Enbrel

Italy
Brand name Enbrel
Form powder for solution for injection
Active substance / Dosage
ETANERCEPT
Prescription type Restricted prescription – hospital or equivalent facility use only
ATC code
L04AB01
Registration number 034675
Manufacturer PFIZER EUROPE MA EEIG
Enbrel powder for solution for injection

Table of Contents

Package leaflet: Information for the user

Enbrel 25 mg powder for injectable solution

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

  • Keep this leaflet. You may need to read it again.
  • Your doctor will provide you with the Patient Safety Information Card containing important safety information that you should be aware of before and during treatment with Enbrel.
  • If you have any questions, ask your doctor, pharmacist, or nurse.
  • This medicine has been prescribed for you or for the child. Do not give it to other people, even if their symptoms are the same as yours or the child's, because it could be harmful.
  • If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet
The information in this package leaflet is divided into the following 7 sections:

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

1. What Enbrel is and what it is used for

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

In adults (18 years of age and older), Enbrel can be used to treat moderate to severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate to severe psoriasis—in each case usually when 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 not suitable for you. Whether used alone or in combination with methotrexate, Enbrel can slow down joint damage caused by rheumatoid arthritis and improve your ability to carry out normal daily activities.

For patients with psoriatic arthritis affecting multiple joints, Enbrel can improve the ability to perform daily activities. For patients with painful or swollen symmetric joints (e.g., hands, wrists, and feet), Enbrel can slow down structural damage to these joints caused by the disease.

Enbrel is also prescribed for the following conditions in children and adolescents:

  • For the following types of juvenile idiopathic arthritis, when treatment with methotrexate has not provided a sufficient response or is not appropriate:
    • 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 widely used treatments have not provided a sufficient response or are not appropriate
  • Severe psoriasis in patients from the age of 6 years who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies

2. What you should know before using Enbrel

Do not use Enbrel

  • if you or the child are allergic to etanercept or to any of the other components of Enbrel (listed in section 6). If you or the child experience allergic reactions such as chest tightness, shortness of breath, dizziness, or skin rash, do not inject any 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 in doubt, contact your doctor.
  • if you or the child have any type of infection. If in doubt, consult 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, shortness of breath, dizziness, or skin rash, do not inject any more Enbrel and contact your doctor immediately.
  • Infections/surgery: If you or the child develop a new infection or are about to undergo any major surgical procedure, your doctor may need to review your treatment with Enbrel.
  • Infections/diabetes: Inform 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: Inform your doctor about any recent travel outside Europe. 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 monitoring you or the child for infections after stopping Enbrel.
  • Tuberculosis: Since cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will check for signs and symptoms of tuberculosis before starting treatment with Enbrel. This may include a thorough medical history, chest X-rays, and a tuberculin skin test. The results of these tests must be recorded in the Patient Record Card. It is very important that you inform your doctor if you or the child have ever had tuberculosis or have been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection appear during or after treatment, inform your doctor immediately.
  • Hepatitis B: Inform your doctor if you or the child have or have had hepatitis B. Your doctor must perform a hepatitis B test before you or the child start treatment with Enbrel. Treatment with Enbrel may cause reactivation of hepatitis B in patients with prior hepatitis B virus infection. In such cases, you must stop using Enbrel.
  • Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may consider monitoring treatment with Enbrel if the infection worsens.
  • Blood disorders: Seek immediate medical attention if you or the child experience any signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness.

These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of Enbrel treatment.

  • Nervous system and eye disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Enbrel is an appropriate treatment.
  • Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure, as Enbrel should be used with caution in these circumstances.
  • Tumors: Inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumor before taking Enbrel. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma. Children and adults taking Enbrel may have an increased risk of developing lymphoma or other tumors. Some children and adolescent patients treated with Enbrel or other medicines that work like Enbrel have developed tumors, including unusual types, sometimes with fatal outcomes. Some patients receiving Enbrel have developed skin tumors. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
  • Chickenpox: Inform your doctor if you or the child are exposed to chickenpox while using Enbrel. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
  • Alcohol abuse: Enbrel must not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child 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 have Wegener's granulomatosis, consult your doctor.
  • Anti-diabetic medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide that you or the child need a lower dose of anti-diabetic medicine while taking Enbrel.

Children and adolescents
Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Enbrel. Some vaccines, such as the oral polio vaccine, must not be taken while receiving Enbrel. Consult your doctor before you or the child receive any vaccine.
Enbrel should generally not be used in children with polyarticular or extended oligoarticular juvenile idiopathic arthritis under 2 years of age, in children with enthesitis-related arthritis or psoriatic arthritis under 12 years of age, or in children with psoriasis under 6 years of age.

Other medicines and Enbrel
Inform 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. You or the child must not use Enbrel together with the active substances anakinra or abatacept.

Pregnancy and breastfeeding
Enbrel should be used during pregnancy only if clearly necessary. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor.
If you have received Enbrel during pregnancy, the newborn may be at increased risk of infection. Furthermore, one study indicated a higher number of birth defects in mothers who received Enbrel during pregnancy compared to mothers who did not receive Enbrel or other similar medicines (TNF antagonists), although no specific pattern of birth defects was identified. Another study did not show an increased risk of birth defects when mothers received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed while being treated with Enbrel. It is important to inform the child's pediatricians and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
Enbrel is not expected to affect the ability to drive vehicles or operate machinery.

3. How to use Enbrel

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
If you think that the effect of Enbrel is too strong or too weak, contact your doctor or
pharmacist.

Dose for adult patients (aged 18 years and above)
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 25 mg administered twice weekly or 50 mg once weekly by subcutaneous injection.
However, your doctor may determine a different frequency for administering Enbrel.

Plaque psoriasis
The usual dose is 25 mg administered twice weekly or 50 mg administered once weekly.
Alternatively, a dose of 50 mg twice weekly may be administered for up to 12 weeks, followed by a dose of 25 mg twice weekly or 50 mg once weekly.
Your doctor will decide how long you should continue taking Enbrel and whether, based on your response, further treatment is needed. If Enbrel has not improved your condition after 12 weeks, your doctor may instruct you to stop treatment.

Use in children and adolescents
The appropriate dose and dosing frequency for a child or adolescent depends on body weight and the disease being treated. Your doctor will provide detailed instructions on how to prepare and measure the correct dose.

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

For psoriasis in patients from 6 years of age, the usual dose is 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg) administered once weekly. If Enbrel has not improved the child's condition after 12 weeks, the doctor may instruct you to discontinue treatment with this medicine.

Method and route of administration:
Enbrel is administered by injection under the skin (subcutaneous injection).
Enbrel may be taken with or without food or beverages.
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 solution with

Enbrel with other medicines.

To help you remember, it may be useful to write in a diary on 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 at one time or by using it
too frequently), speak to a doctor or pharmacist immediately (whether you have injected too much at
one time or used it too frequently). Always keep the medicine pack with you, even if it is empty.
If you forget to take Enbrel
If you forget a dose, take it as soon as you remember, unless the next dose is scheduled for the following day, in which case you should skip the missed dose.
Then continue administering the medicine on the (on the) day(s) scheduled. If you have forgotten the dose until the day when the next dose is due, do not take a double dose (two doses on the same day) to make up for the missed dose.
If you stop using Enbrel
After stopping treatment, symptoms of the disease may return.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Allergic reactions
If any of the following side effects occur, do not inject Enbrel again. Contact your doctor immediately or go to the nearest hospital emergency department.

  • Difficulty swallowing or breathing
  • Swelling of the face, throat, hands or feet
  • Feeling restless or anxious, palpitations, sudden redness of the skin and/or feeling of warmth
  • Severe rash, itching, hives (raised red or pale patches on the skin which are often itchy)

Severe allergic reactions are rare. However, any of the symptoms listed above may indicate an allergic reaction to Enbrel; therefore, you must seek immediate medical attention.

Serious side effects
If you or the child notice any of the following symptoms, urgent medical care may be needed.

  • Symptoms of serious infections, such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a warm, red, tender, painful area on the skin or joints.
  • Symptoms of blood disorders, such as bleeding, bruising or paleness.
  • Symptoms of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or sudden weakness in one arm or leg.
  • Symptoms of heart failure or worsening heart failure, such as fatigue or shortness of breath during activity, swelling of the ankles, a feeling of swelling in the neck or abdomen, shortness of breath at night or cough, bluish colouring of the fingernails or lips.
  • Symptoms of tumours: tumours may affect any part of the body, including the skin and blood, and possible symptoms depend on the type and location of the tumour. These may include weight loss, fever, swelling (with or without pain), persistent cough, or presence of cysts or skin growths.
  • Symptoms of autoimmune reactions (where antibodies are produced that may damage normal body tissues), such as pain, itching, weakness, breathing problems, changes in thinking, sensation or vision.
  • Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, joint or muscle pain, or fatigue.
  • Symptoms of inflammation of blood vessels, such as pain, fever, redness or warmth of the skin, or itching.

These side effects are rare or uncommon, but represent serious conditions (some of which may rarely lead to death). If any of these symptoms occur, contact your doctor immediately or go to the nearest hospital emergency department.

Known side effects of Enbrel include those listed below, grouped by decreasing frequency:

  • Very common (may affect more than 1 in 10 people): Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain and swelling) (these occur less frequently after the first month of treatment; some patients have developed a reaction at a recently used injection site); headache.
  • Common (may affect up to 1 in 10 people): Allergic reactions; fever; rash; itching; antibodies directed against normal tissue (formation of autoantibodies).
  • Uncommon (may affect up to 1 in 100 people): Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); reduced platelet count in the blood; skin tumour (excluding melanoma); localized swelling of the skin (angioedema); urticaria (raised red or pale patches on the skin which are often itchy); eye inflammation; psoriasis (new onset or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in blood (in patients also receiving methotrexate, the frequency of increased liver enzymes in blood is common); abdominal pain and cramps, diarrhoea, weight loss or blood in stools (symptoms of intestinal problems).
  • Rare (may affect up to 1 in 1,000 people): Severe allergic reactions (including severe localized swelling of the skin and breathing difficulties); lymphoma (a type of blood cancer); leukaemia (a cancer affecting blood and bone marrow); melanoma (a type of skin cancer); combined reduction in platelets, red blood cells and white blood cells; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis, or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain and fatigue); skin rash which may lead to blistering and severe peeling of the skin; lichenoid reactions (itchy reddish-purple rash and/or white-grey thread-like lines on mucous membranes); liver inflammation caused by your immune system (autoimmune hepatitis; in patients also receiving methotrexate, the frequency is uncommon); immune disorder which may affect the lungs, skin and lymph nodes (sarcoidosis); lung inflammation or scarring (in patients also receiving methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the tiny filters within the kidneys leading to reduced kidney function (glomerulonephritis).
  • Very rare (may affect up to 1 in 10,000 people): inability of the bone marrow to produce essential blood cells.
  • Not known (frequency cannot be estimated from available data): Merkel cell carcinoma (a type of skin cancer); Kaposi’s sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly presents with purple skin lesions; excessive activation of white blood cells involved in inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness, accompanied by skin rash).

Additional side effects in children and adolescents
The side effects and their frequency observed in children and adolescents are similar to those described above.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enbrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (between 2°C and 8°C). Do not freeze.
Before preparing the Enbrel solution, the medicine may be stored outside the refrigerator at a maximum temperature of 25°C for up to 4 weeks, only once; after this period it must not be returned to the refrigerator. If not used within 4 weeks outside the refrigerator, Enbrel must be discarded. It is recommended to record the date when Enbrel is removed from the refrigerator and the date by which Enbrel must be discarded (no more than 4 weeks outside the refrigerator).
After preparing the Enbrel solution, immediate use is recommended. However, the solution may be used within 6 hours if stored at a maximum temperature of 25°C.
Do not use this medicine if you notice that the solution is not clear or if it contains particles. The solution should appear clear, colourless to pale yellow or pale brown, and free from clumps, flakes, or particles.
Carefully discard any Enbrel solution that has not been injected within 6 hours.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Enbrel contains
The active substance in Enbrel is etanercept. Each Enbrel 25 mg vial contains 25 mg of
etanercept.
The other components are:
Powder: Mannitol (E421), sucrose and tromethamine

Description of the appearance of Enbrel and contents of the pack
Enbrel 25 mg is supplied as a white powder for injectable solution (powder for injection). Each pack contains 4 single-dose vials and 8 alcohol swabs. Not all pack sizes may be marketed.

Marketing Authorization Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

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

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder.

België/Belgique/Belgien Κύπρος
Luxembourg/Luxemburg PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
Pfizer NV/SA T +357 22 817690
Tél/Tel: +32 (0)2 554 62 11

Česká Republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: +36 1 488 3700

Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf: +45 44 201 100 Tel: +35621 344610

Deutschland Nederland
Pfizer Pharma GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

България Norge
Пфайзер Люксембург САРЛ, Pfizer AS
Клон България Tlf: +47 67 52 61 00
Teл: +359 2 970 4333

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
PFIZER EΛΛAΣ A.E. Pfizer Polska Sp. z o.o.
Τηλ.: +30 210 67 85 800 Tel.: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Télf: +34 91 490 99 00 Tel: (+351) 21 423 55 00

France România
Pfizer Pfizer Romania S.R.L
Tél +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL, Pfizer, podružnica
Tel: +385 1 3908 777 za svetovanje s področja farmacevtske
dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ireland Slovenská Republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: +1800 633 363 (toll free) Tel: +421 2 3355 5500
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Tel: +354 540 8000 Puh/Tel: +358 (0)9 430 040

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00

Latvija United Kingdom (Northern Ireland)
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel: +371 67035775 Tel: +44 (0)1304 616161

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel: +3705 2514000

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

7. Instructions for Use

This section is divided into the following subsections:
a. Introduction
b. Preparing the injection
c. Preparing the Enbrel dose for injection
d. Adding the water for injection
e. Withdrawing the Enbrel solution from the vial
f. Choosing an injection site
g. Preparing the injection site and injecting the Enbrel solution
h. Disposal of materials

a. Introduction
The following instructions explain how to prepare and inject Enbrel. Read the instructions carefully and follow them step by step. You will be trained by your doctor or nurse on the technique of self-injection or on how to administer an injection to a child. Do not attempt to give an injection until you are certain you understand how to prepare and administer it correctly.
This injection must not be mixed with any other medicine.

b. Preparing the injection

  • Wash your hands thoroughly.
  • Choose a clean, well-lit, flat work surface.
  • Remove the ENBREL vial from the refrigerator and place it on a flat surface.
  • You will also need the following materials: a sterile syringe, sterile needles of size 25x16 mm or similar, a vial or ampoule of water for injection, 2 alcohol swabs.
  • Check the expiry date on both the ENBREL vial and the water for injection. Do not use either after the month and year indicated.

c. Preparing the Enbrel dose for injection

  • Remove the plastic cap from the Enbrel vial. DO NOT remove the grey stopper or the aluminium ring around the neck of the vial.
  • Use a new alcohol swab to clean the grey stopper on the Enbrel vial. After cleaning, do not touch the grey stopper with your hands.
  • Check that the needle is securely attached to the syringe. If you are unsure how to attach the needle, ask your doctor or nurse.
  • Remove the needle cap by pulling it off firmly, taking care not to touch the needle or allow it to touch any surface (see Figure 1). Be careful not to bend or twist the cap to avoid damaging the needle.

Figure 1

Two hands holding a syringe to remove the protective cap from
  • Check that the syringe contains 1 mL of water for injection.
  • If you are unsure how to fill the syringe, ask your doctor or nurse.
  • Make sure the syringe contains no air bubbles.
  • With the ENBREL vial standing upright on a flat surface, such as a table, insert the syringe needle perpendicularly through the central ring of the grey stopper (see Figure 2). If the needle is correctly aligned, you will feel slight resistance followed by a "pop", indicating that the needle has passed through the center of the stopper. Look at the needle tip through the slit in the stopper (see Figure 3). If the needle is not correctly aligned, you will feel constant resistance as it passes through the stopper, without a "pop". Insert the needle without tilting it; tilting may bend the needle and/or prevent proper introduction of the solvent into the vial (see Figure 4).

Figure 2 Figure 3 Figure 4

Medical diagram showing a syringe with needle penetrating a rubber stopper with metal ring on a vial with stopper slit Two hands gripping a syringe to insert the Black-and-white drawing of a needle penetrating the stopper of a medical vial with a large cross over it indicating a

d. Adding the water for injection

  • Push the plunger VERY SLOWLY until all the water for injection has passed into the vial. This will help reduce foam formation (numerous bubbles) (see Figure 5).

Figure 5

One hand holds a vial with liquid while the
  • Leave the syringe in place. To dissolve the powder, gently swirl the vial several times in a circular motion (see Figure 6). DO NOT shake the vial. Wait until all the powder is dissolved (usually less than 10 minutes). The solution should appear clear and colourless to slightly yellow or slightly brown, with no fragments, flakes, or particles. Some white foam may remain in the vial – this is normal. DO NOT use Enbrel if the powder in the vial does not dissolve within 10 minutes. Start again with a new ENBREL vial, new water for injection, a new syringe, needle, and swabs.

Figure 6

One hand holds a syringe and rotates it following the movement indicated by two curved arrows forming a circle around the base of the device

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 back the plunger to draw the liquid into the syringe (see Figure 7). As the liquid level in the vial drops, you may need to partially withdraw the needle to keep its tip in the liquid. For adult patients, withdraw the full volume. For children, withdraw only the portion of liquid prescribed by the child's doctor.

Figure 7

Line drawing showing two hands handling a syringe with an arrow indicating downward movement to depress the plunger
  • With the needle still in the vial, check for air bubbles in the syringe. Gently tap the syringe to move air bubbles to the top, near the needle (see Figure 8). Slowly push the plunger to expel the air bubbles from the syringe back into the vial. If any liquid is accidentally pushed back into the vial during this process, slowly pull back the plunger to draw the liquid back into the syringe.

Figure 8

Black line drawing showing a hand holding a vial while the
  • Completely remove the needle from the vial. Again, do not touch the needle and avoid letting it touch any surface.

(Note: After completing 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 are: (1) the central front part of the thighs; (2) the abdomen, except for the area within 5 cm around the navel; and (3) the outer upper part of the arms (see Figure 9). If you are self-injecting, do not use the outer upper part of the arms.

Figure 9

Schematic drawing of a human body viewed from front and back with gray areas indicating application sites on abdomen, thighs, and arms
  • A different site must be used for each new injection. Each new injection should be given at least 3 cm away from a previous injection site. DO NOT inject into areas where the skin is tender, bruised, red, or hardened. Avoid areas with scars or stretch marks (it may help to record the location of previous injection sites).
  • If you or the child has psoriasis, try not to inject directly into swollen, thickened, red, or scaly areas of skin ("psoriatic skin lesions").

g. Preparing the injection site and injecting the Enbrel solution

  • Clean the injection site where Enbrel will be injected with an alcohol swab using a circular motion. DO NOT touch this area again before giving the injection.
  • Once the cleaned skin area is dry, pinch and firmly hold it with one hand. With the other hand, hold the syringe like a pencil.
  • With a quick, short motion, insert the needle completely into the skin at an angle between 45° and 90° (see Figure 10). With experience, you will find the angle most comfortable for you or the child. Be careful not to insert the needle too slowly or with excessive force.

Figure 10

Technical drawing showing a hand holding a syringe for a
  • Once the needle is fully inserted into the skin, release the skin you are holding. With your free hand, hold the syringe near its base to stabilize it. Then push the plunger to inject the entire solution at a slow and steady rate (see Figure 11).

Figure 11

Two hands hold a syringe to prepare the
  • When the syringe is empty, remove the needle from the skin, taking care to maintain the same angle as during insertion.
  • Press a cotton swab over the injection site for 10 seconds. Mild bleeding may occur. DO NOT rub the injection site. A bandage is optional.

h. Disposal of materials

  • The syringe and needle must NEVER be reused. Never recap the needle. Dispose of the needle and syringe as instructed by your doctor, nurse, or pharmacist.

If you have any questions, consult a doctor, nurse, or pharmacist familiar with Enbrel.

Package leaflet: information for the user

Enbrel 25 mg powder and solvent for injectable solution

etanercept
Please read this entire leaflet carefully before using this medicine because it contains
important information for you.

  • Keep this leaflet. You may need to read it again.
  • Your doctor will provide you with a Patient Information Card containing important safety information that you should be aware of before and during treatment with Enbrel.
  • If you have any questions, consult your doctor, pharmacist, or nurse.
  • This medicine has been prescribed for you or your child. Do not give it to others, even if their symptoms appear identical to yours or your child's, as it may be harmful.
  • If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet
The information in this package leaflet is divided into the following 7 sections:

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

1. What Enbrel is and what it is used for

Enbrel is a medicine made from two human proteins. It blocks the activity of another protein that causes inflammation in the human body. Enbrel works by reducing the inflammation associated with certain diseases.
In adults (18 years of age and older), Enbrel can be used to treat moderate to severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate to 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 not suitable for you. Whether used alone or in combination with methotrexate, Enbrel can slow down joint damage caused by rheumatoid arthritis and improve your ability to carry out daily activities.
For patients with psoriatic arthritis affecting multiple joints, Enbrel can improve the ability to perform daily activities. For patients with painful or swollen symmetric joints (e.g., hands, wrists, and feet), Enbrel can slow down structural damage to these joints caused by the disease.
Enbrel is also prescribed for the following conditions in children and adolescents:

  • For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not provided an adequate response or is not appropriate:
  • Polyarticular-course (rheumatoid factor positive or negative) and extended oligoarticular arthritis 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 provided an adequate response or are not appropriate.
  • Severe psoriasis in patients from the age of 6 years who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies.

2. What you should know before using Enbrel

Do not use Enbrel

  • If you or the child are allergic to etanercept or to any of the other components of Enbrel (listed in section 6). If you or the child experience allergic reactions such as chest tightness, shortness of breath, dizziness, or skin rash, do not inject any 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 in doubt, contact your doctor.
  • If you or the child have an infection of any kind. If in doubt, consult 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, shortness of breath, dizziness, or skin rash, do not inject any more Enbrel and contact your doctor immediately.
  • Latex: The rubber stopper of the syringe is made of latex (dried natural rubber). Contact your doctor before using Enbrel if the syringe will be handled by, or Enbrel will be administered to, individuals with known or suspected hypersensitivity (allergy) to latex.
  • Infections/surgery: If you or the child develop a new infection or are about to undergo any major surgical procedure. Your doctor may wish to monitor your treatment with Enbrel.
  • Infections/diabetes: Inform 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: Inform your doctor about any recent travel outside Europe. If you or the child develop symptoms of an infection such as fever, chills, or cough, inform your doctor immediately. Your doctor may decide to continue monitoring you or the child for infections after you or the child have stopped taking Enbrel.
  • Tuberculosis: Cases of tuberculosis have been reported in patients treated with Enbrel. Your doctor will check for signs and symptoms of tuberculosis before starting treatment with Enbrel. This may include a thorough medical history, chest X-rays, and a tuberculin skin test. The results of these tests must be recorded in the Patient Record Card. It is very important that you inform your doctor if you or the child have ever had tuberculosis or have been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection appear during or after therapy, inform your doctor immediately.
  • Hepatitis B: Inform your doctor if you or the child have or have had hepatitis B. Your doctor must test for hepatitis B before you or the child start treatment with Enbrel. Treatment with Enbrel may cause reactivation of hepatitis B in patients with prior hepatitis B virus infection. In such cases, you must stop using Enbrel.
  • Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may consider monitoring treatment with Enbrel if the infection worsens.
  • Blood disorders: Seek immediate medical attention if you or the child experience any signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of Enbrel treatment.
  • Nervous system and eye disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Enbrel is an appropriate treatment.
  • Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure, as Enbrel should be used with caution in such cases.
  • Tumors: Inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumor before taking Enbrel. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma. Children and adults taking Enbrel may have an increased risk of developing lymphoma or other tumors. Some children and adolescent patients treated with Enbrel or other medicines that work like Enbrel have developed tumors, including unusual types, sometimes with fatal outcomes. Some patients receiving Enbrel have developed skin tumors. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
  • Chickenpox: Inform your doctor if you or the child are exposed to chickenpox while using Enbrel. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
  • Alcohol abuse: Enbrel must not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child 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 have Wegener’s granulomatosis, consult your doctor.
  • Anti-diabetic medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide that you or the child need a lower dose of anti-diabetic medicine while taking Enbrel.

Children and adolescents
Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Enbrel. Some vaccines, such as the oral polio vaccine, should not be taken while receiving Enbrel. Consult your doctor before you or the child receive any vaccine.
Enbrel should generally not be used in children under 2 years of age with polyarticular or extended oligoarticular juvenile idiopathic arthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Other medicines and Enbrel
Inform your doctor or pharmacist if you or the child are taking, have recently taken, or might take any other medicines (including anakinra, abatacept, or sulfasalazine), even those not requiring a prescription. You or the child must not use Enbrel together with the active substances anakinra or abatacept.

Pregnancy and breastfeeding
Enbrel should be used during pregnancy only if clearly necessary. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor.
If you have received Enbrel during pregnancy, the newborn may be at increased risk of infection. Furthermore, one study indicated a higher number of birth defects in mothers who received Enbrel during pregnancy compared to mothers who did not receive Enbrel or other similar medicines (TNF antagonists), but no specific pattern of birth defects was identified. Another study did not show an increased risk of birth defects when mothers received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed while being treated with Enbrel. It is important to inform the child's pediatricians and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
Enbrel is not expected to affect the ability to drive vehicles or use machinery.

3. How to use Enbrel

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
If you think that the effect of Enbrel is too strong or too weak, contact your doctor or
pharmacist.

Dose for adult patients (aged 18 years and older)
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 25 mg administered twice weekly or 50 mg administered once weekly by subcutaneous injection. However, your doctor may determine a different dosing frequency for Enbrel injections.

Plaque psoriasis
The usual dose is 25 mg administered twice weekly or 50 mg administered once weekly.
Alternatively, a dose of 50 mg twice weekly may be administered for up to 12 weeks, followed by a dose of 25 mg twice weekly or 50 mg once weekly.
Your doctor will decide how long you should continue treatment with Enbrel and whether, based on your response, further treatment is needed. If Enbrel has not improved your condition after 12 weeks, your doctor may instruct you to stop treatment.

Use in children and adolescents
The appropriate dose and dosing frequency for a child or adolescent depends on body weight and the disease being treated. Your doctor will provide detailed instructions on how to prepare and measure the correct dose.

For polyarticular or extended oligoarticular juvenile idiopathic arthritis in patients aged 2 years and older, or for enthesitis-related arthritis or psoriatic arthritis in patients aged 12 years and older, the usual dose is 0.4 mg of Enbrel per kilogram of body weight (up to a maximum of 25 mg), administered twice weekly, or 0.8 mg of Enbrel per kilogram of body weight (up to a maximum of 50 mg) administered once weekly.

For psoriasis in patients aged 6 years and older, the usual dose is 0.8 mg of Enbrel per kilogram of body weight (up to a maximum of 50 mg), administered once weekly. If Enbrel has not improved the child's condition after 12 weeks, the doctor may instruct you to discontinue treatment with this medicine.

Method and route of administration
Enbrel is administered by injection under the skin (subcutaneous injection).
Enbrel may be taken with or without food and beverages.
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 solution with

Enbrel with other medicines

To help you remember, it may be useful to write in a diary on which day(s) of the week Enbrel should be used.
Enbrel must be dissolved before use. The injection must not be mixed in the same syringe or vial with any other medicine.

If you use more Enbrel than you should
If you have used more Enbrel than you should (either by injecting too much at one time or by using it too frequently), speak to a doctor or pharmacist immediately. Always keep the medicine pack with you, even if it is empty.

If you forget to take Enbrel
If you forget a dose, administer it as soon as you remember, unless the next dose is scheduled for the following day, in which case you should skip the missed dose. Then continue administering the medicine on your regularly scheduled day(s). If you have forgotten a dose until the day the next dose is due, do not take a double dose (two doses on the same day) to make up for the missed dose.

If you stop using Enbrel
After stopping treatment, symptoms of the disease may return.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions
If any of the following side effects occur, do not inject Enbrel again. Contact your doctor immediately or go to the nearest hospital emergency department.

  • Difficulty swallowing or breathing
  • Swelling of the face, throat, hands or feet
  • Feeling restless or anxious, palpitations, sudden redness of the skin and/or sensation of warmth
  • Severe rash, itching, hives (raised red or pale patches on the skin which often itch)

Severe allergic reactions are rare. However, any of the symptoms listed above may indicate an allergic reaction to Enbrel; therefore, you must seek immediate medical attention.
Serious side effects
If you or the child notice any of the following effects, urgent medical care may be needed.

  • Symptoms of serious infections , such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a warm, red, tender, painful area on the skin or joints.
  • Symptoms of blood disorders , such as bleeding, bruising or paleness.
  • Symptoms of nerve problems , such as numbness or tingling, changes in vision, eye pain, or sudden weakness in an arm or leg.
  • Symptoms of heart failure or worsening heart failure , such as fatigue or shortness of breath during activity, swelling of the ankles, a feeling of fullness in the neck or abdomen, shortness of breath at night or coughing, bluish discolouration of the fingernails or lips.
  • Symptoms of tumours : tumours may affect any part of the body, including the skin and blood, and possible symptoms depend on the type and location of the tumour. These may include weight loss, fever, swelling (with or without pain), persistent cough, or presence of cysts or skin growths.
  • Symptoms of autoimmune reactions (where antibodies are produced that may damage normal body tissues), such as pain, itching, weakness, breathing problems, changes in thinking, sensation or vision.
  • Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, joint or muscle pain, or fatigue.
  • Symptoms of inflammation of blood vessels , such as pain, fever, redness or warmth of the skin, or itching.

These side effects are rare or uncommon, but are serious conditions (some of which may rarely lead to death). If any of these symptoms occur, contact your doctor immediately or go to the nearest hospital emergency department.
The known side effects of Enbrel include those listed below, grouped by decreasing frequency:

  • Very common (may affect more than 1 in 10 people): Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain and swelling) (these occur less frequently after the first month of treatment; some patients have developed a reaction at a recently used injection site); headache.
  • Common (may affect up to 1 in 10 people): Allergic reactions; fever; rash (skin rash); itching; antibodies directed against normal tissue (formation of autoantibodies).
  • Uncommon (may affect up to 1 in 100 people): Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); reduced number of platelets in the blood; skin tumour (excluding melanoma); localized swelling of the skin (angioedema); hives (raised red or pale patches on the skin which often itch); eye inflammation; psoriasis (new onset or worsening), inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood.

(in patients also being treated with methotrexate, the frequency of increased liver enzymes in the blood is common); abdominal pain and cramps, diarrhoea, weight loss or blood in the stool (symptoms of intestinal problems).

  • Rare (may affect up to 1 in 1,000 people): Severe allergic reactions (including severe localized swelling of the skin and breathing difficulties); lymphoma (a type of blood cancer); leukaemia (a cancer affecting blood and bone marrow); melanoma (a type of skin cancer); combined reduction in the number of platelets, red blood cells and white blood cells; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain and fatigue); skin rash which may lead to blistering and severe skin peeling; lichenoid reactions (itchy reddish/violet rash and/or whitish-grey thread-like lines on mucous membranes); inflammation of the liver caused by your immune system (autoimmune hepatitis; in patients also being treated with methotrexate, the frequency is uncommon), an immune disorder that may affect the lungs, skin and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also being treated with methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the tiny filters within the kidneys leading to reduced kidney function (glomerulonephritis).
  • Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce essential 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 form of cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma usually presents with purple skin lesions; excessive activation of white blood cells involved in inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness accompanied by skin rash).

Additional side effects in children and adolescents
The side effects and their frequency observed in children and adolescents are similar to those described above.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enbrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (between 2°C and 8°C). Do not freeze.
Before preparing the Enbrel solution, the medicine may be stored outside the refrigerator at a maximum temperature of 25°C for up to 4 weeks, for one single time only; after this period it must not be returned to the refrigerator. If not used within 4 weeks outside the refrigerator, Enbrel must be discarded. It is recommended to record the date when Enbrel was removed from the refrigerator and the date by which Enbrel must be discarded (no more than 4 weeks outside the refrigerator).
After preparing the Enbrel solution, immediate use is recommended. However, the solution may be used within 6 hours if stored at a maximum temperature of 25°C.
Do not use this medicine if you notice that the solution is not clear or if it contains particles. The solution should appear clear and colourless to pale yellow or pale brown, without any clumps, flakes, or particles.
Carefully discard any Enbrel solution that has not been injected within 6 hours.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Enbrel contains
The active substance in Enbrel is etanercept. Each vial of Enbrel 25 mg contains 25 mg of
etanercept.
The other components are:
Powder: Mannitol (E421), sucrose and tromethamine
Solvent: water for injections
Description of the appearance of Enbrel and contents of the pack
Enbrel 25 mg is supplied as a white powder and solvent for injectable solution. Each
package contains 4, 8 or 24 single-dose vials, 4, 8 or 24 pre-filled syringes with water for
injections, 4, 8 or 24 needles, 4, 8 or 24 vial adapters, 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 Brussels
Belgium
Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12,
2870 Puurs-Sint-Amands
Belgium
For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder.
België/Belgique/Belgien Κύπρος
Luxembourg/Luxemburg PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
Pfizer NV/SA T \\l : +357 22 817690
Tél/Tel: +32 (0)2 554 62 11
Česká Republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: +36 1 488 3700
Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf: +45 44 201 100 Tel: +35621 344610
Deutschland Nederland
Pfizer Pharma GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636
България/ Norge
Пфайзер Люксембург САРЛ, Pfizer AS
Клон България Tlf: +47 67 52 61 00
Teл: +359 2 970 4333
Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0
Ελλάδα Polska
PFIZER EΛΛAΣ A.E. Pfizer Polska Sp. z o.o.
Τηλ.: +30 210 67 85 800 Tel.: +48 22 335 61 00
España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Télf: +34 91 490 99 00 Tel: (+351) 21 423 55 00
France România
Pfizer Pfizer Romania S.R.L
Tél +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00
Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL, Pfizer, podružnica
Tel: +385 1 3908 777 za svetovanje s področja farmacevtske
dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400
Ireland Slovenská Republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: +1800 633 363 (toll free) Tel: +421 2 3355 5500
Tel: +44 (0)1304 616161
Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Tel: +354 540 8000 Puh/Tel: +358 (0)9 430 040
Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00
Latvija United Kingdom (Northern Ireland)
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel. +371 67035775 Tel: +44 (0)1304 616161
Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu.

7. Instructions for Use

This section is divided into the following subsections:
a. Introduction
b. Preparation of the injection
c. Preparing the Enbrel dose for injection
d. Adding the solvent
e. Drawing the Enbrel solution from the vial
f. Attaching the needle to the syringe
g. Choosing an injection site
h. Preparing the injection site and injecting the Enbrel solution
i. Disposal of materials

a. Introduction
The following instructions explain how to prepare and inject Enbrel. Please read the instructions carefully and follow them step by step. Your doctor or nurse will instruct you on the technique of self-injection or on how to administer an injection to a child. Do not attempt to administer an injection until you are certain you understand how to prepare and give the injection.
This injection must not be mixed with any other medicine.

b. Preparation of the injection

  • Wash your hands thoroughly.

  • Choose a clean, well-lit, flat working surface.

  • The tray containing the dose should include the following materials (if any of these are missing, do not use the tray and consult your pharmacist). Use only the materials 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 adapter
    • 2 alcohol swabs

  • Check the expiration dates on both the vial label and the syringe label. Do not use after the month and year indicated.

c. Preparing the Enbrel dose for injection

  • Remove the contents from the tray.
  • Remove the plastic cap from the Enbrel vial (see Figure 1). DO NOT remove the grey stopper or the aluminium ring around the neck of the vial.

Figure 1

One hand vertically holds a cylindrical vial while the thumb presses downward on the top toward the
  • Use a new alcohol swab to clean the grey stopper on the Enbrel vial. After cleaning, do not touch the grey stopper with your hands or allow it to come into contact with any other surface.
  • Place the vial upright on a clean, flat surface.
  • Remove the paper backing from the vial adapter package.
  • Position the vial adapter onto the top of the Enbrel vial while it is still in its plastic packaging, ensuring that the tip of the adapter is centred over the raised circle on the vial stopper (see Figure 2).
  • With one hand, hold the Enbrel vial firmly on a flat surface. With the other hand, press FIRMLY DOWNWARD on the adapter package until you feel and hear the adapter snap into place and the tip of the adapter pierces the vial stopper AND YOU HEAR A CLICK AS THE ADAPTER LOCKS INTO PLACE (see Figure 3). DO NOT press down on the adapter at an angle (see Figure 4). It is important that the tip of the vial adapter fully penetrates the vial stopper.

Figure 2      Figure 3      Figure 4

Schematic diagram showing a medicine vial with the cap removed and an administration device positioned above it Schematic drawing with a large X indicating the Schematic diagram showing a medicine vial under a dosing device or a separate protective cap

CORRECT INCORRECT

  • Holding the vial in one hand, remove the plastic packaging from the adapter (see Figure 5)

Figure 5

Black-and-white schematic diagram showing a medicine vial with a dosing device placed over the neck of the container
  • Remove the protective cap from the end of the syringe by breaking the white cap along the perforation. This is done by holding the ring of the white cap while grasping the end of the white cap with the other hand and bending it downward and then upward until it breaks (see Figure 6). DO NOT remove the white ring that remains on the syringe.

Figure 6

Two hands separating the cap from the body of an injection pen with a black arrow pointing toward the
  • Do not use the syringe if this perforation has already been broken. Start again with another dose-tray.
  • Holding the glass barrel of the syringe in one hand (not the white ring), and the vial adapter (not the vial) in the other, connect the syringe to the vial adapter by inserting the tip into the opening and turning it clockwise until fully secured (see Figure 7).

Figure 7

Diagram showing the rotational movement of a drug vial to attach the

d. Adding the solvent

  • Holding the vial upright on a flat surface, push the plunger VERY SLOWLY until all the solvent has entered the vial. This will help reduce foam formation (numerous bubbles) (see Figure 8).
  • Once the solvent has been added to Enbrel, the plunger may move on its own. This is caused by air pressure and is not significant.

Figure 8

One hand holds the top of a syringe while the
  • With the syringe still attached, gently swirl the vial several times in a circular motion to dissolve the powder (see Figure 9). DO NOT shake the vial. Wait until all the powder has dissolved (usually less than 10 minutes). The solution should appear clear and colourless to pale yellow or pale brown, with no fragments, flakes, or particles. A small amount of white foam may remain in the vial – this is normal. DO NOT use Enbrel if all the powder in the vial does not dissolve within 10 minutes. Start again with another dose-tray. Figure 9
One hand holds a syringe vertically above a vial with two curved arrows indicating a rotational movement for withdrawal

e. Withdrawing the Enbrel solution from the vial

  • With the syringe still attached to the vial and vial adapter, hold the vial upside down at eye level. Push the plunger fully into the sy游戏副本 (see Figure 10).

Figure 10

Technical drawing showing a syringe held with two hands with an arrow pointing toward the
  • Then, slowly pull back the plunger to draw the liquid into the syringe (see Figure 11). For adult patients, withdraw the entire volume. For children, withdraw only the portion of liquid as prescribed by the child’s doctor. After withdrawing Enbrel from the vial, there may be air in the syringe. Do not worry, as the air can be removed later.

Figure 11

One hand holds the top of a syringe while the
  • Holding the vial upside down, unscrew the syringe from the vial adapter by turning it counterclockwise (see Figure 12).

Figure 12

Diagram showing the rotational movement of a vial and a medical device for the
  • Place the filled syringe on a clean, flat surface. Make sure the tip does not touch anything. Be careful not to push the plunger down.

(Note: After completing these steps, a small amount of liquid may remain in the
vial. This is normal.)
f. Attaching the needle to the syringe

  • The needle is kept sterile inside a plastic container.
  • To open the plastic container, hold the short, wide end in one hand and place the other hand on the longer part of the container.
  • To break the seal, bend the wider end downward and then upward until it breaks (see Figure 13).

Figure 13

Two hands hold an injection pen with curved arrows indicating rotational movement for drug preparation
  • Once the seal is broken, remove the short, wide end of the plastic container.
  • The needle will remain in the long part of the packaging.
  • Holding the needle and container in one hand, take the syringe and insert its tip into the needle opening.
  • Attach the syringe to the needle by turning it clockwise until fully secured (see Figure 14).

Figure 14

Technical diagram showing the
  • Remove the needle cap from the syringe by pulling it off firmly, taking care not to touch the needle or allow the needle to touch any surface (see Figure 15). Be careful not to bend or twist the cap to avoid damaging the needle.

Figure 15

A syringe needle is inserted into a connector with a black arrow indicating the direction of movement toward the
  • Holding the syringe upright, remove the air by slowly pushing the plunger until all air is expelled (see Figure 16).

Figure 16

One hand holds a syringe vertically with the needle pointing toward the

g. Choosing an injection site

  • The three recommended injection sites for Enbrel are: (1) the central front part of the thighs; (2) the abdomen, except for the area within 5 cm around the navel; and (3) the outer area of the upper arms (see Figure 17). If you are self-injecting, do not use the outer area of the upper arms.

Figure 17

Schematic drawing of a human body viewed from front and back with gray areas indicating injection sites on abdomen, thighs, and arms
  • A different site must be used for each new injection. Each new injection should be given at least 3 cm away from a previous injection site. Do not inject into areas where the skin is tender, bruised, red, or hardened. Avoid areas with scars or stretch marks (it may help to record the locations of previous injection sites).
  • If you or the child has psoriasis, try not to inject directly into swollen, thickened, red, or scaly areas of skin (“psoriatic skin lesions”).

h. Preparing the injection site and injecting the Enbrel solution

  • Wipe the injection site where Enbrel will be injected with an alcohol swab using a circular motion. DO NOT touch this area again before administering the injection.
  • Once the cleaned skin area has dried, pinch and firmly hold it with one hand. With the other hand, hold the syringe like a pencil.
  • With a quick, short motion, insert the needle completely into the skin at an angle between 45° and 90° (see Figure 18). With experience, you will find the angle most comfortable
    for you or the child. Be careful not to insert the needle too slowly or with excessive force.
    Figure 18
Technical drawing showing a hand holding a syringe to inject medication into the arm at an angle between 45 and 90 degrees
  • When the needle is fully inserted into the skin, release the skin you are holding. With your free hand, hold the syringe near its base to stabilize it. Then push the plunger to inject the entire solution at a slow and steady rate (see Figure 19).

Figure 19

Two hands hold an injection pen to apply it to the skin with a downward movement indicated by a white arrow
  • When the syringe is empty, remove the needle from the skin, taking care to maintain the same angle used during insertion.
  • Press a cotton pad over the injection site for 10 seconds. Mild bleeding may occur. DO NOT rub the injection site. A bandage is optional.

i. Disposal of materials

  • The syringe and needles must NEVER be reused. Dispose of needles and syringe as instructed by your doctor, nurse, or pharmacist.

If you have any questions, consult a doctor, nurse, or pharmacist familiar with Enbrel.

Package leaflet: Information for the user

Enbrel 25 mg solution for injection in pre-filled syringes, 50 mg solution for injection in pre-filled syringe

etanercept
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

  • Keep this leaflet. You may need to read it again.
  • Your doctor will provide you with a Patient Safety Card containing important safety information you should be aware of before and during treatment with Enbrel.
  • If you have any questions, consult your doctor, pharmacist, or nurse.
  • This medicine has been prescribed for you or for the child. Do not give it to others, even if their symptoms are the same as yours or those of the child, because it could be harmful.
  • If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet
The information in this package leaflet is divided into the following 7 sections:

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

1. What Enbrel is and what it is used for

Enbrel is a medicine made from two human proteins. It blocks the activity of another protein that causes inflammation in the human body. Enbrel works by reducing the inflammation associated with certain diseases.
In adults (aged 18 years and older), Enbrel can be used to treat moderate to severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate to 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 not suitable for you. Whether used alone or in combination with methotrexate, Enbrel can slow down joint damage caused by rheumatoid arthritis and improve your ability to carry out normal daily activities.
For patients with psoriatic arthritis affecting multiple joints, Enbrel can improve the ability to perform daily activities. For patients with painful or swollen symmetric joints (e.g., hands, wrists, and feet), Enbrel can slow down structural damage to these joints caused by the disease.
Enbrel is also prescribed for the treatment of the following conditions in children and adolescents:

  • For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not provided an adequate response or is not appropriate:
  • Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients aged 2 years and older
  • Psoriatic arthritis in patients aged 12 years and older.
  • For enthesitis-related arthritis in patients aged 12 years and older, when other widely used treatments have not provided an adequate response or are not appropriate.
  • Severe psoriasis in patients aged 6 years and older who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies.

2. What you should know before using Enbrel

Do not use Enbrel

  • if you or the child are allergic to etanercept or to any of the other ingredients of Enbrel (listed in section 6). If you or the child experience allergic reactions such as chest tightness, shortness of breath, dizziness, or skin rash, do not inject any 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 in doubt, contact your doctor.
  • if you or the child currently have any type of infection. If in doubt, consult 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, shortness of breath, dizziness, or skin rash, do not inject any more Enbrel and contact your doctor immediately.
  • Infections/surgery: If you or the child develop a new infection or are about to undergo any major surgical procedure. Your doctor may want to review your treatment with Enbrel.
  • Infections/diabetes: Inform 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: Inform your doctor about any recent travel outside Europe. 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 monitoring you or the child for infections even after stopping Enbrel.
  • Tuberculosis: Cases of tuberculosis have been reported in patients treated with Enbrel. Your doctor will check for signs and symptoms of tuberculosis before starting Enbrel treatment. This may include a thorough medical history, chest X-ray, and tuberculin skin test. The results of these tests must be recorded in the Patient Record Card. It is very important that you inform your doctor if you or the child have ever had tuberculosis or have been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection appear during or after treatment, inform your doctor immediately.
  • Hepatitis B: Inform your doctor if you or the child have or have had hepatitis B. Your doctor must test for hepatitis B before starting Enbrel treatment. Treatment with Enbrel may cause reactivation of hepatitis B in patients previously infected with the hepatitis B virus. If this occurs, you must stop using Enbrel.
  • Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may decide to monitor your treatment with Enbrel if the infection worsens.
  • Blood disorders: Seek immediate medical attention if you or the child experience any signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of Enbrel treatment.
  • Nervous system and eye disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Enbrel is an appropriate treatment.
  • Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure, as Enbrel should be used with caution in such cases.
  • Tumors: Inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumor before taking Enbrel. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma. Children and adults taking Enbrel may have an increased risk of developing lymphoma or other tumors. Some children and adolescent patients treated with Enbrel or other medicines that work like Enbrel have developed tumors, including unusual types, sometimes with fatal outcomes. Some patients receiving Enbrel have developed skin tumors. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
  • Chickenpox (varicella): Inform your doctor if you or the child are exposed to chickenpox while using Enbrel. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
  • Latex: The needle cap is made of latex (dried natural rubber). Contact your doctor before using Enbrel if the needle cap will be handled by, or if Enbrel will be administered to, a person with known or suspected hypersensitivity (allergy) to latex.
  • Alcohol abuse: Enbrel must not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child 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 have Wegener’s granulomatosis, consult your doctor.
  • Anti-diabetic medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide that you or the child may need a lower dose of anti-diabetic medicine while taking Enbrel.

Children and adolescents
Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Enbrel. Some vaccines, such as the oral polio vaccine, must not be taken while receiving Enbrel. Consult your doctor before you or the child receive any vaccine.
Enbrel should generally not be used in children under 2 years of age with polyarticular or extended oligoarticular juvenile idiopathic arthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Other medicines and Enbrel
Inform your doctor or pharmacist if you or the child are taking, have recently taken, or might take any other medicines (including anakinra, abatacept, or sulfasalazine), even those not prescribed. You or the child must not use Enbrel together with the active substances anakinra or abatacept.

Pregnancy and breastfeeding
Enbrel should be used during pregnancy only if clearly necessary. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor.
If you received Enbrel during pregnancy, the newborn may be at increased risk of infection. Furthermore, one study indicated a higher number of birth defects in mothers who received Enbrel during pregnancy compared to mothers who did not receive Enbrel or other similar medicines (TNF antagonists), although no specific pattern of birth defects was identified. Another study did not show an increased risk of birth defects when mothers received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed while on Enbrel treatment. It is important to inform the child’s pediatrician and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
Enbrel is not expected to affect the ability to drive or use machines.

Enbrel contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Enbrel

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
If you think that the effect of Enbrel is too strong or too weak, please contact your
doctor or pharmacist.
The pre-filled syringe is available in strengths of 25 mg and 50 mg.
Dose for adult patients (aged 18 years and older)
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 25 mg administered twice weekly or 50 mg administered once weekly by subcutaneous injection. However, your doctor may determine a different dosing frequency for Enbrel.
Plaque psoriasis
The usual dose is 25 mg administered twice weekly or 50 mg administered once weekly.
Alternatively, a dose of 50 mg twice weekly may be administered for up to 12 weeks, followed by a dose of 25 mg twice weekly or 50 mg once weekly.
Your doctor will decide how long you should take Enbrel and whether, based on your response, further treatment is needed. If Enbrel has no effect on your disease after 12 weeks, your doctor may instruct you to stop treatment.
Use in children and adolescents
The appropriate dose and dosing frequency for a child or adolescent will depend on body weight and the condition being treated. Your doctor will determine the correct dose for your child and will prescribe an appropriate Enbrel dosage (10 mg, 25 mg, or 50 mg).
For polyarthritis or extended oligoarthritis in patients from 2 years of age, or enthesitis-related arthritis or psoriatic arthritis in patients from 12 years of age, the usual dose is 0.4 mg of Enbrel per kilogram of body weight (up to a maximum of 25 mg) administered twice weekly, or 0.8 mg of Enbrel per kilogram of body weight (up to a maximum of 50 mg) administered once weekly.
For psoriasis in patients from 6 years of age, the usual dose is 0.8 mg of Enbrel per kilogram of body weight (up to a maximum of 50 mg), administered once weekly. If Enbrel has no effect on the child's condition after 12 weeks, the doctor may advise stopping treatment with this medicine.
Your doctor will provide detailed instructions on how to prepare and measure the appropriate dose.
Method and route of administration
Enbrel is administered by injection under the skin (subcutaneous injection).
Enbrel may be taken with or without food and beverages.
Detailed instructions on how to inject Enbrel are provided in section 7, “Instructions for use”. Do not mix the Enbrel solution with other medicines.
To help you remember, it may be helpful to write in a diary on 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 at one time or by using it too frequently), contact a doctor or pharmacist immediately. Always keep the medicine carton with you, even if it is empty.
If you forget to take Enbrel
If you miss a dose, take it as soon as you remember, unless the next dose is scheduled for the following day, in which case you should skip the missed dose. Then continue administering the medicine on the originally scheduled day(s). If you have forgotten a dose until the day the next dose is due, do not take a double dose (two doses on the same day) to make up for the missed dose.
If you stop treatment with Enbrel
After stopping treatment, symptoms of the disease may return.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Allergic reactions
If any of the following side effects occur, do not inject Enbrel again. Contact your doctor immediately or go to the nearest hospital emergency department.

  • Difficulty swallowing or breathing
  • Swelling of the face, throat, hands or feet
  • Feeling restless or anxious, palpitations, sudden skin redness and/or feeling of warmth
  • Severe rash, itching, hives (raised red or pale patches on the skin that are often itchy)

Severe allergic reactions are rare. However, any of the symptoms listed above may indicate an allergic reaction to Enbrel; therefore, you must seek immediate medical attention.

Serious side effects
If you or the child notice any of the following symptoms, urgent medical care may be needed.

  • Symptoms of serious infections, such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a warm, red, tender, painful area on the skin or joints.
  • Symptoms of blood disorders, such as bleeding, bruising or paleness.
  • Symptoms of nerve problems, such as numbness or tingling, vision changes, eye pain, or sudden weakness in an arm or leg.
  • Symptoms of heart failure or worsening heart failure, such as fatigue or shortness of breath during activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, shortness of breath at night or cough, bluish colouring of the nails or lips.
  • Symptoms of tumours: tumours can affect any part of the body, including the skin and blood, and possible symptoms depend on the type and location of the tumour. These may include weight loss, fever, swelling (with or without pain), persistent cough, or cysts or growths on the skin.
  • Symptoms of autoimmune reactions (where antibodies are produced that may damage normal body tissues), such as pain, itching, weakness, breathing problems, changes in thinking, sensation or vision.
  • Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, joint or muscle pain, or fatigue.
  • Symptoms of inflammation of blood vessels, such as pain, fever, redness or warmth of the skin, or itching.

These side effects are rare or uncommon, but they are serious conditions (some of which may rarely lead to death). If any of these symptoms occur, contact your doctor immediately or go to the nearest hospital emergency department.

Known side effects of Enbrel include the following, listed by 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 occur less frequently after the first month of treatment; some patients have developed a reaction at a recently used injection site); headache.
  • Common (may affect up to 1 in 10 people): Allergic reactions; fever; rash; itching; antibodies directed against normal tissue (formation of autoantibodies).
  • Uncommon (may affect up to 1 in 100 people): Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); reduced platelet count in the blood; skin tumour (excluding melanoma); localized swelling of the skin (angioedema); urticaria (raised red or pale patches on the skin that are often itchy); eye inflammation; psoriasis (new onset or worsening), inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood (in patients also being treated with methotrexate, the frequency of increased liver enzymes in the blood is common); abdominal pain and cramps, diarrhoea, weight loss or blood in the stools (symptoms of intestinal problems).
  • Rare (may affect up to 1 in 1,000 people): Severe allergic reactions (including severe localized swelling of the skin and breathing difficulties); lymphoma (a type of blood cancer); leukaemia (a cancer affecting blood and bone marrow); melanoma (a type of skin cancer); decreased numbers of platelets, red blood cells and white blood cells together; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain and fatigue); skin rash that may lead to severe blistering and peeling of the skin; lichenoid reactions (itchy reddish-purple rash and/or whitish-grey thread-like lines on mucous membranes); liver inflammation caused by your immune system (autoimmune hepatitis; in patients also being treated with methotrexate, the frequency is uncommon); an immune disorder that may affect the lungs, skin and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also being treated with methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the tiny filters in the kidneys leading to reduced kidney function (glomerulonephritis).
  • Very rare (may affect up to 1 in 10,000 people): Failure of the bone marrow to produce essential 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 form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma usually appears as purple lesions on the skin; excessive activation of white blood cells involved in inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness accompanied by a skin rash).

Additional side effects in children and adolescents
The side effects and their frequency observed in children and adolescents are similar to those described above.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enbrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and on the prefilled syringe after “Exp.”. The expiry date refers to the last day of that month.
Store in a refrigerator (between 2°C and 8°C).
Do not freeze.
Keep the prefilled syringes in their outer packaging to protect the medicine from light.
After removing a syringe from the refrigerator, wait approximately 15–30 minutes to allow the Enbrel solution in the syringe to reach room temperature. Do not heat it in any other way. Immediate use is therefore recommended.
Enbrel may be stored at a maximum temperature of 25°C for up to 4 weeks, for one time only; after this period it must not be returned to the refrigerator. If not used within 4 weeks outside the refrigerator, Enbrel must be discarded. It is recommended to record the date when Enbrel was removed from the refrigerator and the date by which Enbrel must be discarded (no more than 4 weeks outside the refrigerator).
Inspect the solution inside the syringe. The solution should be from clear to slightly opalescent, colourless to pale yellow or light brown, and may contain small white or almost transparent protein particles. This is the normal appearance of Enbrel. Do not use this solution if it shows changes in colour, appears cloudy, or if particles different from those described are visible. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Enbrel contains
Enbrel 25 mg solution for injection in pre-filled syringe
The active substance in Enbrel is etanercept. Each pre-filled syringe of Enbrel contains 0.5 mL of solution, containing 25 mg of etanercept.
Enbrel 50 mg solution for injection in pre-filled syringe
The active substance in Enbrel is etanercept. Each pre-filled syringe of Enbrel contains 1.0 mL of solution, containing 50 mg of etanercept.
The other components are sucrose, sodium chloride, L-arginine hydrochloride, monosodium phosphate dihydrate, disodium phosphate dihydrate and water for injections.

Description of the appearance of Enbrel and contents of the pack
Enbrel 25 mg solution for injection in pre-filled syringe
Enbrel is supplied as a pre-filled syringe containing a clear, colourless to pale yellow or pale brown injectable solution. Each carton contains 4, 8, 12 or 24 pre-filled syringes and 4, 8, 12 or 24 alcohol swabs. Not all pack sizes may be marketed.

Enbrel 50 mg solution for injection in pre-filled syringe
Enbrel is supplied as a pre-filled syringe containing a clear, colourless to pale yellow or pale brown injectable solution. Each carton contains 2, 4 or 12 pre-filled syringes and 2, 4 or 12 alcohol swabs. Not all pack sizes may be marketed.

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

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

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

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

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

Luxembourg/Luxemburg
Pfizer Luxembourg SARL
Tel: +352 2717 5555

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: +356 21 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
FIZER EΛΛAΣ A.E.
Τηλ.: +30 210 67 85 800

España
Pfizer, S.L.
Télf: +34 91 490 99 00

Portugal
Laboratórios Pfizer, Lda.
Tel: (+351) 21 423 55 00

France
Pfizer
Tél +33 (0)1 58 07 34 40

România
Pfizer Romania S.R.L
Tel: +40 (0) 21 207 28 00

Hrvatska
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777

Slovenija
Pfizer Luxembourg SARL, Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ireland
Pfizer Healthcare Ireland
Tel: +1800 633 363 (toll free)
Tel: +44 (0)1304 616161

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

United Kingdom (Northern Ireland)
Pfizer Limited
Tel: +44 (0)1304 616161

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel: +3705 2514000

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

7. Instructions for Use

This section is divided into the following subsections:
Introduction
Step 1: Preparing the Injection
Step 2: Choosing an Injection Site
Step 3: Injecting the Enbrel Solution
Step 4: Disposal of Materials

Introduction
The following instructions explain how to prepare and inject Enbrel. Please read these instructions carefully and follow them step by step. Your doctor or nurse will instruct you on the proper techniques for self-injection or for injecting a child. Do not attempt to perform a self-injection or inject a child until you are certain you understand how to prepare and administer the injection correctly.

The Enbrel solution must not be mixed before use with any other medication.

Step 1: Preparing the Injection

  1. Choose a clean, well-lit, flat work surface.
  2. Take the box of Enbrel containing the pre-filled syringes out of the refrigerator and place it on the flat work surface. Starting from one of the top corners, pull off the protective paper covering the top and sides of the tray. Remove one pre-filled syringe and one alcohol swab and place them on the work surface. Do not shake the pre-filled Enbrel syringe. Fold the protective paper back over the tray and return the box containing the remaining pre-filled syringes to the refrigerator. See section 5 for instructions on storing Enbrel. If you have any questions about storage, contact your doctor, nurse, or pharmacist for further guidance.
  3. You must wait 15–30 minutes to allow the Enbrel solution in the syringe to reach room temperature. DO NOT remove the needle cap while waiting for the solution to warm to room temperature. Waiting until the solution reaches room temperature may make the injection more comfortable. Do not heat Enbrel in any other way (for example, do not heat it in a microwave or in warm water).
  4. Prepare the other materials you will need for your injection. These include the alcohol swab from the Enbrel kit and a cotton ball or gauze pad.
  5. Wash your hands thoroughly with soap and warm water.
  6. Inspect the solution inside the syringe. The solution should be from clear to slightly opalescent, colorless to pale yellow or light brown, and may contain small white or nearly transparent protein particles. This is the normal appearance of Enbrel. Do not use this solution if it changes color, appears cloudy, or if particles other than those described are visible. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.

Step 2: Choosing an Injection Site

  1. The three recommended injection sites for Enbrel when using a pre-filled syringe are: (1) the central front area of the thighs; (2) the abdomen, except for the area within 5 cm around the navel; and (3) the outer area of the upper arms (see Figure 1). If you are self-injecting, do not use the outer area of the upper arms.
    Figure 1
Schematic drawing of a human body viewed from front and back with gray areas indicating injection sites on abdomen, thighs, and arms
  1. A different site should be used for each new injection. Each new injection should be administered at least 3 cm away from a previous injection site. Do not inject into areas where the skin is tender, bruised, red, or hardened. Avoid areas with scars or stretch marks (it may be helpful to record the locations of previous injection sites).
  2. If you or the child has psoriasis, try to avoid injecting directly into swollen, thickened, red, or scaly areas of skin (“psoriatic skin lesions”).

Step 3: Injecting the Enbrel Solution

  1. Clean the injection site where Enbrel will be injected using the alcohol swab with a circular motion. DO NOT touch this area again before administering the injection.
  2. Pick up the pre-filled syringe from the flat work surface. Remove the needle cap by firmly pulling it straight off the syringe (see Figure 2). Be careful not to bend or twist the cap during removal to avoid damaging the needle.

When removing the needle cap, a small drop of liquid may appear at the tip of the needle; this is normal. Do not touch the needle or allow it to touch any surface. Do not touch or press the plunger. This could cause the liquid to leak out.
Figure 2

Two hands separating or connecting a cylindrical container from a syringe with needle via a horizontal movement indicated by black arrows
  1. Once the cleaned skin area has dried, pinch and firmly hold the skin with one hand. With the other hand, hold the syringe like a pencil.
  2. With a quick, short motion, insert the needle completely into the skin at an angle between 45° and 90° (see Figure 3). With experience, you will find the angle that is most comfortable for you or the child. Be careful not to insert the needle too slowly or with excessive force.

Figure 3

Technical drawing showing a hand holding a syringe to inject medication into the arm at an angle between 45 and 90 degrees
  1. Once the needle is fully inserted into the skin, release the skin you were holding. With your free hand, hold the syringe near its base to stabilize it. Then slowly and steadily push the plunger to inject all of the solution at a slow and constant rate (see Figure 4).

Figure 4

Two hands hold a syringe with the needle pointing downward while an arrow indicates the movement of depressing the plunger toward the
  1. When the syringe is empty, remove the needle from the skin, taking care to maintain the same angle as during insertion. Mild bleeding at the injection site may occur. You may press a cotton ball or gauze pad over the injection site for 10 seconds. Do not rub the injection site. If needed, the injection site may be covered with a bandage.

Step 4: Disposal of Materials

  • The pre-filled syringe is for single-use only. The syringe and needle must NEVER be reused. Never recap a needle. Dispose of needles and syringes as instructed by your doctor, nurse, or pharmacist.

If you have any questions, consult a doctor, nurse, or pharmacist familiar with Enbrel.

Package leaflet: information for the user

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

etanercept
Please read this entire leaflet carefully before using this medicine because it contains important information for you

  • Keep this leaflet. You may need to read it again.
  • Your doctor will provide you with the Patient Information Card containing important safety information that you need to know before and during treatment with Enbrel.
  • If you have any questions, consult your doctor, pharmacist or nurse.
  • This medicine has been prescribed for you or for a child. Do not give it to others, even if their symptoms are the same as yours or those of the child, as it may be harmful.
  • If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet
The information in this patient information leaflet is divided into the following 7 sections:

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

1. What Enbrel is and what it is used for

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

In adults (aged 18 years and older), Enbrel can be used to treat moderate to severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate to 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 not suitable for you. Whether used alone or in combination with methotrexate, Enbrel can slow down joint damage caused by rheumatoid arthritis and improve your ability to carry out normal daily activities.

For patients with psoriatic arthritis affecting multiple joints, Enbrel can improve the ability to perform daily activities. For patients with painful or swollen symmetrically affected joints (e.g. hands, wrists and feet), Enbrel can slow down structural damage to these joints caused by the disease.

Enbrel is also prescribed for the following conditions in children and adolescents:

  • For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not provided a sufficiently good response or is not appropriate:
    • 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 provided a sufficiently good response or are not appropriate.
  • Severe psoriasis in patients from the age of 6 years who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies.

2. What you should know before using Enbrel

Do not use Enbrel

  • if you or the child are allergic to etanercept or to any of the other ingredients of Enbrel (listed in section 6). If allergic reactions such as chest tightness, shortness of breath, dizziness, or skin rash occur in you or the child, do not inject any 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 unsure, contact your doctor.
  • if you or the child currently have any type of infection. If in doubt, consult 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, shortness of breath, dizziness, or skin rash, do not inject any more Enbrel and contact your doctor immediately.
  • Infections/surgery: If you or the child develop a new infection or are about to undergo any major surgical procedure. Your doctor may wish to review your treatment with Enbrel.
  • Infections/diabetes: Inform 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: Inform your doctor about any recent travel outside Europe. If you or the child develop symptoms of an infection such as fever, chills, or cough, inform your doctor immediately. Your doctor may decide to continue monitoring you or the child for infections even after stopping Enbrel.
  • Tuberculosis: Cases of tuberculosis have been reported in patients treated with Enbrel. Your doctor will check for signs and symptoms of tuberculosis before starting treatment with Enbrel. This may include a thorough medical history, chest X-ray, and tuberculin skin test. The results of these tests must be recorded on the Patient Record Card. It is very important that you inform your doctor if you or the child have ever had tuberculosis or have been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection appear during or after treatment, inform your doctor immediately.
  • Hepatitis B: Inform your doctor if you or the child have or have previously had hepatitis B. Your doctor must perform a test for hepatitis B before you or the child start treatment with Enbrel. Treatment with Enbrel may cause reactivation of hepatitis B in patients who have previously been infected with the hepatitis B virus. In such cases, you must stop using Enbrel.
  • Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may consider monitoring treatment with Enbrel if the infection worsens.
  • Blood disorders: Seek immediate medical help if you or the child experience any signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of Enbrel.
  • Nervous system and eye disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Enbrel is an appropriate treatment.
  • Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure, as Enbrel should be used with caution in such cases.
  • Tumors: Inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumor before taking Enbrel. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma. Children and adults taking Enbrel may have an increased risk of developing lymphoma or other tumors. Some children and adolescent patients treated with Enbrel or with other medicines that work like Enbrel have developed tumors, including unusual types, sometimes with fatal outcomes. Some patients receiving Enbrel have developed skin tumors. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
  • Chickenpox (varicella): Inform your doctor if you or the child are exposed to chickenpox while using Enbrel. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
  • Latex: The needle cap of the MYCLIC pen is made of latex (dried natural rubber). Contact your doctor before using Enbrel if the needle cap will be handled by, or if Enbrel will be administered to, a person with known or possible hypersensitivity (allergy) to latex.
  • Alcohol abuse: Enbrel must not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child 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 have Wegener’s granulomatosis, consult your doctor.
  • Anti-diabetic medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide that you or the child may need a lower dose of anti-diabetic medicine while taking Enbrel.

Children and adolescents
Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Enbrel. Some vaccines, such as oral polio vaccine, must not be taken while receiving Enbrel. Consult your doctor before you or the child receive any vaccine.
Enbrel should normally not be used in children under 2 years of age with polyarthritis or extended oligoarthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Other medicines and Enbrel
Inform your doctor or pharmacist if you or the child are taking, have recently taken, or might take any other medicines (including anakinra, abatacept, or sulfasalazine), even those not prescribed. You or the child must not use Enbrel together with the active substances anakinra or abatacept.

Pregnancy and breastfeeding
Enbrel should be used during pregnancy only if clearly necessary. If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor.
If you have received Enbrel during pregnancy, the newborn may be at increased risk of infection. In addition, one study indicated a higher number of birth defects in mothers who received Enbrel during pregnancy compared to mothers who did not receive Enbrel or other similar medicines (TNF antagonists), but no specific pattern of birth defects was observed among the reported cases. Another study did not show an increased risk of birth defects when mothers received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed while being treated with Enbrel. It is important to inform the child’s pediatrician and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
Enbrel is not expected to affect the ability to drive or use machines.

Enbrel contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Enbrel

Use this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
If you feel the effect of Enbrel is too strong or too weak, talk to your doctor or pharmacist.
You have been prescribed a 25 mg dose of Enbrel. A 50 mg dose of Enbrel is available for 50 mg doses.

Dose for adult patients
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 25 mg administered twice weekly or 50 mg once weekly by subcutaneous injection. However, your doctor may decide on a different frequency for administering Enbrel.

Plaque psoriasis
The usual dose is 25 mg administered twice weekly or 50 mg administered once weekly.
Alternatively, a dose of 50 mg twice weekly may be given for up to 12 weeks, followed by a dose of 25 mg twice weekly or 50 mg once weekly.
Your doctor will decide how long you should take Enbrel and whether, based on your response, further treatment is needed. If Enbrel has not improved your condition after 12 weeks, your doctor may advise you to stop treatment.

Use in children and adolescents
The appropriate dose and dosing frequency for a child or adolescent will depend on body weight and the condition being treated. Your doctor will determine the correct dose for your child and will prescribe an appropriate Enbrel dosage (10 mg, 25 mg, or 50 mg).

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

For psoriasis in patients from 6 years of age, the usual dose is 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg), administered once weekly. If Enbrel has not improved your child’s condition after 12 weeks, your doctor may advise you to stop treatment with this medicine.
Your doctor will provide detailed instructions on how to prepare and measure the correct dose.

Method and route of administration
Enbrel is administered by injection under the skin (subcutaneous injection).
Enbrel may be taken with or without food and drinks.
Detailed instructions on how to inject Enbrel are provided in section 7, “Instructions for use”. Do not mix the Enbrel solution with other medicines.
To help you remember, it may be helpful to write in a diary on 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 at one time or by using it too frequently), contact a doctor or pharmacist immediately. Always keep the medicine pack with you, even if it is empty.

If you forget to take Enbrel
If you forget a dose, take it as soon as you remember, unless the next dose is scheduled for the following day, in which case you should skip the missed dose. Then continue taking the medicine on your regularly scheduled day(s). If you have forgotten a dose until the day the next dose is due, do not take a double dose (two doses on the same day) to make up for the missed dose.

If you stop treatment with Enbrel
After stopping treatment, symptoms of the disease may return.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Allergic reactions
If any of the following side effects occur, do not inject Enbrel again. Contact your doctor immediately or go to the nearest hospital emergency department.

  • Difficulty swallowing or breathing
  • Swelling of the face, throat, hands or feet
  • Feeling nervous or anxious, palpitations, sudden flushing of the skin and/or feeling of warmth
  • Severe rash, itching, hives (raised red or pale patches on the skin that are often itchy)

Severe allergic reactions are rare. However, any of the symptoms listed above may indicate an allergic reaction to Enbrel; therefore, you must seek immediate medical attention.

Serious side effects
If you or the child experience any of the following symptoms, urgent medical care may be needed.

  • Symptoms of serious infections, such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a warm, red, tender, painful area on the skin or joints.
  • Symptoms of blood disorders, such as bleeding, bruising or paleness.
  • Symptoms of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or sudden weakness in an arm or leg.
  • Symptoms of heart failure or worsening heart failure, such as fatigue or shortness of breath during activity, swelling of the ankles, a feeling of fullness in the neck or abdomen, shortness of breath at night or cough, bluish colour of the fingernails or lips.
  • Symptoms of tumours: tumours can affect any part of the body, including the skin and blood, and possible symptoms depend on the type and location of the tumour. These may include weight loss, fever, swelling (with or without pain), persistent cough, or the presence of cysts or skin growths.
  • Symptoms of autoimmune reactions (where antibodies are produced that may damage normal body tissues), such as pain, itching, weakness, or abnormalities in breathing, thinking, sensation or vision.
  • Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, joint or muscle pain, or fatigue.
  • Symptoms of inflammation of blood vessels (vasculitis), such as pain, fever, redness or warmth of the skin, or itching.

These side effects are rare or uncommon, but they are serious conditions (some of which may rarely lead to death). If any of these symptoms occur, contact your doctor immediately or go to the nearest hospital emergency department.

The known side effects of Enbrel include those listed below, grouped by decreasing frequency:

  • Very common (may affect more than 1 in 10 people): Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain and swelling) (these occur less frequently after the first month of treatment; some patients have developed a reaction at a recently used injection site); headache.
  • Common (may affect up to 1 in 10 people): Allergic reactions; fever; rash; itching; antibodies directed against normal tissue (formation of autoantibodies).
  • Uncommon (may affect up to 1 in 100 people): Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); reduced number of platelets in the blood; skin tumour (excluding melanoma); localized swelling of the skin (angioedema); urticaria (raised red or pale itchy patches on the skin); eye inflammation; psoriasis (new onset or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood (in patients also being treated with methotrexate, the frequency of increased liver enzymes in the blood is common); abdominal pain and cramps, diarrhoea, weight loss or blood in the stool (symptoms of intestinal problems).
  • Rare (may affect up to 1 in 1,000 people): Severe allergic reactions (including severe localized swelling of the skin and breathing difficulties); lymphoma (a type of blood cancer); leukaemia (a cancer affecting blood and bone marrow); melanoma (a type of skin cancer); combined reduction in platelets, red blood cells and white blood cells; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain and fatigue); skin rash that may lead to severe blistering and peeling of the skin; lichenoid reactions (itchy reddish/violaceous rash and/or white-greyish thread-like lines on mucous membranes); liver inflammation caused by your immune system (autoimmune hepatitis; in patients also being treated with methotrexate, the frequency is uncommon); an immune disorder that may affect the lungs, skin and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also being treated with methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the tiny filters in the kidneys leading to reduced kidney function (glomerulonephritis).
  • Very rare (may affect up to 1 in 10,000 people): failure of the bone marrow to produce essential 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 form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly appears as purple skin lesions; excessive activation of white blood cells involved in inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness accompanied by a skin rash).

Additional side effects in children and adolescents
The side effects and their frequency observed in children and adolescents are similar to those described above.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enbrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the pre-filled pen MYCLIC, following “Exp.”. The expiry date refers to the last day of that month.
Store in a refrigerator (between 2°C and 8°C).
Do not freeze.
Keep the pre-filled pens in their outer packaging to protect the medicine from light.
After removing 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 heat it in any other way. Immediate use is therefore recommended.
Enbrel may be stored at a maximum temperature of 25°C for up to 4 weeks, for one single period only; after this period, it must not be returned to the refrigerator. If not used within 4 weeks outside the refrigerator, Enbrel must be discarded. It is recommended to record the date when Enbrel was removed from the refrigerator and the date by which Enbrel must be discarded (no more than 4 weeks outside the refrigerator).
Inspect the solution inside the pen by looking through the transparent inspection window. The solution should be from clear to slightly opalescent, colourless to pale yellow or light brown, and may contain small white or almost transparent protein particles. This is the normal appearance of Enbrel. Do not use this solution if it shows changes in colour, appears cloudy, or if particles different from those described are visible. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Enbrel contains
The active substance in Enbrel is etanercept. Each pre-filled pen (MYCLIC) contains 25 mg of
etanercept.
The other components are sucrose, sodium chloride, L-arginine hydrochloride, monobasic sodium phosphate dihydrate, dibasic sodium phosphate dihydrate, and water for injections.
Description of the appearance of Enbrel and contents of the pack
Enbrel is supplied as an injectable solution in a pre-filled pen (MYCLIC) (injectable solution). The MYCLIC pen contains a clear injectable solution, colourless to slightly yellow or slightly brown. Each pack contains 4, 8 or 24 pre-filled pens and 4, 8 or 24 alcohol swabs. Not all pack sizes may be marketed.
Marketing Authorization Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium
Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12
2870 Puurs-Sint-Amands
Belgium
For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder.
België/Belgique/Belgien Κύπρος
Luxembourg/Luxemburg PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
Pfizer NV/SA T \ : +357 22 817690
Tél/Tel: +32 (0)2 554 62 11
Česká Republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: +36 1 488 3700
Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf: +45 44 201 100 Tel: +35621 344610
Deutschland Nederland
Pfizer Pharma GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636
България Norge
Пфайзер Люксембург САРЛ, Pfizer AS
Клон България Tlf: +47 67 52 61 00
Teл: +359 2 970 4333
Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0
Ελλάδα Polska
PFIZER EΛΛAΣ A.E. Pfizer Polska Sp. z o.o.
Τηλ.: +30 210 67 85 800 Tel.: +48 22 335 61 00
España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Télf: +34 91 490 99 00 Tel: (+351) 21 423 55 00
France România
Pfizer Pfizer Romania S.R.L
Tél +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00
Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL , Pfizer, podružnica
Tel: +385 1 3908 777 za svetovanje s področja farmacevtske
dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400
Ireland Slovenská Republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: +1800 633 363 (toll free) Tel: +421 2 3355 5500
Tel: +44 (0)1304 616161
Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Tel: +354 540 8000 Puh/Tel: +358 (0)9 430 040
Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00
Latvija United Kingdom (Northern Ireland)
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel. +371 67035775 Tel: +44 (0)1304 616161
Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://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 following instructions explain how to use the MYCLIC pen to administer Enbrel.
  • Read the instructions carefully and follow them step by step.
  • Your doctor will tell you how to inject Enbrel. Do not attempt to perform an injection until you are certain you understand how to properly use the MYCLIC pen.
  • If you have any questions about how to perform the injection, ask your doctor for help.

The pre-filled pen MYCLIC
Before the injection

White injection pen MYCLIC with batch and expiry information and a transparent window showing the drug content inside

White needle cap
Activation button
Expiry date
Transparent grey control window

After the injection

White injection pen with blue MYCLIC logo, spaces for batch and expiry, viewing window, and dark blue cap on the right side

Filled control window
Open end:
safety shield extended

Step 1: Prepare the Enbrel injection

White disposal container with snap-on lid, a horizontal injection pen, and two small gauze pads or bandages on a light background
  • Gather the following materials needed for each injection on a flat, clean, and well-lit surface:
    o One pre-filled MYCLIC pen.
    o One alcohol swab.
    o A 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, allow the pen to warm to room temperature for 15–30 minutes with the white cap still in place.
  • Do not use any other methods to warm the pen.

Step 2: Check expiry date and dose on the label

Detail of a hand holding a Myclic medical device with magnification on a circle showing fields for batch and expiry
  • Check the expiry date (month/year) printed on the pen label.
  • Ensure the correct dose is indicated on the pen label.
  • Do not use the pen if the expiry date has passed or if the dose indicated is not the one prescribed. Contact your doctor for assistance.

Step 3: Inspect the medicine

One hand holds an elongated medical device with a small central window showing a yellowish liquid inside
  • Inspect the medicine inside the pen by looking through the transparent control window. The solution should be clear or slightly opalescent, colourless to slightly yellow or light brown, and may contain small white or almost transparent protein particles. This appearance is normal for Enbrel.
  • Do not use the medicine if it changes colour, appears cloudy, or if particles different from those described are visible. If you have any doubts about the appearance of the medicine, contact your doctor for assistance.
  • Note: You may observe an air bubble in the window. This is normal.

Step 4: Choose and clean the injection site

Human body diagram showing drug application areas on the Medical diagram indicating injection sites on the
  • Choose the middle front area of the upper thighs or the abdominal area at least 5 cm away from the navel as the injection site. If an assistant is administering the injection, the outer area of the upper arms may also be used.
  • Each injection must be given at least 3 cm away from the previous injection site. Do not inject into areas where the skin is tender, red, or hardened. Avoid areas with scars or stretch marks. If you have psoriasis, do not inject directly into swollen, thickened, red, or scaly skin areas.
  • Clean the injection site with soap and water or, if preferred, with an alcohol swab.
  • Allow the area to dry. Do not touch, blow on, or fan the cleaned injection site.

Step 5: Remove the needle cap

Two hands hold a white cylindrical medical device to attach a protective cap to the top of the device body
  • Remove the white needle cap by pulling it off firmly, taking care not to bend it.
  • Do not reattach the cap once removed.
  • After removing the needle cap, a purple-coloured safety shield will be slightly visible at the tip of the pen. Do not push the safety shield at the end with fingers or thumbs.
  • Do not use the pen if it falls without the needle cap.
  • Note: A drop of liquid may remain at the needle tip. This is normal.

Step 6: Press the pen firmly against the skin

One hand holds a medical device to inject it into the skin with an arrow indicating downward pressure and a detail of the
  • Press the open end of the pen firmly against the skin at a 90-degree angle to fully push the purple safety shield into the pen.
  • Note: You will only be able to press the grey button once the safety shield is fully retracted into the pen. Pinching or stretching the skin before injection may help further stabilize the injection site and facilitate pressing the injection button.

Step 7: Start the injection

Medical diagram showing two steps: press button for first click and continue holding device for ten seconds or second click Horizontal rectangle of uniform purple color on white background Uniform opaque purple background with a thin white stripe in the lower part of the The White background with a vertical purple band on the left side and a small vertical black line in the center The
  • Press the grey button completely until you hear a “click”, indicating the start of the injection.
  • Continue holding the pen firmly against the skin until you hear a second “click” or for a total of 10 seconds after the first click (whichever occurs first).
  • Note: If you are unable to start the injection as described, press the pen more firmly against the skin and then press the grey button again.

Step 8: Lift from the skin

One hand holds a medical device with a blue arrow pointing toward the
  • Remove the pen from the skin by lifting it perpendicularly away from the injection site.
  • The purple-coloured needle safety shield will automatically extend to cover the needle.

Step 9: Check the control window

One hand holds a white elongated medical device with a dark central indicator on a shaded circular background
  • Check the control window on the pen: it should be completely purple.
  • If the window is not purple, the pen may not have delivered the full dose. Contact your doctor for assistance. Do not attempt to use the pen again. Do not attempt to use another pen.
  • If you notice bleeding at the injection site, press a cotton ball or gauze pad on the site for 10 seconds. Do not rub the injection site.
  • Note: The injection button may remain depressed. This is normal.

Step 10: Dispose

One hand holds a white injection pen and another cylindrical device to insert it into a white disposal container
  • Dispose of the used pen as instructed by your doctor. Do not attempt to recap the pen.
  • Do not press on the end of the needle safety shield. For any questions, consult your healthcare provider.
  • —End of instructions for use—

Package leaflet: Information for the user

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

etanercept
Please read this entire leaflet carefully before using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • Your doctor will provide you with a Patient Safety Card containing important safety information that you should be aware of before and during treatment with Enbrel.
  • If you have any questions, ask your doctor, pharmacist, or nurse.
  • This medicine has been prescribed for you or for a child. Do not give it to other people, even if their symptoms are the same as yours or those of the child, as this could be harmful.
  • If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet
The information in this package leaflet is divided into the following 7 sections:

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

1. What Enbrel is and what it is used for

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

In adults (aged 18 years and older), Enbrel can be used to treat moderate to severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate to 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 not suitable for you. Whether used alone or in combination with methotrexate, Enbrel can slow down joint damage caused by rheumatoid arthritis and improve your ability to perform normal daily activities.

For patients with psoriatic arthritis affecting multiple joints, Enbrel can improve the ability to carry out daily activities. For patients with painful or swollen symmetric joints (e.g. hands, wrists and feet), Enbrel can slow down structural damage to these joints caused by the disease.

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

  • For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not provided an adequate response or is not appropriate:
    • 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 provided an adequate response or are not appropriate.
  • Severe psoriasis in patients from the age of 6 years who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies.

2. What you should know before using Enbrel

Do not use Enbrel

  • if you or the child are allergic to etanercept or to any of the other components of Enbrel (listed in section 6). If you or the child experience allergic reactions such as chest tightness, shortness of breath, dizziness, or skin rash, do not inject any 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 in doubt, contact your doctor.
  • if you or the child currently have any type of infection. If in doubt, consult 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, shortness of breath, dizziness, or skin rash, do not inject any more Enbrel and contact your doctor immediately.
  • Infections/surgery: If you or the child develop a new infection or are about to undergo any major surgical procedure. Your doctor may want to review your treatment with Enbrel.
  • Infections/diabetes: Inform 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: Inform your doctor about any recent travel outside Europe. If you or the child develop symptoms of an infection such as fever, chills, or cough, inform your doctor immediately. Your doctor may decide to continue monitoring you or the child for infections after stopping Enbrel.
  • Tuberculosis: Cases of tuberculosis have been reported in patients treated with Enbrel. Your doctor will check for signs and symptoms of tuberculosis before starting treatment with Enbrel. This may include a thorough medical history, chest X-rays, and a tuberculin skin test. The results of these tests must be recorded in the Patient Record Card. It is very important that you inform your doctor if you or the child have ever had tuberculosis or have been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection occur during or after treatment, inform your doctor immediately.
  • Hepatitis B: Inform your doctor if you or the child have or have had hepatitis B. Your doctor must perform a hepatitis B test before you or the child start treatment with Enbrel. Treatment with Enbrel may cause reactivation of hepatitis B in patients previously infected with the hepatitis B virus. In such cases, you must stop using Enbrel.
  • Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may consider monitoring your treatment with Enbrel if the infection worsens.
  • Blood disorders: Seek immediate medical help if you or the child experience any signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of Enbrel treatment.
  • Nervous system and eye disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Enbrel is an appropriate treatment.
  • Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure, as Enbrel should be used with caution in such cases.
  • Tumours: Inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumour before taking Enbrel. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma. Children and adults taking Enbrel may have an increased risk of developing lymphoma or other tumours. Some children and adolescent patients treated with Enbrel or other medicines that work similarly to Enbrel have developed tumours, including unusual types, sometimes with fatal outcomes. Some patients receiving Enbrel have developed skin tumours. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
  • Chickenpox (varicella): Inform your doctor if you or the child are exposed to chickenpox while using Enbrel. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
  • Latex: The needle cap of the MYCLIC pen is made of latex (dried natural rubber). Contact your doctor before using Enbrel if the needle cap will be handled by, or if Enbrel will be administered to, a person with known or suspected hypersensitivity (allergy) to latex.
  • Alcohol abuse: Enbrel should not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child 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 have Wegener’s granulomatosis, consult your doctor.
  • Anti-diabetic medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide that you or the child may need to take a lower dose of anti-diabetic medicine while taking Enbrel.

Children and adolescents
Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Enbrel. Some vaccines, such as oral polio vaccine, should not be taken while receiving Enbrel. Consult your doctor before you or the child receive any vaccine.
Enbrel should normally not be used in children under 2 years of age with polyarthritis or extended oligoarthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Other medicines and Enbrel
Inform your doctor or pharmacist if you or the child are taking, have recently taken, or might take any other medicines (including anakinra, abatacept, or sulfasalazine), even those not prescribed. You or the child must not use Enbrel together with the active substances anakinra or abatacept.

Pregnancy and breastfeeding
Enbrel should be used during pregnancy only if clearly necessary. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor.
If you have received Enbrel during pregnancy, the newborn may be at increased risk of infection. In addition, one study indicated a higher number of birth defects in mothers who received Enbrel during pregnancy compared to mothers who did not receive Enbrel or other similar medicines (TNF antagonists), but no specific pattern of birth defects was identified. Another study did not show an increased risk of birth defects when mothers received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed while being treated with Enbrel. It is important to inform the child’s paediatrician and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
Enbrel is not expected to affect the ability to drive or use machinery.

Enbrel contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Enbrel

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
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 dose of Enbrel. A 25 mg dose of Enbrel is available for 25 mg doses.

Dose for adult patients
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 25 mg administered twice a week or 50 mg once a week by subcutaneous injection. However, your doctor may decide on a different frequency for administering Enbrel.

Plaque psoriasis
The usual dose is 25 mg administered twice a week or 50 mg administered once a week.
Alternatively, a dose of 50 mg twice a week may be given for up to 12 weeks, followed by a dose of 25 mg twice a week or 50 mg once a week.
Your doctor will decide how long you should take Enbrel and whether, based on your response, further treatment is needed. If after 12 weeks Enbrel has not improved your condition, your doctor may tell you to stop treatment.

Use in children and adolescents
The appropriate dose and dosing frequency for a child or adolescent will depend on body weight and the disease being treated. Your doctor will determine the correct dose for your child and will prescribe an appropriate Enbrel dosage (10 mg, 25 mg, or 50 mg).

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

For psoriasis in patients from 6 years of age, the usual dose is 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg), administered once a week. If Enbrel has not improved the child's condition after 12 weeks, your doctor may tell you to stop treatment with this medicine.
Your doctor will provide detailed instructions on how to prepare and measure the appropriate dose.

Method and route of administration
Enbrel is administered by injection under the skin (subcutaneous injection).
Enbrel may be taken with or without food and beverages.
Detailed instructions on how to inject Enbrel are provided in section 7 “Instructions for use”. Do not mix the Enbrel solution with other medicines.
To help you remember, it may be helpful to write in a diary on 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 at one time or by using it too frequently), contact a doctor or pharmacist immediately. Always keep the medicine package, even if empty.

If you forget to take Enbrel
If you miss a dose, take it as soon as you remember, unless the next dose is scheduled for the following day, in which case you should skip the missed dose. Then continue taking the medicine on your regularly scheduled day(s). If you do not remember until the day the next dose is due, do not take a double dose (two doses on the same day) to make up for the missed dose.

If you stop treatment with Enbrel
After stopping treatment, disease symptoms may return.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Allergic reactions
If any of the following side effects occur, do not inject Enbrel again. Contact your doctor immediately or go to the nearest hospital emergency department.

  • Difficulty swallowing or breathing
  • Swelling of the face, throat, hands or feet
  • Feeling nervous or anxious, palpitations, sudden redness of the skin and/or feeling of warmth
  • Severe rash, itching, hives (raised red or pale patches on the skin that often itch)

Severe allergic reactions are rare. However, any of the symptoms listed above may indicate an allergic reaction to Enbrel; therefore, you must seek immediate medical attention.

Serious side effects
If you or the child notice any of the following effects, urgent medical care may be needed.

  • Symptoms of serious infections, such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a warm, red, tender, painful area on the skin or joints.
  • Symptoms of blood disorders, such as bleeding, bruising or paleness.
  • Symptoms of nerve problems, such as numbness or tingling, changes in vision, eye pain, or sudden onset of weakness in an arm or a leg.
  • Symptoms of heart failure or worsening heart failure, such as fatigue or shortness of breath during activity, swelling of the ankles, a feeling of fullness in the neck or abdomen, shortness of breath at night or cough, bluish colouring of the fingernails or lips.
  • Symptoms of tumours: tumours may affect any part of the body, including the skin and blood, and possible symptoms depend on the type and location of the tumour. These symptoms may include weight loss, fever, swelling (with or without pain), persistent cough, presence of cysts or growths on the skin.
  • Symptoms of autoimmune reactions (where antibodies are produced that may damage normal body tissues), such as pain, itching, weakness, breathing problems, changes in thinking, sensation or vision.
  • Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, joint or muscle pain, or fatigue.
  • Symptoms of inflammation of blood vessels, such as pain, fever, redness or warmth of the skin or itching.

These side effects are rare or uncommon, but they are serious conditions (some of which may rarely lead to death). If any of these symptoms occur, contact your doctor immediately or go to the nearest hospital emergency department.

The known side effects of Enbrel include those listed below, grouped by decreasing frequency:

  • Very common (may affect more than 1 in 10 people): Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain and swelling) (these occur less frequently after the first month of treatment; some patients have developed a reaction at a recently used injection site); headache.
  • Common (may affect up to 1 in 10 people): Allergic reactions; fever; rash; itching; antibodies directed against normal tissue (formation of autoantibodies).
  • Uncommon (may affect up to 1 in 100 people): Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); reduced number of platelets in the blood; skin tumour (excluding melanoma); localized swelling of the skin (angioedema); hives (raised red or pale patches on the skin that often itch); eye inflammation; psoriasis (new onset or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood (in patients also being treated with methotrexate, the frequency of increased liver enzymes in the blood is common); abdominal pain and cramps, diarrhoea, weight loss or blood in the stool (symptoms of intestinal problems).
  • Rare (may affect up to 1 in 1,000 people): Severe allergic reactions (including severe localized swelling of the skin and breathing difficulties); lymphoma (a type of blood cancer); leukaemia (a cancer affecting the blood and bone marrow); melanoma (a type of skin cancer); combined reduction in the number of platelets, red blood cells and white blood cells; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain and fatigue); rash that may lead to blistering and severe skin peeling; lichenoid reactions (itchy reddish/violaceous rash and/or whitish-grey thread-like lines on mucous membranes); liver inflammation caused by your immune system (autoimmune hepatitis; in patients also being treated with methotrexate, the frequency is uncommon); an immune disorder that may affect the lungs, skin and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also being treated with methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the tiny filters in the kidneys leading to reduced kidney function (glomerulonephritis).
  • Very rare (may affect up to 1 in 10,000 people): Failure of the bone marrow to produce essential 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 form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma typically presents with purple skin lesions; excessive activation of white blood cells involved in inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness accompanied by skin rash).

Additional side effects in children and adolescents
The side effects and their frequency observed in children and adolescents are similar to those described above.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enbrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date 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 the refrigerator (between 2°C and 8°C).
Do not freeze.
Keep the pre-filled pens in their outer packaging to protect the medicine from light.
After removing 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 heat it in any other way. Immediate use is therefore recommended.
Enbrel may be stored at a maximum temperature of 25°C for up to 4 weeks, for one single period only; after this period it must not be returned to the refrigerator. If not used within 4 weeks outside the refrigerator, Enbrel must be discarded. It is recommended to record the date when Enbrel was removed from the refrigerator and the date by which Enbrel must be discarded (no more than 4 weeks outside the refrigerator).
Inspect the solution inside the pen by looking through the transparent inspection window. The solution should be from clear to slightly opalescent, colourless to pale yellow or light brown, and may contain small white or almost transparent protein particles. This is the normal appearance of Enbrel. Do not use this solution if it shows changes in colour, appears cloudy, or if particles different from those described are visible. If you have any doubts about the appearance of the solution, contact your pharmacist for advice.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Enbrel contains
The active substance in Enbrel is etanercept. Each pre-filled pen (MYCLIC) contains 50 mg of
etanercept.
The other components are sucrose, sodium chloride, L-arginine hydrochloride, monosodium phosphate dihydrate,
disodium phosphate dihydrate, and water for injections.

Description of the appearance of Enbrel and contents of the pack
Enbrel is supplied as an injectable solution in a pre-filled pen (MYCLIC) (injectable solution). The MYCLIC pen contains a clear, colourless to pale yellow or pale brown injectable solution. Each pack contains 2, 4 or 12 pre-filled 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 Brussels
Belgium

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

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

België/Belgique/Belgien Κύπρος
Luxembourg/Luxemburg PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
Pfizer NV/SA T \ \hline: +357 22 817690
Tél/Tel: +32 (0)2 554 62 11

Česká Republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: +36 1 488 3700

Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf: +45 44 201 100 Tel: +35621 344610

Deutschland Nederland
Pfizer Pharma GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

България Norge
Пфайзер Люксембург САРЛ, Pfizer AS
Клон България Tlf: +47 67 52 61 00
Tel: +359 2 970 4333

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
PFIZER EΛΛAΣ A.E. Pfizer Polska Sp. z o.o.
Tηλ.: +30 210 67 85 800 Tel.: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Télf: +34 91 490 99 00 Tel: (+351) 21 423 55 00

France România
Pfizer Pfizer Romania S.R.L
Tél +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL, Pfizer, podružnica
Tel: +385 1 3908 777 za svetovanje s področja farmacevtske
dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ireland Slovenská Republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: +1800 633 363 (toll free) Tel: +421 2 3355 5500
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Tel: +354 540 8000 Puh/Tel: +358 (0)9 430 040

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00

Latvija United Kingdom (Northern Ireland)
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel. +371 67035775 Tel: +44 (0)1304 616161

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000

More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://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 following instructions explain how to use the MYCLIC pen to administer Enbrel.
  • Read the instructions carefully and follow them step by step.
  • Your doctor will tell you how to inject Enbrel. Do not attempt to give an injection until you are sure you understand how to use the MYCLIC pen properly.
  • If you have any questions about how to give the injection, ask your doctor for help.

The pre-filled MYCLIC pen
Before injection

White injection pen MYCLIC with batch and expiry information and a transparent window showing the internal liquid

White needle cap
Activation button Expiry date Transparent green
inspection window
After injection

White and blue injection pen with MYCLIC text, spaces for batch and expiry, a viewing indicator, and a knurled wheel at the

Inspection window fully filled Open end: safety
shield
Step 1: Prepare the Enbrel injection

White disposal container with lid next to an injection pen and two small white rectangular containers on a light surface
  • Gather the following materials needed for each injection on a clean, flat, well-lit surface:
    o One pre-filled MYCLIC pen.
    o One alcohol swab.
    o A sharps container (not included).
    o Cotton balls or clean 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, allow the pen to warm to room temperature for 15–30 minutes with the white cap still in place.
  • Do not use any other method to warm the pen.

Step 2: Check expiry date and dose on the label

Detail of a hand holding a Myclick injection pen with magnification on a circle showing fields for batch and expiry
  • Check the expiry date (month/year) printed on the pen label.
  • Ensure the correct dose is indicated on the pen label.
  • Do not use the pen if the expiry date has passed or if the dose indicated is not the one prescribed. Contact your doctor for assistance.

Step 3: Inspect the medicine

One hand holds a white medical device with a transparent window showing yellow liquid inside
  • Inspect the medicine inside the pen by looking through the transparent 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 protein particles. This appearance is normal for Enbrel.
  • Do not use the medicine if it has changed colour, appears cloudy, or if particles different from those described are visible. If you have any doubts about the appearance of the medicine, contact your doctor for assistance.
  • Note: You may see an air bubble in the window. This is normal.

Step 4: Choose and clean the injection site

Human body diagram indicating application areas on abdomen, thighs, and arms using dark areas highlighted with reference lines Medical diagram showing injection sites on the
  • Choose the front and central area of the upper thighs or the abdominal area at least 5 cm away from the navel as the injection site. If an assistant is administering the injection, the outer area of the upper arms may also be used.
  • Each injection must be given at least 3 cm away from the previous injection site. Do not inject into areas where the skin is tender, red, or hardened. Avoid areas with scars or stretch marks. If you have psoriasis, do not inject directly into swollen, thickened, red, or scaly skin areas.
  • Clean the injection site with water and soap or, if appropriate, with an alcohol swab.
  • Allow the area to dry. Do not touch, fan, or blow on the cleaned injection site.

Step 5: Remove the needle cap

Two hands hold a pen-shaped medical device to separate the upper cap from the main body of the device
  • Remove the white needle cap by pulling firmly, taking care not to bend it.
  • Do not reattach the cap once removed.
  • After removing the needle cap, a purple-coloured needle safety shield will be slightly visible at the end of the pen. Do not push the safety shield at the end with fingers or thumbs.
  • Do not use the pen if it is dropped without the needle cap.
  • Note: A drop of liquid may remain at the needle tip. This is normal.

Step 6: Press the pen firmly against the skin

Medical illustration showing a hand holding an injection pen placed on the skin with enlargements of the insertion mechanism
  • Press the open end of the pen firmly against the skin at a 90-degree angle to fully retract the purple-coloured needle safety shield into the pen.
  • Note: You will only be able to press the green button when the safety shield is fully retracted into the pen. Pinching or stretching the skin before injection may help further stabilize the injection site and facilitate pressing the injection button.

Step 7: Start the injection

Illustrative diagram showing two steps for the
  • Press the green button completely until you hear a “click”, indicating the start of the injection.
  • Continue to hold the pen firmly against the skin until you hear a second “click” or for a total of 10 seconds after the first click (whichever occurs first).
  • Note: If you are unable to start the injection as described, press the pen more firmly against the skin and then press the green button again.

Step 8: Lift from the skin

One hand holds a white injection pen with a blue arrow pointing toward the
  • Remove the pen from the skin by lifting it perpendicularly away from the injection site.
  • The purple-coloured needle safety shield will automatically extend to cover the needle.

Step 9: Check the inspection window

One hand holds a pen-shaped medical device with a transparent window showing dark liquid inside
  • Check the inspection window on the pen: it should be completely purple.
  • If the window is not fully purple, the pen may not have delivered the full dose. Contact your doctor for assistance. Do not attempt to use the pen again. Do not attempt to use another pen.
  • If you notice a blood spot at the injection site, press a cotton ball or gauze pad on the site for 10 seconds. Do not rub the injection site.
  • Note: The injection button may remain depressed. This is normal.

Step 10: Dispose

One hand holds a white injection pen and inserts its tip into a sharps disposal container
  • Dispose of the used pen as instructed by your doctor. Do not attempt to recap the pen.
  • Do not press on the end of the needle safety shield. For any questions, contact your doctor.
  • –End of instructions for use–

Package leaflet: information for the user

Enbrel 10 mg powder and solvent for injectable solution for pediatric use

etanercept
Please read this entire leaflet carefully before using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • Your doctor will provide you with a Patient Information Card containing important safety information you should be aware of before and during treatment with Enbrel.
  • If you have any questions, consult your doctor, pharmacist, or nurse.
  • This medicine has been prescribed for a child. Do not give it to other people, even if their symptoms are the same as the child's, because it could be harmful.
  • If you notice any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet
The information in this leaflet is divided into the following 7 sections:

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

1. What Enbrel is and what it is used for

Enbrel is a medicine made from two human proteins. It blocks the activity of another protein that causes inflammation in the human body. Enbrel works by reducing the inflammation associated with certain diseases.
Enbrel is prescribed for the treatment of the following conditions in children and adolescents:

  • For the following types of juvenile idiopathic arthritis, when treatment with methotrexate has not provided a sufficiently good response or is not appropriate:
  • 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 provided a sufficiently good response or are not appropriate.
  • Severe psoriasis in patients from the age of 6 years who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies.

2. What you should know before using Enbrel

Do not use Enbrel

  • if the child is allergic to etanercept or to any of the other ingredients of Enbrel (listed in section 6). If the child experiences allergic reactions such as chest tightness, shortness of breath, dizziness, or rash, do not inject any more Enbrel and contact the doctor immediately.
  • if the child has or is at risk of developing a serious blood infection called sepsis. If you have any doubts, contact the doctor.
  • if the child has any type of infection. If you have any doubts, consult the doctor.

Warnings and precautions
Talk to the doctor before using Enbrel.

  • Allergic reactions: If the child experiences allergic reactions such as chest tightness, shortness of breath, dizziness, or rash, do not inject any more Enbrel and contact the doctor immediately.
  • Latex: The rubber stopper of the syringe is made of latex (natural dried rubber). Contact the doctor before using Enbrel if the syringe will be handled by, or if Enbrel will be administered to, individuals with known or suspected hypersensitivity (allergy) to latex.
  • Infections/surgery: If the child develops a new infection or is about to undergo any major surgical procedure, the doctor may wish to review the child’s treatment with Enbrel.
  • Infections/diabetes: Inform the 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: Inform the doctor about any recent travel outside Europe. If the child develops symptoms of an infection such as fever, chills, or cough, inform the doctor immediately. The doctor may decide to continue monitoring the child for infections after the child has stopped taking Enbrel.
  • Tuberculosis: Since cases of tuberculosis have been reported in patients treated with Enbrel, the doctor will check for signs and symptoms of tuberculosis before starting treatment with Enbrel. This may include a thorough medical history, chest X-rays, and a tuberculin test. The results of these tests must be recorded in the Patient Record Card. It is very important to inform the doctor if the child has ever had tuberculosis or has been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection occur during or after treatment, report them to the doctor immediately.
  • Hepatitis B: Inform the doctor if the child has hepatitis B. The doctor must perform a test for hepatitis B before the child starts treatment with Enbrel. Treatment with Enbrel may cause reactivation of hepatitis B in patients with prior hepatitis B virus infection. In such cases, Enbrel must be discontinued.
  • Hepatitis C: Inform the doctor if the child has hepatitis C. The doctor may consider monitoring the treatment with Enbrel if the infection worsens.
  • Blood disorders: Seek immediate medical attention if the child shows any signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of Enbrel treatment.
  • Nervous system and eye disorders: Inform the doctor if the child has multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). The doctor will assess whether Enbrel is an appropriate treatment.
  • Tumors: Inform the doctor if the child has or has ever had lymphoma (a type of blood cancer) or any other tumor before taking Enbrel.

Patients with long-standing, severe rheumatoid arthritis may be at higher-than-average risk of developing lymphoma.
Children and adults taking Enbrel may have an increased risk of developing lymphoma or other tumors.
Some children and adolescent patients treated with Enbrel or other medicines that work like Enbrel have developed tumors, including unusual types, sometimes with fatal outcome.
Some patients receiving Enbrel have developed skin tumors. Inform the doctor if the child develops any changes in the appearance of the skin or skin growths.

  • Congestive heart failure: Inform the doctor if the child has a history of congestive heart failure, as Enbrel must be used with caution in such cases.
  • Chickenpox: Inform the doctor if the child is exposed to chickenpox while using Enbrel. The doctor will assess whether prophylactic treatment for chickenpox is appropriate.
  • Alcohol abuse: Enbrel must not be used to treat hepatitis related to alcohol abuse. Inform the doctor if the child 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 has Wegener’s granulomatosis, consult the doctor.
  • Anti-diabetic medicines: Inform the doctor if the child has diabetes or is taking medicines to treat diabetes. The doctor may decide that the child needs to take a lower dose of anti-diabetic medicine while taking Enbrel.

Children and adolescents
Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Enbrel. Some vaccines, such as the oral polio vaccine, must not be given while taking Enbrel. Consult the doctor before the child receives any vaccine.
Generally, Enbrel should not be used in children under 2 years of age with polyarticular or extended oligoarticular juvenile idiopathic arthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Other medicines and Enbrel
Inform the 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 usual doctor. The child must not use Enbrel together with the active substances anakinra or abatacept.

Pregnancy and breastfeeding
Enbrel should be used during pregnancy only if clearly necessary. If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor.
If you have received Enbrel during pregnancy, the newborn may be at increased risk of infection. In addition, one study indicated a higher number of birth defects in mothers who received Enbrel during pregnancy compared to mothers who did not receive Enbrel or other similar medicines (TNF antagonists), but no specific pattern of birth defects was observed. Another study did not show an increased risk of birth defects when mothers received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed while receiving Enbrel. It is important to inform the child’s pediatricians and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
Enbrel is not expected to affect the ability to drive vehicles or use machinery.

3. How to use Enbrel

Use in children and adolescents
Always use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor or pharmacist.
If you think that the effect of Enbrel is too strong or too weak, talk to your doctor or pharmacist.
The appropriate dose and dosing frequency for a child or adolescent will depend on body weight and
the condition being treated. Your doctor will provide detailed instructions on how to prepare and measure
the correct dose.
The 10 mg vial is intended for children who have been prescribed a dose of 10 mg or less. Each vial must
be used only once as a single dose for one patient, and any unused solution remaining in the vial must be
discarded.
For polyarthritis or extended oligoarthritis in patients aged 2 years and older, or enthesitis-related
arthritis or psoriatic arthritis in patients aged 12 years and older, the usual dose is 0.4 mg of Enbrel per
kilogram of body weight (up to a maximum of 25 mg) administered twice weekly, or 0.8 mg of Enbrel per kg
of body weight (up to a maximum of 50 mg) administered once weekly.
For psoriasis in patients aged 6 years and older, the usual dose is 0.8 mg of Enbrel per kilogram of body
weight (up to a maximum of 50 mg), administered once weekly. If Enbrel has not shown effect on the
child’s condition after 12 weeks, the doctor may instruct you to stop treatment with this medicine.
Method and route of administration
Enbrel is administered by subcutaneous injection (injection under the skin).
Enbrel may be taken with or without food and beverages.
Detailed instructions on how to inject Enbrel are provided in “Instructions for Use”. Do not mix the
Enbrel solution with other medicines.
To help you remember, it may be useful to write in a diary on 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 at one time or by using it too
frequently), contact a doctor or pharmacist immediately. Always keep the medicine pack, even if empty.
If you forget to take Enbrel
If you miss a dose, administer it as soon as you remember, unless the next dose is scheduled for the
following day, in which case you should skip the missed dose. Then continue administering the medicine
on the originally scheduled day(s). If you have missed a dose until the day the next dose is due, do not
take a double dose (two doses on the same day) to make up for the missed dose.
If you stop using Enbrel
After stopping treatment, symptoms of the disease may return.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Allergic reactions
If any of the following side effects occur in the child, do not inject Enbrel again. Contact your doctor immediately or go to the nearest hospital emergency department.

  • Difficulty swallowing or breathing
  • Swelling of the face, throat, hands or feet
  • Feeling nervous or anxious, palpitations, sudden redness of the skin and/or feeling of warmth
  • Severe rash, itching, hives (raised red or pale areas of skin that often itch)

Severe allergic reactions are rare. If the child experiences any of the symptoms listed above, this may indicate an allergic reaction to Enbrel; therefore, immediate medical attention must be sought.

Serious side effects
If you notice any of the following effects, the child may need urgent medical care.

  • Symptoms of serious infections, such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a warm, red, tender, painful area on the child’s skin or joints.
  • Symptoms of blood disorders, such as bleeding, bruising or paleness.
  • Symptoms of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or sudden weakness in an arm or leg.
  • Symptoms of heart failure or worsening heart failure, such as fatigue or shortness of breath during activity, swelling of the ankles, a feeling of fullness in the neck or abdomen, shortness of breath at night or cough, bluish colouring of the child’s nails or lips.
  • Symptoms of tumours: tumours may affect any part of the body, including skin and blood, and possible symptoms depend on the type and location of the tumour. These may include weight loss, fever, swelling (with or without pain), persistent cough, or presence of cysts or lumps on the skin.
  • Symptoms of autoimmune reactions (where antibodies are produced that may damage normal body tissues), such as pain, itching, weakness, breathing problems, changes in thinking, sensation or vision.
  • Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, joint or muscle pain, or fatigue.
  • Symptoms of inflammation of blood vessels, such as pain, fever, redness or warmth of the skin, or itching.

These side effects are rare or uncommon, but are serious conditions (some of which may rarely lead to death). If any of these symptoms occur, contact your doctor immediately or take the child to the nearest hospital emergency department.

Known side effects of Enbrel include those listed below, grouped by decreasing frequency:

  • Very common (may affect more than 1 in 10 people): Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain and swelling) (these occur less frequently after the first month of treatment; some patients have developed a reaction at a recently used injection site); headache.
  • Common (may affect up to 1 in 10 people): Allergic reactions; fever; rash (skin rash); itching; antibodies directed against normal tissue (formation of autoantibodies).
  • Uncommon (may affect up to 1 in 100 people): Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); reduced number of platelets in the blood; skin tumour (excluding melanoma); localized swelling of the skin (angioedema); urticaria (raised red or pale areas of skin that often itch); eye inflammation; psoriasis (new onset or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in blood (in patients also treated with methotrexate, the frequency of increased liver enzymes in blood is common); abdominal pain and cramps, diarrhoea, weight loss or blood in stools (symptoms of intestinal problems).
  • Rare (may affect up to 1 in 1,000 people): Severe allergic reactions (including severe localized swelling of the skin and breathing difficulties); lymphoma (a type of blood tumour); leukaemia (a tumour affecting blood and bone marrow); melanoma (a type of skin tumour); combined reduction in platelets, red blood cells and white blood cells; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis or inflammation of the optic nerve or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain and fatigue); skin rash that may lead to blistering and severe peeling of the skin; lichenoid reactions (itchy reddish/violet rash and/or white-grey thread-like lines on mucous membranes); liver inflammation caused by the immune system (autoimmune hepatitis; in patients also treated with methotrexate, the frequency is uncommon); immune disorder that may affect the lungs, skin and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also treated with methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the tiny filters within the kidneys leading to reduced kidney function (glomerulonephritis).
  • Very rare (may affect up to 1 in 10,000 people): Failure of the bone marrow to produce essential blood cells.
  • Not known (frequency cannot be estimated from available data): Merkel cell carcinoma (a type of skin tumour); Kaposi’s sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma most commonly presents with purple lesions on the skin; excessive activation of white blood cells involved in inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness accompanied by skin rash).

Additional side effects in children and adolescents
The side effects and their frequency observed in children and adolescents are similar to those described above.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enbrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after “Expiry”. The expiry date refers to the last day of that month.
Store in a refrigerator (between 2°C and 8°C). Do not freeze.
Before preparing the Enbrel solution, Enbrel may be stored outside the refrigerator at temperatures up to a maximum of 25°C for a single period of four weeks; after this period, it must not be returned to the refrigerator. Enbrel must be discarded if not used within the four weeks during which it has been kept outside the refrigerator. It is recommended to record the date when Enbrel was removed from the refrigerator and the date after which Enbrel must be discarded (no later than four weeks after removal from the refrigerator). This new expiry date must not exceed the one printed on the carton.
It is recommended to use the Enbrel solution immediately after preparation. However, the solution may be used within a maximum of 6 hours if stored at a temperature up to 25°C.
Do not use this medicine if you notice that the solution is not clear or if it contains particles. The solution should appear clear and colourless to slightly yellow or slightly brown, without any clumps, flakes, or particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Enbrel contains
The active substance in Enbrel is etanercept. Each vial of Enbrel 10 mg powder and solvent for
injectable solution for paediatric use contains 10 mg of etanercept. When reconstituted, the solution
contains 10 mg/mL of etanercept.
The other components are:
Powder: Mannitol (E421), sucrose and tromethamine
Solvent: water for injections

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

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

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

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

België/Belgique/Belgien Κύπρος
Luxembourg/Luxemburg PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
Pfizer NV/SA T  : +357 22 817690
Tél/Tel: +32 (0)2 554 62 11

Česká Republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: +36 1 488 3700

Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf: +45 44 201 100 Tel: +35621 344610

Deutschland Nederland
Pfizer Pharma GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

България Norge
Пфайзер Люксембург САРЛ, Pfizer AS
Клон България Tlf: +47 67 52 61 00
Tel: +359 2 970 4333

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
PFIZER EΛΛAΣ A.E. Pfizer Polska Sp. z o.o.
Τηλ.: +30 210 67 85 800 Tel.: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Télf: +34 91 490 99 00 Tel: (+351) 21 423 55 00

France România
Pfizer Pfizer Romania S.R.L
Tél +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL, Pfizer, podružnica
Tel: +385 1 3908 777 za svetovanje s področja farmacevtske
dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ireland Slovenská Republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: +1800 633 363 (toll free) Tel: +421 2 3355 5500
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Tel: +354 540 8000 Puh/Tel: +358 (0)9 430 040

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00

Latvija United Kingdom
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel. +371 67035775 Tel: +44 (0)8 550 520 00

Lietuva United Kingdom (Northern Ireland)
Pfizer Luxembourg SARL filialas Lietuvoje Pfizer Limited
Tel. +3705 2514000 Tel: +44 (0)1304 616161

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

7. Instructions for Use

This section is divided into the following subsections:
a. Introduction
b. Preparation of the injection
c. Preparing the Enbrel dose for injection
d. Adding the solvent
e. Withdrawing the Enbrel solution from the vial
f. Attaching the needle to the syringe
g. Choosing an injection site
h. Preparing the injection site and injecting the Enbrel solution
i. Disposal of materials

a. Introduction
The following instructions explain how to prepare and inject Enbrel. Read the instructions carefully and follow them step by step. Your child’s doctor or nurse will instruct you on the injection technique and the dose to administer to your child. Do not attempt to give an injection until you are certain you understand how to prepare and administer it correctly.
This injection must not be mixed in the same syringe or vial with any other medicine. See section 5 for instructions on how to store Enbrel.

b. Preparation of the injection

  • Wash your hands thoroughly.
  • Choose a clean, well-lit, flat work surface.
  • The tray containing the dose should include the following materials (if any of these items are missing, do not use the tray and consult your pharmacist). Use only the materials listed below. DO NOT use any other syringe.
    1 Enbrel vial
    1 Pre-filled syringe containing clear, colourless solvent (water for injections)
    1 Needle
    1 Vial adapter
    2 Alcohol swabs
  • Check the expiration dates on both the vial label and the syringe label. Do not use after the month and year indicated.

c. Preparing the Enbrel dose for injection

  • Remove the contents from the tray.
  • Remove the plastic cap from the Enbrel vial (see Figure 1). DO NOT remove the grey stopper or the aluminium ring around the neck of the vial.

Figure 1

One hand holds a cylindrical vial vertically while the thumb presses on the top toward the
  • Use a new alcohol swab to clean the grey stopper on the Enbrel vial. After cleaning, do not touch the grey stopper with your hands, and do not let it come into contact with any other surface.
  • Place the vial upright on a clean, flat surface.
  • Remove the paper backing from the vial adapter package.
  • Position the vial adapter onto the top of the Enbrel vial while it is still in its plastic packaging, aligning the tip of the adapter with the raised circle above the vial stopper (see Figure 2).
  • With one hand, firmly hold the Enbrel vial steady on a flat surface. With the other hand, press FIRMLY DOWNWARD on the adapter package until you feel and hear the adapter tip pierce the vial stopper AND THE SNAP OF THE ADAPTER LOCKING INTO PLACE (see Figure 3). DO NOT press down on the adapter at an angle (see Figure 4). It is important that the tip of the vial adapter fully penetrates the vial stopper.

Figure 2 Figure 3 Figure 4

Schematic diagram showing the separation of an upper protective cap from a medicine vial with screw cap Schematic diagram showing the removal of a protective cap from a medicine vial for dose preparation Schematic drawing with a large X indicating the

CORRECT INCORRECT

  • Holding the vial in one hand, remove the plastic packaging from the adapter (see Figure 5).

Figure 5

Black-and-white technical schematic showing a medicine vial with an extraction device positioned over the neck of the container
  • Remove the protective cap from the tip of the syringe by breaking the white cap along the perforation. This is done by holding the ring of the white cap while grasping the end of the white cap with the other hand and bending it downward and then upward until it breaks (see Figure 6). DO NOT remove the white ring that remains on the syringe.

Figure 6

Two hands separating the cap from an injection pen with a black arrow pointing toward the
  • Do not use the syringe if the perforation between the end and the ring is already broken. Start again with another dose-tray.
  • Holding the glass barrel of the syringe in one hand (not the white ring), and the vial adapter (not the vial) in the other hand, connect the syringe to the vial adapter by inserting the tip into the opening and turning it clockwise until securely attached (see Figure 7).

Figure 7

Diagram showing the rotational movement of a vial and a syringe for the

d. Adding the solvent

  • Keeping the vial upright on a flat surface, push the plunger VERY SLOWLY until all the solvent has entered the vial. This will help reduce foam formation (numerous bubbles) (see Figure 8).
  • Once the solvent has been added to Enbrel, the plunger may move on its own. This is caused by air pressure and is not significant.

Figure 8

One hand holds the top of a syringe while the
  • With the syringe still attached, gently swirl the vial several times in a circular motion to dissolve the powder (see Figure 9). DO NOT shake the vial. Wait until all the powder has dissolved (usually less than 10 minutes). The solution should appear clear and colorless to slightly yellow or light brown, with no fragments, flakes, or particles. A small amount of white foam may remain in the vial – this is normal. DO NOT use Enbrel if all the powder in the vial does not dissolve within 10 minutes. Start again with a new dose tray. Figure 9
One hand holds a syringe vertically above a vial with curved arrows indicating a rotational movement for withdrawal

e. Withdrawing the Enbrel solution from the vial

  • Your doctor or nurse will have instructed you on the correct amount of solution to withdraw from the vial. If your doctor has not provided instructions, contact them.
  • With the syringe still attached to the vial and the vial adapter, hold the vial upside down at eye level. Push the plunger fully into the syringe (see Figure 10).

Figure 10

Schematic drawing showing a hand pushing the plunger of a syringe toward the
  • Then, slowly pull back the plunger to draw the liquid into the syringe (see Figure 11). Withdraw only the portion of liquid prescribed by the child’s doctor. After withdrawing Enbrel from the vial, there may be air in the syringe. Do not be concerned, as the air can be removed later.

Figure 11

One hand holds the top of a syringe while the
  • While holding the vial upside down, unscrew the syringe from the vial adapter by turning it counterclockwise (see Figure 12).

Figure 12

Diagram showing the rotational movement of a vial and a medical device for the
  • Place the filled syringe on a clean, flat surface. Make sure the tip does not touch anything. Be careful not to push the plunger down.

f. Attaching the needle to the syringe

  • The needle is kept sterile inside a plastic container.
  • To open the plastic container, hold the short, wide end in one hand and place the other hand on the longer part of the container.
  • To break the seal, bend the wide end downward and then upward until it breaks (see Figure 13).

Figure 13

Two hands hold an injection pen with curved arrows indicating rotational movement for drug preparation
  • Once the seal is broken, remove the short, wide end of the plastic container.
  • The needle will remain in the long part of the packaging.
  • Holding the needle and container in one hand, take the syringe and insert the tip of the syringe into the needle opening.
  • Attach the syringe to the needle by rotating it clockwise until it is securely fastened (see Figure 14).

Figure 14

Technical diagram showing the
  • Remove the needle cap by firmly pulling it off, taking care not to touch the needle or allow the needle to touch any surface (see Figure 15). Be careful not to bend or twist the cap to avoid damaging the needle.

Figure 15

A syringe needle is inserted into a connector via a movement indicated by a black arrow toward the
  • Holding the syringe upright, remove the air by slowly pushing the plunger until all air is expelled (see Figure 16).

Figure 16

One hand holds a syringe vertically with the needle pointing toward the

g. Choosing an injection site

  • The three recommended injection sites for Enbrel are: (1) the central front area of the thighs; (2) the abdomen, except for the area within 5 cm around the navel; and (3) the outer upper area of the arms (see Figure 17). If you are self-injecting, do not use the outer upper area of the arms.

Figure 17

Schematic drawing of a human body viewed from front and back with gray areas indicating injection sites on abdomen, thighs, and arms
  • A different site must be used for each new injection. Each new injection should be given at least 3 cm away from a previous injection site. Do not inject into areas where the skin is tender, bruised, red, or hardened. Avoid areas with scars or stretch marks (it may help to record the locations of previous injection sites).
  • If the child has psoriasis, try to avoid injecting directly into swollen, thickened, red, or scaly areas of skin (“psoriatic skin lesions”).

h. Preparing the injection site and injecting the Enbrel solution

  • Clean the injection site where Enbrel will be injected with a new alcohol swab using a circular motion. Do not touch this area again before administering the injection.
  • Once the cleaned skin area has dried, pinch and firmly hold the skin with one hand. With the other hand, hold the syringe like a pencil.
  • With a quick, short motion, insert the needle completely into the skin at an angle between 45° and 90° (see Figure 18). With experience, you will find the angle most comfortable for the child. Be careful not to insert the needle too slowly or with excessive force.

Figure 18

Technical drawing showing a hand holding a syringe for a
  • Once the needle is fully inserted into the skin, release the skin you are holding. With your free hand, hold the syringe near its base to stabilize it. Then, push the plunger to inject the entire solution at a slow and steady rate (see Figure 19).

Figure 19

Two hands hold a syringe to prepare the
  • When the syringe is empty, remove the needle from the skin, taking care to maintain the same angle used during insertion. Press a cotton swab over the injection site for 10 seconds. Mild bleeding may occur. Do not rub the injection site. A bandage is optional.

i. Disposal of materials

  • The syringe and needles must never be reused. Dispose of the needles and syringe as instructed by your doctor, nurse, or pharmacist.

If you have any questions, consult a doctor, nurse, or pharmacist familiar with Enbrel.

Package leaflet: information for the user

Enbrel 25 mg solution for injection in cartridge for administration device

etanercept
Please read this entire leaflet carefully before using this medicine because it contains
important information for you.

  • Keep this leaflet. You may need to read it again.
  • Your doctor will provide you with the Patient Safety Card containing important safety information you should be aware of before and during treatment with Enbrel.
  • If you have any questions, ask your doctor, pharmacist, or nurse.
  • This medicine has been prescribed for you or for a child. Do not give it to others, even if their symptoms are the same as yours or those of the child, as it could be harmful.
  • If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet
The information in this package leaflet is divided into the following 6 sections:

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

1. What Enbrel is and what it is used for

Enbrel is a medicine made from two human proteins. It blocks the activity of another protein that causes inflammation in the human body. Enbrel works by reducing the inflammation associated with certain diseases.
In adults (18 years of age and older), Enbrel can be used to treat moderate to severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate to 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 not suitable for you. Whether used alone or in combination with methotrexate, Enbrel can slow down joint damage caused by rheumatoid arthritis and improve your ability to carry out normal daily activities.
For patients with psoriatic arthritis involving multiple joints, Enbrel can improve the ability to perform daily activities. For patients with painful or swollen symmetric joints (e.g. hands, wrists and feet), Enbrel can slow down structural damage to these joints caused by the disease.
Enbrel is also prescribed for the following conditions in children and adolescents:

  • For the following types of juvenile idiopathic arthritis, when treatment with methotrexate has not provided an adequate response or is not appropriate:
  • 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 provided an adequate response or are not appropriate.
  • Severe psoriasis in patients from the age of 6 years who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies.

2. What you need to know before using Enbrel

Do not use Enbrel

  • If you or the child are allergic to etanercept or to any of the other ingredients of Enbrel (listed in section 6). If you or the child experience allergic reactions such as chest tightness, shortness of breath, dizziness, or skin rash, do not inject any 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 unsure, contact your doctor.
  • If you or the child have any type of infection. If you are unsure, consult 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, shortness of breath, dizziness, or skin rash, do not inject any more Enbrel and contact your doctor immediately.
  • Infections/surgery: If you or the child develop a new infection or are about to undergo any major surgical procedure. Your doctor may want to review your treatment with Enbrel.
  • Infections/diabetes: Inform your doctor if you or the child have a history of recurring infections or suffer from diabetes or other conditions that increase the risk of infection.
  • Infections/monitoring: Inform your doctor about any recent travel outside Europe. If you or the child develop symptoms of an infection such as fever, chills, or cough, inform your doctor immediately. Your doctor may decide to continue monitoring you or the child for infections even after stopping Enbrel.
  • Tuberculosis: Cases of tuberculosis have been reported in patients treated with Enbrel. Your doctor will check you for signs and symptoms of tuberculosis before starting treatment with Enbrel. This may include a thorough medical history, chest X-rays, and a tuberculin skin test. The results of these tests must be recorded in the Patient Record Card. It is very important that you inform your doctor if you or the child have ever had tuberculosis or have been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection occur during or after treatment, inform your doctor immediately.
  • Hepatitis B: Inform your doctor if you or the child have or have had hepatitis B. Your doctor must test for hepatitis B before you or the child start treatment with Enbrel. Treatment with Enbrel may cause reactivation of hepatitis B in patients with prior hepatitis B virus infection. In such cases, you must stop using Enbrel.
  • Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may consider monitoring your treatment with Enbrel if the infection worsens.
  • Blood disorders: Seek immediate medical attention if you or the child experience any signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of Enbrel treatment.
  • Nervous system and eye disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Enbrel is an appropriate treatment.
  • Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure, as Enbrel should be used with caution in such cases.
  • Tumors: Inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumor before taking Enbrel. Patients with long-standing, severe rheumatoid arthritis may have a higher than average risk of developing lymphoma. Children and adults taking Enbrel may have an increased risk of developing lymphoma or other tumors. Some children and adolescent patients treated with Enbrel or other medicines that work like Enbrel have developed tumors, including unusual types, sometimes with fatal outcomes. Some patients receiving Enbrel have developed skin tumors. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
  • Chickenpox (varicella): Inform your doctor if you or the child are exposed to chickenpox while using Enbrel. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
  • Latex: The needle cover is made of latex (dried natural rubber). Contact your doctor before using Enbrel if the needle cover is to be handled by, or if Enbrel is to be administered to, a person with known or suspected hypersensitivity (allergy) to latex.
  • Alcohol abuse: Enbrel must not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child 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 have Wegener’s granulomatosis, consult your doctor.
  • Anti-diabetic medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide whether you or the child need to reduce the dose of anti-diabetic medicine while taking Enbrel.

Children and adolescents
Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Enbrel. Some vaccines, such as oral polio vaccine, must not be taken while receiving Enbrel. Consult the pediatrician before the child receives any vaccine.
Enbrel should generally not be used in children under 2 years of age with polyarticular juvenile idiopathic arthritis or extended oligoarticular juvenile idiopathic arthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Other medicines and Enbrel
Inform your doctor or pharmacist if you or the child are taking, have recently taken, or might take any other medicines (including anakinra, abatacept, or sulfasalazine), even those not prescribed. You or the child must not use Enbrel together with the active substances anakinra or abatacept.

Pregnancy and breastfeeding
Enbrel should be used during pregnancy only if clearly needed. If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor.
If you received Enbrel during pregnancy, the newborn may be at increased risk of infection. In addition, one study indicated a higher number of birth defects in mothers who received Enbrel during pregnancy compared to mothers who did not receive Enbrel or other similar medicines (TNF antagonists), but no specific pattern of birth defects was identified. Another study did not show an increased risk of birth defects when mothers received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed during treatment with Enbrel. It is important to inform the child’s pediatrician and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
Enbrel is not expected to affect the ability to drive or operate machinery.

Enbrel contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Enbrel

Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
If you think that the effect of Enbrel is too strong or too weak, contact your doctor or
pharmacist.
The administration device cartridge is available in doses of 25 and 50 mg.
Dose for adult patients (aged 18 years and older)
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 25 mg administered twice weekly or 50 mg once weekly by subcutaneous injection.
However, your doctor may determine a different dosing frequency for Enbrel.
Plaque psoriasis
The usual dose is 25 mg administered twice weekly or 50 mg administered once weekly.
Alternatively, a dose of 50 mg twice weekly may be given for up to 12 weeks, followed by a dose of 25 mg twice weekly or 50 mg once weekly.
Your doctor will decide how long you should take Enbrel and whether, based on your response, further treatment is needed. If, after 12 weeks, Enbrel has not improved your condition, your doctor may instruct you to discontinue treatment.
Use in children and adolescents
The appropriate dose and dosing frequency for a child or adolescent will depend on body weight and the disease being treated. Your doctor will determine the correct dose for your child and prescribe an appropriate Enbrel dosage (10 mg, 25 mg, or 50 mg).
For polyarthritis or extended oligoarthritis in patients from 2 years of age, or enthesitis-related arthritis or psoriatic arthritis in patients from 12 years of age, the usual dose is 0.4 mg of Enbrel per kg of body weight (up to a maximum of 25 mg), administered twice weekly, or 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg) administered once weekly.
For psoriasis in patients from 6 years of age, the usual dose is 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg), administered once weekly. If Enbrel has not improved the child's condition after 12 weeks, your doctor may advise you to stop treatment with this medicine.
Your doctor will provide detailed instructions on how to prepare and measure the appropriate dose.
Method and route of administration
Enbrel is administered by injection under the skin (subcutaneous injection).
Enbrel may be taken with or without food and drink.
Detailed instructions on how to inject Enbrel are provided in the “Instructions for Use”. Do not mix
the Enbrel solution with other medicines.
To help you remember, it may be helpful to write in a diary on 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 prescribed (either by injecting too much at one time or by using it too frequently), contact a doctor or pharmacist immediately. Always keep the medicine package, even if empty.
If you forget to take Enbrel
If you miss a dose, administer it as soon as you remember, unless the next dose is scheduled for the following day, in which case you should skip the missed dose. Then continue taking the medicine on your regularly scheduled day(s). If you have missed a dose until the day the next dose is due, do not take a double dose (two doses on the same day) to make up for the missed dose.
If you stop using Enbrel
After stopping treatment, disease symptoms may return.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions
If any of the following side effects occur, do not inject Enbrel again. Contact your doctor immediately or go to the nearest hospital emergency department.

  • Difficulty swallowing or breathing
  • Swelling of the face, throat, hands or feet
  • Feeling restless or anxious, palpitations, sudden redness of the skin and/or feeling of warmth
  • Severe rash, itching, hives (raised red or pale patches on the skin that are often itchy)

Severe allergic reactions are rare. However, any of the symptoms listed above may indicate an allergic reaction to Enbrel; therefore, you must seek immediate medical attention.
Serious side effects
If you or the child notice any of the following effects, urgent medical care may be needed.

  • Symptoms of serious infections , such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a warm, red, tender, painful area on the skin or joints.
  • Symptoms of blood disorders , such as bleeding, bruising or paleness.
  • Symptoms of nerve disorders , such as numbness or tingling, changes in vision, eye pain, or sudden weakness in one arm or leg.
  • Symptoms of heart failure or worsening heart failure , such as fatigue or shortness of breath during activity, swelling of the ankles, a feeling of fullness in the neck or abdomen, shortness of breath at night or cough, bluish colouring of the nails or lips.
  • Symptoms of tumours: tumours may affect any part of the body, including the skin and blood, and possible symptoms depend on the type and location of the tumour. These symptoms may include weight loss, fever, swelling (with or without pain), persistent cough, or presence of cysts or growths on the skin.
  • Symptoms of autoimmune reactions (where antibodies are produced that may damage normal body tissues), such as pain, itching, weakness, or abnormalities in breathing, thinking, sensation or vision.
  • Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, joint or muscle pain, or fatigue.
  • Symptoms of inflammation of blood vessels , such as pain, fever, redness or warmth of the skin, or itching.

These side effects are rare or uncommon, but they are serious conditions (some of which may rarely lead to death). If any of these symptoms occur, contact your doctor immediately or go to the nearest hospital emergency department.
The known side effects of Enbrel include those listed below, grouped by decreasing frequency:

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

  • Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain and swelling) (these occur less frequently after the first month of treatment; some patients have developed a reaction at a recently used injection site); headache.

  • Common (may affect up to 1 in 10 people): Allergic reactions; fever; rash; itching; antibodies directed against normal tissue (formation of autoantibodies).

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

  • Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); reduced number of platelets in the blood; skin tumour (excluding melanoma); localized swelling of the skin (angioedema); hives (raised red or pale itchy patches on the skin); eye inflammation; psoriasis (new onset or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood (in patients also receiving methotrexate, the frequency of increased liver enzymes in the blood is common); abdominal pain and cramps, diarrhoea, weight loss or blood in stools (symptoms of intestinal problems).

  • Rare (may affect up to 1 in 1,000 people): Severe allergic reactions (including severe localized swelling of the skin and breathing difficulties); lymphoma (a type of blood cancer); leukaemia (a cancer affecting blood and bone marrow); melanoma (a type of skin cancer); combined reduction in platelets, red blood cells and white blood cells; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain and fatigue); rash that may lead to severe blistering and peeling of the skin; lichenoid reactions (itchy red/violaceous rash and/or whitish-grey thread-like lines on mucous membranes); liver inflammation caused by your immune system (autoimmune hepatitis; in patients also receiving methotrexate, the frequency is uncommon); an immune disorder that may affect the lungs, skin and lymph nodes (sarcoidosis); lung inflammation or scarring (in patients also receiving methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the tiny filters in the kidneys leading to reduced kidney function (glomerulonephritis).

  • Very rare (may affect up to 1 in 10,000 people): inability of the bone marrow to produce essential 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 form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly presents with purple lesions on the skin; excessive activation of white blood cells involved in inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness accompanied by skin rash).

Side effects in children and adolescents
The side effects and their frequency observed in children and adolescents are similar to those described above.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enbrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "Exp.". The expiry date refers to the last day of that month.
Store in the refrigerator (between 2°C and 8°C). Do not freeze.
Keep the administration device cartridge in the outer packaging to protect the medicine from light.
After removing a cartridge for administration device from the refrigerator, wait approximately 15–30 minutes to allow the Enbrel solution in the cartridge to reach room temperature. Do not heat it in any other way. Immediate use is therefore recommended.
The cartridges for administration device may be stored at room temperature (up to 25°C) for up to 4 weeks, once only, provided they are protected from light; after this period they must not be returned to the refrigerator. If not used within 4 weeks outside the refrigerator, Enbrel must be discarded. It is recommended to record the date when the Enbrel administration device is removed from the refrigerator and the date by which Enbrel must be discarded (no more than 4 weeks outside the refrigerator).
Inspect the solution inside the administration device cartridge by looking through the inspection window. The solution should be from clear to slightly opalescent, colourless to pale yellow or light brown, and may contain small white or almost transparent protein particles. This is the normal appearance of Enbrel. Do not use this solution if it shows changes in colour, appears cloudy, or if particles different from those described are visible. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Enbrel contains
Enbrel 25 mg solution for injection in cartridge for administration device
The active substance in Enbrel is etanercept. Each cartridge for administration device contains 0.5 mL of solution, containing 25 mg of etanercept.
The other ingredients are sucrose, sodium chloride, L-arginine hydrochloride, monobasic sodium phosphate dihydrate, dibasic sodium phosphate dihydrate, and water for injections.

Description of the appearance of Enbrel and package contents
Enbrel is supplied as an injectable solution in a ready-to-use cartridge for administration device. The cartridge for administration device must be used with the SMARTCLIC device. The device is supplied separately. The solution is from clear to opalescent, colourless to pale yellow or pale brown.

Enbrel 25 mg solution for injection in cartridge for administration device
Pack sizes contain 4, 8 or 24 cartridges for administration device 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 Brussels
Belgium

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

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

België/Belgique/Belgien Κύπρος
Luxembourg/Luxemburg PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
Pfizer NV/SA T  : +357 22 817690
Tél/Tel: +32 (0)2 554 62 11

Česká Republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: +36 1 488 3700

Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf: +45 44 201 100 Tel: +35621 344610

Deutschland Nederland
Pfizer Pharma GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

България Norge
Пфайзер Люксембург САРЛ, Pfizer AS
Клон България Tlf: +47 67 52 61 00
Teл: +359 2 970 4333

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
PFIZER EΛΛAΣ A.E. Pfizer Polska Sp. z o.o.
Τηλ.: +30 210 67 85 800 Tel.: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Télf: +34 91 490 99 00 Tel: (+351) 21 423 55 00

France România
Pfizer Pfizer Romania S.R.L
Tél +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL , Pfizer, podružnica
Tel: +385 1 3908 777 za svetovanje s področja farmacevtske
dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ireland Slovenská Republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: +1800 633 363 (toll free) Tel: +421 2 3355 5500
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Tel: +354 540 8000 Puh/Tel: +358 (0)9 430 040

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00

Latvija United Kingdom (Northern Ireland)
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel. +371 67035775 Tel: +44 (0)1304 616161

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000

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

Instructions for use

Enbrel

(etanercept)
25 mg/0.5 mL
For subcutaneous injection only
Important information

  • Keep these Instructions for Use, as they provide detailed guidance on how to prepare and administer an injection.
  • Use Enbrel only after reading and fully understanding these Instructions for Use.
  • Use Enbrel only after receiving training from your healthcare provider.
  • The cartridge for the delivery device contains a single dose of Enbrel and must be used exclusively with the SMARTCLIC device.
  • In these Instructions for Use, the cartridge for the delivery device and the SMARTCLIC device will be referred to as “cartridge” and “device,” respectively.
  • If this is your first time using the device, ensure you follow the setup instructions in the dedicated User Manual. You will not be able to use the device until setup is complete.
  • Do not attempt to use cartridges with other devices.
  • Do not share cartridges or the device with other people.
  • Do not shake cartridges or the device containing a cartridge.
  • Do not reuse cartridges after removing the needle cap.
  • Take care not to spill liquids onto cartridges or the device. Do not rinse or place cartridges or the device under water.
  • Refer to the additional device User Manual for instructions on accessing menus, using the training cartridge, advanced usage modes, and troubleshooting error messages.

Storage

  • Store cartridges in the refrigerator at a temperature between 2°C and 8°C. Do not freeze cartridges. Do not store cartridges in the device.
  • Keep cartridges in their original packaging until use to protect from direct sunlight.
  • Cartridges may be stored at room temperature up to 25°C for a maximum of 4 weeks. Do not return cartridges to the refrigerator after they have reached room temperature.
  • Store cartridges and the device out of sight and reach of children and adolescents.
  • Refer to the device User Manual for instructions on how to store and clean the device.

Materials needed

  • Prepare the following items on a clean, flat surface:
    o Enbrel package containing cartridges
    o SMARTCLIC device
    o Alcohol swabs
    o Cotton balls
    o Clean gauze pads (not included)
    o Suitable sharps container (not included)
  • Do not use the product if the package has been dropped or damaged.
    Note: If you do not have all necessary materials, contact your healthcare provider.

The device:
Refer to the User Manual for more information.

Medical device diagram showing LCD display, injection button, up/down buttons, cancel button, and blue arrow for injection site

The cartridge:

Diagram showing a cartridge before and after the

Preparation procedure

One hand lifts an injection pen from a white plastic tray containing two other white and blue pens with a green arrow pointing toward the
  • Remove 1 cartridge from the tray inside the package.
  • Return the box and tray to the refrigerator with any unused cartridges.
  • Wash and dry your hands.
  • For a more comfortable injection, allow the cartridge to reach room temperature for approximately 15–30 minutes, away from direct sunlight. Do not use other methods to warm the cartridge.
Medical diagram showing a syringe with instructions on the cap of the
  • Check the expiration date and dose printed on the label. Do not use the product if the expiration date has passed or if a different dose was prescribed.
  • Inspect the cartridge; do not use it if:
    o it has been dropped, even if it appears undamaged
    o it is damaged
    o the needle cap is loose
    o it has been frozen or exposed to heat
    o it has been stored at room temperature for more than 4 weeks
    o it was returned to the refrigerator after reaching room temperature
  • Do not remove the needle cap until instructed to do so.
One hand holds an injection pen vertically to inspect the transparent liquid visible through the central viewing window of the device
  • Inspect the medication through the inspection window. The solution should be from clear to slightly opalescent, colorless to pale yellow or light brown, and may contain small white or nearly transparent protein particles. This is normal.
  • Do not use this medication if there are changes in color, if it appears cloudy, or if particles different from those described are visible.
  • Do not shake the cartridge.
    Note: For any questions about the medication, contact your healthcare provider.
Medical schematic showing three areas for the
  • Always select a site on the abdomen, upper thigh, or outer area of the upper arm (only for healthcare professionals).
  • Choose an injection site at least 3 cm away from the previous injection site and at least 5 cm away from the navel.
  • Do not administer the injection in areas with bones or where the skin is damaged, bruised, red, painful (tender), or hardened. Avoid injecting into scarred areas or stretch marks.
  • Do not administer the injection through clothing.
    Note: If you have psoriasis, do not inject directly into areas where the skin is raised, thickened, red, or scaly, or into lesions.
  • Clean the injection site with the provided alcohol swab and wait for it to dry.
Illustration of step 5 showing two hands cleaning the
  • Clean the injection end of the device with the separately provided alcohol swab.
  • Wait for the injection end to dry before proceeding with the injection.

Injection procedure

Illustration of step 6 with green arrow pointing toward the
  • Firmly press the cartridge straight through the cartridge port, without rotating the device, until you feel it fully seated. The device will turn on once the cartridge is correctly inserted.
  • Check that the display shows 25 mg and that the expiration date has not passed.
    Note: The device will turn off after 90 seconds of inactivity. Press and hold the injection button to turn it back on.
One hand grasps the blue needle cap to remove it from a medical device, indicated by a green downward arrow
  • Remove the needle cap by firmly pulling it straight down.
  • Dispose of the needle cap in a suitable sharps container.
  • Administer the injection immediately after removing the needle cap.
  • Do not recap the needle.
    Caution: do not insert fingers into the device after removing the needle cap to avoid needle-stick injury.
Symbol of a large black X-shaped cross at the

Note: To cancel the injection and eject the cartridge, press the Cancel/Eject button for 1 second.

Illustration of step 8 showing a hand holding a white medical device to position it on the skin with a green downward arrow
  • Position the device with the blue arrow pointing at a 90-degree angle toward the injection site.
  • Ensure you can see the device display.
  • Do not pinch the skin around the injection site.
    Caution: If the device is dropped with a cartridge inserted, eject and dispose of the cartridge. Refer to the Troubleshooting section of the device User Manual.
Illustration of step 9 showing a hand pressing the central button of a white medical device with an indicator green arrow
  • Press and hold the injection button to start the injection when prompted by the display.
    Note: You may release the injection button after the injection has started.
Graphic of step 10 with green downward arrow and medical device pressing on the skin with a small blue droplet underneath
  • Keep pressing the device against the skin and wait for the medication to be delivered.
  • Watch the device display.
  • Do not move, tilt, or remove the device from the skin until instructed to do so on the display.
    Note: If you remove the device before instructed, do not reposition it on the injection site or administer another dose. Contact your healthcare provider for guidance.
Diagram of step 11 indicating to lift the device from the skin with a green arrow pointing toward the
  • Lift and hold the device away from the skin. The device will display that the injection is complete.
  • Wait. The cartridge will be partially ejected from the bottom of the device. This may take up to 10 seconds. Do not cover the bottom of the device during this time. Do not insert fingers into the device, as the needle will be exposed.
  • If bleeding occurs, press a cotton ball or gauze pad over the injection site until bleeding stops. Do not rub.
Illustration of step 12 with a green downward arrow indicating to remove the cartridge with fingers from a medical device
  • Remove the cartridge once it has been partially ejected from the device.
  • Check that the medication in the cartridge is fully used by verifying that a gray bar is visible in the inspection window. If not, you may not have received the full dose. Contact your healthcare provider for guidance.
  • Do not reuse or reinsert the cartridge into the device.
  • Dispose of the used cartridge immediately in a suitable sharps container, as instructed by your healthcare provider or pharmacist and in accordance with local health and safety regulations.
  • —End of Instructions for Use—

Package leaflet: information for the user

Enbrel 50 mg solution for injection in cartridge for delivery device

etanercept
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

  • Keep this leaflet. You may need to read it again.
  • Your doctor will provide you with the Patient Information Card containing important safety information you should know about before and during treatment with Enbrel.
  • If you have any questions, consult your doctor, pharmacist, or nurse.
  • This medicine has been prescribed for you or for a child. Do not give it to other people, even if their symptoms are the same as yours or those of the child, because it could be harmful.
  • If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet
The information in this patient information leaflet is divided into the following 6 sections:

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

1. What Enbrel is and what it is used for

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

In adults (aged 18 years and older), Enbrel can be used to treat moderate to severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate to 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 not suitable for you. Whether used alone or in combination with methotrexate, Enbrel can slow down joint damage caused by rheumatoid arthritis and improve your ability to carry out normal daily activities.

For patients with psoriatic arthritis affecting multiple joints, Enbrel can improve the ability to perform daily activities. For patients with painful or swollen symmetric joints (e.g. hands, wrists and feet), Enbrel can slow down structural damage to these joints caused by the disease.

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

  • For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not provided an adequate response or is not appropriate:
    • 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 provided an adequate response or are not appropriate.
  • Severe psoriasis in patients from the age of 6 years who have had an inadequate response to (or cannot tolerate) phototherapy or other systemic therapies.

2. What you need to know before using Enbrel

Do not use Enbrel

  • If you or the child are allergic to etanercept or to any of the other ingredients of Enbrel (listed in section 6). If you or the child experience allergic reactions such as chest tightness, shortness of breath, dizziness or rash, do not inject any 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 in doubt, contact your doctor.
  • If you or the child have any type of infection. If in doubt, consult 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, shortness of breath, dizziness or rash, do not inject any more Enbrel and contact your doctor immediately.
  • Infections/surgery: if you or the child develop a new infection or are about to undergo any major surgical procedure. Your doctor may wish to review your treatment with Enbrel.
  • Infections/diabetes: inform your doctor if you or the child have a history of recurring infections or suffer from diabetes or other conditions that increase the risk of infection.
  • Infections/monitoring: inform your doctor about any recent travel outside Europe. If you or the child develop symptoms of an infection such as fever, chills or cough, inform your doctor immediately. Your doctor may decide to continue monitoring you or the child for infections after stopping Enbrel.
  • Tuberculosis: cases of tuberculosis have been reported in patients treated with Enbrel. Your doctor will check you for signs and symptoms of tuberculosis before starting Enbrel treatment. This may include a thorough medical history, chest X-ray and tuberculin skin test. The results of these tests must be recorded in the Patient Record Card. It is very important that you inform your doctor if you or the child have ever had tuberculosis or have been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection appear during or after treatment, inform your doctor immediately.
  • Hepatitis B: inform your doctor if you or the child have or have had hepatitis B. Your doctor must test for hepatitis B before starting Enbrel treatment. Treatment with Enbrel may cause reactivation of hepatitis B in patients previously infected with the hepatitis B virus. In such cases, you must stop using Enbrel.
  • Hepatitis C: inform your doctor if you or the child have hepatitis C. Your doctor may consider it appropriate to monitor treatment with Enbrel if the infection worsens.
  • Blood disorders: seek immediate medical attention if you or the child experience any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of Enbrel treatment.
  • Nervous system and eye disorders: inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves) or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Enbrel is an appropriate treatment.
  • Congestive heart failure: inform your doctor if you or the child have a history of congestive heart failure, as Enbrel should be used with caution in such cases.
  • Tumours: inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumour before taking Enbrel. Patients with long-standing severe rheumatoid arthritis may have a higher than average risk of developing lymphoma. Children and adults taking Enbrel may have an increased risk of developing lymphoma or other tumours. Some children and adolescent patients treated with Enbrel or other medicines that work like Enbrel have developed tumours, including unusual types, sometimes fatal. Some patients receiving Enbrel have developed skin tumours. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
  • Chickenpox: inform your doctor if you or the child are exposed to chickenpox while using Enbrel. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
  • Latex: the needle cap is made of latex (dried natural rubber). Contact your doctor before using Enbrel if the needle cap is handled by, or if Enbrel is administered to, a person with known or possible hypersensitivity (allergy) to latex.
  • Alcohol abuse: Enbrel must not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child 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 have Wegener’s granulomatosis, consult your doctor.
  • Anti-diabetes medicines: inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide whether you or the child need to take a lower dose of anti-diabetes medicine while taking Enbrel.

Children and adolescents
Vaccinations: whenever possible, children should be up to date with all vaccinations before starting Enbrel. Some vaccines, such as oral polio vaccine, must not be taken while receiving Enbrel. Consult your paediatrician before the child receives any vaccine.
Enbrel should normally not be used in children under 2 years of age with polyarticular or extended oligoarticular juvenile idiopathic arthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Other medicines and Enbrel
Inform your doctor or pharmacist if you or the child are taking, have recently taken or might take any other medicines (including anakinra, abatacept or sulfasalazine), even those not prescribed. You or the child must not use Enbrel together with the active substances anakinra or abatacept.

Pregnancy and breastfeeding
Enbrel should be used during pregnancy only if clearly needed. If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor.
If you received Enbrel during pregnancy, the newborn may be at increased risk of infection. In addition, one study indicated a higher number of birth defects in mothers who received Enbrel during pregnancy compared to mothers who did not receive Enbrel or other similar medicines (TNF antagonists), but no specific pattern of birth defects was observed. Another study did not show an increased risk of birth defects when mothers received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed while being treated with Enbrel. It is important to inform the child’s paediatricians and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
Enbrel is not expected to affect the ability to drive vehicles or use machinery.

Enbrel contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially "sodium-free".

3. How to use Enbrel

Use this medicine exactly as your doctor has told you. If you are in doubt, consult your doctor or pharmacist.
If you think that the effect of Enbrel is too strong or too weak, talk to your doctor or pharmacist.
The cartridge for the delivery device is available in strengths of 25 mg and 50 mg.

Dose for adult patients (aged 18 years and older)
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 25 mg, administered twice weekly or 50 mg once weekly by subcutaneous injection. However, your doctor may decide on a different dosing frequency for Enbrel.

Plaque psoriasis
The usual dose is 25 mg administered twice weekly or 50 mg administered once weekly.
Alternatively, a dose of 50 mg twice weekly may be given for up to 12 weeks, followed by 25 mg twice weekly or 50 mg once weekly.
Your doctor will decide how long you should take Enbrel and whether, based on your response, further treatment is needed. If, after 12 weeks, Enbrel has not had any effect on your disease, your doctor may tell you to stop treatment.

Use in children and adolescents
The appropriate dose and dosing frequency for a child or adolescent will depend on body weight and the condition being treated. Your doctor will determine the correct dose for your child and prescribe an appropriate Enbrel dosage (10 mg, 25 mg, or 50 mg).

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

For psoriasis in patients aged 6 years and older, the usual dose is 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg), administered once weekly. If Enbrel has not had any effect on the child’s condition after 12 weeks, your doctor may tell you to stop treatment with this medicine.
Your doctor will provide detailed instructions on how to prepare and measure the correct dose.

Method and route of administration
Enbrel is administered by injection under the skin (subcutaneous injection).
Enbrel may be taken with or without food and drink.
Detailed instructions on how to inject Enbrel are provided in the “Instructions for use” section. Do not mix the Enbrel solution with other medicines.
To help you remember, it may be helpful to write down in a diary on 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 at one time or by using it too frequently), speak to a doctor or pharmacist immediately. Always keep the medicine carton with you, even if it is empty.

If you forget to take Enbrel
If you forget a dose, take it as soon as you remember, unless the next dose is scheduled for the following day, in which case you should skip the missed dose. Then continue taking the medicine on your regularly scheduled day(s). If you have forgotten the dose until the day the next dose is due, do not take a double dose (two doses on the same day) to make up for the missed dose.

If you stop using Enbrel
After stopping treatment, symptoms of the disease may return.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Allergic reactions
If any of the following side effects occur, do not inject Enbrel again. Contact your doctor immediately or go to the nearest hospital emergency department.

  • Difficulty swallowing or breathing
  • Swelling of the face, throat, hands or feet
  • Feeling nervous or anxious, palpitations, sudden redness of the skin and/or feeling of warmth
  • Severe rash, itching, hives (raised red or pale patches on the skin that are often itchy)

Severe allergic reactions are rare. However, any of the symptoms listed above may indicate an allergic reaction to Enbrel; therefore, you must seek immediate medical attention.

Serious side effects
If you or the child notice any of the following symptoms, urgent medical care may be needed.

  • Symptoms of serious infections, such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a warm, red, tender, painful area on the skin or joints.
  • Symptoms of blood disorders, such as bleeding, bruising or paleness.
  • Symptoms of nerve problems, such as numbness or tingling, changes in vision, eye pain, or sudden weakness in one arm or leg.
  • Symptoms of heart failure or worsening heart failure, such as fatigue or shortness of breath during activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, shortness of breath at night, cough, or bluish colouring of the nails or lips.
  • Symptoms of tumours: tumours may affect any part of the body, including the skin and blood, and possible symptoms depend on the type and location of the tumour. These may include weight loss, fever, swelling (with or without pain), persistent cough, or the presence of cysts or skin growths.
  • Symptoms of autoimmune reactions (where antibodies are produced that may damage normal body tissues), such as pain, itching, weakness, breathing problems, changes in thinking, sensation or vision.
  • Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, joint or muscle pain, or fatigue.
  • Symptoms of inflammation of blood vessels, such as pain, fever, redness or warmth of the skin, or itching.

These side effects are rare or uncommon, but they are serious conditions (some of which may rarely lead to death). If any of these symptoms occur, contact your doctor immediately or go to the nearest hospital emergency department.

The known side effects of Enbrel include those listed below, grouped by decreasing frequency:

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

  • Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain and swelling) (these occur less frequently after the first month of treatment; some patients have developed a reaction at a recently used injection site); headache.

  • Common (may affect up to 1 in 10 people):
    Allergic reactions; fever; rash (skin eruption); itching; antibodies directed against normal tissue (formation of autoantibodies).

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

  • Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections at various sites); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); reduced platelet count in the blood; skin tumour (excluding melanoma); localized swelling of the skin (angioedema); hives (raised red or pale itchy patches on the skin); eye inflammation; psoriasis (new onset or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood (in patients also being treated with methotrexate, the frequency of increased liver enzymes in the blood is common); abdominal pain and cramps, diarrhoea, weight loss or blood in the stools (symptoms of intestinal problems).

  • Rare (may affect up to 1 in 1,000 people):
    Severe allergic reactions (including severe localized swelling of the skin and breathing difficulties); lymphoma (a type of blood cancer); leukaemia (a cancer affecting the blood and bone marrow); melanoma (a type of skin cancer); combined reduction in platelets, red blood cells and white blood cells; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis, or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain and fatigue); skin rash that may lead to blistering and severe peeling of the skin; lichenoid reactions (itchy reddish-purple rash and/or whitish-grey thread-like lines on mucous membranes); liver inflammation caused by the immune system (autoimmune hepatitis; in patients also being treated with methotrexate, the frequency is uncommon); an immune disorder that may affect the lungs, skin and lymph nodes (sarcoidosis); lung inflammation or scarring (in patients also being treated with methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the tiny filters within the kidneys leading to reduced kidney function (glomerulonephritis).

  • Very rare (may affect up to 1 in 10,000 people):
    Failure of the bone marrow to produce essential blood cells.

  • Not known (frequency cannot be estimated from available data):
    Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma, a rare form of cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma usually appears as purple lesions on the skin; excessive activation of white blood cells involved in inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness accompanied by a skin rash).

Side effects in children and adolescents
The side effects and their frequency observed in children and adolescents are similar to those described above.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enbrel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (between 2°C and 8°C). Do not freeze.
Keep the administration device cartridge in its outer packaging to protect the medicine from light.
After removing a cartridge for administration device from the refrigerator, wait approximately 15–30 minutes to allow the Enbrel solution in the cartridge to reach room temperature. Do not heat it in any other way. Immediate use is therefore recommended.
Administration device cartridges may be stored at room temperature (up to 25°C) for up to 4 weeks, for one time only, ensuring they are protected from light; after this period, they must not be returned to the refrigerator. If not used within 4 weeks of removal from the refrigerator, Enbrel must be discarded. It is recommended to record the date when the Enbrel administration device is taken out of the refrigerator and the date by which Enbrel must be discarded (no more than 4 weeks outside the refrigerator).
Inspect the solution inside the administration device cartridge by looking through the inspection window. The solution should be from clear to slightly opalescent, from colourless to pale yellow or light brown, and may contain small white or almost transparent protein particles. This is the normal appearance of Enbrel. Do not use this solution if it shows changes in colour, appears cloudy, or if particles different from those described are visible. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Enbrel contains
Enbrel 50 mg solution for injection in cartridge for delivery device
The active substance in Enbrel is etanercept. Each cartridge for delivery device contains 1.0 mL of solution, containing 50 mg of etanercept.
The other components are sucrose, sodium chloride, L-arginine hydrochloride, monobasic sodium phosphate dihydrate, dibasic sodium phosphate dihydrate, and water for injections.

Description of the appearance of Enbrel and contents of the pack
Enbrel is supplied as a solution for injection in a ready-to-use cartridge for delivery device. The cartridge for delivery device must be used with the SMARTCLIC device. The device is supplied separately. The solution is from clear to opalescent, colourless to pale yellow or light brown.

Enbrel 50 mg solution for injection in cartridge for delivery device
Pack sizes contain 2, 4 or 12 cartridges for delivery device 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 Brussels
Belgium

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

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

België/Belgique/Belgien Κύπρος
Luxembourg/Luxemburg PFIZER EΛΛAΣ A.E. (CYPRUS BRANCH)
Pfizer NV/SA T  : +357 22 817690
Tél/Tel: +32 (0)2 554 62 11

Česká Republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: +36 1 488 3700

Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf: +45 44 201 100 Tel: +35621 344610

Deutschland Nederland
Pfizer Pharma GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

България Norge
Пфайзер Люксембург САРЛ, Pfizer AS
Клон България Tlf: +47 67 52 61 00
Teл: +359 2 970 4333

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
PFIZER EΛΛAΣ A.E. Pfizer Polska Sp. z o.o.
Τηλ.: +30 210 67 85 800 Tel.: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Télf: +34 91 490 99 00 Tel: (+351) 21 423 55 00

France România
Pfizer Pfizer Romania S.R.L
Tél +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL , Pfizer, podružnica
Tel: +385 1 3908 777 za svetovanje s področja farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ireland Slovenská Republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: +1800 633 363 (toll free) Tel: +421 2 3355 5500
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Tel: +354 540 8000 Puh/Tel: +358 (0)9 430 040

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00

Latvija United Kingdom (Northern Ireland)
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel. +371 67035775 Tel: +44 (0)1304 616161

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000

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

Instructions for use

Enbrel

(etanercept)
50 mg/1 mL
For subcutaneous injection only
Important information

  • Keep these Instructions for Use as they provide detailed guidance on how to prepare and administer an injection.
  • Use Enbrel only after reading and understanding these Instructions for Use.
  • Use Enbrel only after receiving training from your healthcare provider.
  • The cartridge for the delivery device contains a single dose of Enbrel and must be used only with the SMARTCLIC device.
  • In these Instructions for Use, the cartridge for the delivery device and the SMARTCLIC device will be referred to as “cartridge” and “device,” respectively.
  • If this is the first time you are using the device, ensure you complete the setup instructions in the dedicated User Manual. You will not be able to use the device until setup is complete.
  • Do not attempt to use cartridges with other devices.
  • Do not share cartridges or the device with other people.
  • Do not shake cartridges or the device containing a cartridge.
  • Do not reuse cartridges after removing the needle cap.
  • Take care not to spill liquids onto cartridges or the device. Do not rinse or place cartridges or the device under water.
  • Refer to the additional device User Manual for instructions on accessing menus, using the training cartridge, advanced usage modes, and troubleshooting error messages.

Storage

  • Store cartridges in the refrigerator at a temperature between 2°C and 8°C. Do not freeze cartridges. Do not store cartridges in the device.
  • Keep cartridges in their original packaging until use to protect from direct sunlight.
  • Cartridges may be stored at room temperature up to 25°C for a maximum of 4 weeks. Do not return cartridges to the refrigerator once they have reached room temperature.
  • Keep cartridges and the device out of sight and reach of children and adolescents.
  • Refer to the device User Manual for instructions on how to store and clean the device.

Materials needed

  • Prepare the following items on a clean, flat surface:
    • Enbrel package containing cartridges
    • SMARTCLIC device
    • Alcohol swabs
    • Cotton balls
    • Clean gauze pads (not included)
    • A sharps disposal container (not included)
  • Do not use the product if the package has been dropped or damaged.
    Note: If you do not have all the required materials, contact your healthcare provider.

The device:
Refer to the User Manual for more information.

Diagram of a medical device with LCD display, injection button, arrow keys, cancel button, tip with blue arrow, and skin sensor

The cartridge:

Diagram showing a cartridge before and after the

Preparation procedure

Illustration of the first step showing a hand removing an injection pen from a tray containing three similar packages
  • Remove 1 cartridge from the tray inside the package.
  • Return the box and tray to the refrigerator along with any unused cartridges.
  • Wash and dry your hands.
  • For a more comfortable injection, allow the cartridge to warm to room temperature for approximately 15–30 minutes, away from direct sunlight. Do not use other methods to warm the cartridge.
Diagram indicating to check the cap of the
  • Check the expiration date and dose printed on the label. Do not use the product if the expiration date has passed or if a different dose was prescribed.
  • Inspect the cartridge; do not use if:
    • It has been dropped, even if it appears undamaged
    • It is damaged
    • The needle cap is loose
    • It has been frozen or exposed to heat
    • It has been stored at room temperature for more than 4 weeks
    • It was returned to the refrigerator after reaching room temperature
  • Do not remove the needle cap until instructed to do so.
Two gloved hands hold an injection pen vertically to inspect the transparent liquid inside
  • Inspect the medicine through the inspection window. The solution should be from clear to slightly opalescent, colorless to pale yellow or light brown, and may contain small white or nearly transparent protein particles. This is normal.
  • Do not use this medicine if it changes color, appears cloudy, or if particles different from those described are visible.
  • Do not shake the cartridge.
    Note: For any questions about the medicine, contact your healthcare provider.
Medical diagram indicating injection sites on abdomen away from the
  • Always select a site on the abdomen, upper thigh, or outer area of the upper arm (only for healthcare professionals).
  • Choose an injection site at least 3 cm away from the previous injection site and at least 5 cm away from the navel.
  • Do not inject into areas with bones or where the skin is damaged, bruised, red, painful (tender), or hard. Avoid injecting into scarred areas or stretch marks.
  • Do not inject through clothing.
    Note: If you have psoriasis, do not inject directly into areas where the skin is raised, thickened, red, scaly, or into lesions.
  • Clean the injection site with the provided alcohol swab and wait for it to dry.
Illustration of step 5 showing a hand cleaning the
  • Clean the injection end of the device with the separately provided alcohol swab.
  • Wait for the injection end to dry before proceeding with the injection.

Injection procedure

Illustration of step six with a green arrow pointing toward the
  • Firmly press the cartridge straight through the cartridge port without rotating the device until you feel it fully seated. The device will power on once the cartridge is correctly inserted.
  • Check that the display shows 50 mg and that the expiration date has not passed.
    Note: The device will turn off after 90 seconds of inactivity. Press and hold the injection button to turn it back on.
One hand grasps and removes the blue cap from the
  • Remove the needle cap by firmly pulling it straight down.
  • Dispose of the needle cap in a suitable sharps disposal container.
  • Administer the injection immediately after removing the needle cap.
  • Do not recap the needle.
    Caution: do not insert fingers into the device after removing the needle cap to avoid needlestick injury.
    Note: To cancel the injection and eject the cartridge, press the Cancel/Eject button
Symbol of a black X-shaped cross enclosed at the

for 1 second.

Illustration of step 8 showing a white medical device with arrows and buttons positioned on the skin with a green downward arrow
  • Position the device with the blue arrow pointing at a 90-degree angle toward the injection site.
  • Ensure you can see the device display.
  • Do not pinch the skin around the injection site.
    Caution: If the device is dropped with a cartridge inserted, eject and dispose of the cartridge. Refer to the Troubleshooting section of the device User Manual.
One hand presses the circular button of a white medical device with a green arrow indicating button press in step 9
  • Press and hold the injection button to start the injection when prompted by the display.
    Note: You may release the injection button after the injection has started.
Illustration of step 10 with a green downward arrow and a medical device pressing on the skin with a blue droplet underneath
  • Keep the device pressed against the skin and wait for the medicine to be delivered.
  • Watch the device display.
  • Do not move, tilt, or remove the device from the skin until instructed to do so on the display.
    Note: If you remove the device before instructed, do not reposition it on the injection site or administer another dose. Contact your healthcare provider for guidance.
Illustration of step 11 with text 'Lift from skin' and a green arrow pointing toward the
  • Lift and hold the device away from the skin. The device will display that the injection is complete.
  • Wait. The cartridge will be partially ejected from the bottom of the device. This may take up to 10 seconds. Do not cover the bottom of the device during this time. Do not insert fingers into the device, as the needle will be exposed.
  • If bleeding occurs, press a cotton ball or gauze pad over the injection site until bleeding stops. Do not rub.
Graphic labeled Step 12 and 'Remove the cartridge' showing a hand pulling the cartridge from a medical device with a green downward arrow
  • Remove the cartridge once it is partially ejected from the device.
  • Check that the medicine in the cartridge is fully used by verifying that a gray bar is visible in the inspection window. If not, you may not have received the full dose. Contact your healthcare provider for guidance.
  • Do not reuse or reinsert the cartridge into the device.
  • Dispose of the used cartridge immediately in a suitable sharps disposal container, as directed by your healthcare provider or pharmacist and in accordance with local health and safety regulations.
  • -End of Instructions for Use-