Enbrel 50 mg solution for injection in pre-filled pens

Patient Information Leaflet

Introduction

Patient Information Leaflet

Enbrel 50 mg solution for injection in pre-filled pen

etanercept

Read the entire leaflet carefully before starting to use this medicine, as it contains important information for you. Keep this leaflet, as you may need to read it again. Your doctor will also provide you with a Patient Information Card, which contains important safety information 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 the child under your care; do not give it to other people, even if they have the same symptoms as you or the child under your care, as it may harm them. If you experience any adverse effects, consult your doctor or pharmacist, even if these adverse effects are not listed in this leaflet. See section 4.

Package leaflet contents

The information in this leaflet is organized 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. Storage of 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 in the body that causes inflammation. Enbrel works by reducing the inflammation associated with certain diseases.

Enbrel can be used in adults aged 18 years and older for the treatment of moderate to severe rheumatoid arthritis, psoriatic arthritis, severe axial spondyloarthritis, including ankylosing spondylitis, and moderate to severe psoriasis, usually when other treatments have not been sufficiently effective or are not suitable for you, depending on the individual case.

In the treatment of rheumatoid arthritis, Enbrel is usually used in combination with methotrexate, although it may also be used as a single medicine if treatment with methotrexate is not suitable for you. Enbrel can slow down the joint damage caused by rheumatoid arthritis and improve your ability to carry out daily activities, whether used alone or in combination with methotrexate.

In patients with psoriatic arthritis affecting multiple joints, Enbrel can improve your ability to perform normal daily activities. In patients with multiple symmetric swollen or painful joints (e.g., in hands, wrists, and feet), Enbrel may delay the progression of structural damage in these joints caused by the disease.

Enbrel is also indicated for treatment in children and adolescents with the following conditions:

• For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not worked adequately or is not suitable for them:

  • Polyarticular course (with positive or negative rheumatoid factor) 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 for whom other commonly used treatments have not worked adequately or are not suitable for them.

• For severe psoriasis in patients aged 6 years and older who have had an inadequate response to (or are unable to take) phototherapy or other systemic therapies.

2. What you need to know before using Enbrel

Do not use Enbrel

• if you or the child in your care 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, wheezing, 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 you are unsure, consult your doctor.

• if you or the child have an infection of any kind. If you are unsure, consult your doctor.

Warnings and precautions

Talk to your doctor before starting to use Enbrel.

• Allergic reactions: If you or the child experience allergic reactions such as chest tightness, wheezing, dizziness, or rash, do not inject any more Enbrel and contact your doctor immediately.

• Infections/surgery: If you or the child develop a new infection or are about to undergo major surgery, your doctor may need to consider adjusting treatment with Enbrel.

• Infections/diabetes: Inform your doctor if you or the child have a history of recurring infections or if you have diabetes or other disorders that increase the risk of infection.

• Infections/monitoring: Inform your doctor about any recent travel outside the European region. If you or the child develop symptoms of infection such as fever, chills, or cough, notify your doctor immediately. Your doctor should decide whether continued monitoring for infections is needed after you or the child stop treatment with 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. This may include a thorough review of your medical history, chest X-ray, and a tuberculosis test. Completion of these assessments must be recorded on the Patient Information Card. It is very important to tell your doctor if you or the child have had tuberculosis or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, lethargy, 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 should test for hepatitis B before you or the child start treatment with Enbrel. Treatment with Enbrel may reactivate 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 wish to monitor treatment with Enbrel in case the infection worsens.

• Blood disorders: Inform your doctor immediately if you or the child have signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate a serious blood disorder requiring discontinuation of Enbrel treatment.

• Nervous system and vision disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will decide whether Enbrel is an appropriate treatment.

• Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure, as Enbrel must be used with caution in such cases.

• Cancer: Inform your doctor if you have or have previously had lymphoma (a type of blood cancer) or any other cancer before Enbrel is administered.

Patients with severe rheumatoid arthritis who have had the disease for a long time 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 cancers.

Some adolescent and pediatric patients who have received Enbrel or other medicines that work similarly to Enbrel have developed cancers, including unusual types, some of which have resulted in death.

Some patients receiving Enbrel have developed skin cancers. 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 determine whether preventive treatment for chickenpox is appropriate.
• Latex: The needle cap of the MYCLIC pen is made of latex (dry natural rubber). Contact your doctor before using Enbrel if the needle cap will be handled by, or if Enbrel will be administered to, someone with known or possible hypersensitivity (allergy) to latex.
• Alcoholism: Enbrel should not be used to treat hepatitis related to alcoholism. Please inform your doctor if you or the child in your care have a history of alcoholism.
• Wegener's granulomatosis: Enbrel is not recommended for the treatment of Wegener's granulomatosis, a rare inflammatory disease. If you or the child in your care have Wegener's granulomatosis, discuss this with your doctor.
• Antidiabetic 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 antidiabetic 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 given while using 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

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

Pregnancy and breastfeeding

Enbrel should only be used during pregnancy if clearly necessary. Consult your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant.

If you have received Enbrel during pregnancy, your baby may have an increased risk of developing an infection. In addition, one study reported a higher number of birth defects when the mother had received Enbrel during pregnancy compared to mothers who had not received Enbrel or other similar medicines (TNF antagonists), but there was no consistent pattern in the types of birth defects reported. Another study found no increased risk of congenital malformations when the mother had received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.

Consult your doctor if you wish to breastfeed while on Enbrel treatment. It is important to inform the pediatrician and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccines.

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 of sodium (23 mg) per dose unit; that is, essentially “sodium-free”.

3. How to use Enbrel

Follow exactly the administration instructions given by your doctor for this medicine. If in doubt, consult your doctor or pharmacist again.

If you think that the effect of Enbrel is too strong or too weak, inform your doctor or pharmacist.

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

Dosage 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 a week or 50 mg administered once a week, as a subcutaneous injection. However, your doctor may determine an alternative dosing frequency for Enbrel.

Plaque psoriasis

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

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

Your doctor will decide how long you should take Enbrel and whether treatment needs to be repeated, based on your response. If Enbrel has no effect on your disease after 12 weeks, your doctor may instruct you to stop using this medicine.

Use in children and adolescents

The appropriate dose and dosing frequency will depend on the child's or adolescent's body weight and condition. Your doctor will determine the appropriate dose for the child and prescribe the most suitable Enbrel formulation (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) twice a week, or 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg) once a week.

For psoriasis in patients aged 6 years and older, the usual dose is 0.8 mg of Enbrel per kg of body weight (up to a maximum of 50 mg) once a week. If Enbrel has no effect on the child's disease after 12 weeks, your doctor may instruct you to stop using this medicine.

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

Method and route of administration

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

Enbrel may be administered with or without food or drink.

Detailed instructions for injecting Enbrel are included in section 7, “Instructions for use.” Enbrel solution must not be mixed with any other medicine.

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

If you use more Enbrel than you should

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

If you forget to inject Enbrel

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

If you stop using Enbrel

Your symptoms may return after stopping treatment.

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

4. Possible adverse effects

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

Allergic reactions

If you notice any of the following reactions, do not inject any more Enbrel. Contact your doctor immediately or go to the nearest hospital Emergency Department.

• Difficulty swallowing or breathing.
• Swelling of the face, throat, hands, and feet.
• Feeling nervous or anxious, palpitations, sudden redness of the skin, and/or sensation of warmth.
• Severe rash, itching, or hives (prominent, red or pale welts on the skin, often accompanied by itching).

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

Serious adverse effects

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

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

These adverse effects are rare or uncommon, but they are serious conditions (some of which may, in rare cases, be fatal). If any of these signs occur, inform your doctor immediately or go to the nearest hospital Emergency Department.

The following is a list of known adverse effects of Enbrel, grouped in decreasing order of frequency:

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

Infections (including cold, 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 reactions at injection sites they had recently used); and headache.

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

Allergic reactions; fever; rash; itching; antibodies directed against normal tissues (formation of autoantibodies).

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

Serious infections (including pneumonia, non-superficial skin infections, joint infections, blood infection, and systemic infections); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); low platelet count; skin cancer (excluding melanoma); localized swelling of the skin (angioedema); hives (prominent, red or pale welts on the skin, often accompanied by itching); eye inflammation, psoriasis (new onset or worsening); inflammation of blood vessels affecting multiple organs; increased liver enzymes in blood tests (in patients also receiving methotrexate, increased liver enzymes are common); abdominal cramps and pain, diarrhea, weight loss, or blood in stools (signs of intestinal problems).

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

Severe allergic reactions (including severe localized swelling of the skin and gasping for breath); lymphoma (a type of blood cancer); leukemia (cancer affecting blood and bone marrow); melanoma (a type of skin cancer); combined low counts of red blood cells, white blood cells, and platelets; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis or inflammation of the optic nerves or spinal cord); tuberculosis; new-onset congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain, and fatigue); skin rash that may lead to severe blistering and peeling of the skin; lichenoid reactions (itchy, reddish-purple skin rash and/or thick, whitish-gray lines on mucous membranes); liver inflammation caused by the 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 small filters in the kidneys, leading to impaired kidney function (glomerulonephritis).

• Very rare (may affect up to 1 in 10,000 people):

Bone marrow failure to produce essential blood cells.

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

Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma, an uncommon cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma usually presents more commonly as purple-colored skin lesions; excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness accompanied by skin rash).

Other adverse effects in children and adolescents

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

Reporting of adverse effects

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

5. Storage of Enbrel

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

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

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

Keep the prefilled pens in their outer carton to protect them from light.

After removing the prefilled pen from the refrigerator, wait approximately 15 to 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 then recommended.

Enbrel may be stored outside the refrigerator at a maximum temperature of 25 °C for a single period of up to 4 weeks; after this time, the medicine must not be refrigerated again. Enbrel must be discarded if it has not been used within 4 weeks after removal from the refrigerator. It is advisable to record the date when Enbrel was removed from the refrigerator and the date from which Enbrel must be discarded (no more than 4 weeks after removal from the refrigerator carton).

Inspect the solution in 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 is the normal appearance of Enbrel. Do not use the solution if it is discoloured or cloudy, or if it contains particles different from those described above. If you are concerned about the appearance of the solution, contact your pharmacist for assistance.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any unused medicines and their containers. This will help protect the environment.

6. Contents of the pack and other information

Composition of Enbrel

The active substance in Enbrel is etanercept. Each Enbrel 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.

Appearance of the product and contents of the pack

Enbrel is presented 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 pens and 2, 4 or 12 alcohol-impregnated cotton pads. Some pack sizes may not 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

You can request further information about this medicinal product by contacting the local representative of the marketing authorization holder:

Spain

Pfizer, S.L.

Tel: +34 91 490 99 00

Date of the most recent review of this leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: 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 inject Enbrel.
• Read the instructions carefully and follow them step by step.
• Your healthcare professional will show you how to self-inject Enbrel. Do not attempt to give yourself an injection until you are certain you understand how to use the MYCLIC pen correctly.
• If you have any doubts about how to inject yourself, ask your healthcare professional for help.

Pre-filled pen MYCLIC

Before the injection

White needle cap
Gray activation button	Expiration date	Transparent inspection window

After the injection

	Inspection window full	Open end – safety shield

Step 1 Prepare for an Enbrel injection

• Gather the following supplies for each injection on a flat, clean, and well-lit surface:

  o One pre-filled MYCLIC pen.
  o One alcohol wipe.
  o A proper 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.

• For a more comfortable injection, allow the pen to reach room temperature for 15 to 30 minutes with the white cap still in place.

• Do not warm the pen in any other way.

Step 2 Check the expiration date and dose on the label

• Check the expiration date (month/year) on the pen label.
• Ensure the correct dose is indicated on the pen label.
• If the expiration date has passed or the dose is not the one prescribed, do not use the pen and contact your healthcare professional for assistance.

Step 3 Inspect the medication

• Inspect the medication in the pen by looking through the transparent inspection window. The solution should be clear or slightly opalescent, colorless to pale yellow or pale brown, and may contain small white or nearly transparent protein particles. This is the normal appearance of Enbrel.
• Do not use the medication if it has changed color, appears cloudy, or contains particles different from those described above. If you are concerned about the appearance of the medication, contact your healthcare professional for assistance.
• Note: You may see an air bubble in the window. This is normal.

Step 4 Choose and clean the injection site

• Choose an injection site in the middle of the upper thigh or in the abdominal area, 5 cm away from the navel. The outer area of the upper arms may also be used by a caregiver.
• Each injection should be given at least 3 cm away from the previous injection site. Do not administer the injection into areas of sensitive, bruised, or hardened skin. Avoid areas with scars or stretch marks. If you have psoriasis, do not administer the injection directly into any raised, thick, red, or scaly skin lesions.
• Clean the injection site with water and soap or, if preferred, with an alcohol wipe.
• Allow the area to dry. Do not touch, fan, or blow on the cleaned injection site.

Step 5 Remove the needle cap

• Remove the white needle cap by pulling it straight off. Do not bend the cap when removing it.
• Do not reattach the cap once removed.
• After removing the cap, you will see a purple safety shield slightly protruding from the end of the pen. Do not press the safety shield at the end with your fingers or thumbs.
• Do not use the pen if it is dropped with the needle cap removed.

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

Step 6 Press the pen firmly against the skin

• Press the open end of the pen firmly against the skin at a 90-degree angle so that the purple safety shield of the needle is fully retracted into the pen.

Note: You will only be able to press the gray button when the needle shield is fully retracted into the pen.

Pinching or stretching the skin before injection may make the injection site firmer and help you press the injection button.

Step 7 Start the injection

• Press the gray button all the way down. You will hear a “click.” The click indicates the start of the injection.
• Continue holding the pen firmly against the skin until you hear a second “click” or for 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 gray button again.

Step 8 Remove the pen from the skin

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

Step 9 Check the inspection window

• Check the inspection window on the pen. It should be completely purple.
• If the window is not fully purple, you may not have received a complete dose. Contact your healthcare professional 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 over the site for 10 seconds. Do not rub the injection site.

Note: The injection button may remain depressed. This is normal.

Step 10 Disposal

• Dispose of the used pen according to your healthcare professional’s instructions. Do not attempt to recap the pen.
• Do not press the end of the needle safety shield. If you have any doubts, consult your healthcare professional.

—End of instructions for use—