ENBREL 50 mg SOLUTION FOR INJECTION IN PRE-FILLED SYRINGES

Introduction

Package Leaflet: Information for the User

Enbrel 25 mg solution for injection in pre-filled syringeinpre-filled syringe

Enbrel 50mg solution for injection in pre-filled syringeinpre-filled syringe

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 start using Enbrel
3. How to use Enbrel
4. Possible side effects
5. Storing Enbrel
6. Contents of the pack and further information
7. Instructions for use

1. What is Enbrel and what is it used for

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

Enbrel can be used in adults aged 18 years or older for the treatment of moderate or severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate or severe 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 the only 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 methotrexate treatment has not worked adequately, or is not suitable for them:

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

• For enthesitis-related arthritis in patients aged 12 years or older 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 aged 6 years or older 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 start using 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

Talk to your doctor before you start using 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 want to monitor your 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 will decide whether to continue monitoring you or the child for the presence of infections after stopping 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 Information 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 will 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 happens, you must stop using Enbrel.
• Hepatitis C:Inform your doctor if you or the child have hepatitis C. Your doctor may want to monitor your 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 interruption 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 whether 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 than average risk 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 decide whether preventive treatment for chickenpox is appropriate.
• Latex:The needle cap 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 must 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, 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 whether 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 is not normally 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

Tell 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 be at 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 an increased risk of congenital malformations when the mother had received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risk to your baby.

Consult your doctor if you want 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

Enbrel is not expected to affect your ability to drive or 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.

The pre-filled syringe is available in doses of 25 mg and 50 mg.

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 decide on an alternative frequency for injecting Enbrel.

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 up to 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 whether you need to repeat the treatment based on your response. If Enbrel has no 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 frequency of administration will depend on the child's or adolescent's 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 aged 2 years or older, or enthesitis-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) 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 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) once a week. If Enbrel has no 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.

Method and route of administration

Enbrel is administered by subcutaneous injection.

Enbrel can be administered with or without food or drink.

In section 7, “Instructions for use”, you will find detailed instructions for injecting Enbrel.The Enbrel solution must 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 too much at one time or by using it too 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 should inject 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 further questions on 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 urticaria (prominent skin rashes, reddened 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 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, reddened, and warm area on the 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 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 of autoimmune reactions(in which antibodies that can damage normal body tissues develop) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, 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 the blood vesselssuch as pain, fever, reddening or warmth 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, reddening, itching, pain, and swelling) (do not occur as frequently after the first month of treatment; some patients have developed an injection site reaction 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); urticaria (prominent skin rashes, reddened or pale, often accompanied by itching); eye inflammation, psoriasis (new or worsening); inflammation of the 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 (pruritic reddish-purple skin rash and/or thick white-gray lines on the mucous membranes); inflammation of the liver caused by the immune system (autoimmune hepatitis; in patients who also receive treatment with methotrexate, the frequency is uncommon); immunological disorder that can affect the lungs, skin, and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients who also receive treatment with 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):

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-colored 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 does not appear in this prospectus. 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 sight and reach of children.

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

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

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

After removing the syringe from the refrigerator, wait approximately 15 to 30 minutes for the Enbrel solution 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 must 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 must be discarded (no later than 4 weeks from the removal of the packaging from the refrigerator).

Observe the solution in the syringe. It should 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 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 any assistance you may need.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This way, you will help protect the environment.

6. Container Contents and Additional Information

Composition of Enbrel

Enbrel 25 mg injectable solution in a pre-filled syringe

The active substance of Enbrel is etanercept. Each Enbrel 25 mg pre-filled syringe contains 0.5 ml of solution with 25 mg of etanercept.

Enbrel 50 mg injectable solution in a pre-filled syringe

The active substance of Enbrel is etanercept. Each Enbrel 50 mg pre-filled syringe contains 1.0 ml of solution with 50 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.

Appearance of the Product and Container Contents

Enbrel 25 mg injectable solution in a pre-filled syringe

Enbrel is presented as a pre-filled syringe containing a clear, colorless to pale yellow or pale brown solution for injection (injectable solution). Each pack contains 4, 8, 12, or 24 pre-filled syringes, and 4, 8, 12, or 24 alcohol swabs. Only certain pack sizes may be marketed.

Enbrel 50 mg injectable solution in a pre-filled syringe

Enbrel is presented as a pre-filled syringe containing a clear, colorless to pale yellow or pale brown solution for injection (injectable solution). Each pack contains 2, 4, or 12 pre-filled syringes, and 2, 4, or 12 alcohol swabs. Only certain pack sizes may be marketed.

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Spain

Pfizer, S.L.

Phone: +34 91 490 99 00

Date of the Last Revision of this Leaflet:

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

1. Instructions for Use

This section is divided into the following subsections:

Introduction

Step 1: Prepare for an Injection

Step 2: Choose an Injection Site

Step 3: Inject the Enbrel Solution

Step 4: Disposal of Materials

Introduction

The following instructions explain how to prepare and inject Enbrel. Read the instructions carefully and follow them step by step. Your doctor or nurse will teach you the techniques of self-injection or administration of an injection to a child. Do not attempt to administer an injection until you are sure you have understood how to prepare the injection and administer the injection.

The Enbrel solution should not be mixed with any other medicine before use.

Step 1: Prepare for an Injection

1. Select a flat, clean, and well-lit work surface.

1. Remove the Enbrel pack, which contains the pre-filled syringes, from the refrigerator and place it on a flat surface. Starting from one of the top corners, remove the paper cover from the top and sides of the tray. Remove a pre-filled syringe and an alcohol swab and place them on the work surface. Do not shake the Enbrel pre-filled syringe. Fold the paper cover back over the tray and return the pack containing the remaining pre-filled syringes to the refrigerator. Please read section 5, which includes instructions for the storage of Enbrel. If you have any doubts about storage, contact your doctor, nurse, or pharmacist for more detailed information.

1. You must wait between 15 and 30 minutes until the Enbrel solution in the syringe reaches room temperature. DO NOTremove the needle cap until the syringe has reached room temperature. Waiting for the solution to reach room temperature may make the injection more comfortable for you. Do not heat Enbrel in any other way (e.g., do not heat it in a microwave or in hot water).

1. Gather the additional components you will need to administer the injection. This includes the alcohol swab from the pack and a cotton ball or gauze.

1. Wash your hands with soap and warm water.

1. Inspect the solution in the syringe. It 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.

Step 2: Choose an Injection Site

1. The three recommended injection sites for Enbrel, using a pre-filled syringe, are: (1) the front of the thighs, (2) the stomach, except for an area of 5 cm around the navel, and (3) the outer upper arm (see Figure 1). If you are self-injecting, you should not inject into the outer upper arm.

Figure 1

1. A different site should be used for each new injection. Each new injection should be given at least 3 cm from the previous injection site. Do notadminister the injection in areas of sensitive, bruised, red, or hardened skin. Avoid areas with scars or stretch marks. (It may be helpful to note the locations of previous injections).

1. If you or the child have psoriasis, you should try not to inject directly into any raised, thick, red, or scaly skin patches (psoriatic skin lesions).

Step 3: Inject the Enbrel Solution

1. Clean the injection site with the alcohol swab using a circular motion. DO NOTtouch this area again until you have administered the injection.
2. Take the pre-filled syringe from the flat work surface. Remove the needle cap by pulling it straight off (see Figure 2). Be careful not to bend or twist the cap while removing it to avoid damaging the needle.

When removing the needle cap, there may be a drop of liquid at the end of the needle; this is normal. Do not touch the needle and avoid touching any surface. Do not touch or shake the plunger. If you do, the liquid may spill.

Figure 2

1. When the previously cleaned skin area has dried, pinch it and hold it firmly with one hand. With the other hand, hold the syringe like a pencil.

1. With a quick, short motion, push the needle all the way in, penetrating the skin at an angle of 45° to 90° (see Figure 3). With practice, you will find the angle that is most comfortable for you or the child. Be careful not to push the needle into the skin too slowly or with too much force.

Figure 3

1. When the needle is fully inserted into the skin, release the skin you are holding. With your free hand, hold the needle near its base to stabilize it. Then, push the plunger to inject the entire solution at a slow and steady speed (see Figure 4).

Figure 4

1. When the syringe is empty, withdraw the needle from the skin; be careful to keep the syringe at the same angle it was at when inserted. There may be a slight 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 necessary, you can cover the injection site with a bandage.

Step 4: Disposal of Materials

• The pre-filled syringe is for single use only. The syringe and needle NEVERshould be reused. NEVERreplace a needle cap. Dispose of the needle and syringe following the instructions of your doctor, nurse, or pharmacist.

If you have any questions, consult a doctor, nurse, or pharmacist who is familiar with the use of Enbrel.