Avonex Pen

In the U.S.

• Avonex
• Avonex Pen
• Rebif
• Rebif Rebidose
• Rebif Rebidose Titration Pack

Available Dosage Forms:

• Solution
• Kit

Therapeutic Class: Immunological Agent

Pharmacologic Class: Interferon, Beta (class)

Interferon beta-1a injection is used to treat the relapsing forms of multiple sclerosis (MS). This medicine will not cure MS, but it may slow some of the disabling effects and decrease the number of relapses of the disease. Interferons are natural substances that are produced in the body to help fight infections. Interferon beta-1a is a synthetic (man-made) version of these substances.

This medicine is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

This medicine may cause some people to be anxious, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you or your caregiver notice any of these side effects, tell your doctor right away.

Check with your doctor right away if you have dark urine, persistent loss of appetite, flu-like symptoms, headache, continuing vomiting, general feeling of tiredness or weakness, light-colored stools, right upper stomach pain or tenderness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may cause serious allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

This medicine may lower the number of white blood cells in the blood. This will increase your chance of getting an infection. It can also lower the number of platelets in the blood. Platelets are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects, such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

This medicine may cause redness, pain, or swelling at the injection site. Some patients have developed skin infections or a permanent depression (necrosis) under the skin at the injection site. Contact your doctor right away if you notice depressed or indented skin, blue-green to black skin discoloration, or pain, redness, or sloughing (peeling) of the skin.

This medicine commonly causes a flu-like reaction, with aching muscles, chills, fever, headaches, joint pain, and nausea. Using your shot at bedtime may allow you to sleep through the symptoms. Your doctor may want you to take a medicine to help control the pain or fever (eg, acetaminophen or ibuprofen). Carefully follow your doctor's instructions about how to prevent or treat these symptoms.

This medicine contains albumin, which comes from human blood. Some human blood products have transmitted certain viruses to people who have received them, although the risk is low. Human donors and donated blood are both tested for viruses to keep the transmission risk low. Talk with your doctor about this risk if you are concerned. The Avonex® prefilled autoinjector pen and prefilled syringe do not contain albumin which comes from donated human blood.

The tip cap of the Avonex® prefilled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions in people who are sensitive to latex. Tell your doctor if you have a latex allergy before you start using this medicine.

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.

• 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.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Avonex Pen is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take Avonex Pen or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Avonex Pen. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

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