Enbrel

Enbrel

Etanercept is injected under the skin.

• Adult rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis: 50 mg weekly
• Plaque psoriasis: 50 mg twice weekly for 3 months, followed by 50 mg once weekly
• Juvenile rheumatoid arthritis: 0.8 mg/kg weekly, with a maximum of 50 mg per week

No dose-limiting toxicities have been observed during clinical trials of Enbrel. Single IV doses up to 60 mg/m² (approximately twice the recommended dose) have been administered to healthy volunteers in an endotoxemia study without evidence of dose-limiting toxicities.

Take Enbrel exactly as prescribed by your doctor. You will receive Enbrel injections at your doctor's office, or you may be instructed to give the injections to yourself at home.

• The recommended dose for adult rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis patients is 50 mg once a week.
• For adult patients with plaque psoriasis, a starting dose of 50 mg twice a week for 3 months is followed with 50 mg once a week for maintenance.

Juvenile idiopathic arthritis and plaque psoriasis in children:

• For children weighing 63 kg (138 pounds) or more, the recommended dose is 50 mg weekly. 
• For children weighing less than 63 kg (138 pounds), the recommended dose is 0.8 mg/kg once a week. 

• A copy of the manufacturer’s patient information (medication guide) for etanercept should be provided to all patients with each prescription of the drug.1 128 Importance of advising patients about potential benefits and risks of etanercept.1 128 137 138 Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.128 136 137 138

• If the patient or caregiver is to administer etanercept, provide careful instructions regarding proper dosage and administration of etanercept, including proper aseptic technique, and proper disposal of needles and syringes.1

• Increased susceptibility to infection.1 136 137 Importance of seeking immediate medical attention if signs and symptoms suggestive of infection (e.g., fever, chills, flu-like symptoms, cough, burning or pain on urination) develop.1 136

• Risk of lymphoma, including hepatosplenic T-cell lymphoma, leukemia, or other malignancies with TNF blocking agents.1 128 138 Importance of informing patients and caregivers about the increased risk of cancer development in children, adolescents, and young adults, taking into account the clinical utility of TNF blocking agents, the relative risks and benefits of these and other immunosuppressive drugs, and the risks associated with untreated disease.1 128 138 Importance of promptly informing clinicians if signs and symptoms of malignancies (e.g., unexplained weight loss; fatigue; abdominal pain; persistent fever; night sweats; easy bruising or bleeding; swollen lymph nodes in the neck, underarm, or groin; easy bruising or bleeding; hepatomegaly or splenomegaly) occur.128 138

• Importance of informing clinician of any new or worsening medical conditions (e.g., neurologic conditions [e.g., demyelinating disorders], heart failure, autoimmune disorders [e.g., lupus-like syndrome, autoimmune hepatitis], psoriasis, cytopenias).1 128 136

• Importance of alerting clinician if allergy to latex exists.1

• Importance of promptly contacting a clinician if manifestations of an allergic reaction (e.g., rash, facial swelling, difficulty breathing) occur.136

• Importance of taking the drug as prescribed and of not altering or discontinuing therapy without first consulting with a clinician.128 138

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of cancer, tuberculosis, HBV infection, or other chronic or recurring infections.1 129 137

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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:

• Chills
• cough
• fever
• sneezing
• sore throat

• Congestion in the chest
• depression
• fast heartbeat
• frequent or painful urination
• itching, pain, redness, or swelling on the skin
• joint or muscle stiffness, tightness, or rigidity
• shortness of breath
• stomach discomfort or pain

• Bladder pain
• blistering, peeling, or loosening of the skin
• bloody, black, or tarry stools
• blue-yellow color blindness
• blurred vision
• chest discomfort or pain
• cloudy or bloody urine
• confusion
• convulsions
• darkened urine
• decreased urine output
• decreased vision
• diarrhea
• difficult, irregular, troubled, or labored breathing (or difficulty with breathing gets worse)
• difficulty with moving
• dilated neck veins
• double vision
• extreme fatigue
• eye pain
• feeling sad or empty
• fruit-like breath odor
• general feeling of discomfort, illness, or weakness
• generalized pain
• heartburn or indigestion
• high blood pressure
• inability to move the arms, legs, or facial muscles
• irregular heartbeat
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• lightheadedness
• loss of consciousness
• muscle tenderness
• pain or discomfort in the arms, jaw, back, or neck
• pain, redness, or swelling in the arm or leg
• problems with bowel or bladder function
• red skin lesions, often with a purple center
• red, scaling, or crusted skin
• severe and continuing nausea
• severe numbness, especially on one side of the face or body
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swelling of the face, fingers, feet, or lower legs
• tenderness
• tightness in the chest
• trouble concentrating
• trouble sleeping
• unexplained weight loss
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds
• weight loss
• yellow eyes or 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:

• Abdominal or stomach pain
• loss of energy or weakness
• nausea and vomiting
• pain or burning in the throat
• redness or itching, pain, or swelling at the injection site (under the skin)
• runny or stuffy nose

• Bumps below the skin
• depression
• dry eyes
• dry mouth
• hair loss or thinning
• heartburn
• irritation or soreness of the mouth
• itching, redness, or tearing of the eye
• skin rash

• Altered sense of taste
• burning, crawling, itching, numb, prickling, “pins and needles”, or tingling feelings
• feeling faint, dizzy, or lightheaded
• feeling of warmth or heat
• flushing or redness of the skin, especially on the face and neck
• loss of appetite
• sweating
• weight gain

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.

1. National Cancer Institute. Surveillance, Epidemiology, and End Results Database (SEER) Program. SEER Incidence Crude Rates, 13 Registries, 1992-2002.
   
2. Bröms G, Granath F, Ekbom A, et al. Low Risk of Birth Defects for Infants Whose Mothers Are Treated With Anti-Tumor Necrosis Factor Agents During Pregnancy. Clin Gastroenterol Hepatol. 2016;14:234-241.e5

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before the patient starts using Enbrel, and each time the prescription is renewed, as there may be new information they need to know.

Patients or their caregivers should be provided the Enbrel “Medication Guide” and provided an opportunity to read it and ask questions prior to initiation of therapy. The healthcare provider should ask the patient questions to determine any risk factors for treatment. Patients developing signs and symptoms of infection should seek medical evaluation immediately. 

Patient Counseling 

Patients should be advised of the potential benefits and risks of Enbrel.  Physicians should instruct their patients to read the Medication Guide before starting Enbrel therapy and to reread each time the prescription is renewed.  

Infections 

Inform patients that Enbrel may lower the ability of their immune system to fight infections.  Advise patients of the importance of contacting their doctor if they develop any symptoms of infection, tuberculosis or reactivation of hepatitis B virus infections.

Other Medical Conditions

Advise patients to report any signs of new or worsening medical conditions, such as central nervous system demyelinating disorders, heart failure or autoimmune disorders, such as lupus-like syndrome or autoimmune hepatitis.  Counsel about the risk of lymphoma and other malignancies while receiving Enbrel.  Advise patients to report any symptoms suggestive of a pancytopenia, such as bruising, bleeding, persistent fever or pallor.

Allergic Reactions  

Advise patients to seek immediate medical attention if they experience any symptoms of severe allergic reactions. Advise latex-sensitive patients that the following components contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex:  the needle cover of the prefilled syringe and the needle cover within the needle cap of the SureClick autoinjector.

Administration of Enbrel

If a patient or caregiver is to administer Enbrel, the patient or caregiver should be instructed in injection techniques and how to measure and administer the correct dose [see the Enbrel (etanercept) “Instructions for Use” insert]. For weight-based dosing, instruct caregivers and patients on the proper techniques for preparing, storing, measuring, and administering Enbrel lyophilized powder for reconstitution.

The first injection should be performed under the supervision of a qualified healthcare professional. The patient’s or caregiver’s ability to inject subcutaneously should be assessed. Patients and caregivers should be instructed in the technique, as well as proper syringe and needle disposal, and be cautioned against reuse of needles and syringes.

When using the SureClick autoinjector to administer Enbrel, the patient or caregiver should be informed that the window turns yellow when the injection is complete. After removing the autoinjector, if the window has not turned yellow, or if it looks like the medicine is still injecting, this means the patient has not received a full dose.  The patient or caregiver should be advised to call their healthcare provider immediately.

A puncture-resistant container for disposal of needles, syringes and autoinjectors should be used. If the product is intended for multiple use, additional syringes, needles and alcohol swabs will be required. 

Patients can be advised to call 1-888-4Enbrel (1-888-436-2735) or visit www.Enbrel.com for more information about Enbrel.

Enbrel® (etanercept)

Manufactured by:
Immunex Corporation
Thousand Oaks, CA 91320-1799
U.S. License Number 1132

Patent: http://pat.amgen.com/Enbrel/

© 1998-2017 Immunex Corporation. All rights reserved.

1XXXXXX – v57

This Medication Guide has been approved by the U.S. Food and Drug Administration.                   Revised: November/2016

Instructions for Use

Welcome!

The Enbrel SureClick autoinjector is a single-dose prefilled autoinjector. It contains one 50 mg dose of Enbrel.

Your healthcare provider has prescribed Enbrel SureClick autoinjector for your injections. If your healthcare provider decides that you or a caregiver may be able to give your injections of Enbrel at home, you should receive training on the right way to prepare and inject Enbrel. Do not try to inject yourself until you have been shown the right way to give the injections by your healthcare provider.

Please read all of the instructions before using Enbrel SureClick autoinjector. Call your healthcare provider if you or your caregiver has any questions about the right way to inject Enbrel.

Instructions for Use
Enbrel® (en-brel)
(etanercept)
injection, for subcutaneous use
Single-dose Prefilled SureClick® Autoinjector

Important: Needle is inside

Important

Before you use an Enbrel SureClick autoinjector, read this important information:

Storing your Enbrel SureClick autoinjectors

• Store Enbrel SureClick autoinjector in the refrigerator at 36°F to 46°F (2°C to 8°C).
  
• Store Enbrel SureClick autoinjector in the original carton to protect from light or physical damage. 
  
• If needed, you may store the Enbrel SureClick autoinjector at room temperature at 68°F to 77°F (20°C to 25°C) for up to 14 days.
  ○ Once Enbrel has reached room temperature, do not put it back in the refrigerator.
  
• Throw away Enbrel SureClick autoinjector that has been stored at room temperature after 14 days.
  
• Do not store the Enbrel SureClick autoinjector in extreme heat or cold. For example, avoid storing Enbrel SureClick autoinjector in your vehicle’s glove box or trunk.
  
• Do not freeze.
  
• Do not shake.
  
• Keep the Enbrel SureClick autoinjector and all medicines out of the reach of children. 

If you have any questions about storage, contact your healthcare provider or call 1-888-4Enbrel (1-888-436-2735) for further instructions.

Using your Enbrel SureClick autoinjector

• It is important that you do not try to give the injection unless you or your caregiver has received training from your healthcare provider.
  
• Do not use an Enbrel SureClick autoinjector after the expiration date on the label.
  
• Do not shake the Enbrel SureClick autoinjector.
  
• Do not remove the white cap from the Enbrel SureClick autoinjector until you are ready to inject.
  
• Do not use an Enbrel SureClick autoinjector if it has been dropped on a hard surface. Part of the Enbrel SureClick autoinjector may be broken even if you cannot see the break. Use a new Enbrel SureClick autoinjector, and call 1-888-4Enbrel (1-888-436-2735). 
  
• The white needle cap on the Enbrel SureClick autoinjector contain dry natural rubber, which is made from latex. Tell your healthcare provider if you are allergic to latex.
  
• Children must weigh at least 138 pounds to use the Enbrel SureClick autoinjector. Children who weigh less than 138 pounds should use a different form of Enbrel.

If you have any questions about usage, contact your healthcare provider, visit www.Enbrel.com or call 1-888-4Enbrel (1-888-436-2735).

Step 1: Prepare

A  Remove one Enbrel SureClick autoinjector from the package.

Carefully lift the autoinjector straight up out of the box.

Put the original package with any unused autoinjectors back in the refrigerator.

Leave the autoinjector at room temperature for at least 30 minutes before injecting.

• Do not put the autoinjector back in the refrigerator once it has reached room temperature.
  
• Do not try to warm the autoinjector by using a heat source such as hot water or microwave.
  
• Do not shake the autoinjector.
  
• Do not remove the white cap from the autoinjector yet.

B  Inspect the Enbrel SureClick autoinjector.

Make sure the medicine in the window is clear and colorless.

It is okay if you see small white particles in the medicine.

• Do not use the autoinjector if:
  ○  The medicine is cloudy or discolored or contains large lumps, flakes, or colored particles.
  ○ Any part appears cracked or broken.
  ○ The white cap is missing or not securely attached.
  ○ The expiration date printed on the label has passed.

In all cases, use a new autoinjector, and call 1-888-4Enbrel (1-888-436-2735).

C  Gather all materials needed for your injection.

Wash your hands thoroughly with soap and water.

On a clean, well-lit work surface, place the:

• New autoinjector
  
• Alcohol wipes
  
• Cotton ball or gauze pad
  
• Adhesive bandage
  
• Sharps disposal container. See “Step 4: Finish”

D  Prepare and clean your injection site.

You can use:

• Your thigh
  
• Stomach area (abdomen), except for a 2-inch area right around your navel (belly button)
  
• Outer area of upper arm (only if someone else is giving you the injection)

Clean your injection site with an alcohol wipe. Let your skin dry.

• Do not touch this area again before injecting.
  
• Choose a different site each time you give yourself an injection. If you need to use the same injection site, just make sure it is not the same spot on that site you used last time.
  ○ Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.
  
• If you have psoriasis, you should avoid injecting directly into raised, thick, red, or scaly skin patch or lesion.

Step 2: Get ready

E Pull white cap straight off when you are ready to inject.

It is normal to see a drop of liquid at the end of the needle or green safety guard.

• Do not twist or bend the white cap.
  
• Do not put the white cap back onto the autoinjector.
  
• Do not remove the white cap from the autoinjector until you are ready to inject.

F Stretch or pinch your injection site to create a firm surface.

Stretch skin firmly by moving your thumb and fingers in opposite directions, creating an area about 2 inches wide.

Pinch skin firmly between your thumb and fingers, creating an area about 2 inches wide.

Important: Keep the skin stretched or pinched while injecting.

Step 3: Inject

G  Hold the stretch or pinch. With the white cap off, place the autoinjector on your skin at 90 degrees.

Important: Do not touch the purple start button yet.

H  Firmly push the autoinjector down onto skin until it stops moving.

Important: You must push all the way down but do not touch purple start button until you are ready to inject.

I  When you are ready to inject, press the purple start button.

J Keep pushing down on your skin. Your injection could take about 15 seconds.

Important: When you remove the autoinjector, if the window has not turned yellow, or if it looks like the medicine is still injecting, this means you have not received a full dose. Call your healthcare provider immediately.

Step 4: Finish

K  Discard the used autoinjector and the white cap.

• Put the used SureClick autoinjector in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the SureClick autoinjector in your household trash.
  
• If you do not have a 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 reuse the autoinjector.
  
• Do not recycle the autoinjector or sharps disposal container or throw them into household trash.

Important: Always keep the sharps disposal container out of the reach of children.

L  Examine the injection site.

If there is blood, press a cotton ball or gauze pad on your injection site. Do not rub the injection site. Apply an adhesive bandage if needed.

Please see the Medication Guide for Enbrel and accompanying Prescribing Information.

Commonly asked questions

What will happen if I press the purple start button before I am ready to do the injection on my skin?

Even when you press the purple start button, the injection will only happen when the green safety guard is also pushed into the autoinjector.

Can I move the autoinjector around on my skin while I am choosing an injection site?

It is okay to move the autoinjector around on the injection site as long as you do not press the purple start button. However, if you press the purple start button and the green safety guard is pushed into the autoinjector, the injection will begin.

Can I release the purple start button after I start my injection?

You can release the purple start button, but continue to hold the autoinjector firmly against your skin during the injection.

Will the purple start button pop up after I release my thumb?

The purple start button may not pop up after you release your thumb if you held your thumb down during the injection. This is okay.

What do I do if I did not hear a click after pushing the device down on my skin for 15 seconds?

If you did not hear a click, you can confirm a complete injection by checking that the

window has turned yellow.

Whom do I contact if I need help with the autoinjector or my injection?

If you have any questions about the autoinjector, its storage, or about your injection, contact your healthcare provider or visit www.Enbrel.com or call 1-888-4Enbrel (1-888-436-2735) for help.

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

Manufactured by:
Immunex Corporation
Thousand Oaks, CA 91320-1799
U.S. License Number 1132

©1998 – 2016 Immunex Corporation. All rights reserved.

<part number>

Revised: 11/2016 v11

Instructions for Use
Enbrel® (en-brel)
(etanercept)
injection, for subcutaneous use
Single-dose Prefilled Syringe

How do I prepare and give an injection with Enbrel Single-dose Prefilled Syringe?

There are 2 types of Enbrel single-dose prefilled syringes:

• The 50 mg/mL single-dose prefilled syringe that contains one 50 mg dose of Enbrel.
  
• The 25 mg/0.5 mL single-dose prefilled syringe that contains one 25 mg dose of Enbrel.

Your healthcare provider will tell you which one to use.

A 50 mg dose can be given as one injection using a 50 mg/mL single-dose prefilled syringe or as two injections using 25 mg/0.5 mL single-dose prefilled syringes. Your healthcare provider will tell you whether the two injections with 25 mg/0.5 mL single-dose prefilled syringes should be given on the same day once a week or on two different days (3 or 4 days apart) in the same week. 

Children must weigh at least 138 pounds to use the Enbrel 50 mg/mL single-dose prefilled syringe. Children who weigh less than 138 pounds should use a different form of Enbrel. The Enbrel 25 mg/0.5 mL single-dose prefilled syringe should not be used in pediatric patients weighing less than 68 pounds.

Important: The needle cover on the single-dose prefilled syringe is composed of dry natural rubber, which is made from latex. Tell your healthcare provider if you are allergic to latex.

Storage of Enbrel prefilled syringe

• Store Enbrel prefilled syringe in the refrigerator at 36°F to 46°F (2°C to 8°C).
  
• Store Enbrel prefilled syringe in the original carton to protect from light or physical damage.
  
• If needed, you may store your Enbrel prefilled syringe at room temperature between 68°F to 77°F (20°C to 25°C) for up to 14 days.
  ○ Once Enbrel prefilled syringe has reached room temperature, do not put it back in the refrigerator.
  
• Throw away Enbrel prefilled syringe that has been stored at room temperature after 14 days.
  
• Do not store Enbrel prefilled syringe in extreme heat or cold. For example, avoid storing Enbrel prefilled syringe in your vehicle’s glove box or trunk.
  
• Do not freeze.
  
• Do not shake.
  
• Keep the Enbrel prefilled syringe and all medicines out of the reach of children.

If you have any questions about storage, contact your healthcare provider or call 1-888-4Enbrel (1-888-436-2735) for further instructions.

Step 1: Setting Up for an Injection

1. Select a clean, well-lit, flat work surface, such as a table.
   
2. Take the Enbrel carton containing the prefilled syringes out of the refrigerator and place it on your flat work surface. Remove one prefilled syringe and place it on your work surface. Carefully lift the prefilled syringe straight up out of the box. Do not shake the prefilled syringe of Enbrel. Place the carton containing any remaining prefilled syringes back into the refrigerator at 36ºF to 46ºF (2ºC to 8ºC).
   
3. Check the expiration date on the prefilled syringe. If the expiration date has passed, do not use the prefilled syringe and contact your pharmacist or call 1-888-4Enbrel (1-888-436-2735) for assistance.
   
4. Do not use the prefilled syringe if the needle cover is missing or not securely attached. Call 1-888-4Enbrel (1-888-436-2735).
   
5. For a more comfortable injection, leave the prefilled syringe at room temperature for about 15 to 30 minutes before injecting. Do not remove the needle cover while allowing it to reach room temperature. Do not warm Enbrel in any other way (for example, do not warm it in a microwave or in hot water).
   
6. Hold the prefilled syringe with the covered needle pointing down. If bubbles are seen in the syringe, very gently tap the prefilled syringe to allow any bubbles to rise to the top of the syringe. Turn the syringe so that the purple horizontal lines on the barrel are directly facing you. Check to see if the amount of liquid in the syringe falls between the purple lines. The top of the liquid may be curved. If the syringe does not have the right amount of liquid, do not use that syringe. Contact your pharmacist or call 1-888-4Enbrel (1-888-436-2735) for assistance.
   
   
7. Assemble the additional supplies you will need for your injection. These include an alcohol swab, a cotton ball or gauze, and a sharps disposal container (see “Step 4: Disposing of Supplies”).
   
8. Wash your hands with soap and warm water.
   
9. Make sure the solution in the prefilled syringe is clear and colorless. You may notice small white particles in the solution. These particles are formed from Enbrel and this is acceptable. However, do not inject the solution if it is cloudy or discolored, or contains large or colored particles –call 1-888-4Enbrel (1-888-436-2735).

Step 2: Choosing and Preparing an Injection Site

1. Recommended injection sites for Enbrel using a prefilled syringe include:
   • the front of the middle thigh
   • the stomach area (abdomen), except for the 2-inch area right around the navel (belly button)
   • the outer area of the upper arm (only if someone else is giving you the injection)
   
   
2. Rotate the site for each injection. Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks.
   
3. If you have psoriasis, you should not inject directly into any raised, thick, red, or scaly skin patches or lesions.
   
4. To prepare the area of skin where Enbrel is to be injected, wipe the injection site with an alcohol swab. Do not touch this area again before giving the injection.

Step 3: Injecting Enbrel Using a Prefilled Syringe

Do not remove the needle cover from the prefilled syringe until you are ready to inject.

1. Pick up the prefilled syringe from your flat work surface. Hold the barrel of the prefilled syringe with one hand and pull the needle cover straight off. To avoid damaging the needle, do not twist or bend the needle cover while you are removing it, and do not try to put the needle cover back onto the prefilled syringe.
   When you remove the needle cover, there may be a drop of liquid at the end of the needle; this is normal. Do not touch the needle or allow it to touch any surface. Do not touch or bump the plunger. Doing so could cause the liquid to leak out.
   
2. Holding the syringe with the needle pointing up, check the syringe for air bubbles. If there are bubbles, gently tap the syringe with your finger until the air bubbles rise to the top of the syringe. Slowly push the plunger up to force the air bubbles out of the syringe.
   
3. Holding the syringe in one hand like a pencil, use the other hand to gently pinch a fold of skin at the cleaned injection site and hold it firmly.
   
4. With a quick and “dart-like” motion, insert the needle at a 45-degree angle into the skin.
   
   
5. When the needle is completely inserted into the skin, let go of the skin that you are holding. With your free hand, hold the syringe near its base to stabilize it. Then push the plunger to inject all of the Enbrel solution at a slow, steady rate.
   
6. When the syringe is empty, pull the needle out of the skin, being careful to keep it at the same angle as inserted. There may be a little bleeding at the injection site. You can press a cotton ball or gauze over the injection site for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with a bandage.

Step 4: Disposing of Supplies

The syringe should never be reused. Never recap a needle.

• Put the used prefilled syringes in a FDA-cleared sharps disposal container right away after use.  Do not throw away (dispose of) prefilled syringes in your household trash.
  
• If you do not have a 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 syringes and needles. 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 reuse the syringe.
  
• Do not recycle the syringe or sharps disposal container or throw them into household trash.

Important: Always keep the sharps disposal container out of the reach of children.

A healthcare provider familiar with Enbrel should answer all questions. Call 1-888-4Enbrel (1-888-436-2735) or visit www.Enbrel.com for more information about Enbrel.

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

Manufactured by:
Immunex Corporation
Thousand Oaks, CA 91320-1799
U.S. License Number 1132
© 1998 – 2016 Immunex Corporation. All rights reserved.

1XXXXXX – v7                                           PMVx
Revised: 11/2016

Instructions for Use
Enbrel® (en-brel)
(etanercept)
for injection, for subcutaneous use
Multiple-dose Vial

How do I prepare and give an injection with Enbrel multiple-dose vial?

A multiple-dose vial contains 25 mg of Enbrel.

Storage of Enbrel multiple-dose vial

• Store Enbrel multiple-dose vial in the refrigerator at 36°F to 46°F (2°C to 8°C).
  
• Store Enbrel multiple-dose vial in the original carton to protect from light or physical damage.
  
• If needed, you may store your Enbrel multiple-dose vial and diluent syringe (dose tray) at room temperature between 68°F to 77°F (20°C to 25°C) for up to 14 days.
  ○ Once Enbrel multiple-dose vial has reached room temperature, do not put it back in the refrigerator.
  
• Throw away Enbrel multiple-dose vial that has been stored at room temperature after 14 days.
  
• Mixed (reconstituted) Enbrel multiple-dose vial should be used right away or kept in the refrigerator at 36°F to 46°F (2°C to 8°C) for up to 14 days.
  
• Do not store Enbrel multiple-dose vial in extreme heat or cold. For example, avoid storing Enbrel multiple-dose vial in your vehicle’s glove box or trunk.
  
• Do not freeze.
  
• Do not shake.
  
• Keep Enbrel multiple-dose vial and all medicines out of the reach of children.

If you have any questions about storage, contact your healthcare provider or call 1-888-4Enbrel (1-888-436-2735) for further instructions.

Step 1: Setting Up for an Injection

1. Select a clean, well-lit, flat work surface, such as a table.
   
2. Take the Enbrel dose tray out of the refrigerator and place it on your flat work surface.
   
3. Check the expiration date on the dose tray. If the expiration date has passed, do not use the dose tray. Also check to make sure the dose tray has 5 items as pictured below:
   • One prefilled diluent syringe containing 1 mL of diluent (liquid) with attached adapter and twist-off cap
   • One plunger
   • One Enbrel vial
   • One 27-gauge ½ inch needle in hard plastic cover
   • One vial adapter
   
   If the expiration date has passed, the five items are not included in the dose tray or if any item looks damaged, contact your pharmacist or call 1-888-4Enbrel (1-888-436-2735) for assistance.
   
4. For a more comfortable injection, leave the dose tray at room temperature for about 15 to 30 minutes before injecting.
   
5. Wash your hands with soap and warm water.
   
6. Peel the paper seal off the dose tray and remove all items.
   
7. Inspect the volume of diluent in the syringe with the twist-off cap pointing down. Use the unit markings on the side of the syringe to make sure there is at least 1 mL of liquid in the syringe. If the level of liquid is below the 1 mL mark, do not use. Contact your pharmacist or call 1-888-4Enbrel (1-888-436-2735) for assistance.
   
8. Do not use the syringe if the twist-off cap is missing or not securely attached. Call 1-888-4Enbrel (1-888-436-2735).
   
9. Two alcohol swabs should be available for the preparation and injection of Enbrel. Alcohol swabs can be found at your local drug store.

Step 2: Preparing the Enbrel Solution

There are two methods for preparing the Enbrel solution. For some children, one vial of Enbrel solution can be used for more than one dose. The free-hand method should be used for children on Enbrel who are using one vial of Enbrel solution for more than one dose. You should not use the vial adapter method if you will be using the vial more than once. Ask your healthcare provider if you have questions about which method to use.  

• The Vial Adapter Method

Adults and larger children on Enbrel may use the vial adapter device to assist with mixing the powder with the liquid and withdrawing Enbrel, and then use a 27-gauge needle to inject the dose. This method should not be used for children using multiple doses from the same vial of Enbrel. The instructions for using the vial adapter method are in Step 2A.

• The Free-Hand Method

In the free-hand method, a 25-gauge needle is used to assist with mixing the powder with the liquid and withdrawing Enbrel, and a 27-gauge needle is used to inject the dose. Obtain 25-gauge needles from your healthcare provider. Instructions for using the free-hand method are in Step 2B. 

The instructions for preparing additional doses from the same vial of Enbrel solution are in Step 3. For each additional dose, you will need two new needles (one 25-gauge needle to withdraw the solution and one 27-gauge needle for injection) and one new empty syringe (1 mL). Never reuse a syringe or needle.

If you are using the vial of Enbrel for more than one dose, you should write the date you mixed the powder and liquid in the area marked “Mixing Date:” on the sticker supplied with these instructions, and attach the sticker to the Enbrel vial.

After you have withdrawn the dose of Enbrel that you need, store the Enbrel vial (in the dose tray) in the refrigerator at 36º to 46ºF (2º to 8ºC) as soon as possible, but always within 4 hours of mixing the solution. Do not freeze. If you have any questions about storage, contact your healthcare provider or call 1-888-4Enbrel (1-888-436-2735) for further instructions.

The Enbrel solution must be used within 14 days of the mixing date. You should discard the Enbrel vial and any remaining solution if it is not used within 14 days. Do not mix any remaining liquid in one vial of Enbrel solution with another.

STEP 2A: Vial Adapter Method

1. Remove the pink plastic cap from the Enbrel vial. Do not remove the gray stopper or silver metal ring around the top of the Enbrel vial.
        
   
2. Place the Enbrel vial on your flat work surface or turn your dose tray upside down and place your Enbrel vial in the round space marked “V”. Use one alcohol swab to clean the gray stopper on the Enbrel vial. Do not touch the gray stopper with your hands.
   
3. Open the wrapper that contains the 27-gauge needle by peeling apart the tabs and set the needle aside for later use.
   
   
4. Open the wrapper that contains the vial adapter by peeling apart the tabs and set the vial adapter aside for later use. Do not touch the vial adapter’s twist-on end or the spike inside.
   
   
5. Slide the plunger into the flange end of the syringe.
   
   
6. Attach the plunger to the gray rubber stopper in the syringe by turning the plunger clockwise until you feel a slight resistance.
   
   
7. Remove the twist-off cap from the prefilled diluent syringe by turning counter-clockwise. Do not bump or touch the plunger. Doing so could cause the liquid to leak out. You may see a drop of liquid when removing the cap. This is normal. Place the cap on your flat work surface. Do not touch the syringe tip.
   
   
8. Once the twist-off cap is removed, pick up the vial adapter with your free hand. Twist the vial adapter onto the syringe, turning clockwise until you feel a slight resistance. Do not over-tighten.
   
   
9. Hold the Enbrel vial upright on your flat work surface. Grasp the sides of the vial adapter and place it over the top of the Enbrel vial. Do not bump or touch the plunger. Doing so could cause the liquid to leak out. Insert the vial adapter into the gray stopper on the Enbrel vial. The plastic spike inside the vial adapter should puncture the gray stopper. The vial adapter should fit snugly.
   
   
10. Hold the Enbrel vial upright on your flat work surface and push the plunger down until all the liquid from the syringe is in the Enbrel vial. You may see foaming (bubbles) in the vial. This is normal.
    
    
11. Gently swirl the Enbrel vial in a circular motion to dissolve the powder. If you used the dose tray to hold your Enbrel vial, take the vial (with the vial adapter and syringe still attached) out of the dose tray, and gently swirl the vial in a circular motion to dissolve the powder.
    
    Do not shake. Wait until all the powder dissolves (usually less than 10 minutes). The solution should be clear and colorless. After the powder has completely dissolved, foam (bubbles) may still be present. This is normal. Do not inject the solution if it is discolored, contains lumps, flakes, or particles. If all the powder in the Enbrel vial is not dissolved or there are particles present after 10 minutes, call 1 888 4Enbrel (1 888 436 2735).
    
12. Turn the Enbrel vial upside down. Hold the syringe at eye level and slowly pull the plunger down to the unit markings on the side of the syringe that correspond with your/your child’s dose. For adult patients, remove the entire volume (1 mL), unless otherwise instructed by your healthcare provider. Be careful not to pull the plunger completely out of the syringe. Some white foam may remain in the Enbrel vial. This is normal.
    
    
13. Check for air bubbles in the syringe. Gently tap the syringe to make any air bubbles rise to the top of the syringe. Slowly push the plunger up to remove the air bubbles. If you push solution back into the vial, slowly pull back on the plunger to again draw the correct amount of solution back into the syringe.
    
    
14. Remove the syringe from the vial adapter, by holding the vial adapter with one hand and turning the syringe counter-clockwise with your other hand. Do not touch or bump the plunger. Place the Enbrel vial with the vial adapter on your flat work surface.
    
    
15. Continue to hold the barrel of the syringe. With your free hand, twist the 27-gauge needle onto the tip of the syringe until it fits snugly. Do not remove the needle cover from the syringe. Place the syringe on your flat work surface until you are ready to inject Enbrel.
    

Go to Step 4: Choosing and Preparing an Injection Site.

Step 2B: Free-Hand Method

If you are preparing a dose from an Enbrel vial that was previously used, go to Step 3: Preparing Additional Doses from a Single Enbrel Vial.

1. Remove the pink plastic cap from the Enbrel vial. Do not remove the gray stopper or silver metal ring around the top of the Enbrel vial. Write the date you mix the powder and solution on the supplied “Mixing Date:” sticker and attach it to the Enbrel vial.
    
   
2. Place the Enbrel vial on your flat work surface. Use one alcohol swab to clean the gray stopper on the Enbrel vial. Do not touch the gray stopper with your hands.
   
3. Open the wrapper that contains the 25-gauge needle by peeling apart the tabs and set the needle aside for later use. The 25-gauge needle will be used to mix the liquid with the powder and for withdrawing Enbrel from the vial.
   
   
4. Slide the plunger into the flange end of the syringe.
   
   
5. Attach the plunger to the gray rubber stopper in the syringe by turning the plunger clockwise until you feel a slight resistance.
   
   
6. Remove the twist-off cap from the prefilled diluent syringe by turning counter-clockwise. Do not touch or bump the plunger. Doing so could cause the liquid to leak out. You may see a drop of liquid when removing the cap. This is normal. Place the cap on your flat work surface. Do not touch the syringe tip.
   
   
7. Continue to hold the barrel of the syringe. With your free hand, twist the 25-gauge needle onto the tip of the syringe until it fits snugly. Place the syringe on your flat work surface.
   
   
8. Open the wrapper that contains the 27-gauge needle by peeling apart the tabs and set the needle aside for later use.  The 27-gauge needle will be used to inject the dose.
    
   
9. Pick up the syringe from your flat work surface. Hold the barrel of the syringe with one hand, and pull the needle cover straight off. To avoid damaging the needle, do not twist or bend the needle cover while you are removing it. Do not touch the needle or allow it to touch any surface. Do not touch or bump the plunger. Doing so could cause the liquid to leak out.
   
   
10. Place the needle cover (open side up) in the round space marked “N” in the Enbrel dose tray.
     
    
11. Place the Enbrel vial on your flat work surface. Hold the syringe with the needle facing up, and gently pull back on the plunger to pull a small amount of air into the syringe. Then, insert the needle straight down through the center ring of the gray stopper (see illustrations). You should feel a slight resistance and then a “pop” as the needle goes through the center of the stopper. Look for the needle tip inside the open stopper window. If the needle is not correctly lined up with the center of the stopper, you will feel constant resistance as it goes through the stopper and no “pop”. The needle may enter at an angle and bend, break or prevent you from adding diluent into the Enbrel vial.
      
    
12. Push the plunger down very slowly until all liquid from the syringe is in the Enbrel vial. Adding the liquid too fast will cause foaming (bubbles).
    
    
13. Leave the syringe in place. Gently swirl the Enbrel vial in a circular motion to dissolve the powder.
    
    Do not shake. Wait until all the powder dissolves (usually less than 10 minutes). The solution should be clear and colorless. After the powder has completely dissolved, foam (bubbles) may still be present. This is normal. Do not inject the solution if it is discolored, contains lumps, flakes, or particles. If all the powder in the Enbrel vial is not dissolved or there are particles present after 10 minutes, call 1-888-4Enbrel (1-888-436-2735).
    
14. With the needle in the Enbrel vial, turn the vial upside down. Hold the syringe at eye level and slowly pull the plunger down to the unit markings on the side of the syringe that correspond with the correct dose. Make sure to keep the tip of the needle in the solution. Some white foam may remain in the Enbrel vial. This is normal.
    
    
15. With the needle still inserted in the Enbrel vial, check for air bubbles in the syringe. Gently tap the syringe to make any air bubbles rise to the top of the syringe. Slowly push the plunger up to remove the air bubbles. If you push solution back into the vial, slowly pull back on the plunger to draw the correct amount of solution back into the syringe.
    
    
16. Remove the syringe and needle from the Enbrel vial. Keep the needle attached to the syringe and insert the 25-gauge needle straight down into the needle cover in the Enbrel dose tray.
    
    You should hear a “snap” when the needle is secure in the needle cover. Once the needle is secure in the needle cover, untwist the 25-gauge needle from the syringe and dispose of the needle in your sharps disposal container (see “Step 6: Disposing of Supplies”).
    
17. Twist the 27-gauge needle onto the syringe until it fits snugly. Do not remove the needle cover from the syringe. Place the syringe on your flat work surface until you are ready to inject Enbrel.
    
    
18. If there is enough solution left in the Enbrel vial for another dose, write the date you mixed the powder and liquid in the area marked “Mixing Date:” on the sticker supplied with these instructions, and attach the sticker to the Enbrel vial. Refrigerate the reconstituted (mixed) Enbrel vial (in the dose tray) after mixing. Prepare additional doses from the Enbrel vial as described in Step 3. Otherwise, throw away (discard) the Enbrel vial and any remaining solution.

Go to Step 4: Choosing and Preparing an Injection Site. 

Step 3: Preparing Additional Doses from a Single Enbrel Vial

1. Select a clean, well-lit, flat work surface, such as a table.
   
2. Do not reuse the needles and syringes supplied with Enbrel dose tray. You will need new needles and syringes for each additional dose. Your healthcare provider will tell you what type of syringes (1 mL) and needles (25-gauge and 27-gauge) to use. Place the sterile syringe with a 25-gauge needle (for withdrawing Enbrel), a 27-gauge needle (for injecting Enbrel) and two alcohol swabs on your flat work surface.
   
3. Take the vial of Enbrel solution that is stored in the dose tray out of the refrigerator and place it on your flat work surface.
   
4. Check the mixing date you wrote on the sticker on the Enbrel vial. Discard the Enbrel vial if more than 14 days have passed since the Enbrel solution was mixed.
   
5. Wash your hands with soap and warm water.
   
6. Use one alcohol swab to clean the gray stopper on the Enbrel vial. Do not touch the stopper with your hands.
   
7. If the syringe and the 25-gauge needle are not pre-assembled, assemble them as instructed by your healthcare provider.
   
8. Open the wrapper that contains the 27-gauge needle by peeling apart the tabs and set the needle aside for later use. The 27-gauge needle will be used to inject the dose of Enbrel.
   
9. Hold the syringe and pull the needle cover straight off. To avoid damaging the needle, do not twist or bend the needle cover while you are removing it. Do not touch the needle or allow it to touch any surface. Place the needle cover (open side up) in the round space marked “N” in the Enbrel dose tray.
   
10. Place the Enbrel vial on your flat work surface. Hold the syringe with the needle facing up, and gently pull back the plunger to pull a small amount of air into the syringe. Then, insert the 25-gauge needle straight down through the center ring of the gray stopper. You should feel a slight resistance and then a “pop” as the needle goes through the center of the stopper. Look for the needle tip inside the open stopper window. If the needle is not correctly lined up with the center of the stopper, you will feel constant resistance as it goes through the stopper and no “pop”. The needle may enter at an angle and bend, break, or prevent proper withdrawal of Enbrel solution from the vial.
    
11. Keep the needle in the Enbrel vial and turn the vial upside down. Hold the syringe at eye level, and slowly pull the plunger down to the unit markings on the syringe that correspond to your child’s dose. As the amount of solution in the Enbrel vial drops, you may need to pull the needle back just enough to keep the tip of the needle in the solution.
    
12. With the needle still inserted in the Enbrel vial, check for air bubbles in the syringe. Gently tap the syringe to make any air bubbles rise to the top of the syringe. Slowly push the plunger up to remove the air bubbles. If you push solution back into the Enbrel vial, slowly pull back on the plunger to again draw the correct amount of solution back into the syringe.
    
13. Remove the syringe and needle from the Enbrel vial. Keep the needle attached to the syringe and insert the 25-gauge needle straight down into the needle cover in the Enbrel dose tray. You should hear a “snap” when the needle is secure in the needle cover. Once the needle is secure in the needle cover, remove the 25-gauge needle from the syringe and dispose of the needle in a sharps disposal container (see “Step 6: Disposing of Supplies”).
    
14. Attach the 27-gauge needle onto the tip of the syringe until it fits snugly. Do not remove the needle cover from the syringe. Place the syringe on your flat work surface until you are ready to inject Enbrel. 

Step 4: Choosing and Preparing an Injection Site

1. The 3 recommended injection sites for Enbrel include:
   • the front of the middle thighs
   • the stomach area (abdomen), except for the 2-inch area right around the navel (belly button)
   • the outer area of the upper arms (only if someone else is giving you the injection)
   
   
2. Rotate the site for each injection. Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks.
   
3. If you have psoriasis, you should not inject directly into any raised, thick, red, or scaly skin patches or lesions.
   
4. To prepare the area of skin where Enbrel is to be injected, wipe the injection site with a new alcohol swab. Do not touch this area again before giving the injection.

Step 5: Injecting the Enbrel Solution

Do not remove the needle cover from the syringe until you are ready to inject.

1. Pick up the syringe from your flat work surface. Hold the barrel of the syringe with one hand and pull the needle cover straight off. To avoid damaging the needle, do not twist or bend the needle cover while you are removing it, and do not try to put the needle cover back onto the syringe. When you remove the needle cover, there may be a drop of liquid at the end of the needle. This is normal.  Do not touch the needle or allow it to touch any surface. Do not touch or bump the plunger. Doing so could cause the liquid to leak out.
   
   
2. With one hand, gently pinch the cleaned area of skin and hold it firmly. With the other hand, hold the syringe (like a pencil) at a 45-degree angle to the skin.
     
   
3. With a quick and "dart-like" motion, insert the needle at a 45-degree angle into the skin.
   
4. When the needle is completely inserted into the skin, let go of the skin that you are holding. With your free hand, hold the syringe near its base to stabilize it. Then push the plunger to inject all of the Enbrel solution at a slow, steady rate.
   
   
5. When the syringe is empty, pull the needle out of the skin, being careful to keep it at the same angle as inserted.
   
6. There may be a little bleeding at the injection site. You can press a cotton ball or gauze over the injection site for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with a bandage.
   
7. If your healthcare provider has instructed you to take two Enbrel injections on the same day, repeat the steps to prepare and give an injection of Enbrel. Choose and prepare a new injection site for the second injection.
   
8. For the Free-Hand Method: If there is enough solution left in the Enbrel vial for another dose, refrigerate the reconstituted (mixed) Enbrel vial (in the dose tray) after use. Otherwise, discard the Enbrel vial and any remaining solution.

Step 6: Disposing of Supplies

The syringe, needles, and vial adapter should never be reused. Never recap a needle.

• Put the used syringes, needles, and vials in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the needles, syringes, and vials in your household trash.
  
• If you do not have a 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 syringes and needles. 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 reuse the syringe or vial.
  
• Do not recycle the syringe, vial, or sharps disposal container or throw them into household trash.

Important: Always keep the sharps disposal container out of the reach of children.

A healthcare provider familiar with Enbrel should answer all questions. Call 1-888-4Enbrel (1-888-436-2735) or visit www.Enbrel.com for more information about Enbrel.

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

Manufactured by:
Immunex Corporation
Thousand Oaks, CA 91320-1799
U.S. License Number 1132

© 1998 – 2016 Immunex Corporation. All rights reserved.      

1XXXXXX – v8                                           PMVx

Revised: 11/2016

Contains 4 Single-Dose Prefilled Syringes
NDC 58406-455-04
Enbrel®
etanercept
25 mg/0.5 mL
Single-Dose Prefilled Syringe
25 mg/0.5 mL
Attention: Not for use in pediatric patients under 31 kg (68 pounds).
For Subcutaneous Use Only
Sterile Solution – No Preservative
Refrigerate at 2° to 8°C (36° to 46°F). DO NOT FREEZE.
Each single-dose prefilled syringe contains 0.51 mL of a clear and 
colorless solution containing 25 mg/0.5 mL etanercept and is formulated at 
pH 6.3 ± 0.2, with 25 mM L-arginine hydrochloride, 100 mM sodium chloride,
25 mM sodium phosphate and 1% sucrose.
Specific activity: approximately 1.7 x 106 U/mg.
Manufactured by Immunex Corporation, Thousand Oaks, CA 91320
U.S. License No. 1132
©2013, 2016 Immunex Corporation
Patent: http://pat.amgen.com/Enbrel/

Contains 4 Single-Dose Prefilled Syringes
NDC 58406-435-04
Enbrel®
etanercept
50 mg/mL
Single-Dose Prefilled Syringe
50 mg/mL
Attention: Not for use in pediatric patients under 63 kg (138 pounds).
For Subcutaneous Use Only
Sterile Solution – No Preservative
Refrigerate at 2° to 8°C (36° to 46°F). DO NOT FREEZE.
Each single-dose prefilled syringe contains 0.98 mL of a clear and
colorless solution containing 50 mg/mL etanercept and is formulated at
pH 6.3 ± 0.2, with 25 mM L-arginine hydrochloride, 100 mM sodium chloride,
25 mM sodium phosphate and 1% sucrose.
Specific activity: approximately 1.7 x 106 U/mg.
Manufactured by Immunex Corporation, Thousand Oaks, CA 91320
U.S. License No. 1132
©2013, 2016 Immunex Corporation
Patent: http://pat.amgen.com/Enbrel/

Contains 4 Single-Dose Prefilled Autoinjectors
NDC 58406-445-04
Enbrel®
etanercept
SureClick® Autoinjector
50 mg/mL
Single-Dose Prefilled Autoinjector
50 mg/mL
Attention: Not for use in pediatric patients under 63 kg (138 pounds).
For Subcutaneous Use Only
Sterile Solution – No Preservative
Refrigerate at 2° to 8°C (36° to 46°F). DO NOT FREEZE.
Each single-dose prefilled autoinjector contains 0.98 mL of a clear and colorless solution containing
50 mg/mL etanercept and is formulated at pH 6.3 ± 0.2, with 25 mM L-arginine hydrochloride,
100 mM sodium chloride, 25 mM sodium phosphate and 1% sucrose.
Specific activity: approximately 1.7 x 106 U/mg.
Manufactured by Immunex Corporation, Thousand Oaks, CA 91320-1799
U.S. License No. 1132
©2015, 2016 Immunex Corporation
Patent: http://pat.amgen.com/Enbrel/

Contains 4 Multi-Dose Trays
NDC 58406-425-34
AMGEN®
Enbrel®
etanercept
25 mg/vial
Multiple-Dose Vial
See package insert for full prescribing information
and instructions for preparation and administration.
25 mg/vial
Each vial contains a sterile lyophilized preparation
of 25 mg etanercept (a recombinant CHO cell-derived
product), 40 mg mannitol, 10 mg sucrose, and
1.2 mg tromethamine.
Specific activitiy: approximately 1.7 x 106 U/mg.
No U.S. standard of potency. Volume after reconstitution
with 1 mL diluent is 1 mL.
Before and after reconstitution refrigerate
at 2° to 8°C (36° to 46°F). DO NOT FREEZE.
For Subcutaneous Use Only
AMGEN®
Manufactured by Immunex Corporation, Thousand Oaks, CA 91320
Contains diluent syringes (Made in Germany)
U.S. License No. 1132
©2013, 2016 Immunex Corporation
Patent: http://pat.amgen.com/Enbrel/

Before you start treatment with Enbrel, your doctor may perform tests to make sure you do not have an infection.

Enbrel is injected under the skin. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

You may need to mix Enbrel with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medication.

A child who weighs less than 138 pounds may not be able to use certain forms of Enbrel. If a child is using this medicine, tell your doctor if the child has any changes in weight.

Your care provider will show you the best places on your body to inject Enbrel. Do not inject into the same place two times in a row. Avoid injecting into skin that is bruised, tender, red, or hard.

You may have pain, redness, swelling, or warmth where the medicine was injected. Call your doctor if these symptoms continue for longer than 5 days.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

A single-use prefilled syringe or injection pen is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Do not shake this medicine. Prepare your dose only when you are ready to give an injection. Do not use the medicine if it looks cloudy or has changed colors. Call your pharmacist for new medicine.

Enbrel can weaken your immune system. Your blood may need to be tested often.

If you have ever had hepatitis B, Enbrel can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

If you need surgery, tell the surgeon ahead of time that you are using Enbrel.

Store Enbrel in its original carton in the refrigerator. Do not freeze. Do not use after the expiration date on the label has passed. After mixing Enbrel with a diluent, store in the refrigerator and use within 14 days.

If you need to store Enbrel at room temperature, protect the medicine from light and from extreme hot or cold temperatures. Once the medicine has reached room temperature, you should not put it back into the refrigerator.

Throw away any Enbrel not used within 14 days. Throw away any Erelzi not used within 28 days.

Usual Adult Dose of Enbrel for Ankylosing Spondylitis:

50 mg subcutaneously once a week

Comments:
-Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics may be continued during treatment with this drug.
-Doses higher than 50 mg per week are not recommended.

Uses:
-Rheumatoid Arthritis: To reduce symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis (RA). This drug can be used alone or in combination with methotrexate (MTX).
-Ankylosing Spondylitis: To reduce symptoms in patients with active ankylosing spondylitis (AS).
-Psoriatic Arthritis: To reduce symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). This drug can be used alone or in combination with methotrexate (MTX).

Usual Adult Dose of Enbrel for Rheumatoid Arthritis:

50 mg subcutaneously once a week

Comments:
-Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics may be continued during treatment with this drug.
-Doses higher than 50 mg per week are not recommended.

Uses:
-Rheumatoid Arthritis: To reduce symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis (RA). This drug can be used alone or in combination with methotrexate (MTX).
-Ankylosing Spondylitis: To reduce symptoms in patients with active ankylosing spondylitis (AS).
-Psoriatic Arthritis: To reduce symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). This drug can be used alone or in combination with methotrexate (MTX).

Usual Adult Dose for Psoriatic Arthritis:

50 mg subcutaneously once a week

Comments:
-Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics may be continued during treatment with this drug.
-Doses higher than 50 mg per week are not recommended.

Uses:
-Rheumatoid Arthritis: To reduce symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis (RA). This drug can be used alone or in combination with methotrexate (MTX).
-Ankylosing Spondylitis: To reduce symptoms in patients with active ankylosing spondylitis (AS).
-Psoriatic Arthritis: To reduce symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis (PsA). This drug can be used alone or in combination with methotrexate (MTX).

Usual Adult Dose of Enbrel for Plaque Psoriasis:

Initial dose: 50 mg subcutaneously 2 times a week (administered 3 to 4 days apart) for 3 months; alternatively, starting doses of 25 to 50 mg once a week have been shown to be effective
Maintenance dose: 50 mg subcutaneously once a week

Use: For the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.

Usual Pediatric Dose for Juvenile Idiopathic Arthritis:

2 years and older:
-Less than 63 kg: 0.8 mg/kg subcutaneously once a week
-Greater than or equal to 63 kg: 50 mg subcutaneously once a week
-Maximum dose: 50 mg subcutaneously once a week

Comments:
-Glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics may be continued during treatment with this drug.

Use:
-For reducing symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients 2 years and older

Usual Pediatric Dose for Plaque Psoriasis:

4 years and older:
-Less than 63 kg: 0.8 mg/kg subcutaneously once a week
-Greater than or equal to 63 kg: 50 mg subcutaneously once a week
-Maximum: 50 mg subcutaneously once a week

Comments:
-Glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics may be continued during treatment with this drug.

Use: For the treatment of patients 4 years and older with chronic moderate to severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.

Substance Name

Etanercept

CAS Registry Number

185243-69-0

Drug Class

Antirheumatic Agents

Etanercept is a tumor necrosis factor (TNF) blocker. It works by decreasing TNF, a protein produced by the immune system to helps the body fight infections. In people with autoimmune disorders, the immune system produces too much TNF and mistakenly attacks healthy cells.

Etanercept is used to treat rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, and to prevent joint damage caused by these conditions. Etanercept is also used to treat polyarticular juvenile idiopathic arthritis in children who are at least 2 years old.

Etanercept is also used to treat plaque psoriasis in adults and children who are at least 4 years old.

Etanercept may also be used for purposes not listed in this medication guide.

You should not use etanercept if you are allergic to it, or if you have a severe infection such as sepsis (infection of the blood).

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

• a weak immune system, HIV or AIDS, tuberculosis, or any type of recurring infection;

• symptoms of an active infection such as fever, flu symptoms, diarrhea, or painful urination;

• an open cut or skin sores;

• diabetes;

• congestive heart failure;

• a history of nerve disorders such as multiple sclerosis, Guillain-Barré syndrome, myelitis, or optic neuritis;

• epilepsy or other seizure disorder;

• asthma or other breathing disorder;

• if you have ever had hepatitis B;

• if you are allergic to latex rubber; or

• if you are scheduled to receive any vaccines, or if you have recently been vaccinated with BCG (Bacille Calmette-Guerin).

Tell your doctor if you have ever had tuberculosis, if anyone in your household has tuberculosis, or if you have recently traveled to an area where certain infections are common (Ohio River Valley, Mississippi River Valley, and the Southwest).

Children using this medication should be current on all childhood immunizations before starting treatment with etanercept.

Using etanercept may increase your risk of developing certain types of cancer, including a fast-growing lymphoma that can be fatal. This rare lymphoma has occurred in male teenagers and young men using a combination of immunosuppressant medicines to treat Crohn's disease or ulcerative colitis. However, people with autoimmune disorders (including rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, and psoriasis) may have a higher risk of lymphoma. Talk to your doctor about your individual risk.

Tell your doctor if you are pregnant or plan to become pregnant while using this medicine. If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of etanercept on the baby.

Etanercept can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Call your doctor for instructions if you miss a dose of etanercept.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• abatacept (Orencia);

• anakinra (Kineret);

• cyclophosphamide (Cytoxan); or

• insulin or oral diabetes medicine.

This list is not complete. Other drugs may interact with etanercept, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.