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some patients using interferon medicines have become very depressed or had thoughts of suicide. Stop using interferon beta-1a 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.

Call your doctor at once if you have:

• fever, chills, body aches, chest pain, flu symptoms;

• pale skin, easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

• severe pain, swelling, bruising, redness, oozing, or skin changes where the injection was given;

• changes in your vision;

• seizure (convulsions);

• feeling hot or cold, unexplained weight changes;

• kidney problems--blood in your urine, swelling or rapid weight gain, little or no urination;

• signs of a serious blood cell disorder--confusion, feeling tired or irritable, stomach pain, bloody diarrhea, vomiting;

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• stomach pain;

• flu symptoms;

• headache, drowsiness;

• abnormal liver function tests; or

• minor irritation where the injection was given.

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 FDA at 1-800-FDA-1088.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• chest pain
• chills
• cough
• diarrhea
• fever
• flu-like symptoms
• headache
• joint pain
• muscle aches
• nausea
• pain
• painful or difficult urination
• shortness of breath
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• unusual bleeding or bruising
• unusual tiredness or weakness

• Abdominal or stomach pain
• clumsiness or unsteadiness
• convulsions (seizures)
• decreased hearing
• difficulty with swallowing
• dizziness
• fainting
• feeling of warmth
• hives or itching
• mood changes, especially with thoughts of suicide
• muscle spasms
• pain or discharge from the vagina
• pelvic discomfort, aching, or heaviness
• redness of the face, neck, arms, and occasionally, upper chest
• redness, swelling, or tenderness at the injection site
• runny or stuffy nose
• skin lesions
• sneezing
• sore throat
• speech problems
• swelling of the face, lips, or eyelids
• troubled breathing

• Earache
• general feeling of discomfort or illness
• loss of appetite
• painful blisters on trunk of the body
• painful cold sores or blisters on the lips, nose, eyes, or genitals

• Bleeding gums
• blood in the urine or stools
• bloody nose
• chest discomfort
• confusion
• constipation
• dark urine
• decreased urine output
• depressed mood
• dilated neck veins
• dry skin and hair
• extreme fatigue
• fast, irregular, or pounding heartbeat
• feeling cold
• general tiredness and weakness
• hair loss
• heavier menstrual periods
• high fever
• irregular breathing
• light-colored stools
• loss of bladder control
• mental depression
• mood or other mental changes
• muscle cramps and stiffness
• nausea or vomiting
• nervousness
• pale skin
• persistent loss of appetite
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids, or around the eyes, face, lips, or tongue
• redness, blistering, peeling, or loosening of the skin
• sensitivity to heat
• skin rash
• slowed heartbeat
• sudden loss of consciousness
• sweating
• swelling of the face, fingers, feet, or lower legs
• swelling of the mouth or throat
• tightness in the chest
• tightness in the throat
• upper right abdominal or stomach pain or tenderness
• weight gain or loss
• yellow eyes and skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Heartburn
• indigestion
• sour stomach

• Hair loss
• trouble sleeping

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Dosing Information

Avonex is administered intramuscularly.

The recommended dose is 30 micrograms once a week. To reduce the incidence and severity of flu-like symptoms that may occur when initiating Avonex therapy at a dose of 30 micrograms, Avonex may be started at a dose of 7.5 micrograms and the dose may be increased by 7.5 micrograms each week for the next three weeks until the recommended dose of 30 micrograms is achieved (see Table 1). An AVOSTARTGRIP™ kit containing 3 titration devices can be used for titration and is to be used only with Avonex Prefilled Syringes.

Important Administration Instructions (All Dosage Forms)

All Avonex dosage forms are single-use (injection of reconstituted solution, prefilled syringe, and prefilled autoinjector). See Patient's Instructions for Use for complete administration instructions.

The first Avonex injection should be performed under the supervision of an appropriately qualified healthcare professional. If patients or caregivers are to administer Avonex, train them in the proper intramuscular injection technique and assess their ability to inject intramuscularly to ensure the proper administration of Avonex.

Advise patients and caregivers to:

• Rotate sites for intramuscular injections with each injection to minimize the likelihood of injection site reactions
• NOT inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way
• Check the injection site after 2 hours for redness, swelling, or tenderness
• Contact their healthcare provider if they have a skin reaction and it does not clear up in a few days

A 25 gauge, 1” needle for intramuscular injection with Avonex prefilled syringe or injection of reconstituted solution may be substituted for the 23 gauge, 1 ¼” needle by the healthcare provider, if deemed appropriate. A 25 gauge, 5/8” needle specific to the prefilled autoinjector is supplied with the Avonex PEN® Administration Dose Pack. DO NOT use any other needle with the autoinjector.

Use safe disposal procedures for needles and syringes. Do not re-use needles, syringes, prefilled syringes, or autoinjectors. Following the administration of each titrated dose, discard any remaining product.

Premedication for Flu-like Symptoms

Concurrent use of analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with Avonex use.

Avonex is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, or any other component of the formulation [see Warnings and Precautions (5.3)].

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

Depression, Suicide, and Psychotic Disorders

Patients treated with Avonex and their caregivers should be advised to report immediately any symptoms of depression, suicidal ideation, and/or psychosis to their prescribing physicians. If a patient develops depression or other severe psychiatric symptoms, cessation of Avonex therapy should be considered.

Depression and suicide have been reported to occur with increased frequency in patients receiving Avonex. In Study 1, the incidence of depression was similar in placebo-treated and in Avonex-treated patients, but suicidal tendency was seen more frequently in Avonex-treated patients (4% in Avonex group vs. 1% in placebo group). In Study 2, there was a greater incidence of depression in Avonex-treated patients than in placebo-treated patients (20% in Avonex group vs. 13% in placebo group) [see Clinical Studies (14)].

Additionally, there have been postmarketing reports of depression, suicidal ideation, and/or development of new or worsening of other pre-existing psychiatric disorders, including psychosis. For some of these patients, symptoms of depression improved upon cessation of Avonex.

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 starting Avonex, or before starting hepatotoxic drugs. Patients should be monitored for signs of hepatic injury [see Warnings and Precautions (5.9)].

Anaphylaxis and Other Allergic-Reactions

Anaphylaxis has been reported as a rare complication of Avonex use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria. Discontinue Avonex if anaphylaxis or other allergic reactions occur.

Congestive Heart Failure

Patients with pre-existing congestive heart failure should be monitored for worsening of their cardiac condition during initiation of and continued treatment with Avonex. While beta interferons do not have any known direct cardiac toxicity, during the postmarketing period 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 etiologies being established. In some cases, these events have been temporally related to the administration of Avonex. In some of these instances recurrence upon rechallenge was observed.

Decreased Peripheral Blood Counts

Decreased peripheral blood counts in all cell lines, including rare pancytopenia and thrombocytopenia, have been reported from postmarketing experience in Avonex-treated patients [see Adverse Reactions (6.2)]. In some cases, platelet counts were below 10,000/microliter. Some cases recurred with rechallenge [see Adverse Reactions (6.2)]. Patients should be monitored for symptoms or signs of decreased blood counts.

Thrombotic Microangiopathy

Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported with interferon beta products, including Avonex. Cases have been reported several weeks to years after starting interferon beta products. Discontinue Avonex if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.

Seizures

Seizures have been temporally associated with the use of beta interferons in clinical trials and postmarketing safety surveillance. In the two placebo-controlled studies in multiple sclerosis (Studies 1 and 2), 4 patients receiving Avonex experienced seizures, while no seizures occurred in the placebo group [see Clinical Studies (14)]. Three of these 4 patients had no prior history of seizure [see Adverse Reactions (6.1)]. It is not known whether these events were related to the effects of multiple sclerosis alone, to Avonex, or to a combination of both.

Autoimmune Disorders

Postmarketing reports of autoimmune disorders of multiple target organs in Avonex-treated patients included idiopathic thrombocytopenia, hyper- and hypothyroidism, and rare cases of autoimmune hepatitis. If Avonex-treated patients develop a new autoimmune disorder, consider stopping the therapy.

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 and Precautions (5.2, 5.5, 5.8)]. 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.

Avonex is a 166 amino acid glycoprotein with a 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) International Standard for Interferon, Avonex has a specific activity of approximately 200 million international units 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 micrograms contains approximately 6 million international units 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.

Avonex Lyophilized Powder Vial

A vial of Avonex is 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 micrograms 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.

Avonex Single-Use Prefilled Syringe

A prefilled syringe of Avonex is a sterile liquid for intramuscular injection. Each 0.5 mL (30 microgram dose) of Avonex in a prefilled glass syringe contains 30 micrograms 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.

Avonex PEN Single-Use Prefilled Autoinjector

Avonex PEN is a sterile liquid for intramuscular injection in a prefilled glass syringe surrounded by an autoinjector. Each 0.5 mL (30 microgram dose) in the Avonex PEN contains 30 micrograms 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.

Avonex Lyophilized Powder Vial

A vial of Avonex is supplied as a lyophilized powder in a single-use vial containing 33 micrograms (6.6 million international units) 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 59627-111-03): 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).

Vials of Avonex should be stored in a 2°C to 8°C (36°F to 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°C to 8°C (36°F to 46°F). DO NOT FREEZE RECONSTITUTED Avonex.

Avonex Single-Use Prefilled Syringe

A prefilled syringe of Avonex is supplied as a sterile liquid albumin-free formulation containing 30 micrograms 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 Intramuscular injection.

Avonex prefilled syringes are available in the following package configuration (NDC 59627-222-05): 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.

Avonex in prefilled syringes should be stored in a 2°C to 8°C (36°F to 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 PEN Single-Use Prefilled Autoinjector

Avonex PEN is supplied as a sterile liquid albumin-free formulation containing 30 micrograms 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 single-use prefilled autoinjector contains 0.5 mL for intramuscular injection.

Avonex PEN single-use prefilled autoinjectors are available in the following package configuration (NDC 59627-333-04): A package containing four Avonex PEN Administration Dose Packs (each containing one Avonex PEN autoinjector, one 25 gauge, 5/8 inch needle and an Avonex PEN cover), and a recloseable accessory pouch containing 4 alcohol wipes, 4 gauze pads, and 4 adhesive bandages.

Avonex PEN should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Once removed from the refrigerator, Avonex PEN should be allowed to warm to room temperature (about 30 minutes). Do not use external heat sources such as hot water to warm Avonex. Should refrigeration be unavailable, Avonex PEN 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 prefilled autoinjector.

• Drugs Used for Treating Multiple Sclerosis
• Genital Warts in Women (HPV)
• Hepatitis (Viral Hepatitis, A, B, C, D, E, G)
• Hepatitis B (HBV, Hep B)
• Hepatitis C (HCV, Hep C)
• Leukemia
• Multiple Sclerosis (MS Symptoms, Causes, and Life Expectancy)

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

Some patients using interferon medications have become very depressed or had thoughts of suicide. Stop using Avonex 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.

To make sure Avonex 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.

Avonex may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

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.

Common side effects of Avonex include: flu-like symptoms, fever, headache, myalgia, nausea, and chills. Other side effects include: anemia. See below for a comprehensive list of adverse effects.

Applies to interferon beta-1a: kit, solution

Along with its needed effects, interferon beta-1a (the active ingredient contained in Avonex) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking interferon beta-1a:

• Black, tarry stools
• chest pain
• chills
• cough
• diarrhea
• fever
• flu-like symptoms
• headache
• joint pain
• muscle aches
• nausea
• pain
• painful or difficult urination
• shortness of breath
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• unusual bleeding or bruising
• unusual tiredness or weakness

• Abdominal or stomach pain
• clumsiness or unsteadiness
• convulsions (seizures)
• decreased hearing
• difficulty with swallowing
• dizziness
• fainting
• feeling of warmth
• hives or itching
• mood changes, especially with thoughts of suicide
• muscle spasms
• pain or discharge from the vagina
• pelvic discomfort, aching, or heaviness
• redness of the face, neck, arms, and occasionally, upper chest
• redness, swelling, or tenderness at the injection site
• runny or stuffy nose
• skin lesions
• sneezing
• sore throat
• speech problems
• swelling of the face, lips, or eyelids
• troubled breathing

• Earache
• general feeling of discomfort or illness
• loss of appetite
• painful blisters on trunk of the body
• painful cold sores or blisters on the lips, nose, eyes, or genitals

• Bleeding gums
• blood in the urine or stools
• bloody nose
• chest discomfort
• confusion
• constipation
• dark urine
• decreased urine output
• depressed mood
• dilated neck veins
• dry skin and hair
• extreme fatigue
• fast, irregular, or pounding heartbeat
• feeling cold
• general tiredness and weakness
• hair loss
• heavier menstrual periods
• high fever
• irregular breathing
• light-colored stools
• loss of bladder control
• mental depression
• mood or other mental changes
• muscle cramps and stiffness
• nausea or vomiting
• nervousness
• pale skin
• persistent loss of appetite
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids, or around the eyes, face, lips, or tongue
• redness, blistering, peeling, or loosening of the skin
• sensitivity to heat
• skin rash
• slowed heartbeat
• sudden loss of consciousness
• sweating
• swelling of the face, fingers, feet, or lower legs
• swelling of the mouth or throat
• tightness in the chest
• tightness in the throat
• upper right abdominal or stomach pain or tenderness
• weight gain or loss
• yellow eyes and skin

Some side effects of interferon beta-1a may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Heartburn
• indigestion
• sour stomach

• Hair loss
• trouble sleeping

Applies to interferon beta-1a: intramuscular kit, intramuscular powder for injection, subcutaneous kit, subcutaneous solution

General

Influenza-like symptoms (e.g., myalgia, fever, chills, sweating, asthenia, headache, nausea) are the most common adverse reactions.[Ref]

Hematologic

Very common (10% or more): Lymphopenia (14%), leukopenia (11%), neutropenia, thrombocytopenia, anemia
Common (1% to 10%): Neutrophil count decreased, hematocrit decreased, blood potassium increased, blood urea nitrogen increased
Uncommon (0.1% to 1%): Platelet count decreased
Rare (Less than 0.1%): Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome,
Frequency not reported: Pancytopenia[Ref]

Gastrointestinal

Very common (10% or more): Nausea (27%), diarrhea (17%), constipation (12%), vomiting (10%)
Common (1% to 10%): Abdominal pain, toothache
Frequency not reported: Dry mouth, dyspepsia[Ref]

Dermatologic

Very common (10% or more): Skin rashes (25%), increased sweating
Common (1% to 10%): Contusion, pruritus, erythematous rash, maculopapular rash, night sweats
Uncommon (0.1% to 1%): Alopecia, allergic dermatitis, erythema, urticaria
Rare (0.01% to 0.1%): Skin ulceration/necrosis at the site of injection, Quincke's edema (angioedema), erythema multiforme, Stevens-Johnson syndrome
Very rare (less than 0.01%): Calcified subcutaneous nodules, psoriasis, periungual and nail alterations
Frequency not reported: Rash vesicular[Ref]

Endocrine

Uncommon (0.1% to 1%): Hypothyroidism, hyperthyroidism[Ref]

Cardiovascular

Frequency not reported: Cardiomyopathy, congestive heart failure, palpitations, arrhythmia, tachycardia, vasodilatation, chest pain, pulmonary arterial hypertension (PAH) (sometimes reported up to several years after starting treatment)[Ref]

Genitourinary

Very common (10% or more): Urinary tract infection (19%), cystitis (11%)
Frequency not reported: Metrorrhagia, menorrhagia, urinary incontinence, increase in the frequency of micturition[Ref]

Hepatic

Very common (10% or more): Alanine aminotransferase increased (26%), aspartate aminotransferase increased (16%)
Common (1% to 10%): Gamma-glutamyl-transferase increased
Uncommon (0.1% to 1%): Hepatitis (with or without icterus)
Rare (Less than 0.1%): Hepatic failure, autoimmune hepatitis
Frequency not reported: Elevation of hepatic transaminases (SGPT and SGOT), bilirubinemia, jaundice[Ref]

Hypersensitivity

Rare (Less than 0.1%): Anaphylactic reactions
Frequency not reported: Other allergic reactions[Ref]

Immunologic

Very common (10% or more): Influenza-like symptoms (49%)
Frequency not reported: Systemic lupus erythematosus, anaphylactic reaction, anaphylactic shock, hypersensitivity reactions (angioedema, dyspnea, urticaria, rash, pruritic rash)[Ref]

Local

Very common (10% or more): Injection site erythema (62%), injection site pain (15%), injection site pruritus (13%), injection site bruising
Common (1% to 10%): Injection site edema, injection site warmth, injection site hematoma, injection site rash
Uncommon (0.1% to 1%): Injection site infections (which could be severe)
Rare (Less than 0.1%): Injection site cellulitis (which could be severe)
Frequency not reported: Injection site abscess, injection site reaction, injection site inflammation, injection site necrosis, injection site bleeding[Ref]

Musculoskeletal

Very common (10% or more): Myalgia (19%), back pain (20%), pain in extremity (19%), arthralgia (16%), muscular weakness (12%), muscle spasms (10%)
Common (1% to 10%): Muscle spasticity, muscle cramp, neck pain, arthralgia, muscle stiffness, musculoskeletal stiffness
Rare (0.01% to 0.1%): Drug induced lupus erythematosus
Frequency not reported: Arthritis[Ref]

Nervous system

Very common (10% or more): Headache (67%), dizziness (16%), paresthesia (12%)
Common (1% to 10%): Hypoesthesia
Uncommon (0.1% to 1%): Facial hypoesthesia
Frequency not reported: Neurological symptoms, syncope, hypertonia, seizures, migraine[Ref]

Metabolic

Frequency not reported: Weight decreased, weight increased[Ref]

Ocular

Common (1% to 10%): Eye pain
Uncommon (0.1% to 1%): Retinal vascular disorders (i.e. retinopathy, cotton wool spots, obstruction of retinal artery or vein)
Frequency not reported: Eye disorder, abnormal vision, xerophthalmia[Ref]

Other

Very common (10% or more): Pyrexia (45%), asthenia (24%), pain (23%), fever (20%), chills (19%)
Common (1% to 10%): Fatigue, malaise, hyperthermia, vertigo
Frequency not reported: Tachyphylaxis, sudden hearing loss, tinnitus (ototoxic effects resolved 7 to 14 days after discontinuation of the drug)[Ref]

Psychiatric

Common (1% to 10%): Depression/suicidal ideation, insomnia, somnolence
Uncommon (0.1% to 1%): Anxiety
Frequency not reported: Suicide attempt, suicide, psychosis, anxiety, confusion, emotional lability, anhedonia, psychotic thoughts, mood disturbances, hypersexuality, aggressive behavior, panic attacks[Ref]

Respiratory

Very common (10% or more): Oropharyngeal pain (28%), nasopharyngitis (24%), upper respiratory tract infection (21%), cough (16%), sinusitis (14%)
Common (1% to 10%): Rhinorrhea, bronchitis
Rare (0.01% to 0.1%): Dyspnea
Frequency not reported: Pulmonary arterial hypertension[Ref]

Renal

Rare (Less than 0.1%): Nephrotic syndrome, glomerulosclerosis[Ref]

Some side effects of Avonex may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.