Product Information for the User

Enbrel 50 mg injectable solutioninpre-filled syringe

etanercept

The information inthisproduct information is organizedinthe following 7 sections:

1.What Enbrel is and what it is used for

2.What you need to know before starting to use Enbrel

3.How to use Enbrel

4.Possible side effects

5.Storage of Enbrel

6.Contents of the pack and additional information

7.Instructions for use

Enbrel is a medication made from two human proteins. It blocks the activity of another protein found in the body that produces inflammation. Enbrel acts by reducing the inflammation associated with certain diseases.

Enbrel can be used in adults 18 years of age or older for the treatment ofmoderate to severe rheumatoid arthritis,psoriatic arthritis,axial spondyloarthritisincludingankylosing spondylitisandpsoriasismoderate to severe, usually, depending on each case, when other treatments have not been sufficiently effective or are not appropriate for you.

In the treatment of rheumatoid arthritis, Enbrel is usually used in combination with methotrexate, although it can also be used as a single medication, in the case where methotrexate treatment is not suitable for you. Enbrel can slow down the damage caused by rheumatoid arthritis in your joints and improve your ability to perform daily activities, whether used alone or in combination with methotrexate.

In the case of patients with psoriatic arthritis with multiple joint involvement, Enbrel can improve your ability to perform normal daily activities.In the case of patients with multiple symmetrical, swollen, or painful joints (for example, in hands, wrists, and feet), Enbrel can delay the progression of structural damage to these joints caused by the disease.

Enbrel is also indicated for the treatment of children and adolescents with the following diseases:

• For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not been adequately effective, or well-suited for them:

• Poliarthritis (with positive or negative rheumatoid factor) and oligoarthritis extended in patients from 2 years old.
• Psoriatic arthritis in patients from 12 years old.

• For arthritis related to enthesitis in patients from 12 years of age for whom the use of other commonly used treatments has not been adequately effective, or well-suited for them.

• Severe psoriasis in patients from 6 years of age who have had an inadequate response to (or are unable to take) phototherapy or other systemic therapies.

No use Enbrel

• if you or the child in your care are allergic to etanercept or any of the other components of Enbrel (listed in section 6). If you or the child experience allergic reactions, such as chest tightness, rapid breathing, dizziness, or rash, do not inject more Enbrel and contact your doctor immediately.

• if you or the child have or are at risk of developing a severe blood infection called sepsis. If unsure, consult your doctor.

• if you or the child have any type of infection. If unsure, consult your doctor.

Warnings and precautions

Consult your doctor before starting to use Enbrel.

• Allergic reactions:If you or the child experience allergic reactions such as chest tightness, rapid breathing, dizziness, or rash, do not inject more Enbrel and contact your doctor immediately.
• Infections/surgery:If you or the child develop a new infection or are about to undergo major surgery, your doctor may be interested in controlling Enbrel treatment.
• Infections/diabetes:Inform your doctor if you or the child have a history of recurrent infections or have diabetes or other conditions that increase the risk of infection.

• Infections/monitoring:Inform your doctor of any recent travel outside the European region. If you or the child develop symptoms of an infection such as fever, chills, or cough, notify your doctor immediately. Your doctor will decide whether to continue monitoring you or the child to see if there are any infections after you or the child stop Enbrel treatment.
• Tuberculosis:Since cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will examine signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, chest X-ray, and tuberculosis test. The performance of these tests must be recorded in the Patient Information Card. It is very important to tell your doctor if you or the child have had tuberculosis, or if you have been in direct contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, apathy, moderate fever), or any other infection appear during or after treatment, inform your doctor immediately.
• Hepatitis B:Inform your doctor if you or the child have or have had hepatitis B at any time. Your doctor must perform a hepatitis B test before you or the child start Enbrel treatment. Enbrel treatment can reactivate hepatitis B in patients who have been previously infected with the hepatitis B virus. If this occurs, you must stop using Enbrel.
• Hepatitis C:Inform your doctor if you or the child have hepatitis C. Your doctor may want to monitor Enbrel treatment in case the infection worsens.

• Blood disorders:Inform your doctor immediately if you or the child experience symptoms such as persistent fever, sore throat, bruises, bleeding, or paleness. These symptoms may indicate the presence of a serious blood disorder that requires Enbrel treatment to be stopped.
• Nervous system and vision disorders:Inform your doctor if you or the child experience multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will decide if Enbrel is an appropriate treatment.
• Heart failure:Inform your doctor if you or the child have a history of congestive heart failure, as Enbrel should be used with caution in these circumstances.
• Cancer:Inform your doctor if you have or have had lymphoma (a type of blood cancer) or any other cancer before Enbrel is administered.

Patients with severe rheumatoid arthritis who have had the disease for a long time may be at higher risk of developing lymphoma.

Children and adults taking Enbrel may be at increased risk of developing lymphoma or other cancers.

Some adolescent and child patients who have received Enbrel or other medications that work in the same way as Enbrel have developed cancers, including rare types that sometimes resulted in death.

Some patients taking Enbrel have developed skin cancers. Inform your doctor if you or the child develop any changes in skin appearance or growths on the skin.

• Chickenpox:Inform your doctor if you or the child are exposed to chickenpox while using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
• Latex:The plunger cap of the MYCLIC pen is made of latex (natural dried rubber). Contact your doctor before using Enbrel if the plunger cap will be handled by, or if Enbrel will be administered to, someone with known or possible latex hypersensitivity (allergy).
• Alcoholism:Enbrel should not be used to treat alcohol-related hepatitis. Please inform your doctor if you or the child in your care have a history of alcoholism.
• Wegener's granulomatosis:Enbrel is not recommended for the treatment of Wegener's granulomatosis, a rare inflammatory disease. If you or the child in your care have Wegener's granulomatosis, please inform your doctor.
• Antidiabetic medications: Inform your doctor if you or the child have diabetes or are taking medications to treat diabetes. Your doctor may decide if you or the child need less antidiabetic medication while taking Enbrel.

Children and adolescents

Vaccinations:If possible, children should have all vaccinations updated before using Enbrel. Some vaccines, such as the oral polio vaccine, should not be administered while using Enbrel. Consult with your doctor before using any vaccine.

Enbrel should not be used in children under 2 years with polyarthritis or oligoarthritis, in children under 12 years with arthritis related to enthesitis or psoriatic arthritis, or in children under 6 years with psoriasis.

Other medications and Enbrel

Inform your doctor or pharmacist if you or the child are using, have used recently, or may need to use any other medication (including anakinra, abatacept, or sulfasalazine), even those not prescribed by your doctor.You or the child should not use Enbrel with medications containing the active principles anakinra or abatacept.

Pregnancy and breastfeeding

Enbrel should only be used during pregnancy if clearly necessary. Consult your doctor if you are pregnant, think you may be pregnant, or intend to become pregnant.

If you have received Enbrel during pregnancy, your baby may be at increased risk of infection. Additionally, in one study, more birth defects were observed when the mother had received Enbrel during pregnancy, compared to mothers who had not received Enbrel or similar medications (TNF antagonists), but no pattern was observed in the types of birth defects reported. Another study found no increased risk of congenital defects when the mother had received Enbrel during pregnancy. Your doctor will help you decide if the benefits of treatment outweigh the potential risk to your baby.

Consult your doctor if you wish to breastfeed while on Enbrel treatment. It is essential to inform the pediatrician and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and operating machinery

It is not expected that the use of Enbrel will affect the ability to drive and operate machinery.

Enbrel contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose unit; it is essentially "sodium-free".

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

If you estimate that the action of Enbrel is too strong or too weak, inform your doctor or pharmacist.

Your doctor has prescribed a dose of 50 mg of Enbrel. Additionally, a presentation of 25 mg of Enbrel is available for the administration of 25 mg doses.

Dosage for adult patients (18 years of age or older)

Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis

The usual dose is 25 mg administered twice a week or 50 mg administered once a week, in the form of a subcutaneous injection under the skin. However, your doctor may determine an alternative frequency for injecting Enbrel.

Plaque psoriasis

The usual dose is 25 mg twice a week or 50 mg once a week.

Alternatively, 50 mg can be administered twice a week for a maximum of 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Your doctor will decide how long you should take Enbrel and if you need a repeat of the treatment based on your response. If Enbrel has no effect on your disease after 12 weeks, your doctor may instruct you to stop using this medication.

Use in children and adolescents

The appropriate dose and dosing frequency will depend on the child's or adolescent's body weight and disease.Your doctor will determine the appropriate dose for the child and prescribe the most suitable Enbrel presentation (10 mg, 25 mg, or 50 mg).

For extended oligoarthritis or polyarthritis in patients aged 2 years or older, or psoriatic arthritis-related arthritis or psoriatic arthritis in patients aged 12 years or older, the usual dose is 0.4 mg of Enbrel per kg of body weight (up to a maximum of 25 mg) administered twice a week, or 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg) administered once a week.

For plaque psoriasis in patients aged 6 years or older, the usual dose is 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg) administered once a week. If Enbrel has no effect on the child's disease after 12 weeks, your doctor may instruct you to stop using this medication.

Your doctor will give you precise instructions to prepare and calculate the correct dose.

Form and route of administration

Enbrel is administered via a subcutaneous injection under the skin.

Enbrel can be administered with or without food or beverages.

InSection 7, “Instructions for use”, detailed instructions for Enbrel injection are included.The Enbrel solution should not be mixed with any other medication.

To help you remember, it may be helpful to note in a diary which day(s) of the week you should use Enbrel.

If you use more Enbrel than you should

If you use more Enbrel than you should (either by injecting a high amount in one occasion or by using it too frequently), you should speak with a doctor or pharmacist immediately. Always carry the medication packaging with you, even if it is empty.

If you forget to inject Enbrel

If you forget a dose, you should inject it as soon as you remember, unless the next dose is scheduled for the following day, in which case you should omit the missed dose. Then, continue injecting the medication on the usual day(s). If you do not remember until the day you should administer the next dose, do not inject a double dose (two doses on the same day) to compensate for the missed dose.

If you interrupt Enbrel treatment

Your symptoms may return after treatment interruption.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Allergic reactions

If you notice any of the following reactions, do not inject Enbrel again. Inform your doctor immediately or go to the nearest hospital emergency department.

• Difficulty swallowing or breathing.
• Swelling of the face, throat, hands, and feet.
• Feeling of nervousness or anxiety, palpitations, sudden redness of the skin, and/or feeling of heat.
• Severe rash, itching, or urticaria (prominent skin rashes, red or pale, often accompanied by itching).

Severe allergic reactions are rare. However, any of the above symptoms may be a sign of an allergic reaction to Enbrel, so you must seek urgent medical attention immediately.

Severe side effects

If you notice any of the following side effects, you or the child may need emergency medical attention.

• Signs ofserious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a painful, sensitive, red, and warm area of the skin or joints.
• Signs ofblood disorders, such as bleeding, bruises, or paleness.
• Signs ofneurological disorders, such as numbness or tingling, visual disturbances, eye pain, or weakness in one arm or leg.
• Signs ofheart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling of the ankles, feeling of fullness in the neck or abdomen, shortness of breath at night, or cough, blue discoloration of the nails or around the lips.
• Signs ofcancer: cancer can affect any part of the body, including the skin and blood, and the possible signs will depend on the type and location of the cancer. These signs may include weight loss, fever, swelling (with or without pain), persistent cough, presence of lumps or thickening of the skin.
• Signs ofautoimmune reactions(in which antibodies may form that can damage normal body tissues) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision.
• Signs oflupus or lupus-like syndromesuch as weight changes, persistent rash, fever, joint pain, or fatigue.
• Signs ofvasculitissuch as pain, fever, redness, or warmth of the skin, or itching.

These side effects are rare or uncommon, but are serious (some of them may be fatal in rare cases). If these signs occur, inform your doctor immediately or go to the nearest hospital emergency department.

The following are known side effects of Enbrel, grouped by decreasing frequency:

• Very common(may affect more than 1 in 10 people):

Infections (including colds, sinusitis, bronchitis, urinary tract infections, and skin infections); reactionsatthe injection site (including bleeding, bruising, redness, itching, pain, and swelling) (do not occur as frequently after the first month of treatment; some patients have developed a reactionatthe injection site that they had recently used); and headache.

• Common(may affect up to 1 in 10 people):

Allergic reactions; fever; rash; itching; antibodies directed against normal tissues (autoantibody formation).

• Uncommon(may affect up to 1 in 100 people):

Severe infections (including pneumonia, non-superficial skin infections, joint infections, blood infections, and generalized infections); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); low platelet count; skin cancer (excluding melanoma); localized skin swelling (angioedema); urticaria (prominent skin rashes, red or pale, often accompanied by itching); eye inflammation, psoriasis (new or worsening); inflammation of blood vessels affecting multiple organs; increased liver enzymes in blood tests (in patients also receiving methotrexate, the increase in liver enzymes is common); abdominal cramps and pain, diarrhea, weight loss, or blood in the stool (signs of intestinal problems).

• Rare(may affect up to 1 in 1,000 people):

Severe allergic reactions (including localized skin swelling and labored breathing); lymphoma (a type of blood cancer); leukemia (cancer affecting the blood and bone marrow); melanoma (a type of skin cancer); combined low red blood cell, white blood cell, and platelet count; neurological disorders (with severe muscle weakness and symptoms and signs similar to multiple sclerosis or inflammation of the optic nerves or spinal cord); tuberculosis; new-onset congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain, and fatigue); skin eruption that may lead to severe blistering and peeling of the skin;lichenoid reactions (pruritic, red-brown skin rash and/or thick white-gray lines on mucous membranes);autoimmune hepatitis (inflammation of the liver caused by the immune system; in patients also receiving methotrexate, the frequency is uncommon);immunological disorder that may affect the lungs, skin, and lymph nodes (sarcoidosis);inflammation or scarring of the lungs (in patients also receiving methotrexate, the frequency of inflammation or scarring of the lungs is uncommon); damage to the small filters within the kidneys, leading to impaired kidney function (glomerulonephritis).

• Very rare(may affect up to 1 in 10,000 people):

Bone marrow failure to produce critical blood cells.

• Frequency not known(cannot be estimated from available data):

Merkel cell carcinoma (a type of skin cancer);Kaposi's sarcoma, a rare cancer related to infection with human herpesvirus 8. Kaposi's sarcoma usually manifests as purple skin lesions;excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection);worsening of a disease called dermatomyositis (inflammation and weakness of the muscles accompanied by skin rash).

Other side effects in children and adolescents

The side effects observed in children and adolescents, as well as their frequencies, are similar to those previously described.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appearsonthe packaging andonthe pre-filled MYCLIC syringe after “EXP”. The expiration date is the last day of the month indicated.

Storeinthe refrigerator (2°C-8°C).Do not freeze.

Keep the pre-filled syringesinthe outer packaging to protect them from light.

After removing the pre-filled syringe from the refrigerator,wait approximately 15 to 30 minutes to allow the Enbrel solution in the syringe to reach room temperature.Do not heat it in any other way. It is then recommended to use it immediately.

Enbrel can be stored outside the refrigerator at a maximum temperature of 25°C, and for a single period of up to 4 weeks; after which, the medication cannot be refrigerated again. Enbrel must be discarded if not used within 4 weeks after removal from the refrigerator. It is recommended to note the date on which Enbrel was removed from the refrigerator and the date from which Enbrel must be discarded (not exceeding 4 weeks from the removal of the packaging from the refrigerator).

Inspect the solutioninthe syringe by looking through the transparent inspection window. The solution must be transparent or slightly opalescent, colorless to pale yellow or pale brown, and may contain small white or almost transparent protein particles. This is the normal appearance of Enbrel. Do not use the solution if it is discolored or turbid, or if it contains particles other than those described above. If you are concerned about the appearance of the solution, contact your pharmacist for assistance.

Medicines should not be thrown away through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

Composition of Enbrel

The active ingredient of Enbrel is etanercept. Each pre-filled MYCLIC syringe of Enbrel contains 50mg of etanercept.

The other components are sucrose, sodium chloride, L-arginine hydrochloride, monobasic sodium phosphate dihydrate, dibasic sodium phosphate dihydrate, and water for injection.

Appearance of the product and contents of the pack

Enbrel is presented as a pre-filled syringeina pre-filled syringe (MYCLIC) (solution for injection). The MYCLIC syringe contains a transparent, colourless to pale yellow or pale brown solution. Each pack contains 2, 4 or 12syringes and 2, 4 or 12 alcohol wipes.Only some pack sizes may be marketed.

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country.

Spain

Pfizer, S.L.

Tel: +34 91 490 99 00

Date of the last revision of this leaflet:

The detailed information on this medicinal product is availableonthe website of the European Medicines Agency:http://www.ema.europa.eu.

7.Instructions for use

Enbrel50mg solution for injection in pre-filled syringe

(etanercept)

For subcutaneous injection only

Introduction

Pre-filled syringe MYCLIC

Before injection

After injection

Step 1 Prepare for an Enbrel injection

• Gatherthe following materials for each injection on a flat, clean, and well-lit surface:

o A pre-filled MYCLIC syringe.

o An alcohol wipe.

o A suitable container for sharp objects (not included).

o Cotton balls or gauze (not included).

Step 2 Check the expiry date and dose on the label

Step 3 Inspect the medicine

Step 4 Choose and clean the injection site

• Choosea suitable injection site in the centre of the upper outer thigh or in the abdominal area, 5cm from the navel. The outer area of the upper arm may also be used by a caregiver.
• Eachinjection should be administered at a distance of at least 3cm from the site of the previous injection.Do notadminister the injectioninareas of sensitive skin, bruising, or thickening. Avoid areas with scars or stretch marks. If you have psoriasis,do notadminister the injection directlyinanyraised, thickened, red, or scaly skin.
• Cleanthe injection site with water and soap or, if preferred, with an alcohol wipe.
• Allowit to dry.Do nottouch, fan, or blow on the cleaned injection site.

Step 5 Remove the needle cap

• Removethe white needle cap by pulling it straight off.Do nottwist the cap when removing it.
• Do notreplace the cap once removed.
• Once the cap is removed, you will see a violet safety shield protruding slightly from the end of the syringe.Do notpush the safety shield with your fingers or thumbs.
• Do notuse the syringe if it falls with the needle cap removed.

Nota:it is possible to see a drop of liquid at the tip of the needle. This is normal.

Step 6 Press the syringe firmly against the skin

• Pushthe exposed end of the syringe firmly against the skin at a 90degree angle, so that the violet safety shield of the needle is completely inside the syringe.

Nota:you will only be able to press the injection button when the safety shield is completely inserted into the syringe.

Pinch or stretch the skin before injection may make the injection site firmer, making it easier to press the injection button.

Step 7 Start the injection

• Pressthe grey activation button until it clicks and you will hear a“click”. The click means the injection has started.
• Continueto hold the syringe firmly against the skin until you hear asecond “click”, or until 10seconds after the first click (whichever comes first).

Nota:if you are unable to start the injection as described, press the syringe more firmly against the skin and then press the grey activation button again.

Step 8 Separate the syringe from the skin

Step 9 Check the inspection window

• Checkthe inspection window of the syringe. It should be completely violet.
• If the inspection window is not violet, it is possible that you did not receive a full dose. Contact your healthcare professional for assistance.Do notattempt to use the syringe again.Do notattempt to use another syringe.
• If you see a blood stain on the injection site, press a cotton ball or gauze over the injection site for 10seconds.Do notrub the injection site.

Nota:the injection button may remain pressed. This is normal.

Step 10 Disposal

• Disposeof the used syringe according to the instructions of your healthcare professional.Do notattempt to re-cap the syringe.
• Do notpress the exposed end of the safety shield. If you are unsure, consult your healthcare professional.

—End of instructions for use—