etanercept: package leaflet

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.

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.

Talk to your doctor if you want to breastfeed while on Enbrel treatment. It is important that you tell your baby’s doctors and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and using machines

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

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 use.” 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.

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); damage to the tiny filters inside your kidneys leading to poor kidney function (glomerulonephritis).

• 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.

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.

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

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
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12,
2870 Puurs-Sint-Amands
Belgium

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

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Kύπρος
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
T: +357 22 817690

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)800 63 34 636

България
Пфайзер Люксембург САРЛ,
Клон България
Teл: +359 2 970 4333

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

Ελλάδα
PFIZER EΛΛAΣ A.E.
Τηλ.: +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 Unlimited Company
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 filiāle Latvijā
Tel. +371 67035775

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:
https://www.ema.europa.eu

7.
Instructions for use

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.

Diagram 1

• 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
Diagram 3
Diagram 4

d.
Adding water for injections

• 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).

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.

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.

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.
• Latex: The syringe rubber tip is made from latex (dry natural rubber). Contact your doctor before using Enbrel if the syringe will be handled by, or Enbrel will be given to, someone with a known or possible hypersensitivity (allergy) to latex.
• 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.

Talk to your doctor if you want to breastfeed while on Enbrel treatment. It is important that you tell your baby’s doctors and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and using machines

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

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 use.” 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.

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 in 10 people):
Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections);
injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling) (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); damage to the tiny filters inside your kidneys leading to poor kidney function (glomerulonephritis).

• 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.

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.

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
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12,
2870 Puurs-Sint-Amands
Belgium

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

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Kύπρος
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
T: +357 22 817690

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)800 63 34 636

България
Пфайзер Люксембург САРЛ,
Клон България
Teл: +359 2 970 4333

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

Ελλάδα
PFIZER EΛΛAΣ A.E.
Τηλ.: +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 Unlimited Company
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 filiāle Latvijā
Tel. +371 67035775

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:
https://www.ema.europa.eu

7.
Instructions for use

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 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.
- 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.

Diagram 2.
Diagram 3.
Diagram 4.

CORRECT
INCORRECT

- 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 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.

Diagram 11

• 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.

NOT touch this area again before giving the injection.

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

hand, hold the syringe like a pencil.

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

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

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.

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.

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

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.

Talk to your doctor if you want to breastfeed while on Enbrel treatment. It is important that you tell your baby’s doctors and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

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’.

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.

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. 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).

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.

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 use.” 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.

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 in 10 people):
Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections);
injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling) (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); damage to the tiny filters inside your kidneys leading to poor kidney function (glomerulonephritis).

• 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.

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 pre- filled 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.

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 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.

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
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12,
2870 Puurs-Sint-Amands
Belgium

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

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Kύπρος
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
T: +357 22 817690

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)800 63 34 636

България
Пфайзер Люксембург САРЛ,
Клон България
Teл: +359 2 970 4333

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

Ελλάδα
PFIZER EΛΛAΣ A.E.
Τηλ.: +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 Unlimited Company
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 filiāle Latvijā
Tel. +371 67035775

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:
https://www.ema.europa.eu

7.
Instructions for use

Enbrel 25 mg solution for injection in pre-filled pen
(etanercept)
For subcutaneous injection only
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 healthcare provider 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 healthcare provider for help.
The MYCLIC pre-filled pen

Before injection

White needle cap
Grey activation button
Expiry date
Clear inspection window

After injection

Filled inspection window
Open end – safety shield

Step 1 Preparing for an Enbrel injection

- Gather the following items for each injection on a clean, well-lit flat surface:
o One MYCLIC pre-filled pen.
o One alcohol swab.
o A suitable sharps container (not included).
o Clean cotton balls or gauze pads (not included).
- Do not shake the pen.
- Do not remove the white cap until instructed to do so.
- For a more comfortable injection, leave your pen at room temperature for 15 to 30 minutes with the white cap in place.
- Do not warm the pen in any other way.
Step 2 Check label for expiry and dose

• Check the expiry date (month/year) on the pen label.
• Make sure the correct dose strength is shown on the pen label.
• If the expiry date has passed or it is not your prescribed dose, do not use the pen and contact your healthcare provider for assistance.

Step 3 Inspect the medicine

- Inspect the medicine 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 medicine if it is discoloured, cloudy, or if particles other than those described above are present. If you are concerned with the appearance of the medicine, then contact your healthcare provider for assistance.
- Note: You may see an air bubble in the window. This is normal.
Step 4 Choose and clean injection site

• Choose an injection site in the middle of the front of your upper thighs or stomach area 5 cm away from the belly button (navel). The outer area of the back of the upper arms may also be used by a caregiver.
• 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. If you have psoriasis, do not inject directly into any raised, thick, red or scaly skin.
• Clean the injection site with soap and water, or an alcohol swab if convenient.
• Allow the site to dry. Do not touch, fan or blow on the cleaned injection site.

Abdomen:
Keep at least 5 cm away from your belly button (navel).
Upper thighs
Outer area of upper arms
Caregiver only

Step 5 Remove needle cap

- Remove the white needle cap by pulling it straight off. Do not bend the cap while removing it.
- Do not re-attach the cap once it has been removed.
- After removal of the cap, you will see a purple needle safety shield extending slightly from the end of the pen. Do not push on the end safety shield with your fingers or thumbs.
- Do not use the pen if it is dropped with the needle cap off.
Note: You may notice a drop of liquid at the needle tip. This is normal.

Step 6 Push pen firmly against skin

- Push the open end of your pen firmly against the skin at 90 degrees so the purple needle safety shield is pushed completely inside the pen.
Note: You will only be able to press the grey button when the needle shield is completely pushed inside the pen.
Pinching or stretching the skin before injection may make the injection site firmer, making it easier to press the injection button.

Step 7 Start your injection

- Press the grey button all the way down and you will hear a “click”. The click means the start of the injection.
- Continue to hold your pen firmly against the skin until you hear a 2nd “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.

Step 8 Lift off skin

• Remove your pen from your skin by lifting it straight off the injection site.
• The purple needle safety shield will automatically extend to cover the needle.

Step 9 Check inspection window

- Check the pen’s inspection window. It should be completely purple.
- If the window is not purple, you may not have received a full dose. Contact your healthcare provider for assistance. Do not try to use the pen again. Do not try to use another pen.
- 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.
Press button
1st click start
Continue to hold
2nd click
Or
10 secs finish

Note: The injection button may stay pressed in. This is normal.

Step 10 Dispose

- Dispose of the used pen as instructed by your healthcare provider. Do not attempt to recap the pen.
- Do not press on the end of the needle safety shield. If you have any questions, please talk to your healthcare provider.
--End of Instructions for Use—

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.

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

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.

Talk to your doctor if you want to breastfeed while on Enbrel treatment. It is important that you tell your baby’s doctors and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

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’.

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.

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. 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).

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.

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 use”. 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.

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 in 10 people):
Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections);
injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling) (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); damage to the tiny filters inside your kidneys leading to poor kidney function (glomerulonephritis).

• 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.

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 pre- filled 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.

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 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.

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
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12,
2870 Puurs-Sint-Amands
Belgium

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

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Kύπρος
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
T: +357 22 817690

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)800 63 34 636

България
Пфайзер Люксембург САРЛ,
Клон България
Teл: +359 2 970 4333

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

Ελλάδα
PFIZER EΛΛAΣ A.E.
Τηλ.: +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 Unlimited Company
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 filiāle Latvijā
Tel. +371 67035775

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:
https://www.ema.europa.eu

7.
Instructions for use

Enbrel 50 mg solution for injection in pre-filled pen
(etanercept)
For subcutaneous injection only

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 healthcare provider 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 healthcare provider for help.
The MYCLIC pre-filled pen

Before injection

White needle cap
Green activation button
Expiry date
Clear inspection window

After injection

Filled inspection window
Open end – safety shield

Step 1 Preparing for an Enbrel injection

- Gather the following items for each injection on a clean, well-lit flat surface:
o One MYCLIC pre-filled pen.
o One alcohol swab.
o A suitable sharps container (not included).
o Clean cotton balls or gauze pads (not included).
- Do not shake the pen.
- Do not remove the white cap until instructed to do so.
- For a more comfortable injection, leave your pen at room temperature for 15 to 30 minutes with the white cap in place.
- Do not warm the pen in any other way.
Step 2 Check label for expiry and dose

• Check the expiry date (month/year) on the pen label.
• Make sure the correct dose strength is shown on the pen label.
• If the expiry date has passed or it is not your prescribed dose, do not use the pen and contact your healthcare provider for assistance.

Step 3 Inspect the medicine

- Inspect the medicine 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 medicine if it is discoloured, cloudy, or if particles other than those described above are present. If you are concerned with the appearance of the medicine, then contact your healthcare provider for assistance.
- Note: You may see an air bubble in the window. This is normal.
Step 4 Choose and clean injection site

• Choose an injection site in the middle of the front of your upper thighs or stomach area 5 cm away from the belly button (navel). The outer area of the back of the upper arms may also be used by a caregiver.
• 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. If you have psoriasis, do not inject directly into any raised, thick, red or scaly skin.
• Clean the injection site with soap and water, or an alcohol swab if convenient.
• Allow the site to dry. Do not touch, fan or blow on the cleaned injection site.

Abdomen:
Keep at least 5 cm away from your belly button (navel).
Upper thighs
Outer area of upper arms
Caregiver only

Step 5 Remove needle cap

- Remove the white needle cap by pulling it straight off. Do not bend the cap while removing it.
- Do not re-attach the cap once it has been removed.
- After removal of the cap, you will see a purple needle safety shield extending slightly from the end of the pen. Do not push on the end safety shield with your fingers or thumbs.
- Do not use the pen if it is dropped with the needle cap off.
Note: You may notice a drop of liquid at the needle tip. This is normal.

Step 6 Push pen firmly against skin

- Push the open end of your pen firmly against the skin at 90 degrees so the purple needle safety shield is pushed completely inside the pen.
Note: You will only be able to press the green button when the needle shield is completely pushed inside the pen.
Pinching or stretching the skin before injection may make the injection site firmer, making it easier to press the injection button.

Step 7 Start your injection

Press button
Continue to hold
1st click start
2nd click
Or
10 secs finish

- Press the green button all the way down and you will hear a “click”. The click means the start of the injection.
- Continue to hold your pen firmly against the skin until you hear a 2nd “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.

Step 8 Lift off skin

• Remove your pen from your skin by lifting it straight off the injection site.
• The purple needle safety shield will automatically extend to cover the needle.

Step 9 Check inspection window

- Check the pen’s inspection window. It should be completely purple.
- If the window is not purple, you may not have received a full dose. Contact your healthcare provider for assistance. Do not try to use the pen again. Do not try to use another pen.
- 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.
Note: The injection button may stay pressed in. This is normal.

Step 10 Dispose

- Dispose of the used pen as instructed by your healthcare provider. Do not attempt to recap the pen.
- Do not press on the end of the needle safety shield. If you have any questions, please talk to your healthcare provider.
--End of Instructions for Use—

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.

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.

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.
- Latex: The syringe rubber tip is made from latex (dry natural rubber). Contact your doctor before using Enbrel if the syringe will be handled by, or Enbrel will be given to, someone with a known or possible hypersensitivity (allergy) to latex.
- 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.

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 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.

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.

Talk to your doctor if you want to breastfeed while on Enbrel treatment. It is important that you tell your baby’s doctors and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and using machines

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

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 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.

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.

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 use”. 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.

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):
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); damage to the tiny filters inside your kidneys leading to poor kidney function (glomerulonephritis).

• 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.

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.

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). This new expiry date should not exceed the expiry date recorded on the outer carton.

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.

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 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
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12,
2870 Puurs-Sint-Amands
Belgium

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

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Kύπρος
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
T: +357 22 817690

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)800 63 34 636

България
Пфайзер Люксембург САРЛ,
Клон България
Teл: +359 2 970 4333

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

Ελλάδα
PFIZER EΛΛAΣ A.E.
Τηλ.: +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 Unlimited Company
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 filiāle Latvijā
Tel. +371 67035775

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:
https://www.ema.europa.eu

7.
Instructions for use

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.

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.

Diagram 2
Diagram 3
Diagram 4

CORRECT
INCORRECT

• 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.

Diagram 11

• 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).

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.

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

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.

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 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

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.

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 the 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.

Talk to your doctor if you want to breastfeed while on Enbrel treatment. It is important that you tell your baby’s doctors and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

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’.

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 dose-dispenser cartridge 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.

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. 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).

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.

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 “Instructions for use”. 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.

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 in 10 people):
Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections);
injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling) (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); damage to the tiny filters inside your kidneys leading to poor kidney function (glomerulonephritis).

• 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).

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.

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.

Keep the dose-dispenser cartridge in the outer carton in order to protect from light.

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

The dose-dispenser cartridges may be stored at room temperature (up to 25°C) for a single period of up to 4 weeks with protection from light; after which they 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 the Enbrel dose-dispenser 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 dose-dispenser cartridge by looking through the 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.

What Enbrel contains

Enbrel 25 mg solution for injection in dose-dispenser cartridge
The active substance in Enbrel is etanercept. Each dose-dispenser cartridge contains 0.5 ml of solution, providing 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 provided as a solution for injection in a ready to use dose-dispenser cartridge. The dose-dispenser cartridge is to be used with SMARTCLIC device. The device is provided separately.
The solution is clear to opalescent, colourless to pale yellow or pale brown.

Enbrel 25 mg solution for injection in dose-dispenser cartridge
Cartons contain 4, 8 or 24 dose-dispenser cartridges with 8, 16 or 48 alcohol swabs. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12,
2870 Puurs-Sint-Amands
Belgium

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

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Kύπρος
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
T: +357 22 817690

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)800 63 34 636

България
Пфайзер Люксембург САРЛ,
Клон България
Teл: +359 2 970 4333

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

Ελλάδα
PFIZER EΛΛAΣ A.E.
Τηλ.: +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 Unlimited Company
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 filiāle Latvijā
Tel. +371 67035775

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:
https://www.ema.europa.eu

Instructions for use
Enbrel
(etanercept)
25 mg / 0.5 ml
For Subcutaneous Injection Only

Important Information

• Keep this Instructions for use, it shows step-by-step how to prepare and give an injection.
• Only use Enbrel after you read and understand this Instructions for use.
• Only use Enbrel after you have received training from your healthcare professional.
• Your Dose Dispenser Cartridge contains a single dose of Enbrel and must only be used with your SMARTCLIC Device.
• Dose Dispenser Cartridge and SMARTCLIC Device will be referred to as “Cartridge” and “Device” in this Instructions for use.
• If this is the first time you are using your Device, make sure you follow the setup instructions in the separate User Manual. You will not be able to use your Device until you complete the setup.
• Do not attempt to use your Cartridges with any other Device.
• Do not share your Cartridges or your Device with another person.
• Do not shake your Cartridges or your Device containing a Cartridge.
• Do not remove your Cartridge needle cap until instructed to do so.
• Do not reuse your Cartridge if the needle cap has been removed.
• Avoid spilling liquid on your Cartridges or your Device. Never rinse or put your Cartridges or your Device under water.
• Refer to the additional Device User Manual for accessing menus, using a Training Cartridge, advanced use and troubleshooting error messages.

Storage

• Store Cartridges in the refrigerator between 2 ºC to 8 ºC. Do not freeze your Cartridges. Do not store your Cartridges in your Device.
• Store Cartridges in their original Carton until use to protect from direct sunlight.
• You may store your Cartridges at room temperature up to 25 ºC for up to 4 weeks. Do not return them to the refrigerator after they have reached room temperature.
• Keep your Cartridges and your Device out of sight and reach of children and adolescents.
• Refer to your Device User Manual for how to store and clean your Device.

Supplies you need

- Gather the following supplies on a clean flat surface:
o
Enbrel Carton containing Cartridges o your SMARTCLIC Device o alcohol wipes o clean cotton balls or gauze pads (not included) o a suitable sharps container (not included).

- Do not use if the Carton is dropped or damaged.
Note: If you do not have everything you need, ask your healthcare professional.

Your Device:

Refer to User Manual for more information.

Your Cartridge:

Preparation Steps

- Remove 1 Cartridge from the tray inside the Carton.
- Put the Carton and tray with any unused Cartridges back in the refrigerator.
- Wash and dry your hands.
- For a more comfortable injection leave your Cartridge at room temperature for approximately 15 - 30 minutes away from direct sunlight.
Do not use any other methods to warm up your Cartridge.

- Check the expiry date and medication dose printed on the label. Do not use if the expiry date has passed or if it is not your prescribed medication dose.
- Do not remove the needle cap until instructed to do so.
- Check your Cartridge, do not use if:
o it has been dropped even if it does not look damaged o it is damaged o the needle cap is loose o it has been frozen or exposed to heat o it has been at room temperature for more than 4 weeks o it has been returned to the refrigerator after reaching room temperature.

- Inspect the medicine through the Inspection window, 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 is normal.
- Do not use the medicine if it is discoloured, cloudy, or has particles other than those described above.
- Do not shake your Cartridge.
Note: If you have any questions about your medicine, contact your healthcare professional.

- Always choose an area in your abdomen, upper thighs or the outer area of the upper arms (caregiver only).
- Choose an injection site at least 3 cm from where you last injected and at least 5 cm away from your belly button (navel).
- Do not inject into bony areas or areas on your skin that are broken, bruised, red, sore (tender) or hard. Avoid injecting into areas with scars or stretch marks.
- Do not inject through your clothes.
Note: If you have psoriasis, do not inject directly into any raised, thick, red, or scaly skin patches or lesions on your skin.
- Clean your injection site with the supplied alcohol wipe and allow to dry.

• Clean the injection end of your Device with the separate supplied alcohol wipe.
• Allow the injection end to dry before giving an injection.

Injection Steps

- Push your Cartridge firmly straight through the Cartridge door without twisting until you cannot push it any further. Your Device will turn on when your Cartridge has been inserted correctly.
- Check the Display shows 25 mg and the expiry date has not passed.
Note: Your Device will turn off after 90 seconds of inactivity. Press and hold the Injection button to turn your Device back on.

- Remove the needle cap by pulling it firmly downwards.
- Dispose of the needle cap in a suitable sharps container.
- Inject as soon as possible after removing the needle cap.
- Do not replace the needle cap.
Caution: Do not insert your fingers into your Device after removing the needle cap to avoid a needle stick injury.
Note: To cancel the injection and eject your Cartridge, press the Cancel / Eject button for 1 second.

- Place your Device with the blue arrow pointing at 90 degrees towards your injection site.
- Make sure you can see the Display on your Device.
- Do not pinch the skin around your injection site.
Caution: If you drop your Device with a Cartridge inserted, eject and dispose of your Cartridge.
Refer to the Troubleshooting page in the Device User Manual.

- Press & hold the Injection button to begin your injection when instructed by the Display.
Note: You can release the Injection button after your injection has started.

- Hold your Device against your skin and wait while your medication is injected.
- Watch the Display on your Device.
- Do not move, tilt or remove your Device from your skin until instructed by the Display.
Note: If you remove your Device before instructed, do not place it back on the injection site or inject another dose. Contact your healthcare professional for advice.

- Lift & hold your Device away from your skin. Your Device will display that your injection is complete.
- Wait. Your Cartridge will be partially ejected from the bottom of your Device. This may take up to 10 seconds.
Do not cover the bottom of your Device during this time.
Do not insert your fingers inside your Device as the needle will be exposed during this time.
- If you notice a spot of blood, press a cotton ball or gauze over the injection site until the bleeding stops. Do not rub.

- Pull your Cartridge straight out after your Device has partially ejected it.
- Check your Cartridge is empty of medicine with a grey bar visible in the Inspection window.
If not, you may not have received your full dose. Contact your healthcare professional for advice.
- Do not reuse your Cartridge or reinsert it into your Device.
- Dispose of the used Cartridge straight away in a suitable sharps container as instructed by your healthcare professional or pharmacist and in accordance with local health and safety laws.

--End of Instructions for Use--

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.

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 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

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.

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 the 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.

Talk to your doctor if you want to breastfeed while on Enbrel treatment. It is important that you tell your baby’s doctors and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

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’.

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 dose-dispenser cartridge 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.

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. 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).

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.

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 “Instructions for use”. 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.

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 in 10 people):
Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections);
injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling) (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); damage to the tiny filters inside your kidneys leading to poor kidney function (glomerulonephritis).

• 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).

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.

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.

Keep the dose-dispenser cartridge in the outer carton in order to protect from light.

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

The dose-dispenser cartridges may be stored at room temperature (up to 25°C) for a single period of up to 4 weeks with protection from light; after which they 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 the Enbrel dose-dispenser 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 dose-dispenser cartridge by looking through the 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.

What Enbrel contains

Enbrel 50 mg solution for injection in dose-dispenser cartridge
The active substance in Enbrel is etanercept. Each dose-dispenser cartridge 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 is provided as a solution for injection in a ready to use dose-dispenser cartridge. The dose-dispenser cartridge is to be used with SMARTCLIC device. The device is provided separately.
The solution is clear to opalescent, colourless to pale yellow or pale brown.

Enbrel 50 mg solution for injection in dose-dispenser cartridge
Cartons contain 2, 4 or 12 dose-dispenser cartridges with 4, 8 or 24 alcohol swabs. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12,
2870 Puurs-Sint-Amands
Belgium

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

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Kύπρος
PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
T: +357 22 817690

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)800 63 34 636

България
Пфайзер Люксембург САРЛ,
Клон България
Teл: +359 2 970 4333

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

Ελλάδα
PFIZER EΛΛAΣ A.E.
Τηλ.: +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 Unlimited Company
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 filiāle Latvijā
Tel. +371 67035775

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:
https://www.ema.europa.eu

Instructions for use
Enbrel
(etanercept)
50 mg / 1 ml
For Subcutaneous Injection Only

Important Information

• Keep this Instructions for use, it shows step-by-step how to prepare and give an injection.
• Only use Enbrel after you read and understand this Instructions for use.
• Only use Enbrel after you have received training from your healthcare professional.
• Your Dose Dispenser Cartridge contains a single dose of Enbrel and must only be used with your SMARTCLIC Device.
• Dose Dispenser Cartridge and SMARTCLIC Device will be referred to as “Cartridge” and “Device” in this Instructions for use.
• If this is the first time you are using your Device, make sure you follow the setup instructions in the separate User Manual. You will not be able to use your Device until you complete the setup.
• Do not attempt to use your Cartridges with any other Device.
• Do not share your Cartridges or your Device with another person.
• Do not shake your Cartridges or your Device containing a Cartridge.
• Do not remove your Cartridge needle cap until instructed to do so.
• Do not reuse your Cartridge if the needle cap has been removed.
• Avoid spilling liquid on your Cartridges or your Device. Never rinse or put your Cartridges or your Device under water.
• Refer to the additional Device User Manual for accessing menus, using a Training Cartridge, advanced use and troubleshooting error messages.

Storage

• Store Cartridges in the refrigerator between 2 ºC to 8 ºC. Do not freeze your Cartridges. Do not store your Cartridges in your Device.
• Store Cartridges in their original Carton until use to protect from direct sunlight.
• You may store your Cartridges at room temperature up to 25 ºC for up to 4 weeks. Do not return them to the refrigerator after they have reached room temperature.
• Keep your Cartridges and your Device out of sight and reach of children and adolescents.
• Refer to your Device User Manual for how to store and clean your Device.

Supplies you need

- Gather the following supplies on a clean flat surface:
o
Enbrel Carton containing Cartridges o your SMARTCLIC Device o alcohol wipes o clean cotton balls or gauze pads (not included) o a suitable sharps container (not included).

- Do not use if the Carton is dropped or damaged.
Note: If you do not have everything you need, ask your healthcare professional.

Your Device:

Refer to User Manual for more information.

Your Cartridge:

Preparation Steps

- Remove 1 Cartridge from the tray inside the Carton.
- Put the Carton and tray with any unused Cartridges back in the refrigerator.
- Wash and dry your hands.
- For a more comfortable injection leave your Cartridge at room temperature for approximately 15 - 30 minutes away from direct sunlight.
Do not use any other methods to warm up your Cartridge.

- Check the expiry date and medication dose printed on the label. Do not use if the expiry date has passed or if it is not your prescribed medication dose.
- Do not remove the needle cap until instructed to do so.
- Check your Cartridge, do not use if:
o it has been dropped even if it does not look damaged o it is damaged o the needle cap is loose o it has been frozen or exposed to heat o it has been at room temperature for more than 4 weeks o it has been returned to the refrigerator after reaching room temperature.

- Inspect the medicine through the Inspection window, 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 is normal.
- Do not use the medicine if it is discoloured, cloudy, or has particles other than those described above.
- Do not shake your Cartridge.
Note: If you have any questions about your medicine, contact your healthcare professional.

- Always choose an area in your abdomen, upper thighs or the outer area of the upper arms (caregiver only).
- Choose an injection site at least 3 cm from where you last injected and at least 5 cm away from your belly button (navel).
- Do not inject into bony areas or areas on your skin that are broken, bruised, red, sore (tender) or hard. Avoid injecting into areas with scars or stretch marks.
- Do not inject through your clothes.
Note: If you have psoriasis, do not inject directly into any raised, thick, red, or scaly skin patches or lesions on your skin.
- Clean your injection site with the supplied alcohol wipe and allow to dry.

• Clean the injection end of your Device with the separate supplied alcohol wipe.
• Allow the injection end to dry before giving an injection.

Injection Steps

- Push your Cartridge firmly straight through the Cartridge door without twisting until you cannot push it any further. Your Device will turn on when your Cartridge has been inserted correctly.
- Check the Display shows 50 mg and the expiry date has not passed.
Note: Your Device will turn off after 90 seconds of inactivity. Press and hold the Injection button to turn your Device back on.

- Remove the needle cap by pulling it firmly downwards.
- Dispose of the needle cap in a suitable sharps container.
- Inject as soon as possible after removing the needle cap.
- Do not replace the needle cap.
Caution: Do not insert your fingers into your Device after removing the needle cap to avoid a needle stick injury.
Note: To cancel the injection and eject your Cartridge, press the Cancel / Eject button for 1 second.

- Place your Device with the blue arrow pointing at 90 degrees towards your injection site.
- Make sure you can see the Display on your Device.
- Do not pinch the skin around your injection site.
Caution: If you drop your Device with a Cartridge inserted, eject and dispose of your Cartridge.
Refer to the Troubleshooting page in the Device User Manual.

- Press & hold the Injection button to begin your injection when instructed by the Display.
Note: You can release the Injection button after your injection has started.

- Hold your Device against your skin and wait while your medication is injected.
- Watch the Display on your Device.
- Do not move, tilt or remove your Device from your skin until instructed by the Display.
Note: If you remove your Device before instructed, do not place it back on the injection site or inject another dose. Contact your healthcare professional for advice.

- Lift & hold your Device away from your skin. Your Device will display that your injection is complete.
- Wait. Your Cartridge will be partially ejected from the bottom of your Device. This may take up to 10 seconds.
Do not cover the bottom of your Device during this time.
Do not insert your fingers inside your Device as the needle will be exposed during this time.
- If you notice a spot of blood, press a cotton ball or gauze over the injection site until the bleeding stops. Do not rub.

- Pull your Cartridge straight out after your Device has partially ejected it.
- Check your Cartridge is empty of medicine with a grey bar visible in the Inspection window.
If not, you may not have received your full dose. Contact your healthcare professional for advice.
- Do not reuse your Cartridge or reinsert it into your Device.
- Dispose of the used Cartridge straight away in a suitable sharps container as instructed by your healthcare professional or pharmacist and in accordance with local health and safety laws.

--End of Instructions for Use