Patient leaflet - Enbrel

B. PACKAGE LEAFLET

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Instructions for preparing and giving an injection of Enbrel (See overleaf).

1. What Enbrel is and what it is used for

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

In adults (aged 18 and over), Enbrel can be used for moderate or severe rheumatoid arthritis , psoriatic arthritis , severe axial spondyloarthritis including ankylosing spondylitis, and moderate or severe psoriasis – in each case usually when other widely used treatments have not worked well enough or are not suitable for you.

For rheumatoid arthritis, Enbrel is usually used in combination with methotrexate, although it may also be used alone if treatment with methotrexate is unsuitable for you. Whether used alone or in combination with methotrexate, Enbrel can slow down the damage to your joints caused by the rheumatoid arthritis and improve your ability to do normal daily activities.

For psoriatic arthritis patients with multiple joint involvement, Enbrel can improve your ability to do normal daily activities. For patients with multiple symmetrical painful or swollen joints (e.g., hands, wrists and feet), Enbrel can slow down the structural damage to those joints caused by the disease.

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If you are not sure, please contact your doctor.
if you or the child, have an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse. Please tell your doctor if you or the child in your care have a history of alcohol abuse.
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, talk to your doctor.
Anti-diabetic medicines: Tell 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 be up to date with all vaccinations before using Enbrel. Some vaccines, such as oral polio vaccine, should not be given while using Enbrel. Please consult your doctor before you or the child receive any vaccines.

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

Other medicines and Enbrel

Tell your doctor or pharmacist if you or the child are taking, have recently taken or might take any other medicines (including anakinra, abatacept or sulfasalazine), even those not prescribed by the doctor. You or the child should not use Enbrel with medicines that contain the active substance anakinra or abatacept.

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

If you received Enbrel during pregnancy, your baby may have a higher risk of getting an infection. In addition, one study found more birth defects when the mother had received Enbrel in pregnancy, compared with mothers who had not received Enbrel or other similar medicines (TNF-antagonists), but there was no particular kind of birth defect reported. Another study found no increased risk of birth defects when the mother had received Enbrel in pregnancy. Your doctor will help you to decide whether the benefits of treatment outweigh the potential risk to your baby. It is important that you tell the baby’s doctors and other healthcare professionals about the use of Enbrel during pregnancy before the baby receives any vaccine (for more information see section 2, “Vaccinations”).

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

3. How to use Enbrel

Always use this medicine exactly as the doctor has told you. Check with the doctor or pharmacist if you are not sure.

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

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given 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 retreatment is needed based on your response. If Enbrel has no effect on your condition after 12 weeks, your doctor may tell you to stop taking this medicine.

Use in children and adolescents

The appropriate dose and frequency of dosing for the child or adolescent will depend on body weight and disease. The doctor will provide you with detailed directions for preparing and measuring the appropriate dose.

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

For psoriasis in patients from the age of 6 years, the usual dose is 0.8 mg of Enbrel per kg bodyweight (up to a maximum of 50 mg), and should be given once weekly. If Enbrel has no effect on the child’s condition after 12 weeks, your doctor may tell you to stop using this medicine.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

The powder must be dissolved before use. Detailed instructions on how to prepare and inject Enbrel are provided in section 7, “Instructions for preparing and giving an injection of Enbrel”. Do not mix the Enbrel solution with any other medicine.

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

If you use more Enbrel than you should

If you have used more Enbrel than you should (either by injecting too much on a single occasion or by using it too frequently), talk to a doctor or pharmacist immediately. Always have the outer carton of the medicine 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 scheduled dose is the next day; in which case you should skip the missed dose. Then continue to inject the medicine on the usual day(s). If you do not remember until the day that the next injection is due, do not take a double dose (two doses on the same day) to make up for a forgotten dose.

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

These are rare or uncommon side effects, but are serious conditions (some of which may rarely be fatal). If these signs occur, tell your doctor immediately, or visit the casualty department at your nearest hospital.

The known side effects of Enbrel include the following in groups of decreasing frequency:

Very common (may affect more than 1 in10 people):

Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling) (these do not occur as often after the first month of treatment; some patients have developed a reaction at an injection site that was recently used); and headache.

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

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

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

Serious infections (including pneumonia, deep skin infections, joint infections, blood infection, and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil (a type of white blood cell) count; low blood platelet count; skin cancer (excluding melanoma); localised swelling of the skin (angioedema); hives (elevated patches of red or pale skin that often itch); eye inflammation; psoriasis (new or worsening); inflammation of the blood vessels affecting multiple organs; elevated liver blood tests (in patients also receiving methotrexate treatment, the frequency of elevated liver blood tests is common); abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (signs of bowel problems).

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

Serious allergic reactions (including severe localised swelling of the skin and wheezing); lymphoma (a type of blood cancer); leukaemia (cancer affecting the blood and bone marrow); melanoma (a type of skin cancer); combined low platelet, red, and white blood cell count; nervous system disorders (with severe muscle weakness and signs and symptoms similar to those of multiple sclerosis or inflammation of the nerves of the eyes or spinal cord); tuberculosis; new onset congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain, and tiredness); skin rash, which may lead to severe blistering and peeling of the skin; lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-grey lines on mucous membranes); inflammation of the liver caused by the body's own immune system (autoimmune hepatitis; in patients also receiving methotrexate treatment, the frequency is uncommon); immune disorder that can affect the lungs, skin and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also receiving methotrexate treatment, the frequency of inflammation or scarring of the lungs is uncommon).

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and the label after “EXP”. The expiry date refers to the last day of that month.

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

Before preparing the Enbrel solution, Enbrel may be stored outside of the refrigerator at temperatures up to a maximum of 25°C for a single period of up to four weeks; after which, it should not be refrigerated again. Enbrel should be discarded if not used within four weeks after removal from the refrigerator. It is recommended that you record the date that Enbrel is removed from the refrigerator and the date after which Enbrel should be discarded (no more than 4 weeks following the removal from the refrigerator).

After preparing the Enbrel solution, immediate use is recommended. However, the solution may be used for up to 6 hours when stored at temperatures of up to 25°C.

Do not use this medicine if you notice the solution is not clear or contains particles. The solution should be clear, colourless to pale yellow or pale brown, with no lumps or flakes or particles.

Carefully dispose of any Enbrel solution that has not been injected within 6 hours.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

The active substance in Enbrel is etanercept. Each vial of Enbrel 25 mg contains 25 mg of etanercept.

The other ingredients are:

Powder: Mannitol (E421), sucrose and trometamol

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Instructions for preparing and giving an injection of Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If you are not sure, please contact your doctor.
if you or the child have an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse. Please tell your doctor if you or the child in your care have a history of alcohol abuse.
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, talk to your doctor.
Anti-diabetic medicines: Tell 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

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

3. How to use Enbrel

Always use this medicine exactly as the doctor has told you. Check with the doctor or pharmacist if you are not sure.

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

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Use in children and adolescents

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and the label after “EXP”. The expiry date refers to the last day of that month.

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

After preparing the Enbrel solution, immediate use is recommended. However, the solution may be used for up to 6 hours when stored at temperatures of up to 25°C.

Do not use this medicine if you notice the solution is not clear or contains particles. The solution should be clear, colourless to pale yellow or pale brown, with no lumps or flakes or particles.

Carefully dispose of any Enbrel solution that has not been injected within 6 hours.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

The active substance in Enbrel is etanercept. Each vial of Enbrel 25 mg contains 25 mg of etanercept.

The other ingredients are:

Powder: Mannitol (E421), sucrose and trometamol

Solvent: Water for injections

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Instructions for preparing and giving an injection of Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If

you are not sure, please contact your doctor.

if you or the child have an infection of any kind. If you are not sure, please talk to your doctor.

Warning and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Latex: The needle cover is made from latex (dry natural rubber). Contact your doctor before using Enbrel if the needle cover will be handled by, or Enbrel will be given to, someone with a known or possible hypersensitivity (allergy) to latex.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse. Please tell your doctor if you or the child in your care have a history of alcohol abuse.
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, talk to your doctor.
Anti-diabetic medicines: Tell 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

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

Enbrel contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

3. How to use Enbrel

Always use this medicine exactly as the doctor has told you. Check with the doctor or pharmacist if you are not sure.

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

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

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Use in children and adolescents

The appropriate dose and frequency of dosing for the child or adolescent will depend on body weight and disease. Your doctor will determine the correct dose for the child and will prescribe an appropriate strength of Enbrel (10 mg, 25 mg or 50 mg).

The doctor will provide you with detailed directions for preparing and measuring the appropriate dose.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

Detailed instructions on how to inject Enbrel are provided in section 7, “Instructions for preparing and giving an injection of Enbrel”. Do not mix the Enbrel solution with any other medicine.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and pre-filled syringe after EXP. The expiry date refers to the last day of that month.

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

Keep the pre-filled syringes in the outer carton in order to protect from light.

After taking a syringe from the refrigerator, wait approximately 15–30 minutes to allow the Enbrel solution in the syringe to reach room temperature. Do not warm in any other way. Immediate use is then recommended.

Enbrel may be stored outside of the refrigerator at temperatures up to a maximum of 25°C for a single period of up to four weeks; after which, it should not be refrigerated again. Enbrel should be discarded if not used within four weeks after removal from the refrigerator. It is recommended that you record the date that Enbrel is removed from the refrigerator and the date after which Enbrel should be discarded (no more than 4 weeks following the removal from the refrigerator).

Inspect the solution in the syringe. It should be clear or slightly opalescent, colourless to pale yellow or pale brown, and may contain small white or almost transparent particles of protein. This appearance is normal for Enbrel. Do not use the solution if it is discoloured, cloudy, or if particles other than those described above are present. If you are concerned with the appearance of the solution, then contact your pharmacist for assistance.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

Enbrel 25 mg solution for injection in pre-filled syringe

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

Enbrel 50 mg solution for injection in pre-filled syringe

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

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

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Using the MYCLIC pre-filled pen to inject Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If

you are not sure, please contact your doctor.

if you or the child have an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Latex: The needle cap of the MYCLIC pen is made from latex (dry natural rubber). Contact your doctor before using Enbrel if the needle cap will be handled by, or Enbrel will be given to, someone with a known or possible hypersensitivity (allergy) to latex.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse. Please tell your doctor if you or the child in your care have a history of alcohol abuse.
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, talk to your doctor.

Anti-diabetic medicines: Tell 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

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

Enbrel contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

3. How to use Enbrel

Always use this medicine exactly as your doctor has told you. Check with your doctor if or pharmacist you are not sure.

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

You have been prescribed a 25 mg strength of Enbrel. A 50 mg strength of Enbrel is available for doses of 50 mg.

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Use in children and adolescents

The doctor will provide you with detailed directions for preparing and measuring the appropriate dose.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

Detailed instructions on how to inject Enbrel are provided in section 7, “Using the MYCLIC pre-filled pen to inject Enbrel”. Do not mix the Enbrel solution with any other medicine.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and on the MYCLIC prefilled pen after EXP. The expiry date refers to the last day of that month.

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

Keep the pre-filled pens in the outer carton in order to protect from light.

After taking a pre-filled pen from the refrigerator, wait approximately 15–30 minutes to allow the Enbrel solution in the pen to reach room temperature. Do not warm in any other way. Immediate use is then recommended.

Inspect the solution in the pen by looking through the clear inspection window. The solution should be clear or slightly opalescent, colourless to pale yellow or pale brown, and may contain small white or almost transparent particles of protein. This appearance is normal for Enbrel. Do not use the solution if it is discoloured, cloudy, or if particles other than those described above are present. If you are concerned with the appearance of the solution, then contact your pharmacist for assistance.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

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

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

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Using the MYCLIC pre-filled pen to inject Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If

you are not sure, please contact your doctor.

if you or the child have an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Latex: The needle cap of the MYCLIC pen is made from latex (dry natural rubber). Contact your doctor before using Enbrel if the needle cap will be handled by, or Enbrel will be given to, someone with a known or possible hypersensitivity (allergy) to latex.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse.

Please tell your doctor if you or the child in your care have a history of alcohol abuse.

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, talk to your doctor.
Anti-diabetic medicines: Tell 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

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

Enbrel contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

3. How to use Enbrel

Always use this medicine exactly as your doctor has told you. Check with your doctor if or pharmacist you are not sure.

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

You have been prescribed a 50 mg strength of Enbrel. A 25 mg strength of Enbrel is available for doses of 25 mg.

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Use in children and adolescents

The doctor will provide you with detailed directions for preparing and measuring the appropriate dose.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

Detailed instructions on how to inject Enbrel are provided in section 7, “Using the MYCLIC pre-filled pen to inject Enbrel”. Do not mix the Enbrel solution with any other medicine.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and on the MYCLIC prefilled pen after EXP. The expiry date refers to the last day of that month.

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

Keep the pre-filled pens in the outer carton in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

The active substance in Enbrel is etanercept. Each MYCLIC pre-filled pen contains 50 mg of etanercept.

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

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Instructions for preparing and giving an injection of Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 the child you are caring for is allergic to etanercept or any of the other ingredients of Enbrel (listed in section 6). If the child experiences allergic reactions such as chest tightness, wheezing, dizziness or rash, do not inject more Enbrel, and contact your doctor immediately.
if the child has, or is at risk of developing a serious blood infection called sepsis. If you are not sure, please contact your doctor.
if the child has an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking Enbrel.

Allergic reactions: If the child experiences allergic reactions such as chest tightness, wheezing, dizziness or rash, do not inject more Enbrel, and contact your doctor immediately.
Infections/surgery: If the child develops a new infection, or is about to have any major surgery, the doctor may wish to monitor the child's treatment with Enbrel.
Infections/diabetes: Tell your doctor if the child has a history of recurrent infections, or suffers from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell your doctor of any recent travel outside the European region. If the child develops symptoms of an infection such as fever, chills or cough, notify your doctor immediately. Your doctor may decide to continue to monitor the child for the presence of infections after the child stops using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if the child has ever had tuberculosis, or has been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if the child has or has ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before the child begins treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if the child has hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if the child has any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if the child has multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if the child has a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if the child has or has ever had lymphoma (a type of blood cancer) or any other cancer before the child is given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if the child develops any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if the child is exposed to chickenpox when using Enbrel. Your doctor will determine if preventative treatment for chickenpox is appropriate.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse.

Please tell your doctor if the child in your care has a history of alcohol abuse.

Wegener’s granulomatosis: Enbrel is not recommended for the treatment of Wegener’s granulomatosis, a rare inflammatory disease. If the child in your care has Wegener’s granulomatosis, talk to your doctor.
Anti-diabetic medicines: Tell your doctor if the child has diabetes or is taking medicines to treat diabetes. Your doctor may decide if the child needs less anti-diabetic medicine while taking Enbrel.

Children and adolescents

Vaccinations: If possible, children should be up to date with all vaccinations before using Enbrel. Some vaccines, such as oral polio vaccine, should not be given while using Enbrel. Please consult the child’s doctor before the child receives any vaccines.

Other medicines and Enbrel

Tell your doctor or pharmacist if the child is taking, has recently taken or might take any other medicines (including anakinra, abatacept or sulfasalazine), even those not prescribed by the child's doctor. The child should not use Enbrel with medicines that contain the active substance anakinra or abatacept.

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

3. How to use Enbrel

Use in children and adolescents

Always use this medicine exactly as the doctor has told you. Check with the doctor or pharmacist if you are not sure.

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

The 10 mg vial is for children prescribed a dose of 10 mg or less. Each vial should be used for just one dose in one patient, and any remaining solution should be discarded.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen to the child, do not give the child more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. If the child has any of the above symptoms he/she may be having an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

These are rare or uncommon side effects, but are serious conditions (some of which may rarely be fatal). If these signs occur, tell your doctor immediately, or take the child to the casualty department at your nearest hospital.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

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

After preparing the Enbrel solution, immediate use is recommended. However, the solution may be used for up to 6 hours when stored at a temperature up to 25°C.

Do not use this medicine if you notice the solution is not clear or contains particles. The solution should be clear, colourless to pale yellow or pale brown, with no lumps or flakes or particles.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

The active ingredient in Enbrel is etanercept. Each vial of Enbrel 10 mg powder and solvent for solution for injection for paediatric use contains 10 mg of etanercept. When reconstituted, the solution contains 10 mg/ml of etanercept.

The other ingredients are:

Powder: Mannitol (E421), sucrose, and trometamol.

Solvent: Water for injections.

What Enbrel looks like and contents of the pack

Enbrel 25 mg is supplied as a white powder for solution for injection (powder for injection). Each pack contains 4 single-dose vials and 8 alcohol swabs.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer:

Pfizer Manufacturing Belgium NV

Rijksweg 12,

2870 Puurs

Belgium

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Luxembourg/Luxemburg

Pfizer S.A. / N.V.

Tél/Tel: +32 (0)2 554 62 11

Česká Republika

Pfizer, spol. s r.o.

Tel: +420–283–004–111

Danmark

Pfizer ApS

Tlf: +45 44 201 100

Deutschland

Pfizer Pharma GmbH

Tel: +49 (0)30 550055–51000

Btnrapua

n<|)aÜ3ep ^æKceMÔypr C’AP^.

K.toh Eijrapna

Ten: +359 2 970 4333

Kùnpoç

PFIZER EAAAE A.E. (CYPRUS BRANCH)

TqX: +357 22 817690

Magyarország

Pfizer Kft.

Tel: +36 1 488 3700

Malta

Vivian Corporation Ltd.

Tel: +35621 344610

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Österreich

Pfizer Corporation Austria Ges.m.b.H.

Tel: +43 (0)1 521 15–0

EXXáóa

PFIZER EAAAE A.E.

T^.: +30 210 67 85 800

Polska

Pfizer Polska Sp. z o.o.

Tel.: +48 22 335 61 00

España

Pfizer, S.L.

Télf: +34 91 490 99 00

Portugal

Laboratórios Pfizer, Lda.

Tel: (+351) 21 423 55 00

France

Pfizer

Tél +33 (0)1 58 07 34 40

România

Pfizer Romania S.R.L

Tel: +40 (0) 21 207 28 00

Hrvatska

Pfizer Croatia d.o.o.

Tel: +385 1 3908 777

Slovenija

Pfizer Luxembourg SARL, Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana

Tel: +386 (0)1 52 11 400

Ireland

Pfizer Healthcare Ireland

Tel: +1800 633 363 (toll free)

Tel: +44 (0)1304 616161

Slovenská Republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421 2 3355 5500

Ísland

Icepharma hf.

Tel: +354 540 8000

Suomi/Finland

Pfizer Oy

Puh/Tel: +358 (0)9 430 040

Italia

Pfizer S.r.l.

Tel: +39 06 33 18 21

Sverige

Pfizer AB

Tel: +46 (0)8 550 520 00

Latvija

Pfizer Luxembourg SARL filiale Latvijä

Tel. +371 67035775

United Kingdom (Northern Ireland)

Pfizer Limited

Tel: +44 (0)1304 616161

Lietuva

Pfizer Luxembourg SARL filialas Lietuvoje

Tel. +3705 2514000

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

7. Instructions for preparing and giving an injection of Enbrel

This section is divided into the following sub-sections:

a. Introduction
b. Setting up for an injection
c. Preparing the Enbrel dose for injection
d. Adding water for injections
e. Withdrawing the Enbrel solution from the vial
f. Choosing an injection site
g. Preparing the injection site and injecting the Enbrel solution
h. Disposing of supplies

a. Introduction

The following instructions explain how to prepare and inject Enbrel. Please read the instructions carefully and follow them step by step. You will be instructed by your doctor or his/her assistant on the techniques of self-injection or on giving an injection to a child. Do not attempt to administer an injection until you are sure that you understand how to prepare and give the injection.

This injection should not be mixed with any other medicine.

b. Setting up for an injection

Wash your hands thoroughly.
Select a clean, well-lit, flat working surface.
Take the ENBREL vial out of the refrigerator and place it on a flat surface.
You will also need the following items:

A sterile syringe and needle(s) of 25 gauge x 16 mm or similar

A vial or ampoule of water for injections

2 alcohol swabs

Inspect the expiry dates on both the Enbrel vial label and the water for injections. They should not be used after the month and year shown.
c. Preparing the Enbrel dose for injection

Remove the plastic cap from the Enbrel vial. Do NOT remove the grey stopper or aluminium ring around the top of the vial.
Use a new alcohol swab to clean the grey stopper on the Enbrel vial. After cleaning, do not touch the stopper with your hands.
Check that a needle is on your syringe; if you are not sure how to attach a needle ask your doctor or nurse.
Remove the needle cover by firmly pulling it straight off the syringe taking care not to touch the needle or allow the needle to touch any surfaces (see Diagram 1). Be careful not to bend or twist the cover during removal to avoid damage to the needle.
Check your syringe contains 1 ml of water for injections.
If you are not sure how to fill your syringe ask your doctor or nurse.
Make sure your syringe does not contain any air bubbles.
With the Enbrel vial upright on a flat surface, such as a table, insert the syringe needle straight

down through the centre ring of the grey stopper of the vial (see Diagram 2). If the needle is correctly lined up, you should feel a slight resistance and then a “pop” as the needle goes through the centre of the stopper. Look for the needle tip inside the stopper window (see Diagram 3). If the needle is not correctly lined up, you will feel constant resistance as it goes through the stopper and no “pop”. Do not insert the needle at an angle, this may cause the needle to bend and/or prevent proper addition of the solvent into the vial (see Diagram 4).

Diagram 2

d. Adding water for injections

Diagram 3

CORRECT

Push the plunger in VERY SLOWLY until all the water for injections is in the vial. This will help reduce foaming (lots of bubbles) (see Diagram 5).
Leave the syringe in place. Gently move the vial in circles a few times, to dissolve the powder (see Diagram 6). Do NOT shake the vial. Wait until all the powder dissolves (usually less than 10 minutes). The solution should be clear and colourless to pale yellow or pale brown, with no lumps, flakes, or particles. Some white foam may remain in the vial this is normal. Do NOT use Enbrel if all the powder in the vial is not dissolved within 10 minutes. Start again with a new Enbrel vial, water for injections, syringe, needle and swabs.

Diagram 6

e. Withdrawing the Enbrel solution from the vial

With the needle still in the vial, hold the vial upside down at eye level. Slowly pull the plunger back to draw the liquid into the syringe (see Diagram 7). As the liquid level drops in the vial, you may need to withdraw the needle partially to keep the tip of the needle in the liquid. For adult patients, withdraw the entire volume. For children, remove only the portion of liquid as directed by your child’s doctor.

Diagram 7

With the needle still inserted in the vial, check the syringe for air bubbles. Gently tap the syringe to make any bubbles rise to the top of the syringe, near the needle (see Diagram 8). Slowly press the plunger to push bubbles out of the syringe and into the vial. When you do this, if you accidentally push liquid back into the vial, slowly pull the plunger to draw the liquid back into the syringe.

Diagram 8

Pull the needle completely out of the vial. Again, do not touch the needle or allow it to touch any surface.

(Note: After you have completed these steps, a small amount of liquid may remain in the vial. This is normal.)

f. Choosing an injection site

The three recommended injection sites for Enbrel include: (1) the front of the middle thighs; (2) the abdomen, except for the 5 cm area right around the navel; and (3) the outer area of the upper arms (see Diagram 9). If you are self injecting, you should not use the outer area of the upper arms.

Diagram 9

A different site should be used for each new injection. Each new injection should be given at least 3 cm from an old site. Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks. (It may be helpful to keep notes on the location of the previous injections.)
If you or the child have psoriasis, you should try not to inject directly into any raised, thick, red, or scaly skin patches (“psoriasis skin lesions”).
g. Preparing the injection site and injecting the Enbrel solution

Wipe the site where Enbrel is to be injected with an alcohol swab, using a circular motion. Do NOT touch this area again before giving the injection.
When the cleaned area of skin has dried, pinch and hold it firmly with one hand. With the other hand, hold the syringe like a pencil.
With a quick, short motion, push the needle all the way into the skin at an angle between 45° and 90° (see Diagram 10). With experience, 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 great force.

Diagram 10

When the needle is completely inserted into the skin, release the skin that you are holding. With your free hand, hold the syringe near its base to stabilise it. Then push the plunger to inject all of the solution at a slow, steady rate (see Diagram 11).

Diagram 11

When the syringe is empty, remove the needle from the skin, being careful to keep it at the same angle it was when it was inserted.
Press a cotton ball over the injection site for 10 seconds. Slight bleeding may occur. Do NOT rub the injection site. A bandage is optional.
h. Disposing of supplies

The syringe and needle should NEVER be re-used. Never recap a needle. Dispose of the needle and syringe as instructed by your doctor, nurse or pharmacist.

If you have any questions, please talk to a doctor, nurse or pharmacist who is familiar with Enbrel.

Package Leaflet: Information for the User

Enbrel 25 mg powder and solvent for solution for injection etanercept

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
Your doctor will also give you a Patient Card, which contains important safety information that

you need to be aware of before and during treatment with Enbrel.

If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you or a child in your care. Do not pass it on to others. It

may harm them, even if their signs of illness are the same as yours or those of the child you are caring for.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Instructions for preparing and giving an injection of Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If you are not sure, please contact your doctor.
if you or the child have an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse. Please tell your doctor if you or the child in your care have a history of alcohol abuse.
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, talk to your doctor.
Anti-diabetic medicines: Tell 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

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

3. How to use Enbrel

Always use this medicine exactly as the doctor has told you. Check with the doctor or pharmacist if you are not sure.

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

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Use in children and adolescents

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and the label after “EXP”. The expiry date refers to the last day of that month.

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

After preparing the Enbrel solution, immediate use is recommended. However, the solution may be used for up to 6 hours when stored at temperatures of up to 25°C.

Do not use this medicine if you notice the solution is not clear or contains particles. The solution should be clear, colourless to pale yellow or pale brown, with no lumps or flakes or particles.

Carefully dispose of any Enbrel solution that has not been injected within 6 hours.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

The active substance in Enbrel is etanercept. Each vial of Enbrel 25 mg contains 25 mg of etanercept.

The other ingredients are:

Powder: Mannitol (E421), sucrose and trometamol

Solvent: Water for injections

What Enbrel looks like and contents of the pack

Enbrel 25 mg is supplied as a white powder and solvent for solution for injection (powder for injection). Each pack contains 4, 8 or 24 single dose vials, 4, 8 or 24 pre-filled syringes of water for injections, 4, 8 or 24 needles, 4, 8 or 24 vial adaptors and 8, 16 or 48 alcohol swabs. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer:

Pfizer Manufacturing Belgium NV

Rijksweg 12, 2870 Puurs

Belgium

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Luxembourg/Luxemburg

Pfizer S.A. / N.V.

Tél/Tel: +32 (0)2 554 62 11

Česká Republika

Pfizer, spol. s r.o.

Tel: +420–283–004–111

Danmark

Pfizer ApS

Tlf: +45 44 201 100

Deutschland

Pfizer Pharma GmbH

Tel: +49 (0)30 550055–51000

Btnrapua

n<|)aÜ3ep ^æKceMÔypr C’AP^.

K.toh Eijrapna

Ten: +359 2 970 4333

Kùnpoç

PFIZER EAAAE A.E. (CYPRUS BRANCH)

TqX: +357 22 817690

Magyarország

Pfizer Kft.

Tel: +36 1 488 3700

Malta

Vivian Corporation Ltd.

Tel: +35621 344610

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Österreich

Pfizer Corporation Austria Ges.m.b.H.

Tel: +43 (0)1 521 15–0

EXXáóa

PFIZER EAAAE A.E.

T^.: +30 210 67 85 800

Polska

Pfizer Polska Sp. z o.o.

Tel.: +48 22 335 61 00

España

Pfizer, S.L.

Télf: +34 91 490 99 00

Portugal

Laboratórios Pfizer, Lda.

Tel: (+351) 21 423 55 00

France

Pfizer

Tél +33 (0)1 58 07 34 40

România

Pfizer Romania S.R.L

Tel: +40 (0) 21 207 28 00

Hrvatska

Pfizer Croatia d.o.o.

Tel: +385 1 3908 777

Slovenija

Pfizer Luxembourg SARL, Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana

Tel: +386 (0)1 52 11 400

Ireland

Pfizer Healthcare Ireland

Tel: +1800 633 363 (toll free)

Tel: +44 (0)1304 616161

Slovenská Republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421 2 3355 5500

Ísland

Icepharma hf.

Tel: +354 540 8000

Suomi/Finland

Pfizer Oy

Puh/Tel: +358 (0)9 430 040

Italia

Pfizer S.r.l.

Tel: +39 06 33 18 21

Sverige

Pfizer AB

Tel: +46 (0)8 550 520 00

Latvija

Pfizer Luxembourg SARL filiale Latvijä

Tel. +371 67035775

United Kingdom (Northern Ireland)

Pfizer Limited

Tel: +44 (0)1304 616161

Lietuva

Pfizer Luxembourg SARL filialas Lietuvoje

Tel. +3705 2514000

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

7. Instructions for preparing and giving an injection of Enbrel

This section is divided into the following sub-sections:

a. Introduction
b. Setting up for an injection
c. Preparing the Enbrel dose for injection
d. Adding solvent
e. Withdrawing the Enbrel solution from the vial
f. Placing the needle on the syringe
g. Choosing an injection site
h. Preparing the injection site and injecting the Enbrel solution
i. Disposing of supplies

a. Introduction

This injection should not be mixed with any other medicine.

b. Setting up for an injection

Wash your hands thoroughly.
Select a clean well-lit, flat working surface.
The dose tray should contain the items listed below. (If not, don’t use the dose tray and consult your pharmacist). Use only the items listed. Do NOT use any other syringe.
1 Enbrel vial
1 Pre-filled syringe containing clear, colourless solvent (water for injections)
1 Needle
1 Vial adaptor
2 Alcohol swabs

Inspect the expiry dates on both the vial label and the syringe label. They should not be used after the month and year shown.
c. Preparing the Enbrel dose for injection

Remove the contents of the tray
Remove the plastic cap from the Enbrel vial (see Diagram 1). Do NOT remove the grey stopper or aluminium ring around the top of the vial.

Diagram 1

Use a new alcohol swab to clean the grey stopper on the Enbrel vial. After cleaning, do not touch the stopper with your hands or allow it to touch any surface.
Place the vial upright on a clean, flat surface.
Remove the paper backing from the vial adaptor package.
While still in the plastic package, place the vial adaptor on top of the Enbrel vial so that the vial adaptor spike is centered within the raised circle on top of the vial stopper (see Diagram 2).
Hold the vial firmly on the flat surface with one hand. With the other hand, push STRAIGHT DOWN FIRMLY on the adaptor package until you feel the adaptor spike penetrate the vial stopper and FEEL AND HEAR THE ADAPTOR RIM LOCK INTO PLACE (see Diagram 3). Do NOT push down the adaptor at an angle (see Diagram 4). It is important that the vial adaptor spike completely penetrates the vial stopper.

While holding the vial in one hand, remove the plastic packaging from the vial adaptor (see Diagram 5).

Diagram 5.

Remove the protective cover from the syringe tip by breaking the white cap along the perforation. This is done by holding the collar of the white cap while grasping the end of the white cap with the other hand and bending it down and then up until it is broken (see Diagram 6). Do NOT remove the white collar that remains on the syringe.
Do not use the syringe if this perforation is already broken. Start again with another dose tray.
Holding the glass barrel of the syringe (not the white collar) in one hand, and the vial adaptor (not the vial) in the other, connect the syringe to the vial adaptor by inserting the tip into the opening and turn clockwise until completely secured (see Diagram 7).

Diagram 7

d. Adding solvent

While holding the vial upright on the flat surface, push the plunger VERY SLOWLY until all the solvent is in the vial. This will help to reduce foaming (lots of bubbles) (see Diagram 8).
Once the solvent is added to the Enbrel, the plunger may move up by itself. This is due to air pressure and should not be of concern.

Diagram 8

With the syringe still attached, gently move the vial in circles a few times, to dissolve the powder (see Diagram 9). Do NOT shake the vial. Wait until all the powder dissolves (usually less than 10 minutes). The solution should be clear and colourless to pale yellow or pale brown, with no lumps, flakes, or particles. Some white foam may remain in the vial this is normal. Do NOT use Enbrel if all the powder in the vial is not dissolved within 10 minutes. Start again with another dose tray.

Diagram 9

e. Withdrawing the Enbrel solution from the vial

With the syringe still attached to the vial and vial adaptor, hold the vial upside down at eye level. Push the plunger all the way into the syringe (see Diagram 10).

Diagram 10

Then, slowly pull the plunger back to draw the liquid into the syringe (see Diagram 11). For adult patients, withdraw the entire volume. For children, remove only the portion of liquid as directed by your child’s doctor. After you have withdrawn the Enbrel from the vial, you may have some air in the syringe. Do not be concerned, as you will remove the air in a later step.
With the vial held upside down, unscrew the syringe from the vial adaptor by turning it anti-clockwise (see Diagram 12).

Diagram 12

Place the filled syringe on the clean, flat surface. Make sure that the tip does not touch anything. Be careful not to push down on the plunger.

(Note: After you have completed these steps, a small amount of liquid may remain in the vial. This is normal.)

f. Placing the needle on the syringe

The needle has been placed in a plastic container to keep it sterile.
To open the plastic container, hold the short, wide end in one hand. Place your other hand on the

longer portion of the container.

To break the seal, bend the larger end down and then up until broken (see Diagram 13).

Diagram 13

Once the seal has been broken, remove the short, wide end of the plastic container.
The needle will remain in the long part of the package.
While holding the needle and container in one hand, pick up the syringe and insert the syringe tip into the needle opening.
Attach the syringe to the needle by turning it clockwise until completely secured (see Diagram

14).

Diagram 14

Remove the needle cover by firmly pulling it straight off the syringe taking care not to touch the needle or allow the needle to touch any surfaces (see Diagram 15). Be careful not to bend or twist the cover during removal to avoid damage to the needle.

Diagram 15

While holding the syringe upright, remove any air bubbles by slowly pushing on the plunger until the air is removed (see Diagram 16).

Diagram 16

g. Choosing an injection site

The three recommended injection sites for Enbrel include: (1) the front of the middle thighs; (2) the abdomen, except for the 5 cm area right around the navel; and (3) the outer area of the upper arms (see Diagram 17). If you are self injecting, you should not use the outer area of the upper arms.

Diagram 17

A different site should be used for each new injection. Each new injection should be given at least 3 cm from an old site. Do NOT inject into areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks. (It may be helpful to keep notes on the location of the previous injections.)
If you or the child have psoriasis, you should try not to inject directly into any raised, thick, red,

or scaly skin patches (“psoriasis skin lesions”).

h. Preparing the injection site and injecting the Enbrel solution

Wipe the site where Enbrel is to be injected with an alcohol swab, using a circular motion. Do NOT touch this area again before giving the injection.
When the cleaned area of skin has dried, pinch and hold it firmly with one hand. With the other hand, hold the syringe like a pencil.
With a quick, short motion, push the needle all the way into the skin at an angle between 45° and 90° (see Diagram 18). With experience, 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 great force.

Diagram 18

When the needle is completely inserted into the skin, release the skin that you are holding. With your free hand, hold the syringe near its base to stabilise it. Then push the plunger to inject all of the solution at a slow, steady rate (see Diagram 19).

Diagram 19

When the syringe is empty, remove the needle from the skin; being careful to keep it at the same angle it was when it was inserted.
Press a cotton ball over the injection site for 10 seconds. Slight bleeding may occur. Do NOT rub the injection site. A bandage is optional.
i. Disposing of supplies

The syringe and needles should NEVER be re-used. Dispose of the needles and syringe as instructed by your doctor, nurse or pharmacist.

If you have any questions, please talk to a doctor, nurse or pharmacist who is familiar with Enbrel.

Package Leaflet: Information for the User

Enbrel 25 mg solution for injection in pre-filled syringe

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

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
Your doctor will also give you a Patient Card, which contains important safety information that

you need to be aware of before and during treatment with Enbrel.

If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you or a child in your care. Do not pass it on to others. It

may harm them, even if their signs of illness are the same as yours or those of the child you are caring for.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Instructions for preparing and giving an injection of Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If

you are not sure, please contact your doctor.

if you or the child have an infection of any kind. If you are not sure, please talk to your doctor.

Warning and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Latex: The needle cover is made from latex (dry natural rubber). Contact your doctor before using Enbrel if the needle cover will be handled by, or Enbrel will be given to, someone with a known or possible hypersensitivity (allergy) to latex.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse. Please tell your doctor if you or the child in your care have a history of alcohol abuse.
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, talk to your doctor.
Anti-diabetic medicines: Tell 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

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

Enbrel contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

3. How to use Enbrel

Always use this medicine exactly as the doctor has told you. Check with the doctor or pharmacist if you are not sure.

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

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

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Use in children and adolescents

The doctor will provide you with detailed directions for preparing and measuring the appropriate dose.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and pre-filled syringe after EXP. The expiry date refers to the last day of that month.

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

Keep the pre-filled syringes in the outer carton in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

Enbrel 25 mg solution for injection in pre-filled syringe

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

Enbrel 50 mg solution for injection in pre-filled syringe

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

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

What Enbrel looks like and contents of the pack

Enbrel 25 mg solution for injection in pre-filled syringe

Enbrel is supplied as a pre-filled syringe containing a clear, colourless to pale yellow or pale brown solution for injection (solution for injection). Each pack contains 4, 8, 12 or 24 pre-filled syringes and 4, 8, 12 or 24 alcohol swabs. Not all pack sizes may be marketed.

Enbrel 50 mg solution for injection in pre-filled syringe

Enbrel is supplied as a pre-filled syringe containing a clear, colourless to pale yellow or pale brown solution for injection (solution for injection). Each pack contains 2, 4 or 12 pre-filled syringes and 2, 4 or 12 alcohol swabs. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer:

Pfizer Manufacturing Belgium NV

Rijksweg 12,

2870 Puurs

Belgium

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien

Luxembourg/Luxemburg

Pfizer S.A. / N.V.

Kùnpoç

PFIZER EAAAE A.E. (CYPRUS BRANCH)

TqX: +357 22 817690

Tél/Tel: +32 (0)2 554 62 11

Česká Republika Pfizer, spol. s r.o.

Tel: +420–283–004–111

Magyarország

Pfizer Kft.

Tel: +36 1 488 3700

Danmark

Pfizer ApS

Tlf: +45 44 201 100

Malta

Vivian Corporation Ltd.

Tel: +35621 344610

Deutschland

Pfizer Pharma GmbH

Tel: +49 (0)30 550055–51000

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Bt^rapuH

n<|)aÜ3ep ^æKceMÔypr C’AP^.

K.toh Btnrapua

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Ten: +359 2 970 4333

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Österreich

Pfizer Corporation Austria Ges.m.b.H.

Tel: +43 (0)1 521 15–0

EZZáóa

PFIZER EAAAS A.E.

T^.: +30 210 67 85 800

Polska

Pfizer Polska Sp. z o.o.

Tel.: +48 22 335 61 00

España

Pfizer, S.L.

Télf: +34 91 490 99 00

Portugal

Laboratórios Pfizer, Lda.

Tel: (+351) 21 423 55 00

France

Pfizer

Tél +33 (0)1 58 07 34 40

România

Pfizer Romania S.R.L

Tel: +40 (0) 21 207 28 00

Hrvatska

Pfizer Croatia d.o.o.

Tel: +385 1 3908 777

Slovenija

Pfizer Luxembourg SARL, Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana

Tel: +386 (0)1 52 11 400

Ireland

Pfizer Healthcare Ireland

Tel: +1800 633 363 (toll free)

Tel: +44 (0)1304 616161

Slovenská Republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421 2 3355 5500

Ísland

Icepharma hf.

Tel: +354 540 8000

Suomi/Finland

Pfizer Oy

Puh/Tel: +358 (0)9 430 040

Italia

Pfizer S.r.l.

Tel: +39 06 33 18 21

Sverige

Pfizer AB

Tel: +46 (0)8 550 520 00

Latvija

Pfizer Luxembourg SARL filiäle Latvijä

Tel. +371 67035775

United Kingdom (Northern Ireland)

Pfizer Limited

Tel: +44 (0)1304 616161

Lietuva

Pfizer Luxembourg SARL filialas Lietuvoje

Tel. +3705 2514000

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

7. Instructions for preparing and giving an injection of Enbrel

This section is divided into the following subsections:

Introduction

Step 1: Setting up for an injection

Step 2: Choosing an injection site

Step 3: Injecting the Enbrel solution

Step 4: Disposing of supplies

Introduction

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

Step 1: Setting up for an injection

1. Select a clean, well-lit, flat working surface.
2. Take the Enbrel carton containing the pre-filled syringes out of the refrigerator and place it on the flat work surface. Starting from one of the top corners, pull back the paper cover from the top and sides of the tray. Remove one pre-filled syringe and one alcohol swab and place them on the work surface. Do not shake the pre-filled syringe of Enbrel. Fold the paper cover back over the tray and place the carton containing any remaining pre-filled syringes back into the refrigerator. Please see section 5 for instructions on how to store Enbrel. If you have any questions about storage, contact your doctor, nurse, or pharmacist for further instructions.
3. You should allow 15 to 30 minutes for the Enbrel solution in the syringe to reach room temperature. Do NOT remove the needle cover while allowing it to reach room temperature. Waiting until the solution reaches room temperature may make the injection more comfortable for you. Do not warm Enbrel in any other way (for example, do not warm it in a microwave or in hot water).
4. Assemble the additional supplies you will need for your injection. These include the alcohol swab from the Enbrel carton and a cotton ball or gauze.
5. Wash your hands with soap and warm water.
6. Inspect the solution in the syringe. It should be clear or slightly opalescent, colourless to pale yellow or pale brown, and may contain small white or almost transparent particles of protein. This appearance is normal for Enbrel. Do not use the solution if it is discoloured, cloudy, or if particles other than those described above are present. If you are concerned with the appearance of the solution, then contact your pharmacist for assistance.

Step 2: Choosing an injection site

1. The three recommended injection sites for Enbrel using a pre-filled syringe include: (1) the front of the middle thighs; (2) the abdomen, except for the 5 cm area right around the navel; and (3) the outer area of the upper arms (see Diagram 1). If you are self injecting, you should not use the outer area of the upper arms.

Diagram 1

2. A different site should be used for each new injection. Each new injection should be given at least 3 cm from an old site. Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks. (It may be helpful to keep notes on the location of the previous injections.)
3. If you or the child have psoriasis, you should try not to inject directly into any raised, thick, red, or scaly skin patches (“psoriasis skin lesions”).

Step 3: Injecting the Enbrel solution

1. Wipe the site where Enbrel is to be injected with the alcohol swab, using a circular motion. Do NOT touch this area again before giving the injection.
2. Pick up the pre-filled syringe from the flat work surface. Remove the needle cover by firmly pulling it straight off the syringe (see Diagram 2). Be careful not to bend or twist the cover during removal to avoid damage to the needle.

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.

Diagram 2

3. When the cleaned area of skin has dried, pinch and hold it firmly with one hand. With the other hand, hold the syringe like a pencil.
4. With a quick, short motion, push the needle all the way into the skin at an angle between 45° and 90° (see Diagram 3). With experience, 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 great force.

Diagram 3

5. When the needle is completely inserted into the skin, release the skin that you are holding. With your free hand, hold the syringe near its base to stabilise it. Then push the plunger to inject all of the solution at a slow , steady rate (see Diagram 4).

Diagram 4

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 pre-filled syringe is for single-use administration only. The syringe and needle should NEVER be re-used. NEVER re-cap a needle. Dispose of the needle and syringe as instructed by your doctor, nurse or pharmacist.

If you have any questions, please talk to a doctor, nurse or pharmacist who is familiar with Enbrel.

Package Leaflet: Information for the User

Enbrel 25 mg solution for injection in pre-filled pen etanercept

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
Your doctor will also give you a Patient Card, which contains important safety information that

you need to be aware of before and during treatment with Enbrel.

If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you or a child in your care. Do not pass it on to others. It

may harm them, even if their signs of illness are the same as yours or those of the child you are caring for.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Using the MYCLIC pre-filled pen to inject Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If

you are not sure, please contact your doctor.

if you or the child have an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Latex: The needle cap of the MYCLIC pen is made from latex (dry natural rubber). Contact your doctor before using Enbrel if the needle cap will be handled by, or Enbrel will be given to, someone with a known or possible hypersensitivity (allergy) to latex.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse. Please tell your doctor if you or the child in your care have a history of alcohol abuse.
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, talk to your doctor.

Anti-diabetic medicines: Tell 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

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

Enbrel contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

3. How to use Enbrel

Always use this medicine exactly as your doctor has told you. Check with your doctor if or pharmacist you are not sure.

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

You have been prescribed a 25 mg strength of Enbrel. A 50 mg strength of Enbrel is available for doses of 50 mg.

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Use in children and adolescents

The doctor will provide you with detailed directions for preparing and measuring the appropriate dose.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

Detailed instructions on how to inject Enbrel are provided in section 7, “Using the MYCLIC pre-filled pen to inject Enbrel”. Do not mix the Enbrel solution with any other medicine.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and on the MYCLIC prefilled pen after EXP. The expiry date refers to the last day of that month.

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

Keep the pre-filled pens in the outer carton in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

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

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

What Enbrel looks like and contents of the pack

Enbrel is supplied as a solution for injection in a pre-filled pen (MYCLIC) (solution for injection). The MYCLIC pen contains a clear, colourless to pale yellow or pale brown solution for injection. Each pack contains 4, 8 or 24 pens and 4, 8 or 24 alcohol swabs. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer:

Pfizer Manufacturing Belgium NV

Rijksweg 12, 2870 Puurs Belgium

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Luxembourg/Luxemburg Pfizer S.A. / N.V. Tél/Tel: +32 (0)2 554 62 11	Kùnpoç PFIZER EAAAE A.E. (CYPRUS BRANCH) T^X: +357 22 817690
Česká Republika	Magyarország
Pfizer, spol. s r.o.	Pfizer Kft.
Tel: +420–283–004–111	Tel: +36 1 488 3700

Danmark

Pfizer ApS

Tlf: +45 44 201 100

Malta

Vivian Corporation Ltd.

Tel: +35621 344610

Deutschland

Pfizer Pharma GmbH

Tel: +49 (0)30 550055–51000

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

B'ixiiapiiH

n<|)aÜ3ep ^æKceMÔypr C’AP^. KnoH Btnrapua

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Ten: +359 2 970 4333

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Österreich

Pfizer Corporation Austria Ges.m.b.H.

Tel: +43 (0)1 521 15–0

EZZàôa

PFIZER EAAAL A.E.

T^.: +30 210 67 85 800

Polska

Pfizer Polska Sp. z o.o.

Tel.: +48 22 335 61 00

España

Pfizer, S.L.

Télf: +34 91 490 99 00

Portugal

Laboratórios Pfizer, Lda.

Tel: (+351) 21 423 55 00

France

Pfizer

Tél +33 (0)1 58 07 34 40

România

Pfizer Romania S.R.L

Tel: +40 (0) 21 207 28 00

Hrvatska

Pfizer Croatia d.o.o.

Tel: +385 1 3908 777

Slovenija

Pfizer Luxembourg SARL, Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana

Tel: +386 (0)1 52 11 400

Ireland

Pfizer Healthcare Ireland

Tel: +1800 633 363 (toll free)

Tel: +44 (0)1304 616161

Slovenská Republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421 2 3355 5500

Ísland

Icepharma hf.

Tel: +354 540 8000

Suomi/Finland

Pfizer Oy

Puh/Tel: +358 (0)9 430 040

Italia

Pfizer S.r.l.

Tel: +39 06 33 18 21

Sverige

Pfizer AB

Tel: +46 (0)8 550 520 00

Latvija

Pfizer Luxembourg SARL filiäle Latvijä

Tel. +371 67035775

United Kingdom (Northern Ireland)

Pfizer Limited

Tel: +44 (0)1304 616161

Lietuva

Pfizer Luxembourg SARL filialas Lietuvoje

Tel. +3705 2514000

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

7. Using the MYCLIC pre-filled pen to inject Enbrel

This section is divided into the following subsections:

Introduction

Step 1: Preparing for an Enbrel injection

Step 2: Choosing an injection site

Step 3: Injecting the Enbrel solution

Step 4: Disposing of the used MYCLIC pen

Introduction

The instructions below explain how to use the MYCLIC pen to inject Enbrel. Please read the instructions carefully, and follow them step by step. Your doctor or nurse will tell you how to inject Enbrel. Do not attempt to administer an injection until you are sure that you understand how to use the MYCLIC pen properly. If you have questions about how to inject, please ask your doctor or nurse for help.

Diagram 1

needle

Step 1: Preparing for an Enbrel injection

1. Select a clean, well-lit, flat surface.
2. Gather the items that you will need for your injection, and place them on the chosen surface:

a. One MYCLIC pre-filled pen and one alcohol swab (take these from the carton of pens you keep in your refrigerator). Do not shake the pen.
b. One cotton ball or gauze

3. Check the expiry date (month/year) on the pen. If the date has passed, do not use the pen and contact your pharmacist for assistance.
4. Inspect the solution in the pen by looking through the clear inspection window. The solution should be clear or slightly opalescent, colourless to pale yellow or pale brown, and may contain small white or almost transparent particles of protein. This appearance is normal for Enbrel. Do not use the solution if it is discoloured, cloudy, or if particles other than those described above are present. If you are concerned with the appearance of the solution, then contact your pharmacist for assistance.
5. Leave the white needle cap in place and wait approximately 15–30 minutes to allow the Enbrel solution in the pen to reach room temperature. Waiting until the solution reaches room temperature may make the injection more comfortable for you. Do not warm in any other way. Always leave the pen out of sight and reach of children.

Whilst waiting for the solution in the pen to reach room temperature, read Step 2 (below), and choose an injection site.

Step 2: Choosing an injection site (see Diagram 2)

1. The recommended injection site is the middle of the front of the thighs. If you prefer, you may alternatively use the stomach area, but make sure you choose a site at least 5 cm away from the belly button (navel). If someone else is giving you the injection, the outer area of the upper arms may also be used.
2. Each injection should be given at least 3 cm from where you last injected. Do not inject into tender, bruised or hard skin. Avoid scars or stretch marks. (It may be helpful to keep notes on the location of the previous injections.)
3. If you have psoriasis, you should try not to inject directly into any raised, thick, red, or scaly skin.

Step 3: Injecting the Enbrel solution

1. After waiting approximately 15–30 minutes for the solution in the pen to warm to room temperature, wash your hands with soap and water.
2. Clean the injection site with the alcohol swab using a circular motion, and allow it to dry. Do not touch this area again before injecting.
3. Pick up the pen, and remove the white needle cap by pulling it straight off (see Diagram 3). To avoid damaging the needle inside the pen, do not bend the white needle cap while you are removing it, and do not re-attach it once it has been removed. After removal of the needle cap, you will see a purple needle safety shield extending slightly from the end of the pen. The needle will remain protected inside the pen until the pen is activated. Do not use the pen if it is dropped with the needle cap off.
4. Lightly pinching the skin around the injection site between the thumb and index finger of your free hand may make the injection easier and more comfortable.
5. Hold the pen at a right angle (90°) to the injection site. Push the open end of the pen firmly against the skin , so that the needle safety shield is pushed completely inside of the pen. A slight depression in the skin will be seen (see Diagram 4). The pen can only be activated when the needle shield is completely pushed inside the pen.

Diagram 4

Needle safety shield disappears inside the pen

6. Whilst pushing the pen firmly against the skin to ensure that the needle safety shield is fully depressed inside the pen, press the centre of the grey button on top of the pen with your thumb to start the injection (see Diagram 5). On pressing the centre of the button, you will hear a click. Continue to hold the pen firmly against your skin until you hear a second click, or until 10 seconds after the first click (whichever happens first).

Note – If you are unable to start the injection as described, press the pen more firmly against your skin, then press the grey button again.

Diagram 5

7. On hearing the second ‘click’ (or, if you do not hear a second ‘click’, after 10 seconds have passed), your injection will be complete (see Diagram 6). You may now lift the pen from your skin (see Diagram 7). As you lift the pen, the purple needle safety shield will automatically extend to cover the needle.
8. The pen’s inspection window should now be completely purple, confirming that the dose has been injected correctly (see Diagram 8). If the window is not completely purple, contact your nurse or pharmacist for assistance, since the pen may not have injected the Enbrel solution completely. Do not try to use the pen again, and do not try to use another pen without agreement from your nurse or pharmacist.
9. If you notice a spot of blood at the injection site, you should press the cotton ball or gauze over the injection site for 10 seconds. Do not rub the injection site.

Step 4: Disposing of the used MYCLIC pen

The pen should be used once only – it should never be re-used. Dispose of the used pen as instructed by your doctor, nurse or pharmacist. Do not attempt to recap the pen.

If you have any questions, please talk to a doctor, nurse or pharmacist who is familiar with Enbrel.

Package Leaflet: Information for the User

Enbrel 50 mg solution for injection in pre-filled pen etanercept

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
Your doctor will also give you a Patient Card, which contains important safety information that

you need to be aware of before and during treatment with Enbrel.

If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you or a child in your care. Do not pass it on to others. It

may harm them, even if their signs of illness are the same as yours or those of the child you are caring for.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Using the MYCLIC pre-filled pen to inject Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is also prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 you are caring for, 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 serious blood infection called sepsis. If

you are not sure, please contact your doctor.

if you or the child have an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking 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 have any major surgery, your doctor may wish to monitor the treatment with Enbrel.
Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell 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 may decide to continue to monitor you or the child for the presence of infections after you or the child stop using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if you or the child have ever had tuberculosis, or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before you or the child begin treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if you or the child develop any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Enbrel. Your doctor will determine if preventive treatment for chickenpox is appropriate.
Latex: The needle cap of the MYCLIC pen is made from latex (dry natural rubber). Contact your doctor before using Enbrel if the needle cap will be handled by, or Enbrel will be given to, someone with a known or possible hypersensitivity (allergy) to latex.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse.

Please tell your doctor if you or the child in your care have a history of alcohol abuse.

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, talk to your doctor.
Anti-diabetic medicines: Tell 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

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

Enbrel contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

3. How to use Enbrel

Always use this medicine exactly as your doctor has told you. Check with your doctor if or pharmacist you are not sure.

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

You have been prescribed a 50 mg strength of Enbrel. A 25 mg strength of Enbrel is available for doses of 25 mg.

Dosing for adult patients (aged 18 years or over)

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

The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. However, your doctor may determine an alternative frequency at which to inject Enbrel.

Plaque psoriasis

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

Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 50 mg once a week.

Use in children and adolescents

The doctor will provide you with detailed directions for preparing and measuring the appropriate dose.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

Detailed instructions on how to inject Enbrel are provided in section 7, “Using the MYCLIC pre-filled pen to inject Enbrel”. Do not mix the Enbrel solution with any other medicine.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen, do not inject more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton and on the MYCLIC prefilled pen after EXP. The expiry date refers to the last day of that month.

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

Keep the pre-filled pens in the outer carton in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

The active substance in Enbrel is etanercept. Each MYCLIC pre-filled pen contains 50 mg of etanercept.

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

What Enbrel looks like and contents of the pack

Enbrel is supplied as a solution for injection in a pre-filled pen (MYCLIC) (solution for injection). The MYCLIC pen contains a clear, colourless to pale yellow or pale brown solution for injection. Each pack contains 2, 4 or 12 pens and 2, 4 or 12 alcohol swabs. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer:

Pfizer Manufacturing Belgium NV

Rijksweg 12, 2870 Puurs Belgium

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Luxembourg/Luxemburg Pfizer S.A. / N.V. Tél/Tel: +32 (0)2 554 62 11	Kùnpoç PFIZER EAAAE A.E. (CYPRUS BRANCH) T^X: +357 22 817690
Česká Republika	Magyarország
Pfizer, spol. s r.o.	Pfizer Kft.
Tel: +420–283–004–111	Tel: +36 1 488 3700

Danmark

Pfizer ApS

Tlf: +45 44 201 100

Malta

Vivian Corporation Ltd.

Tel: +35621 344610

Deutschland

Pfizer Pharma GmbH

Tel: +49 (0)30 550055–51000

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

B'ixiiapiiH

n<|)aÜ3ep ^æKceMÔypr C’AP^. KnoH Btnrapua

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Ten: +359 2 970 4333

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Österreich

Pfizer Corporation Austria Ges.m.b.H.

Tel: +43 (0)1 521 15–0

EZZàôa

PFIZER EAAAL A.E.

T^.: +30 210 67 85 800

Polska

Pfizer Polska Sp. z o.o.

Tel.: +48 22 335 61 00

España

Pfizer, S.L.

Télf: +34 91 490 99 00

Portugal

Laboratórios Pfizer, Lda.

Tel: (+351) 21 423 55 00

France

Pfizer

Tél +33 (0)1 58 07 34 40

România

Pfizer Romania S.R.L

Tel: +40 (0) 21 207 28 00

Hrvatska

Pfizer Croatia d.o.o.

Tel: +385 1 3908 777

Slovenija

Pfizer Luxembourg SARL, Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana

Tel: +386 (0)1 52 11 400

Ireland

Pfizer Healthcare Ireland

Tel: +1800 633 363 (toll free)

Tel: +44 (0)1304 616161

Slovenská Republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421 2 3355 5500

Ísland

Icepharma hf.

Tel: +354 540 8000

Suomi/Finland

Pfizer Oy

Puh/Tel: +358 (0)9 430 040

Italia

Pfizer S.r.l.

Tel: +39 06 33 18 21

Sverige

Pfizer AB

Tel: +46 (0)8 550 520 00

Latvija

Pfizer Luxembourg SARL filiäle Latvijä

Tel. +371 67035775

United Kingdom (Northern Ireland)

Pfizer Limited

Tel: +44 (0)1304 616161

Lietuva

Pfizer Luxembourg SARL filialas Lietuvoje

Tel. +3705 2514000

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

7. Using the MYCLIC pre-filled pen to inject Enbrel

This section is divided into the following subsections:

Introduction

Step 1: Preparing for an Enbrel injection

Step 2: Choosing an injection site

Step 3: Injecting the Enbrel solution

Step 4: Disposing of the used MYCLIC pen

Introduction

Diagram 1

Green activation button

The MYCLIC pre-filled pen

White needle

Expiry date

Clear inspection window

cap

Step 1: Preparing for an Enbrel injection

1. Select a clean, well-lit, flat surface.
2. Gather the items that you will need for your injection, and place them on the chosen surface:

a. One MYCLIC pre-filled pen and one alcohol swab (take these from the carton of pens you keep in your refrigerator). Do not shake the pen.
b. One cotton ball or gauze

3. Check the expiry date (month/year) on the pen. If the date has passed, do not use the pen and contact your pharmacist for assistance.
4. Inspect the solution in the pen by looking through the clear inspection window. The solution should be clear or slightly opalescent, colourless to pale yellow or pale brown, and may contain small white or almost transparent particles of protein. This appearance is normal for Enbrel. Do not use the solution if it is discoloured, cloudy, or if particles other than those described above are present. If you are concerned with the appearance of the solution, then contact your pharmacist for assistance.
5. Leave the white needle cap in place and wait approximately 15–30 minutes to allow the Enbrel solution in the pen to reach room temperature. Waiting until the solution reaches room temperature may make the injection more comfortable for you. Do not warm in any other way. Always leave the pen out of sight and reach of children.

Whilst waiting for the solution in the pen to reach room temperature, read Step 2 (below), and choose an injection site.

Step 2: Choosing an injection site (see Diagram 2)

1. The recommended injection site is the middle of the front of the thighs. If you prefer, you may alternatively use the stomach area, but make sure you choose a site at least 5 cm away from the belly button (navel). If someone else is giving you the injection, the outer area of the upper arms may also be used.

Diagram 2

2. Each injection should be given at least 3 cm from where you last injected. Do not inject into tender, bruised or hard skin. Avoid scars or stretch marks. (It may be helpful to keep notes on the location of the previous injections.)
3. If you have psoriasis, you should try not to inject directly into any raised, thick, red, or scaly skin.

Step 3: Injecting the Enbrel solution

1. After waiting approximately 15–30 minutes for the solution in the pen to warm to room temperature, wash your hands with soap and water.
2. Clean the injection site with the alcohol swab using a circular motion, and allow it to dry. Do not touch this area again before injecting.
3. Pick up the pen, and remove the white needle cap by pulling it straight off (see Diagram 3). To avoid damaging the needle inside the pen, do not bend the white needle cap while you are removing it, and do not re-attach it once it has been removed. After removal of the needle cap, you will see a purple needle safety shield extending slightly from the end of the pen. The needle will remain protected inside the pen until the pen is activated. Do not use the pen if it is dropped with the needle cap off.

Diagram 3

White needle cap

Purple needle safety shield

4. Lightly pinching the skin around the injection site between the thumb and index finger of your free hand may make the injection easier and more comfortable.
5. Hold the pen at a right angle (90°) to the injection site. Push the open end of the pen firmly against the skin , so that the needle safety shield is pushed completely inside of the pen. A slight depression in the skin will be seen (see Diagram 4). The pen can only be activated when the needle shield is completely pushed inside the pen.

Diagram 4

Needle safety shield disappears inside the pen

6. Whilst pushing the pen firmly against the skin to ensure that the needle safety shield is fully depressed inside the pen, press the centre of the green button on top of the pen with your thumb to start the injection (see Diagram 5). On pressing the centre of the button, you will hear a click. Continue to hold the pen firmly against your skin until you hear a second click, or until 10 seconds after the first click (whichever happens first).

Note – If you are unable to start the injection as described, press the pen more firmly against your skin, then press the green button again.

Diagram 5

7. On hearing the second ‘click’ (or, if you do not hear a second ‘click’, after 10 seconds have passed), your injection will be complete (see Diagram 6). You may now lift the pen from your skin (see Diagram 7). As you lift the pen, the purple needle safety shield will automatically extend to cover the needle.

Diagram 6

Diagram 7

Inspection window will have turned purple

Purple needle safety shield extends to cover needle

8. The pen’s inspection window should now be completely purple, confirming that the dose has been injected correctly (see Diagram 8). If the window is not completely purple, contact your nurse or pharmacist for assistance, since the pen may not have injected the Enbrel solution completely. Do not try to use the pen again, and do not try to use another pen without agreement from your nurse or pharmacist.
9. If you notice a spot of blood at the injection site, you should press the cotton ball or gauze over the injection site for 10 seconds. Do not rub the injection site.

Step 4: Disposing of the used MYCLIC pen

The pen should be used once only – it should never be re-used. Dispose of the used pen as instructed by your doctor, nurse or pharmacist. Do not attempt to recap the pen.

If you have any questions, please talk to a doctor, nurse or pharmacist who is familiar with Enbrel.

Package Leaflet: Information for the User

Enbrel 10 mg powder and solvent for solution for injection for paediatric use etanercept

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
Your doctor will also give you a Patient Card, which contains important safety information that

you need to be aware of before and during treatment with Enbrel.

If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for a child in your care. Do not pass it on to others. It may

harm them, even if their signs of illness are the same as those of the child you are caring for.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

Information in this leaflet is organised under the following 7 sections:

1. What Enbrel is and what it is used for
2. What you need to know before you use Enbrel
3. How to use Enbrel
4. Possible side effects
5. How to store Enbrel
6. Contents of the pack and other information
7. Instructions for preparing and giving an injection of Enbrel (See overleaf)

1. What Enbrel is and what it is used for

Enbrel is prescribed for the treatment of the following diseases in children and adolescents

For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked well enough or is not suitable for them:
Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from the age of 2 years
Psoriatic arthritis in patients from the age of 12 years
For enthesitis-related arthritis in patients from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them
Severe psoriasis in patients from the age of 6 years 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 the child you are caring for is allergic to etanercept or any of the other ingredients of Enbrel (listed in section 6). If the child experiences allergic reactions such as chest tightness, wheezing, dizziness or rash, do not inject more Enbrel, and contact your doctor immediately.
if the child has, or is at risk of developing a serious blood infection called sepsis. If you are not sure, please contact your doctor.
if the child has an infection of any kind. If you are not sure, please talk to your doctor.

Warnings and precautions

Talk to your doctor before taking Enbrel.

Allergic reactions: If the child experiences allergic reactions such as chest tightness, wheezing, dizziness or rash, do not inject more Enbrel, and contact your doctor immediately.
Infections/surgery: If the child develops a new infection, or is about to have any major surgery, the doctor may wish to monitor the child's treatment with Enbrel.
Infections/diabetes: Tell your doctor if the child has a history of recurrent infections, or suffers from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Tell your doctor of any recent travel outside the European region. If the child develops symptoms of an infection such as fever, chills or cough, notify your doctor immediately. Your doctor may decide to continue to monitor the child for the presence of infections after the child stops using Enbrel.
Tuberculosis: As cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should be recorded on the Patient Card. It is very important that you tell your doctor if the child has ever had tuberculosis, or has been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild fever), or any other infection appear during or after therapy, tell your doctor immediately.
Hepatitis B: Tell your doctor if the child has or has ever had hepatitis B. Your doctor should test for the presence of hepatitis B infection before the child begins treatment with Enbrel. Treatment with Enbrel may result in reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Enbrel.
Hepatitis C: Tell your doctor if the child has hepatitis C. Your doctor may wish to monitor the treatment with Enbrel in case the infection worsens.
Blood disorders: Seek medical advice immediately if the child has any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms may point to the existence of potentially life-threatening blood disorders, which may require discontinuation of Enbrel.
Nervous system and eye disorders: Tell your doctor if the child has multiple sclerosis, optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the spinal cord). Your doctor will determine if Enbrel is an appropriate treatment.
Congestive heart failure: Tell your doctor if the child has a history of congestive heart failure, because Enbrel needs to be used with caution under these circumstances.
Cancer: Tell your doctor if the child has or has ever had lymphoma (a type of blood cancer) or any other cancer before the child is given Enbrel.

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

Children and adults taking Enbrel may have an increased risk of developing lymphoma or another cancer.

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

Some patients receiving Enbrel have developed skin cancers. Tell your doctor if the child develops any change in the appearance of the skin or growths on the skin.

Chickenpox: Tell your doctor if the child is exposed to chickenpox when using Enbrel. Your doctor will determine if preventative treatment for chickenpox is appropriate.
Alcohol abuse: Enbrel should not be used for the treatment of hepatitis related to alcohol abuse.

Please tell your doctor if the child in your care has a history of alcohol abuse.

Wegener’s granulomatosis: Enbrel is not recommended for the treatment of Wegener’s granulomatosis, a rare inflammatory disease. If the child in your care has Wegener’s granulomatosis, talk to your doctor.
Anti-diabetic medicines: Tell your doctor if the child has diabetes or is taking medicines to treat diabetes. Your doctor may decide if the child needs less anti-diabetic medicine while taking Enbrel.

Children and adolescents

Vaccinations: If possible, children should be up to date with all vaccinations before using Enbrel. Some vaccines, such as oral polio vaccine, should not be given while using Enbrel. Please consult the child’s doctor before the child receives any vaccines.

Other medicines and Enbrel

Pregnancy and breast-feeding

Enbrel should only be used during pregnancy if clearly needed. You should consult your doctor if you become pregnant, think you may be pregnant, or are planning to have a baby.

Women using Enbrel should not breast-feed, since Enbrel passes into human breast milk.

Driving and using machines

The use of Enbrel is not expected to affect the ability to drive or use machines.

3. How to use Enbrel

Use in children and adolescents

Always use this medicine exactly as the doctor has told you. Check with the doctor or pharmacist if you are not sure.

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

The 10 mg vial is for children prescribed a dose of 10 mg or less. Each vial should be used for just one dose in one patient, and any remaining solution should be discarded.

Method and route of administration

Enbrel is administered by an injection under the skin (by subcutaneous injection).

Enbrel can be taken with or without food or drink.

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

If you use more Enbrel than you should

If you forget to inject Enbrel

If you stop using Enbrel

Your symptoms may return upon discontinuation.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

If any of the following happen to the child, do not give the child more Enbrel. Tell your doctor immediately, or go to the casualty department at your nearest hospital.

Trouble swallowing or breathing
Swelling of the face, throat, hands, or feet
Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm feeling
Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Serious allergic reactions are rare. If the child has any of the above symptoms he/she may be having an allergic reaction to Enbrel, so you should seek immediate medical attention.

Serious side effects

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

Signs of serious infections, such as high fever that may be accompanied by cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints
Signs of blood disorders, such as bleeding, bruising, or paleness
Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of

weakness in an arm or leg

Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness of breath or coughing, bluish colour of the nails or the lips
Signs of cancers: Cancers may 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 growths on the skin
Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision
Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue
Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or itching.

The known side effects of Enbrel include the following in groups of decreasing frequency:

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

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

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

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

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

Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce crucial blood cells.
Not known (frequency cannot be estimated from the available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma (a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appear as purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness with an accompanying skin rash).

Additional side effects in children and adolescents

The side effects and their frequencies seen in children and adolescents are similar to those described above.

Reporting of side effects

5. How to store Enbrel

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

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

After preparing the Enbrel solution, immediate use is recommended. However, the solution may be used for up to 6 hours when stored at a temperature up to 25°C.

Do not use this medicine if you notice the solution is not clear or contains particles. The solution should be clear, colourless to pale yellow or pale brown, with no lumps or flakes or particles.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Enbrel contains

The other ingredients are:

Powder: Mannitol (E421), sucrose, and trometamol.

Solvent: Water for injections.

What Enbrel looks like and contents of the pack

Enbrel 10 mg powder and solvent for solution for injection for paediatric use is supplied as a white powder with solvent for solution for injection (powder for injection). Each pack contains 4 vials, 4 pre-filled syringes of water for injections, 4 needles, 4 vial adaptors and 8 alcohol swabs.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer:

Pfizer Manufacturing Belgium NV

Rijksweg 12,

2870 Puurs

Belgium

For any information about this medicinal product, please contact the local representative of the

Marketing Authorisation Holder.

België/Belgique/Belgien

Luxembourg/Luxemburg

Pfizer S.A. / N.V.

Tél/Tel: +32 (0)2 554 62 11

Česká Republika

Pfizer, spol. s r.o.

Tel: +420–283–004–111

Danmark

Pfizer ApS

Tlf: +45 44 201 100

Deutschland

Pfizer Pharma GmbH

Tel: +49 (0)30 550055–51000

Btnrapua

n<|)aÜ3ep ^æKceMÔypr C’AP^.

K.toh Eijrapna

Ten: +359 2 970 4333

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

EZZàôa

PFIZER EAAAE A.E.

T^.: +30 210 67 85 800

Kùnpoç

PFIZER EAAAE A.E. (CYPRUS BRANCH)

TpX: +357 22 817690

España

Pfizer, S.L.

Télf: +34 91 490 99 00

France

Pfizer

Tél +33 (0)1 58 07 34 40

Magyarország

Pfizer Kft.

Tel: +36 1 488 3700

Malta

Vivian Corporation Ltd.

Tel: +35621 344610

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Österreich

Pfizer Corporation Austria Ges.m.b.H.

Tel: +43 (0)1 521 15–0

Polska

Pfizer Polska Sp. z o.o.

Tel.: +48 22 335 61 00

Portugal

Laboratórios Pfizer, Lda.

Tel: (+351) 21 423 55 00

România

Pfizer Romania S.R.L

Tel: +40 (0) 21 207 28 00

Hrvatska

Pfizer Croatia d.o.o.

Tel: +385 1 3908 777

Ireland

Pfizer Healthcare Ireland

Tel: +1800 633 363 (toll free)

Tel: +44 (0)1304 616161

Ísland

Icepharma hf.

Tel: +354 540 8000

Italia

Pfizer S.r.l.

Tel: +39 06 33 18 21

Latvija

Pfizer Luxembourg SARL filiäle Latvijä

Tel. +371 67035775

Lietuva

Pfizer Luxembourg SARL filialas Lietuvoje

Tel. +3705 2514000

Slovenija

Pfizer Luxembourg SARL, Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana

Tel: +386 (0)1 52 11 400

Slovenská Republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421 2 3355 5500

Suomi/Finland

Pfizer Oy

Puh/Tel: +358 (0)9 430 040

Sverige

Pfizer AB

Tel: +46 (0)8 550 520 00

United Kingdom (Northern Ireland)

Pfizer Limited

Tel: +44 (0)1304 616161

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

7. Instructions for preparing and giving an injection of Enbrel

This section is divided into the following sub-sections:

a. Introduction
b. Setting up for an injection
c. Preparing the Enbrel dose for injection
d. Adding solvent
e. Withdrawing the Enbrel solution from the vial
f. Placing the needle on the syringe
g. Choosing an injection site
h. Preparing the injection site and injecting the Enbrel solution
i. Disposing of supplies

a. Introduction

The following instructions explain how to prepare and inject Enbrel. Please read the instructions carefully and follow them step by step. You will be instructed by the child's doctor or his/her assistant on the technique of giving an injection and on the amount to be given to the child. Do not attempt to administer an injection until you are sure that you understand how to prepare and give the injection.

This injection should not be mixed in the same syringe or vial with any other medicine. See section 5 for instructions on how to store Enbrel.

b. Setting up for an injection

Wash your hands thoroughly.
Select a clean well-lit, flat working surface.
The dose tray should contain the items listed below. (If not, don’t use the dose tray and consult your pharmacist). Use only the items listed. Do NOT use any other syringe.
1 Enbrel vial
1 Pre-filled syringe containing clear, colourless solvent (water for injections)
1 Needle
1 Vial adaptor
2 Alcohol swabs

Inspect the expiry dates on both the vial label and the syringe label. They should not be used after the month and year shown.
c. Preparing the Enbrel dose for injection

Remove the contents of the tray
Remove the plastic cap from the Enbrel vial (see Diagram 1). Do NOT remove the grey stopper or aluminium ring around the top of the vial.
Use a new alcohol swab to clean the grey stopper on the Enbrel vial. After cleaning, do not touch the stopper with your hands or allow it to touch any surface.
Place the vial upright on a clean, flat surface.
Remove the paper backing from the vial adaptor package.
While still in the plastic package, place the vial adaptor on top of the Enbrel vial so that the vial adaptor spike is centered within the raised circle on top of the vial stopper (see Diagram 2).
Hold the vial firmly on the flat surface with one hand. With the other hand, push STRAIGHT DOWN FIRMLY on the adaptor package until you feel the adaptor spike penetrate the vial stopper and FEEL AND HEAR THE ADAPTOR RIM LOCK INTO PLACE (see Diagram 3). Do NOT push down the adaptor at an angle (see Diagram 4). It is important that the vial adaptor spike completely penetrates the vial stopper.
While holding the vial in one hand, remove the plastic packaging from the vial adaptor (see Diagram 5).

Diagram 5

Remove the protective cover from the syringe tip by breaking the white cap along the perforation. This is done by holding the collar of the white cap while grasping the end of the white cap with the other hand and bending it down and then up until it is broken (see Diagram 6). Do NOT remove the white collar that remains on the syringe.

Diagram 6

Do not use the syringe if the perforation between the tip and collar is already broken. Start again with another dose tray.
Holding the glass barrel of the syringe (not the white collar) in one hand, and the vial adaptor (not the vial) in the other, connect the syringe to the vial adaptor by inserting the tip into the opening and turn clockwise until completely secured (see Diagram 7).

Diagram 7

d. Adding solvent

While holding the vial upright on the flat surface, push the plunger VERY SLOWLY until all the solvent is in the vial. This will help to reduce foaming (lots of bubbles) (see Diagram 8).
Once the solvent is added to the Enbrel, the plunger may move up by itself. This is due to air pressure and should not be of concern.

Diagram 8

With the syringe still attached, gently move the vial in circles a few times, to dissolve the powder (see Diagram 9). Do NOT shake the vial. Wait until all the powder dissolves (usually less than 10 minutes). The solution should be clear and colourless to pale yellow or pale brown, with no lumps, flakes, or particles. Some white foam may remain in the vial this is normal. Do NOT use Enbrel if all the powder in the vial is not dissolved within 10 minutes. Start again with another dose tray.

Diagram 9

e. Withdrawing the Enbrel solution from the vial

The doctor or his/her assistant should have instructed you on the proper amount of solution to be withdrawn from the vial. If the doctor has not given this instruction, please contact him/her.
With the syringe still attached to the vial and vial adaptor, hold the vial upside down at eye level. Push the plunger all the way into the syringe (see Diagram 10).

Diagram 10

Then, slowly pull the plunger back to draw the liquid into the syringe (see Diagram 11).

Remove only the portion of liquid as directed by your child’s doctor. After you have withdrawn the Enbrel from the vial, you may have some air in the syringe. Do not be concerned, as you will remove the air in a later step.

With the vial held upside down, unscrew the syringe from the vial adaptor by turning it anti-clockwise (see Diagram 12).

Diagram 12

Place the filled syringe on the clean, flat surface. Make sure that the tip does not touch anything. Be careful not to push down on the plunger.
f. Placing the needle on the syringe

The needle has been placed in a plastic container to keep it sterile.
To open the plastic container, hold the short, wide end in one hand. Place your other hand on the

longer portion of the container.

To break the seal, bend the larger end down and then up until broken (see Diagram 13).

Diagram 13

Once the seal has been broken, remove the short, wide end of the plastic container.
The needle will remain in the long part of the package.
While holding the needle and container in one hand, pick up the syringe and insert the syringe tip into the needle opening.
Attach the syringe to the needle by turning it clockwise until completely secured (see Diagram 14).

Diagram 14

Remove the needle cover by firmly pulling it straight off the syringe taking care not to touch the needle or allow the needle to touch any surfaces (see Diagram 15). Be careful not to bend or twist the cover during removal to avoid damage to the needle.

Diagram 15

While holding the syringe upright, remove any air bubbles by slowly pushing on the plunger until the air is removed (see Diagram 16).

g. Choosing an injection site

The three recommended injection sites for Enbrel include: (1) the front of the middle thighs; (2) the abdomen, except for the 5 cm area right around the navel; and (3) the outer area of the upper arms (see Diagram 17). If you are self injecting, you should not use the outer area of the upper arms.

Diagram 17

A different site should be used for each new injection. Each new injection should be given at least 3 cm from an old site. Do NOT inject into areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks. (It may be helpful to keep notes on the location of the previous injections.)
If the child has psoriasis, you should try not to inject directly into any raised, thick, red, or scaly skin patches (“psoriasis skin lesions”).
h. Preparing the injection site and injecting the Enbrel solution

Wipe the site where Enbrel is to be injected with a new alcohol swab, using a circular motion. Do NOT touch this area again before giving the injection.
When the cleaned area of skin has dried, pinch and hold it firmly with one hand. With the other hand, hold the syringe like a pencil.
With a quick, short motion, push the needle all the way into the skin at an angle between 45° and 90° (see Diagram 18). With experience, you will find the angle that is most comfortable for the child. Be careful not to push the needle into the skin too slowly, or with great force.

Diagram 18

When the needle is completely inserted into the skin, release the skin that you are holding. With your free hand, hold the syringe near its base to stabilise it. Then push the plunger to inject all of the solution at a slow, steady rate (see Diagram 19).

Diagram 19

When the syringe is empty, remove the needle from the skin; being careful to keep it at the same angle it was when it was inserted.
Press a cotton ball over the injection site for 10 seconds. Slight bleeding may occur. Do NOT rub the injection site. A bandage is optional.
i. Disposing of supplies

The syringe and needles should NEVER be re-used. Dispose of the needles and syringe as instructed by your doctor, nurse or pharmacist.

Enbrel - patient leaflet, side effects, dosage

Table of contents

Patient leaflet - Enbrel

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

What Enbrel looks like and contents of the pack

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Enbrel is and what it is used for

2. What you need to know before you use Enbrel

3. How to use Enbrel

4. Possible side effects

5. How to store Enbrel

6. Contents of the pack and other information

What Enbrel looks like and contents of the pack