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Avonex (Interferon Beta-1A) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Depression, suicidal ideation, and new or worsening other psychiatric disorders have been observed to be increased in patients using interferon compounds including AVONEX® (see WARNINGS: Depression and Suicide). Anaphylaxis and other allergic reactions have been reported in patients using AVONEX® (see WARNINGS: Anaphylaxis). Decreased peripheral blood counts have been reported in patients using AVONEX® (see WARNINGS: Decreased Peripheral Blood Counts). Seizures, cardiovascular adverse events, and autoimmune disorders also have been reported in association with the use of AVONEX® (see Precautions).

The adverse reactions most commonly reported in patients associated with the use of AVONEX® were flu-like and other symptoms occurring within hours to days following an injection. Symptoms can include myalgia, fever, fatigue, headaches, chills, nausea, and vomiting. Some patients have experienced paresthesias, hypertonia and myasthenia.

The most frequently reported adverse reactions resulting in clinical intervention (e.g., discontinuation of AVONEX®, or the need for concomitant medication to treat an adverse reaction symptom) were flu-like symptoms and depression.

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

The data described below reflect exposure to AVONEX® in 351 patients, including 319 patients exposed for 6 months, and 288 patients exposed for greater than one year in placebo-controlled trials. The mean age of patients receiving AVONEX® was 35 years, 74% were women and 89% were Caucasian. Patients received either 30 mcg AVONEX® or placebo.

Table 3 enumerates adverse events and selected laboratory abnormalities that occurred at an incidence of at least 2% higher frequency in AVONEX®-treated subjects than was observed in the placebo group. Reported adverse events have been classified using standard COSTART terms.

Table 3
Adverse Events and Selected Laboratory Abnormalities in the
Placebo-Controlled Studies
Adverse Event Placebo
(N = 333)
AVONEX®
(N = 351)
Body as a Whole    
   Headache 55% 58%
   Flu-like symptoms (otherwise unspecified) 29% 49%
   Pain 21% 23%
   Asthenia 18% 24%
   Fever   9% 20%
   Chills   5% 19%
   Abdominal pain   6%   8%
   Injection site pain   6%   8%
   Infection   4%   7%
   Injection site inflammation   2%   6%
   Chest pain   2%   5%
   Injection site reaction   1%   3%
   Toothache   1%   3%
Nervous System    
   Depression 14% 18%
   Dizziness 12% 14%
Respiratory System    
   Upper respiratory tract infection 12% 14%
   Sinusitis 12% 14%
   Bronchitis   5%   8%
Digestive System    
   Nausea 19% 23%
Musculoskeletal System    
   Myalgia 22% 29%
   Arthralgia   6%   9%
Urogenital    
   Urinary tract infection 15% 17%
   Urine constituents abnormal   0%   3%
Skin and Appendages    
   Alopecia   2%   4%
Special Senses    
   Eye disorder   2%   4%
Hemic and Lymphatic System    
   Injection site ecchymosis   4%   6%
   Anemia   1%   4%
Cardiovascular System    
   Migraine   3%   5%
   Vasodilation   0%   2%

No AVONEX®-treated patients attempted suicide in the two placebo-controlled studies. In Study 2, AVONEX®-treated patients were more likely to experience depression than placebo-treated patients (20% in AVONEX® group vs. 13% in placebo group). The incidences of depression in the placebo-treated and AVONEX®-treated patients in Study 1 were similar. In Study 1, suicidal tendency was seen more frequently in AVONEX®-treated patients (4% in AVONEX® group vs. 1% in placebo group) (see WARNINGS).

SEIZURES

Seizures have been reported in 4 of 351 AVONEX®-treated patients in the placebo-controlled studies, compared to none in the placebo-treated patients (see Precautions: Seizures).

POST-MARKETING EXPERIENCE

The following adverse events have been identified and reported during post-approval use of AVONEX®: New or worsening other psychiatric disorders, and anaphylaxis (see WARNINGS). Autoimmune disorders including autoimmune hepatitis, idiopathic thrombocytopenia, hyper- and hypothyroidism, and seizures in patients without prior history (see Precautions).

Infrequent reports of congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure with rare cases being temporally related to the administration of AVONEX® (see Precautions: Cardiomyopathy and Congestive Heart Failure).

Decreased peripheral blood counts in all cell lines, including rare pancytopenia and thrombocytopenia (see WARNINGS: Decreased Peripheral Blood Counts). Some cases of thrombocytopenia have had nadirs below 10,000/µL. Some of these cases reoccur upon rechallenge.

Hepatic injury including elevated serum hepatic enzyme levels and hepatitis, some of which have been severe, has been reported post-marketing (see Precautions: Hepatic Injury).

Meno- and metrorrhagia, rash (including vesicular rash), rare cases of injection site abscess or cellulitis that may require surgical intervention have also been reported in post-marketing experience.

Because reports of these reactions are voluntary and the population is of an uncertain size, it is not always possible to reliably estimate the frequency of the event or establish a causal relationship to drug exposure.

ADVERSE REACTIONS ASSOCIATED WITH SUBCUTANEOUS USE

AVONEX® has also been evaluated in 290 patients with diseases other than multiple sclerosis, primarily chronic viral hepatitis B and C, in which the doses studied ranged from 15 mcg to 75 mcg, given SC, 3 times a week, for up to 6 months. Inflammation at the site of the subcutaneous injection was observed in 52% of treated patients in these studies. Subcutaneous injections were also associated with the following local reactions: injection site necrosis, injection site atrophy, injection site edema and injection site hemorrhage. None of the above was observed in the multiple sclerosis patients participating in Study 1. Injection site edema and injection site hemorrhage were observed in multiple sclerosis patients participating in Study 2.

IMMUNOGENICITY

As with all therapeutic proteins, there is a potential for immunogenicity. In recent studies assessing immunogenicity in multiple sclerosis patients administered AVONEX® for at least 1 year, 5% (21 of 390 patients) showed the presence of neutralizing antibodies at one or more times. The clinical significance of neutralizing antibodies to AVONEX® is unknown.

These data reflect the percentage of patients whose test results were considered positive for antibodies to AVONEX® using a two-tiered assay (ELISA binding assay followed by an antiviral cytopathic effect assay), and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of neutralizing activity 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 AVONEX® with the incidence of antibodies to other products may be misleading.

Anaphylaxis has been reported as a rare complication of AVONEX® use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria (see WARNINGS: Anaphylaxis).

DRUG ABUSE AND DEPENDENCE

There is no evidence that abuse or dependence occurs with AVONEX® therapy. However, the risk of dependence has not been systematically evaluated.

WHAT ARE THE POSSIBLE SIDE EFFECTS OF AVONEX®?

  • Flu-like symptoms-- Most people who take AVONEX® have flu-like symptoms (fever, chills, sweating, muscle aches, and tiredness) early during the course of therapy. Usually, these symptoms last for a day after the injection. You may be able to manage these flu-like symptoms by injecting your AVONEX® dose at bedtime and taking over-the-counter pain and fever reducers. For many people, these symptoms lessen or go away over time. Talk to your doctor if these symptoms continue longer than the first few months of therapy, or if they are difficult to manage.
  • Depression-- Some patients taking interferons have become severely depressed and/or anxious. If you feel sad or hopeless you should tell a friend or family member right away and call your doctor immediately. Your doctor or healthcare provider may ask that you stop taking AVONEX®, and/or may recommend that you take a medication to treat your depression. (See "What is the most important information I should know about AVONEX®?")
  • Blood problems-- A drop in the levels of white (infection-fighting) blood cells, red blood cells, or a part of your blood that helps to form blood clots (platelets) can happen. If this drop in blood levels is severe, it can lessen your ability to fight infections, make you feel very tired or sluggish, or cause you to bruise or bleed easily. Your doctor may ask you to have periodic blood tests. (See "What is the most important information I should know about AVONEX®?")
  • Liver problems-- Your liver function may be affected. Symptoms of changes in your liver include yellowing of the skin and whites of the eyes and easy bruising.
  • Thyroid problems-- Some people taking AVONEX® develop changes in the function of their thyroid. Symptoms of these changes include feeling cold or hot all the time, a change in your weight (gain or loss) without a change in your diet or amount of exercise you get, or feeling emotional.
  • Seizures-- Some patients have had seizures while taking AVONEX®, including patients who have never had seizures before. It is not known whether the seizures were related to the effects of their MS, to AVONEX®, or to a combination of both. If you have a seizure while taking AVONEX®, you should call your doctor right away. (See "What is the most important information I should know about AVONEX®?")
  • Heart problems-- While AVONEX® is not known to have any direct effects on the heart, a few patients who did not have a history of heart problems developed heart muscle problems or congestive heart failure after taking AVONEX®. Some of the symptoms of heart problems are swollen ankles, shortness of breath, decreased ability to exercise, fast heartbeat, tightness in chest, increased need to urinate at night, and not being able to lay flat in bed. If you develop these symptoms or any heart problems while taking AVONEX®, you should call your doctor right away. (See "What is the most important information I should know about AVONEX®?")

If you get any of the symptoms listed in this section or any listed in the section "What is the most important information I should know about AVONEX®?", you should call your doctor right away. Whether you experience any side effects or not, you and your doctor should periodically discuss your general health. Your doctor may want to monitor you more closely or may ask you to have blood tests more frequently.

GENERAL ADVICE ABOUT PRESCRIPTION MEDICINES

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. This medication has been prescribed for your particular condition. Do not use it for another condition or give this drug to anyone else. If you have questions you should speak with your doctor or healthcare professional. You may also ask your doctor or pharmacist for a copy of the information provided to them with the product.

Keep this and all drugs out of the reach of children.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen, Inc.

14 Cambridge Center

Cambridge, MA 02142 USA

©2004 Biogen, Inc. All rights reserved.

1-800-456-2255

I61018- 3(Issue date 03/2004)

MEDICATION GUIDE APPENDIX: INSTRUCTIONS FOR PREPARING AND GIVING A DOSE WITH AN AVONEX® PREFILLED SYRINGE

STORING AVONEX® PREFILLED SYRINGES

AVONEX® in prefilled syringes should be refrigerated (36-46°F or 2-8°C). Once removed from the refrigerator, AVONEX® in a prefilled syringe should be allowed to warm to room temperature (about 30 minutes) and used within 12 hours. Do not use external heat sources such as hot water to warm AVONEX® in a prefilled syringe. Do not expose to high temperatures. Do not freeze. Protect from light.

HOW DO I PREPARE AND INJECT A DOSE OF AVONEX®?

Find a well lit, clean, flat work surface like a table and collect all the supplies you will need to give yourself or receive an injection. Take one AVONEX® Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting your dose to allow it to reach room temperature. A room temperature solution is more comfortable to inject.

You will need the following supplies:

  • single-use prefilled syringe
  • sterile needle
  • alcohol wipe
  • gauze pad
  • adhesive bandage
  • a puncture resistant container for disposal of used syringes and needles
  • 1 syringe diagram card

PREPARING THE AVONEX® PREFILLED SYRINGE

It is important to keep your work area, your hands, and your injection site clean to minimize risk of infection. You should wash your hands prior to handling the syringe.

  1. Check the expiration date. The expiration date is printed on the AVONEX® prefilled syringe, syringe package and the carton. Do not use if the medication is expired.
  2. Check the contents of the syringe. The solution in the syringe should be clear and colorless. If the solution is colored or cloudy, do not use the syringe. Get a new syringe.
  3. Hold the syringe so the rubber cap is facing down. Take the card with the drawing of the syringe and hold it next to the real syringe so the drawing and the real syringe are side-by-side. Check to make sure the amount of liquid in the syringe is the same or very close to the 0.5 mL arrow shown on the card with the drawing of the prefilled syringe. The top of the liquid may be curved as shown in the drawing. The 0.5 mL arrow should point near the middle of the curved liquid. If the real syringe does not have the correct amount of liquid, DO NOT USE THAT SYRINGE. Call your pharmacist.
  4. Hold the AVONEX® prefilled syringe upright (rubber cap facing up).
  5. Remove the protective rubber cap by turning and gently pulling the cap in a clockwise motion.
  6. Open the package with the 23 gauge 1 ¼ inch needle. Attach the needle by firmly pressing it onto the syringe and turning it a half turn clockwise.

NOTE: If you do not firmly attach the needle to the syringe, it may leak so you may not get your full dose of AVONEX®.

SELECTING AN INJECTION SITE

You should use a different site each time you inject. This can be as simple as switching between thighs (if you are always injecting yourself), or if another person is helping you, you can rotate between your upper arms and your thighs. Keeping a record of the date and location of each injection will help you.

Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.

The best sites for intramuscular injection are the thigh and upper arm:

  • thigh

  • upper arm

INJECTING THE AVONEX® DOSE

  1. Use the alcohol wipe to clean the skin at the injection site you choose. Then, pull the protective cover straight off the needle; do not twist the cover off.
  2. With one hand, stretch the skin out around the injection site. Hold the syringe like a pencil with the other hand, and using a quick motion insert the needle at a 90° angle, through the skin and into the muscle.
  3. Once the needle is in, let go of the skin and slowly push the plunger down until the syringe is empty.
  4. Take the gauze pad and hold it near the needle at the injection site and pull the needle straight out. Use the gauze pad to apply pressure to the site for a few seconds or rub gently in a circular motion.
  5. If there is bleeding at the site, wipe it off and, if necessary, apply an adhesive bandage.
  6. After 2 hours, check the injection site for redness, swelling or tenderness. If you have a skin reaction and it does not clear up in a few days, contact your doctor or nurse.
  7. Dispose of the used syringe and needle in your puncture resistant container. This is a single-use syringe. DO NOT USE a syringe or needle more than once.

DISPOSAL OF SYRINGES AND NEEDLES

There may be special state and/or local laws for disposing of used needles and syringes. Your doctor, nurse or pharmacist should provide you with instructions on how to dispose of your used needles and syringes.

  • Always keep your disposal container out of the reach of children.
  • DO NOT throw used needles and syringes into the household trash and DO NOT RECYCLE.

Appendix Revision Date: 05/2003

MEDICATION GUIDE APPENDIX: INSTRUCTIONS FOR PREPARING AND GIVING A DOSE WITH AN AVONEX® VIAL

Storing AVONEX® Vials

Prior to use, AVONEX® should be refrigerated (36-46°F or 2-8°C) but can be kept for up to 30 days at room temperature (77°F or 25°C). You should avoid exposing AVONEX® to high temperatures and freezing. After mixing, AVONEX® solution should be used immediately, within 6 hours when stored refrigerated at 36-46°F or 2-8°C. Do not freeze the AVONEX® solution.

HOW DO I PREPARE AND INJECT A DOSE OF AVONEX®?

Find a well-lit, clean, flat work surface like a table and collect all the supplies you will need to give yourself or receive an injection. You may want to take one AVONEX® Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting your dose to allow it to reach room temperature. A room temperature solution is more comfortable to inject.

You will need the following supplies:

  • vial of AVONEX® (white to off-white powder or cake)
  • vial of diluent, single-use (Sterile Water for Injection, USP)
  • 3 mL syringe
  • blue MICRO PIN® (vial access pin)
  • sterile needle
  • alcohol wipes
  • gauze pad
  • adhesive bandage
  • a puncture resistant container for disposal of used syringes, needles, and MICRO PINS.

Preparing the AVONEX® solution

It is important to keep your work area, your hands, and your injection site clean to minimize risk of infection. You should wash your hands prior to preparing the medication.

  1. Check the expiration date on the AVONEX® vial and the vial of diluent; do not use if the medication or diluent is expired.
  2. Remove the caps from the vial of AVONEX® and the vial of diluent, and clean the rubber stopper on the top of each vial with an alcohol wipe.
  3. Remove the small light blue protective cover from the end of the syringe barrel with a counterclockwise turn.
  4. Attach the blue MICRO PIN® to the syringe by turning clockwise until secure. NOTE: Over-tightening can make the MICRO PIN® difficult to remove.
  5. Pull the MICRO PIN® cover straight off; do not twist. Save the cover for later use.
  6. Pull back the syringe plunger to the 1.1 mL mark.
  7. Firmly push the MICRO PIN® down through the center of the rubber stopper of the diluent vial.
  8. Inject the air in the syringe into the diluent vial by pushing down on the plunger until it cannot be pushed any further.
  9. Keeping the MICRO PIN® in the vial, turn the diluent vial and syringe upside down.
  10. While keeping the MICRO PIN® in the fluid, slowly pull back on the plunger to withdraw 1.1 mL of diluent into the syringe.
  11. Gently tap the syringe with your finger to make any air bubbles rise to the top. If bubbles are present, slowly press the plunger in (to push just the bubbles out through the needle). Make sure there is still 1.1 mL of diluent in the syringe.
  12. Slowly pull the MICRO PIN® out of the diluent vial.
  13. Carefully insert the MICRO PIN® through the center of the rubber stopper of the vial of AVONEX®. NOTE: Off-center punctures can push the stopper into the vial. If the stopper falls into the vial, do not use.
  14. Slowly inject the diluent into the vial of AVONEX®. DO NOT aim the stream of diluent directly on the AVONEX® powder. Too direct or forceful a stream of diluent onto the powder may cause foaming, and make it difficult to withdraw AVONEX®.
  15. Without removing the syringe, gently swirl the vial until the AVONEX® is dissolved. DO NOT SHAKE.
  16. Check to see that all of the AVONEX® is dissolved. Check the solution in the vial of AVONEX®. It should be clear to slightly yellow in color and should not have any particles. Do not use the vial if the solution is cloudy, has particles in it or is a color other than clear to slightly yellow.
  17. Turn the vial and syringe upside down. Slowly pull back on the plunger to withdraw 1.0 mL of AVONEX®. If bubbles appear, push solution slowly back into the vial and withdraw the solution again.
  18. With the vial still upside down, tap the syringe gently to make any air bubbles rise to the top. Then press the plunger in until the AVONEX® is at the top of the syringe. Check the volume (should be 1.0 mL) and withdraw more medication if necessary. Withdraw the MICRO PIN® and syringe from the vial.
  19. Replace the cover on the MICRO PIN® and remove from the syringe with a counterclockwise turn.
  20. Attach the sterile needle for injection to the syringe turning clockwise until the needle is secure. A secure attachment will prevent leakage during the injection.

Selecting an injection site

You should use a different site each time you inject. This can be as simple as switching between thighs (if you are always injecting yourself), or if another person is helping you, you can rotate between your upper arms and your thighs. Keeping a record of the date and location of each injection will help you.

Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.

The best sites for intramuscular injection are the thigh and upper arm:

  • thigh

  • upper arm

You should rotate injection sites each week. This can be as simple as switching between thighs (if you are always injecting yourself). If another person is helping you, you can rotate among your thighs and upper arms. Make sure that the site you choose is free from any skin irritations.

Injecting the AVONEX® dose

  1. Use a new alcohol wipe to clean the skin at one of the recommended intramuscular injection sites. Then, pull the protective cover straight off the needle; do not twist the cover off.
  2. With one hand, stretch the skin out around the injection site. Hold the syringe like a pencil with the other hand, and using a quick motion insert the needle at a 90° angle, through the skin and into the muscle.
  3. Once the needle is in, let go of the skin and slowly push the plunger down until the syringe is empty.
  4. Hold a gauze pad near the needle at the injection site and pull the needle straight out. Use the pad to apply pressure to the site for a few seconds or rub gently in a circular motion.
  5. If there is bleeding at the site, wipe it off and, if necessary, apply an adhesive bandage.
  6. Dispose of the used syringe, needle and blue MICRO PIN® in your puncture resistant container. DO NOT USE a syringe, MICRO PIN®, or needle more than once. The AVONEX® and diluent vials should be put in the trash.

Disposal of syringes and needles

There may be special state and/or local laws for disposing of used needles and syringes. Your doctor, nurse or pharmacist should provide you with instructions on how to dispose of your used needles and syringes.

  • Always keep your disposal container out of the reach of children.
  • DO NOT throw used needles and syringes into the household trash and DO NOT RECYCLE.

Appendix Revision Date: 03/2004



REPORTS OF SUSPECTED AVONEX SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Avonex. The information is not vetted and should not be considered as verified clinical evidence.

Possible Avonex side effects / adverse reactions in 35 year old female

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 35 year old female

Reactions: Nausea, Headache, Abortion Spontaneous

Suspect drug(s):
Avonex



Possible Avonex side effects / adverse reactions in 57 year old male

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 57 year old male

Reactions: Musculoskeletal Disorder

Suspect drug(s):
Avonex
    Start date: 1999-01-07

Avonex
    Indication: Multiple Sclerosis
    Start date: 2000-04-12
    End date: 2004-01-01

Avonex
    Start date: 2004-01-01
    End date: 2004-01-01

Avonex
    Start date: 2004-01-01

Other drugs received by patient: Motrin



Possible Avonex side effects / adverse reactions in 49 year old female

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 49 year old female

Reactions: Back Pain, Dysstasia, Gait Disturbance, Ankle Fracture, Fall

Adverse event resulted in: hospitalization

Suspect drug(s):
Avonex



See index of all Avonex side effect reports >>

Drug label data at the top of this Page last updated: 2006-09-13

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