ENBREL 25 mg SOLUTION FOR INJECTION IN PRE-FILLED PEN

Introduction

Package Leaflet: Information for the User

Enbrel 25mg solution for injectioninpre-filled pen

etanercept

Contents of the pack

The information in this leaflet is organized into the following 7 sections:

1. What is Enbrel and what is it used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. Storing Enbrel
6. Contents of the pack and other information
7. Instructions for use

1. What is Enbrel and what is it used for

Enbrel is a medicine made from two human proteins. It blocks the action of another protein, which is found in the body, that causes inflammation. Enbrel works by reducing inflammation associated with certain diseases.

Enbrel can be used in adults aged 18 years or older to treat moderate or severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate or severe plaque psoriasis, usually depending on each case, when other treatments have not been effective enough or are not suitable 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 medicine, in case methotrexate treatment is not suitable for you. Enbrel can slow down the damage caused by rheumatoid arthritis to 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 their ability to perform normal daily activities. In the case of patients with multiple symmetrical joints that are swollen or painful (e.g., 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 worked adequately, or is not suitable for them:

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

• For enthesitis-related arthritis in patients from 12 years of age for whom the use of other more commonly used treatments has not worked adequately, or such treatments are not suitable for them.

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

2. What you need to know before you use Enbrel

Do not use Enbrel

• if you or the child in your care are allergic to etanercept or any of the other ingredients of Enbrel (listed in section 6). If you or the child experience allergic reactions, such as chest tightness, wheezing, 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 you are not sure, consult your doctor.

• if you or the child have any type of infection. If you are not sure, 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, wheezing, 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 monitoring the treatment with Enbrel.
• Infections/diabetes:Inform your doctor if you or the child have a history of recurrent infections or have diabetes or other disorders 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 must decide whether to continue monitoring you or the child for the presence of infections after you or the child stop treatment with Enbrel.
• Tuberculosis:Since cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will examine the signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough review of your medical history, chest X-ray, and a tuberculosis test. The performance of these tests must be recorded on the Patient Alert Card. It is very important that you tell your doctor if you or the child have had tuberculosis or have been in close 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. Your doctor must perform a hepatitis B test before you or the child start treatment with Enbrel. Treatment with Enbrel may 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 the treatment with Enbrel in case the infection worsens.

• Blood disorders:Inform your doctor immediately if you or the child have signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. Such symptoms may indicate a serious blood problem that requires discontinuation of treatment with Enbrel.
• Nervous system and vision disorders:Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will decide if Enbrel is a suitable treatment.
• Congestive heart failure:Inform your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to 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 you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or other cancers.

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

Some patients who receive Enbrel have developed skin cancers. Inform your doctor if you or the child develop any changes in the appearance of the skin 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 needle cap of the MYCLIC pen is made of latex (dry natural rubber). Contact your doctor before using Enbrel if the needle cap is to be handled by, or if Enbrel is to be administered to, someone with known or possible latex allergy.
• Alcoholism:Enbrel should not be used to treat hepatitis related to alcoholism. 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, discuss this with your doctor.
• Anti-diabetic medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide if you or the child need less anti-diabetic medicine while taking Enbrel.

Children and adolescents

Vaccinations:If possible, children should have all vaccinations up to date before using Enbrel. Some vaccines, such as oral polio vaccine, should not be given while using Enbrel. Consult your doctor before you or the child use any vaccine.

Enbrel should not normally be used in children under 2 years of age with polyarthritis or extended oligoarthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Other medicines and Enbrel

Inform your doctor or pharmacist if you or the child are using, have recently used, or might use any other medicines (including anakinra, abatacept, or sulfasalazine), even those not prescribed by your doctor. You or the child must not use Enbrel with medicines that contain the active substances 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 plan to become pregnant.

If you have received Enbrel during pregnancy, your baby may have a higher risk of getting an 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 other similar medicines (TNF antagonists), but there was no pattern in the types of birth defects reported. Another study did not find a higher 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 being treated with Enbrel. It is important that you inform the pediatrician and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and using machines

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

Enbrel contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose unit; this is essentially “sodium-free”.

3. How to use Enbrel

Follow exactly the instructions for administration of this medicine given by your doctor. If you are not sure, consult your doctor or pharmacist again.

If you think that the action of Enbrel is too strong or too weak, talk to your doctor or pharmacist.

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

Dose for adult patients (aged 18 years 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, by subcutaneous injection. 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 may 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 to repeat the treatment based on your response. If Enbrel does not have an effect on your disease after 12 weeks, your doctor may advise you to stop using this medicine.

Use in children and adolescents

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

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

For psoriasis in patients from 6 years of age, the usual dose is 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg) once a week. If Enbrel does not have an effect on the child's disease after 12 weeks, your doctor may advise you to stop using this medicine.

Your doctor will give you precise instructions for preparing and calculating the correct dose.

Form and route of administration

Enbrel is administered by subcutaneous injection.

Enbrel can be administered with or without food or drink.

Insection 7, “Instructions for use”, detailed instructions for injecting Enbrel are included.The Enbrel solution should not be mixed with any other medicine.

To help you remember, it may be useful to note down 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 higher dose at one time or by using it more frequently), you should talk to a doctor or pharmacist immediately. Always carry the medicine pack with you, even if it is empty.

If you forget to inject Enbrel

If you miss a dose, you should inject it as soon as you remember, unless the next dose is scheduled for the next day, in which case you should omit the missed dose. Then, continue injecting the medicine on the usual day(s). If you do not remember until the day you are due to take the next dose, do not inject a double dose (two doses on the same day) to make up for the missed dose.

If you stop treatment with Enbrel

Your symptoms may return after stopping treatment.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Allergic Reactions

If you observe any of the following reactions, do not inject more Enbrel. Inform your doctor immediately or go to the Emergency Service of the nearest hospital.

• Difficulty swallowing or breathing.
• Swelling of the face, throat, hands, and feet.
• Feeling of nervousness or anxiety, palpitations, sudden reddening of the skin, and/or feeling of heat.
• Severe rash, itching, or hives (prominent red or pale skin rashes, 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 should seek immediate emergency medical attention.

Severe Adverse Effects

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

• Signs of severe infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a painful, sensitive, red, and hot area of skin or joints.
• Signs of blood disorders, such as bleeding, bruising, or paleness.
• Signs of nervous system disorders, such as numbness or tingling, vision changes, eye pain, or weakness in an arm or leg.
• Signs of heart failure or worsening of 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 of cancer: cancer can affect any part of the body, including the skin and blood, and 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 of autoimmune reactions(in which antibodies that can damage normal body tissues develop) such as pain, itching, weakness, and abnormal breathing, thinking, feeling, or vision.
• Signs of lupus or lupus-like syndromesuch as weight changes, persistent rash, fever, muscle or joint pain, or fatigue.
• Signs of inflammation of blood vesselssuch as pain, fever, redness or heat of the skin, or itching.

These adverse effects are rare or infrequent, but they are serious conditions (some of which can be life-threatening). If these signs occur, inform your doctor immediately or go to the Emergency Service of the nearest hospital.

The following are the known adverse effects of Enbrel, grouped in decreasing order of frequency:

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

Infections (including colds, sinusitis, bronchitis, urinary tract infections, and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling) (do not occur as frequently after the first month of treatment; some patients have developed injection site reactions 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 (formation of autoantibodies).

• 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); hives (prominent red or pale skin rashes, 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 who also receive treatment with methotrexate, the increase in liver enzymes is frequent); 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 severe localized skin swelling and wheezing); lymphoma (a type of blood cancer); leukemia (cancer that affects the blood and bone marrow); melanoma (a type of skin cancer); combined low red blood cell count, white blood cell count, and platelet count; nervous system disorders (with severe muscle weakness and signs and symptoms similar to those of 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 rash that can lead to severe blistering and peeling of the skin; lichenoid reactions (itchy reddish-purple skin rash and/or thick white-gray lines on the mucous membranes); autoimmune hepatitis (in patients who also receive treatment with methotrexate, the frequency is uncommon); sarcoidosis (an immune disorder that can affect the lungs, skin, and lymph nodes); lung inflammation or scarring (in patients who also receive treatment with methotrexate, the frequency of lung inflammation or scarring 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):

Failure of the bone marrow to produce crucial blood cells.

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

Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma, a rare cancer related to human herpesvirus 8 infection. Kaposi's sarcoma usually manifests more frequently 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 Adverse Effects in Children and Adolescents

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

Reporting of Adverse Effects

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

5. Storage of Enbrel

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

Do not use this medicine after the expiry date that appears on the packaging and on the pre-filled MYCLIC pen after "EXP". The expiry date is the last day of the month indicated.

Store in a refrigerator (2°C - 8°C). Do not freeze.

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

After removing the pre-filled pen from the refrigerator, wait approximately15 to30 minutes for the Enbrel solutioninthe pen to reach room temperature.Do not heat it in any other way. Then, it is 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 medicine cannot be refrigerated again. Enbrel should be discarded if it has not been used within 4 weeks of being removed from the refrigerator. It is recommended that you note the date on which Enbrel was removed from the refrigerator and the date from which Enbrel should be discarded (not later than 4 weeks from the removal of the packaging from the refrigerator).

Inspect the solution in the pen by looking through the transparent inspection window. The solution should be clear 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 cloudy, 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 disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Container Contents and Additional Information

Enbrel Composition

The active ingredient of Enbrel is etanercept. Each MYCLIC pre-filled pen of Enbrel contains 25 mg of etanercept.

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

Product Appearance and Container Contents

Enbrel is presented as an injectable solution in a pre-filled pen (MYCLIC) (injectable solution). The MYCLIC pen contains a clear, colorless to pale yellow or pale brown injectable solution. Each container contains 4, 8, or 24 pens and 4, 8, or 24 alcohol swabs.

You can request more information about this medication by contacting the local representative of the Marketing Authorization Holder:

Spain

Pfizer, S.L.

Phone: +34 91 490 99 00

Date of Last Revision of this Prospectus:

Detailed information about this medication is available on the European Medicines Agency website: http://www.ema.europa.eu.

1. Instructions for Use

Enbrel 25 mg Solution for Injection in Pre-filled Pen

(etanercept)

For subcutaneous injection only

Introduction

• The following instructions explain how to use the MYCLIC pen to inject Enbrel.
• Read the instructions carefully and follow them step by step.
• Your healthcare professional will show you how to inject Enbrel. Do not attempt to administer an injection until you are sure you understand how to use the MYCLIC pen correctly.
• If you have any doubts about how to inject, ask your healthcare professional for help.

Pre-filled Pen 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 MYCLIC pre-filled pen.

o An alcohol swab.

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

o Cotton balls or clean gauze (not included).

• Do notshake the pen.
• Do notremove the white cap until instructed to do so.
• For a more comfortable injection, leave the pen at room temperature between 15 and 30 minutes with the white cap on.
• Do notheat the pen in any other way.

Step 2 Check the Expiration Date and Dose on the Label

• Checkthe expiration date (month/year) on the pen label.
• Make surethe correct dose appears on the pen label.
• If the expiration date has passed or it is not the prescribed dose, do notuse the pen and contact your healthcare professional for assistance.

Step 3 Inspect the Medication

• Inspectthe medication in the pen by looking through the transparent inspection window. The solution should be clear 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 notuse the medication if it has changed color, is cloudy, or contains particles other than those described above. If you are concerned about the appearance of the medication, contact your healthcare professional for assistance.
• Note:you may see an air bubble in the window. This is normal.

Step 4 Choose and Clean the Injection Site

• Choosean injection site on the middle of the top of the thighs or on the stomach area, 5 cm from the navel. The outer area of the upper arms can also be used by a caregiver.
• Eachinjection should be administered at a minimum distance of 3 cm from the previous injection site. Do notadminister the injection in sensitive, bruised, or hardened skin areas. Avoid areas with scars or stretch marks. If you have psoriasis, do notadminister the injection directly into any raised, thick, red, or scaly skin plaque.
• Cleanthe injection site with water and soap or, if you prefer, with an alcohol swab.
• Letit 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 notbend the cap when removing it.
• Do notreplace the cap once removed.
• After removing the cap, you will see a purple safety protector that slightly protrudes from the end of the pen. Do notpush the safety protector at the end with your fingers or thumbs.
• Do notuse the pen if it falls with the needle cap removed.

Note:you may notice a drop of liquid at the tip of the needle. This is normal.

Step 6 Press the Pen Firmly Against the Skin

• Pushthe open end of the pen firmly against the skin at a 90-degree angle, so that the purple needle safety protector is completely inside the pen.

Note:you will only be able to press the gray button when the needle safety protector is completely inserted into the pen.

Pinning or stretching the skin before injection can make the injection site firmer, making it easier to press the injection button.

Step 7 Start the Injection

• Pressthe gray button all the way down and you will hear a “click”. The click means the injection has started.
• Continue to holdthe pen firmly against the skin until you hear a second “click”, or until 10 seconds after the first click (whichever comes first).

Note:if you cannot start the injection as described, press the pen more firmly against the skin and then press the gray button again.

Step 8 Remove the Pen from the Skin

• Removethe pen from the skin by lifting it straight up from the injection site.
• The purple needle safety protector will automatically extend to cover the needle.

Step 9 Check the Inspection Window

• Checkthe inspection window on the pen. It should be completely purple.
• If the window is not purple, you may not have received a complete dose. Contact your healthcare professional for assistance. Do notattempt to use the pen again. Do notattempt to use another pen.
• If you notice a blood spot at the injection site, press a cotton ball or gauze over the injection site for 10 seconds. Do notrub the injection site.

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

Step 10 Disposal

• Dispose ofthe used pen by following the instructions of your healthcare professional. Do notattempt to recap the pen.
• Do notpress the end of the needle safety protector. If you have any doubts, consult your healthcare professional.

—End of Instructions for Use—