AVONEX is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

• Injection: 30 micrograms per 0.5 mL clear, colorless solution in a single-dose prefilled syringe
• Injection: 30 micrograms per 0.5 mL clear, colorless solution in a single-dose prefilled autoinjector

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 formerly available lyophilized vial formulation of AVONEX is contraindicated in patients with a history of hypersensitivity to albumin (human).

The following serious adverse reactions are discussed in more detail in other sections of labeling:

• Depression, Suicide, and Psychotic Disorders [see Warnings and Precautions (5.1)]
• Hepatic Injury [see Warnings and Precautions (5.2)]
• Anaphylaxis and Other Allergic-Reactions [see Warnings and Precautions (5.3)]
• Injection Site Reactions Including Necrosis [see Warnings and Precautions (5.4)]
• Congestive Heart Failure [see Warnings and Precautions (5.5)]
• Decreased Peripheral Blood Counts [see Warnings and Precautions (5.6)]
• Thrombotic Microangiopathy [see Warnings and Precautions (5.7)]
• Seizures [see Warnings and Precautions (5.8)]
• Autoimmune Disorders [see Warnings and Precautions (5.9)]
• Laboratory Tests [see Warnings and Precautions (5.10)]

Interferon beta-1a, an interferon beta, 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 (interferon beta-1a) injection is a sterile liquid for intramuscular injection available in a prefilled glass syringe or a prefilled glass syringe surrounded by an autoinjector. Each single-dose prefilled glass syringe or single-dose prefilled autoinjector delivers 0.5 mL of solution containing 30 micrograms of interferon beta-1a, arginine hydrochloride, USP (15.8 mg), glacial acetic acid, USP (0.25 mg), polysorbate 20 (0.025 mg), sodium acetate trihydrate, USP (0.79 mg), and Water for Injection, USP at a pH of approximately 4.8.

The clinical effects of AVONEX in patients with relapsing forms of multiple sclerosis (MS) were studied in two randomized, multicenter, double-blind, placebo-controlled studies in patients with MS (Studies 1 and 2). Safety and efficacy of treatment with AVONEX beyond 3 years is not known.

In Study 1, 301 patients received either 30 micrograms of AVONEX (n=158) or placebo (n=143) by intramuscular injection once weekly. Patients received injections for up to 2 years, and continued to be followed until study completion. Two hundred eighty-two patients completed 1 year on study, and 172 patients completed 2 years on study. There were 144 patients treated with AVONEX for more than 1 year, 115 patients for more than 18 months and 82 patients for 2 years.

All patients had a definite diagnosis of multiple sclerosis of at least 1 year duration and had at least 2 exacerbations in the 3 years prior to study entry (or 1 per year if the duration of disease was less than 3 years). At entry, study participants were without exacerbation during the prior 2 months and had Kurtzke Expanded Disability Status Scale (EDSS3) scores ranging from 1.0 to 3.5. The EDSS is a scale that quantifies disability in patients with MS and ranges from 0 (normal neurologic exam) to 10 (death due to MS). Patients with chronic progressive multiple sclerosis were excluded from this study.

Disability

The primary outcome assessment was time to progression in disability, measured as an increase in the EDSS score of at least 1 point that was sustained for at least 6 months. An increase in EDSS score reflects accumulation of disability. This endpoint was used to help distinguish permanent increase in disability from a transient increase due to an exacerbation.

As shown in Figure 1, the time to onset of sustained progression in disability was significantly longer in AVONEX-treated patients than in placebo-treated patients in Study 1 (p = 0.02). The percentage of patients progressing by the end of 2 years was 35% for placebo-treated patients and 22% for AVONEX-treated patients. This represents a 37% relative reduction in the risk of accumulating disability in the AVONEX-treated group compared to the placebo-treated group.

1Kaplan-Meier Methodology; Disability progression was defined as at least a 1 point increase in EDSS score sustained for at least 6 months.

The distribution of confirmed EDSS change from study entry (baseline) to the end of the study is shown in Figure 2. There was a statistically significant difference between the AVONEX and placebo groups in confirmed change for patients with at least 2 scheduled visits (p = 0.006).

Exacerbations

In Study 2, the primary outcome measure was time to development of a second exacerbation in an anatomically distinct region of the central nervous system. Time to development of a second exacerbation was significantly delayed in AVONEX-treated compared to placebo-treated patients (p = 0.002). The Kaplan-Meier estimates of the percentage of patients developing an exacerbation within 24 months were 39% in the placebo group and 21% in the AVONEX group (see Figure 3). The relative rate of developing a second exacerbation in the AVONEX group was 0.56 of the rate in the placebo group (95% confidence interval 0.38 to 0.81).

1 Kaplan-Meier Methodology

See FDA-approved patient labeling (Medication Guide and Patient's Instructions for Use).

Instruct patients to carefully read the supplied AVONEX Medication Guide and caution patients not to change the AVONEX dose or schedule of administration without medical consultation.

Inform patients that the tip cap of the AVONEX Prefilled Syringe and AVONEX PEN contains natural rubber latex which may cause allergic reactions.

INSTRUCTIONS FOR USE

AVONEX PEN® (a-vuh-necks)

(interferon beta-1a)

injection for intramuscular use

single-dose prefilled autoinjector pen

Read the Instructions for Use before you start using AVONEX and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Your healthcare provider should show you or your caregiver how to prepare the dose of AVONEX and how to inject your AVONEX PEN the right way before AVONEX PEN is used for the first time.  Your healthcare provider or nurse should watch you inject the dose of AVONEX the first time AVONEX PEN is used.

Important information: The tip of the cap of the AVONEX PEN is made of natural rubber latex. Tell your healthcare provider if you are allergic to rubber or latex.

How should I store AVONEX?

• Store AVONEX in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze AVONEX. Do not use AVONEX that has been frozen.
• If you cannot refrigerate your AVONEX PEN, you can store your AVONEX PEN at room temperature up to 77°F (25°C) for up to 7 days.
• Do not store AVONEX above 77°F (25°C). Do not use AVONEX that is stored at temperatures higher than 77°F (25°C).
• Throw AVONEX away in an FDA-cleared sharps disposal container if it has not been stored as stated above. (See After the AVONEX injection section at the end of this Instructions for Use.)
• Keep AVONEX in the original carton to protect it from light.

Preparing the AVONEX PEN:

• 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 1 AVONEX PEN Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting the AVONEX dose to allow it to reach room temperature. Do not use external heat sources such as hot water to warm the AVONEX PEN.
• Check the expiration date printed on the AVONEX PEN, AVONEX PEN Administration Dose Pack carton, and the outer carton. Do not use the AVONEX PEN past the expiration date.
• Wash your hands with soap and water.

Supplies you will need to give the AVONEX PEN injection:

• 1 AVONEX Administration Dose Pack that contains:
  • 1 AVONEX PEN
  • a 25 gauge, 5/8 inch long sterile needle
  • 1 AVONEX PEN cover
• 1 alcohol wipe
• 1 gauze pad
• 1 adhesive bandage
• a puncture resistant container for disposal of used AVONEX PEN and needle

Identifying parts of the AVONEX PEN (See Figure A).

Single-Dose Administration Dose Pack Contents – AVONEX PEN, Supplied Needle and AVONEX PEN Cover

(Figure A)

Preparing the AVONEX PEN injection:

Step 1: Hold the AVONEX PEN with the white tamper-evident cap (cap) pointing up (See Figure B). Check that the cap is intact and has not been removed. If the cap has been removed or is not tightly attached, do not use it. Throw it away and get a new AVONEX PEN. (See After the AVONEX injection section at the end of this Instructions for Use.)	(Figure B)
Step 2: With your other hand, grasp the cap and bend it at a 90° angle until the cap snaps off (See Figure C). After the cap comes off, you will see the glass tip of the syringe. Do not touch the glass tip of the syringe (See Figure D).	(Figure C) (Figure D)
Step 3: Place the AVONEX PEN down on a flat work surface.
Step 4: Pull off the sterile foil from the needle cover (See Figure E). Only use the needle that comes with your AVONEX PEN.	(Figure E)
Step 5: Hold the AVONEX PEN with the glass syringe tip pointing up. Press the needle onto the AVONEX PEN glass syringe tip (See Figure F).	(Figure F)
Step 6: Gently turn the needle to the right (clockwise) until it is firmly attached (See Figure G). If the needle is not firmly attached, it may leak, and you may not get your full dose of AVONEX.	(Figure G)
Do not remove the plastic cover from the needle (See Figure H).	(Figure H)
Step 7: Hold the body of the AVONEX PEN in 1 hand with the needle and needle cover pointing away from you and other people. Do not remove the plastic cover from the needle (See Figure I).	(Figure I)
Step 8: Using your other hand, hold onto the injector shield (grooved area) tightly and quickly pull up on the injector shield until the injector shield covers the needle all the way. The plastic needle cover will “pop” off after the injector shield has been fully extended (See Figure J).	(Figure J)
When the injector shield is extended the right way, you will see a small blue rectangular area next to the oval medicine display window (See Figure K).	(Figure K)
Step 9: Check the oval medicine display window and make sure the AVONEX is clear and colorless (See Figure L). You might see air bubbles in the oval medicine display window. This is normal and will not affect your dose. Do not use AVONEX PEN if the liquid is colored, cloudy, or contains any lumps or particles. Throw away the AVONEX PEN in an FDA-cleared sharps container and get a new one, then repeat steps 1 to 9. (See After the AVONEX injection section at the end of this Instructions for Use .)	(Figure L)

Giving the AVONEX injection:

• Your healthcare provider should show you or your caregiver how to prepare the dose of AVONEX and how to inject your AVONEX PEN the right way before AVONEX PEN is used for the first time. Your healthcare provider or nurse should watch you inject the dose of AVONEX the first time AVONEX PEN is used.
• Inject your AVONEX PEN exactly as your healthcare provider has shown you.
• AVONEX PEN is injected into the muscle (intramuscularly).
• AVONEX PEN should be injected into the upper, outer thigh (See Figure M).
• Change (rotate) injection sites for each dose. Do not use the same injection site for each injection.
• Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.
• Do not push down on the injector shield and the blue activation button at the same time until you are ready to give your injection.

Figure M

Step 10: Choose an injection site and wipe the skin with an alcohol wipe (See Figure N). Let the injection site dry before injecting the dose. Do not touch this area again before giving the injection.	(Figure N)
Step 11: Place the AVONEX PEN on the injection site (See Figure O).	(Figure O)
Step 12: Hold the body of the AVONEX PEN at a 90º angle to the injection site, and make sure you can see the window (See Figure P).	(Figure P)
Step 13: Keeping your fingers away from the blue activation button, firmly push the body of the AVONEX PEN down against the thigh to release the safety lock (See Figure Q). Do not lift the AVONEX PEN off the injection site. Check to make sure the safety lock has been released. You will know the safety lock is released when the small blue rectangular area above the oval medicine display window is gone (See Figure R).	(Figure Q) (Figure R)
Step 14: Continue to firmly maintain pressure and push down on the AVONEX PEN against the injection site, then push down on the blue activation button with your thumb (See Figure S). Keep the AVONEX PEN pushed down against the injection site and slowly count to 10. You will hear a “click” when the injection starts. If you do not hear a “click”, your injection was not given the right way. If this happens, make sure that the injector shield is extended, the safety lock is completely released, and that you are firmly maintaining pressure and pushing down against the injection site. Press the blue activation button with your thumb again. If you still do not hear a “click”, call Biogen at 1-800-456-2255.	(Figure S)
Step 15: After you count to 10, pull the AVONEX PEN straight out of the skin (See Figure T). Use the gauze pad to apply pressure to the injection site for a few seconds or rub gently in a circular motion. • If you see blood after you press the injection site for a few seconds, wipe it off with the gauze pad and apply an adhesive bandage.	(Figure T)
Step 16: Check the circular display window on the AVONEX PEN to make sure that it is yellow. This is to be sure that you have been given your full dose (See Figure U). If you did not receive your full dose of AVONEX, throw away the AVONEX PEN in a FDA-cleared sharps disposal container and call your healthcare provider. Do not re-use the AVONEX PEN.	(Figure U)
Step 17: Do not hold the AVONEX PEN cover with your hands. Place the AVONEX PEN cover on a flat work surface. Line up the exposed needle with the hole of the AVONEX PEN cover, and insert directly into the opening (See Figure V).	(Figure V)
Step 18: Firmly press the AVONEX PEN down until you hear a “click” to seal the needle (See Figure W). You may need to hold both hands around the AVONEX PEN body to snap the AVONEX PEN cover into place.	(Figure W)

After the AVONEX injection:

Throw Away your AVONEX:

• Put your used needles and PENS in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Check Your Injection Site:

• 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 healthcare provider.

General information about the safe and effective use of AVONEX PEN

• Always use a new AVONEX PEN and needle for each injection. Do not re-use your AVONEX PEN or needle.
• Do not share your AVONEX PEN or needles.
• Keep AVONEX PEN and needles and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License # 1697

1-800-456-2255

AVONEX is a registered trademark of Biogen.

©Biogen 1996-2020. All rights reserved.

Revised: 03/2020

41610-03

INSTRUCTIONS FOR USE

AVONEX® (a-vuh-necks)

(interferon beta-1a)

injection for intramuscular use

single-dose prefilled syringe

Read the Instructions for Use before you start using AVONEX and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Important information: The tip of the cap of the AVONEX prefilled syringe is made of natural rubber latex. Tell your healthcare provider if you are allergic to rubber or latex.

How should I store AVONEX?

• Store AVONEX in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze AVONEX. Do not use AVONEX that has been frozen.
• If you cannot refrigerate your AVONEX prefilled syringes, you can store your AVONEX prefilled syringes at room temperature up to 77°F (25°C) for up to 7 days.
• Do not store AVONEX above 77°F (25°C). Do not use AVONEX that is stored at temperatures higher than 77°F (25°C).
• Throw AVONEX away in an FDA-cleared sharps disposal container if it has not been stored as stated above. (See After the AVONEX injection section at the end of this Instructions for Use.)
• Keep AVONEX in the original carton to protect it from light.

Supplies you will need for the AVONEX injection:

• 1 AVONEX Administration Dose Pack that contains:
  • 1 AVONEX prefilled syringe
  • 23 gauge, 1¼ inch long sterile needle
• 1 alcohol wipe
• 1 gauze pad
• 1 adhesive bandage
• a puncture resistant container for disposal of used syringes and needles

Preparing the 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 1 AVONEX Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting the AVONEX dose to allow it to reach room temperature. Do not use external heat sources such as hot water to warm the AVONEX prefilled syringe.
• Check the expiration date printed on AVONEX prefilled syringe, AVONEX Administration Dose Pack, and the outer carton. Do not use AVONEX prefilled syringe past the expiration date.
• Wash your hands with soap and water.

Identifying parts of the AVONEX prefilled syringe (See Figure A):

Preparing the AVONEX injection:

Step 1: Hold the AVONEX prefilled syringe with the cap pointing down and with the 0.5 mL mark at eye level (See Figure A). Check the syringe: The syringe should not have any cracks or damage. Check that the cap is intact and has not been removed. The amount of liquid in the syringe should be at or very close to the 0.5 mL mark. AVONEX should look clear, colorless, and should not have any particles in it. Do not use the AVONEX prefilled syringe if: the syringe is cracked or damaged the solution is cloudy, colored, or has lumps or particles in it the cap has been removed or is not tightly attached or there is not enough liquid in the syringe If you cannot use that syringe, you will need to get a new syringe. Contact Biogen at 1-800-456-2255.	(Figure A)
Step 2: With 1 hand, hold the AVONEX prefilled syringe right under the cap and with the cap pointing up (See Figure B). Make sure you are holding the AVONEX prefilled syringe by the ridged part, directly under the cap.	(Figure B)
Step 3: With the other hand, grasp the cap and bend it at a 90º angle until the cap snaps off (See Figure C and Figure D).	(Figure C) (Figure D)
Step 4: Open the sterile needle package and take out the covered needle. Hold the AVONEX prefilled syringe with the glass syringe tip pointing up. Press the needle on the AVONEX prefilled syringe glass tip (See Figure E).	(Figure E)
Step 5: Gently turn the needle to the right (clockwise) until it is tight and firmly attached (See Figure F). If the needle is not firmly attached, it may leak and you may not get your full dose of AVONEX. Do not remove the plastic cover from the needle.	(Figure F)

Giving the AVONEX injection:

• Your healthcare provider should show you or a caregiver how to prepare and inject the dose of AVONEX before AVONEX prefilled syringe is used for the first time. Your healthcare provider or nurse should watch you inject the dose of AVONEX the first time AVONEX prefilled syringe is used.
• Inject your AVONEX exactly as your healthcare provider has shown you.
• AVONEX is injected into the muscle (intramuscularly).
• AVONEX should be injected into the thigh or upper arm (See Figures G and H).
• Change (rotate) your injection sites for each dose. Do not use the same injection site for each injection.
• Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.

Step 6: Choose an injection site and wipe the skin with an alcohol wipe (See Figures G and H). Let the injection site dry before injecting the dose. Do not touch this area again before giving the injection.	(Figure G)	(Figure H)
Step 7: Pull the protective cover straight off the needle (See Figure I). Do not twist the cover off.	(Figure I)
Step 8: With 1 hand, stretch the skin out around the injection site. With the other hand, hold the syringe like a pencil. Use a quick dart-like motion and insert the needle at a 90 degree angle, through the skin and into the muscle (See Figure J). After the needle is in, let go of the skin.	(Figure J)
Step 9: Slowly push the plunger down until the syringe is empty (See Figure K).	(Figure K)
Step 10: Pull the needle out of the skin (See Figure L). Press down on the injection site with the gauze pad for a few seconds or rub gently in a circular motion. If you see blood after you press the injection site for a few seconds, wipe it off with the gauze pad and apply an adhesive bandage.	(Figure L)

After the AVONEX injection:

• Do not recap the needle. Recapping the needle can lead to a needle stick injury.
• Put your used needles and syringes in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Check Your Injection Site:

• 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 healthcare provider.

General information about the safe and effective use of AVONEX

• Always use a new AVONEX prefilled syringe and needle for each injection. Do not re-use your AVONEX prefilled syringe or needles.
• Do not share your AVONEX prefilled syringe or needles.
• Keep the AVONEX prefilled syringe and needles and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License # 1697

1-800-456-2255

AVONEX is a registered trademark of Biogen.

©Biogen 1996-2020. All rights reserved.

Revised: 03/2020

41611-03

Instructions for Use

AVOSTARTGRIP®Titration Kit

Use with AVONEX®(interferon beta-1a) Prefilled Syringe Only

Read the Instructions for Use before you start using AVONEX and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Preparing the AVONEX Prefilled Syringe:

• 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 1 AVONEX Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting the AVONEX dose to allow it to reach room temperature. Do not use external heat sources such as hot water to warm the AVONEX prefilled syringe.
• Check the expiration date printed on the AVONEX prefilled syringe, AVONEX prefilled syringe Administration Dose Package carton, and the outer carton. Do not use the AVONEX prefilled syringe past the expiration date.
• Wash your hands with soap and water.

Supplies you will need for the AVONEX injection:

• 1 AVONEX Administration Dose Pack that contains:
  • 1 AVONEX prefilled syringe
  • 23 gauge, 1¼ inch long sterile needle
• 1 alcohol wipe
• 1 gauze pad
• 1 adhesive bandage
• a puncture resistant container for disposal of used syringes and needles

Identifying parts of the AVONEX prefilled syringe (See Figure A):

Preparing the AVONEX injection:

Step 1: Hold the AVONEX prefilled syringe with the cap pointing down and with the 0.5 mL mark at eye level (See Figure A). Check the syringe: The syringe should not have any cracks or damage. Check that the cap is intact and has not been removed. The amount of liquid in the syringe should be at or very close to the 0.5 mL mark. AVONEX should look clear, colorless, and should not have any particles in it. Do not use the AVONEX prefilled syringe if: the syringe is cracked or damaged the solution is cloudy, colored, or has lumps or particles in it the cap has been removed or is not tightly attached or there is not enough liquid in the syringe Do not use that syringe. Get a new syringe. Contact MS ACTIVESOURCE at 1-800-456-2255.	(Figure A)
Step 2: With 1 hand, hold the AVONEX prefilled syringe right under the cap and with the cap pointing up (See Figure B). Make sure you are holding the AVONEX prefilled syringe by the ridged part, directly under the cap.	(Figure B)
Step 3: With the other hand, grasp the cap and bend it at a 90º angle until the cap snaps off (See Figure C and Figure D).	(Figure C) (Figure D)
Step 4: Open the sterile needle package and take out the covered needle. Hold the AVONEX prefilled syringe with the glass syringe tip pointing up. Press the needle on the AVONEX prefilled syringe glass tip (See Figure E).	(Figure E)
Step 5: Gently turn the needle forward (clockwise) until it is tight and firmly attached (See Figure F). If the needle is not firmly attached, it may leak and you may not get your full dose of AVONEX. Do not remove the plastic cover from the needle.	(Figure F)

Using the AVONEX prefilled syringe with the AVOSTARTGRIP titration kit:

• Your AVONEX dose may be titrated over 3 weeks by using AVONEX prefilled syringe with the AVOSTARTGRIP titration kit. The AVOSTARTGRIP is used for giving the week 1, 2, and 3 (¼, ½, ¾) injections.
  • Week 1: ¼ dose (white device)
  • Week 2: ½ dose (yellow device)
  • Week 3: ¾ dose (purple device)
  • Week 4: a full dose
• The 3 AVOSTARTGRIP devices are for single-use only with the AVONEX prefilled syringe. Do not re-use the AVONEX prefilled syringe and AVOSTARTGRIP devices.
• You must prepare the AVONEX prefilled syringe and needle before you put it into the AVOSTARTGRIP device. Follow steps 1 to 5 above to prepare the AVONEX prefilled syringe.

Identifying the parts of AVOSTARTGRIP titration kit (See Figure G):

                                                                                                                                    (Figure G)

• AVOSTARTGRIP has a “collar” on top of the device that will stop the syringe from injecting a full dose (See Figure H). The “collar” makes sure that you do not get the full dose of AVONEX.

                                                                                                                                    (Figure H)

Attaching the AVOSTARTGRIP device:

Step 6: Choose the right AVOSTARTGRIP titration device for your weekly dose. Week 1 Injection: Choose the white device to give ¼ dose (See Figure I).	(Figure I)
Week 2 Injection: Choose the yellow device to give ½ dose (See Figure J).	(Figure J)
Week 3 Injection: Choose the purple device to give ¾ dose (See Figure K).	(Figure K)
Step 7: Put the right AVOSTARTGRIP device on a flat surface with the door open (See Figure L).	(Figure L)
Step 8: Line up the AVONEX prefilled syringe over the AVOSTARTGRIP device with the plunger pointing to the left and the needle pointing to the right (See Figure M).	(Figure M)
Step 9: Push the AVONEX prefilled syringe down into the AVOSTARTGRIP device until both ends “snap” into place (See Figure N).	(Figure N)
Step 10: Using two fingers, push the door down until it closes over the AVONEX prefilled syringe (See Figure O). You will hear a “snap” when the door is closed the right way. Do not open door after it is closed.	(Figure O)
Step 11: Check to make sure that the AVONEX prefilled syringe is in the AVOSTARTGRIP device the right way and that the door is tightly closed.

Giving the AVONEX injection:

• Your healthcare provider should show you or a caregiver how to prepare and inject the dose of AVONEX before AVONEX prefilled syringe is used for the first time. Your healthcare provider or nurse should watch you inject the dose of AVONEX the first time AVONEX prefilled syringe is used.
• Inject your AVONEX exactly as your healthcare provider has shown you.
• AVONEX is injected into the muscle (intramuscularly).
• AVONEX should be injected into the thigh or upper arm (See Figures P and Q).
• Change (rotate) your injection sites for each dose. Do not use the same injection site for each injection.
• Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.

Step 12: Choose an injection site and wipe the skin with an alcohol wipe (See Figures P and Q). Let the injection site dry before injecting the dose. Do not touch this area again before giving the injection.	(Figure P)	(Figure Q)
Step 13: Pull the protective cover straight off the needle (See Figure R). Do not twist the cover off.	(Figure R)
Step 14: With 1 hand, stretch the skin out around the injection site. With the other hand, hold the syringe like a pencil. Use a quick dart-like motion and insert the needle at a 90º angle, through the skin and into the muscle (See Figure S). Once the needle is in, let go of the skin.	(Figure S)
Step 15: Make sure that you push the plunger all the way down until it touches the collar (See Figure T).	(Figure T)
Step 16: Pull the needle out of the skin (See Figure U). Press down on the injection site with the gauze pad for a few seconds or rub gently in a circular motion. If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.	(Figure U)

After the AVONEX injection:

Do not recap the needle. Recapping the needle can lead to a needle stick injury.

• Throw away the used AVONEX prefilled syringes, AVOSTARTGRIP devices, and needles in a sharps container or some type of hard plastic or metal container with a screw cap such as a detergent bottle or coffee can. Check with your healthcare provider about the right way to throw away the container. There may be local or state laws about how to throw away used AVONEX prefilled syringes, AVOSTARTGRIP devices, and needles. Do not throw away used AVONEX prefilled syringes, AVOSTARTGRIP devices, and needles in household trash or recycling bins.
• 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 healthcare provider.

General information about the safe and effective use of AVONEX

• Always use a new AVONEX prefilled syringe, AVOSTARTGRIP device, and needle for each injection. Do not re-use your AVONEX prefilled syringe, AVOSTARTGRIP device, or needles.
• Do not share your AVONEX prefilled syringe, AVOSTARTGRIP device, or needles.
• Keep the AVONEX prefilled syringe, AVOSTARTGRIP device, and needles out of the reach of children.
• You can use the table below to keep track of your weekly injections.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised 09/2016
Manufactured for:
Biogen Inc.
250 Binney Street
Cambridge, MA 02142 USA
©2012-2016 Biogen. All rights reserved.
1-800-456-2255

I11073-05

Principal Display Panel - 30 mcg Carton Label

NDC 59627-003-01

Avonex Pen®

(interferon beta-1a)

Injection

30 mcg/0.5 mL Single-Use Prefilled Autoinjector

For Intramuscular Injection

Once a Week

Avonex Pen® Administration Dose Pack

ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.

Store refrigerated at 2-8°C (36-46°F).

Do not freeze or expose to high temperatures. Protect from light.

The recommended dosage of Avonex® is 30 mcg injected intramuscularly
once weekly. See package insert for full prescribing information.

This Product Contains Dry Natural Rubber.

Rx only

Principal Display Panel - 30 mcg Carton Label

NDC 59627-002-06

Avonex®
(interferon beta-1a)
Injection

30 mcg/0.5 mL Single-Use Prefilled Syringe

For Intramuscular Injection

Once a Week

Avonex® Administration Dose Pack

ATTENTION PHARMACIST: Each patient is required
to receive the enclosed Medication Guide.

Store refrigerated at 2-8°C (36-46°F)

Do not freeze or expose to high temperatures.

Protect from light.

See package insert for dosage and administration.

This Product Contains Dry Natural Rubber.

Rx only

Principal Display Panel - Carton Label

NDC 59627-333-04

Avonex Pen®
(interferon beta-1a)
Injection

30 mcg/0.5 mL Single-Use Prefilled Autoinjector

For Intramuscular Injection

Once a Week

Contents:

4 Avonex Pen® Administration Dose Packs

Store refrigerated at 2-8°C (36-46°F)

Do not freeze or expose to high temperatures. Protect from light.

The recommended dosage of Avonex® is 30 mcg injected intramuscularly
once weekly. See package insert for full prescribing information.

ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.

Principal Display Panel - Carton Label

NDC 59627-222-05

Avonex®
(interferon beta-1a)
Injection

30 mcg/0.5 mL Single-Use Prefilled Syringe

For Intramuscular Injection

Once a Week

Contents:

4 Avonex®Administration Dose Packs

ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.

This Product Contains Dry Natural Rubber.

Rx only

Store refrigerated at 2-8°C (36-46°F).

Do not freeze or expose to high temperatures.

Protect from light.

See package insert for dosage and administration.

Principal Display Panel - Tray Lid Label

Avonex®(interferon beta-1a)

30 mcg/0.5 mL Single-Use Prefilled Syringe

For Intramuscular Injection

Store refrigerated at 2-8°C (36-46°F). Do not freeze or expose to high temperatures.

Protect from light. Contents: 1 single-use prefilled syringe of Avonex® and 1, 23G, 1 1/4" needle. See package insert for dosage and administration. This Product Contains Dry Natural Rubber. ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide. U.S. License# 1697

Biogen Inc., Cambridge, MA 02142 1-800-456-2255 Rx only 46043 -02

NDC 59627-002-07