ENBREL 10 mg POWDER AND SOLVENT FOR SOLUTION FOR INJECTION FOR PAEDIATRIC USE

Introduction

Package Leaflet: Information for the User

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

etanercept

Contents of the package leaflet

The information in this leaflet is organized into the following 7 sections:

1. What is Enbrel and what is it used for
2. What you need to know before you start using Enbrel
3. How to use Enbrel
   1. Possible side effects
   2. Storage of Enbrel
   3. Package contents and additional information
   4. Instructions for use

1. What is Enbrel and what is it used for

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

Enbrel is indicated for the treatment of children and adolescents with the following diseases:

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

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

• For enthesitis-related arthritis in patients from 12 years of age for whom the use of other commonly used treatments has not worked adequately, or is not suitable for them.
• Severe psoriasis in patients from 6 years of age who have had an inadequate response to (or are unable to take) phototherapies or other systemic therapies.

2. What you need to know before you start using Enbrel

Do not use Enbrel

• if the child in your care is allergic to etanercept or any of the other ingredients of Enbrel (listed in section 6). If the child experiences allergic reactions, such as chest tightness, wheezing, dizziness, or rash, do not inject more Enbrel and contact your doctor immediately.

• if the child has a severe blood infection, called sepsis. If you are not sure, consult your doctor.

• if the child has any type of infection. If you are not sure, consult your doctor.

Warnings and precautions

Consult your doctor before you start using Enbrel.

• Allergic reactions: If the child experiences allergic reactions such as chest tightness, wheezing, dizziness, or rash, do not inject more Enbrel and contact your doctor immediately.
• Latex: The syringe cap is made of latex (dry natural rubber). Contact your doctor before using Enbrel if the syringe is to be handled by, or if Enbrel is to be administered to, someone with known or possible latex hypersensitivity (allergy).
• Infections/surgery: If the child develops a new infection or is about to undergo major surgery, your doctor may want to monitor the child's treatment with Enbrel.
• Infections/diabetes: Inform your doctor if the child has a history of recurrent infections or has diabetes or other disorders that increase the risk of infection.

• Infections/monitoring: Inform your doctor of any recent travel outside the European region. If the child develops symptoms of an infection such as fever, chills, or cough, notify your doctor immediately. Your doctor will decide whether to continue monitoring the child for the presence of infections after the child stops treatment with Enbrel.
• Tuberculosis: Since cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will examine the signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough review of the child's medical history, chest X-ray, and a tuberculosis test. The results of these tests should be recorded on the Patient Information Card. It is very important that you tell your doctor if the child has had tuberculosis, or if they have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, moderate fever) or any other infection appear during or after treatment, inform your doctor immediately.
• Hepatitis B: Inform your doctor if the child has or has had hepatitis B. Your doctor will perform a hepatitis B test before the child starts treatment with Enbrel. Treatment with Enbrel may reactivate hepatitis B in patients who have previously been infected with the hepatitis B virus. If this happens, the child must stop using Enbrel.
• Hepatitis C: Inform your doctor if the child has hepatitis C. Your doctor may want to monitor the treatment with Enbrel in case the infection worsens.

• Blood disorders: Inform your doctor immediately if the child has symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate a serious blood problem that requires discontinuation of treatment with Enbrel.
• Nervous system and vision disorders: Inform your doctor if the child has multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will decide whether Enbrel is a suitable treatment.
• Congestive heart failure: Inform your doctor if the child has a history of congestive heart failure, because Enbrel needs to be used with caution in these circumstances.
• Cancer: Inform your doctor if the child has or has had lymphoma (a type of blood cancer) or any other cancer before Enbrel is administered to the child.

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

Children and adults who are 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 in a similar way to Enbrel have developed cancers, including unusual types, which sometimes resulted in death.

Some patients who receive Enbrel have developed skin cancers. Inform your doctor if the child develops any changes in the appearance of the skin or growths on the skin.

• Chickenpox: Inform your doctor if the child is exposed to chickenpox while using Enbrel. Your doctor will determine whether preventive treatment for chickenpox is appropriate.
• Alcoholism: Enbrel should not be used to treat alcohol-related hepatitis. Please inform your doctor if the child in your care has a history of alcoholism.
• Wegener's granulomatosis: Enbrel is not recommended for the treatment of Wegener's granulomatosis, a rare inflammatory disease. If the child in your care has Wegener's granulomatosis, discuss this with your doctor.
• Anti-diabetic medicines: Inform your doctor if the child has diabetes or is taking medicines to treat diabetes. Your doctor may decide whether the child needs less anti-diabetic medicine while taking Enbrel.

Children and adolescents

Vaccinations: If possible, children should have all vaccinations up to date before using Enbrel. Some vaccines, such as oral polio vaccine, should not be given while Enbrel is being used. Consult the child's doctor before the child receives any vaccine.

Enbrel should not normally 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 the child is using, has recently used, or might use any other medicines (including anakinra, abatacept, or sulfasalazine), even those not prescribed by the child's doctor. The child must not use Enbrel with medicines that contain the active substances anakinra or abatacept.

Pregnancy and breastfeeding

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

If you have received Enbrel during pregnancy, your baby may have a higher risk of getting an infection. Additionally, in one study, more birth defects were observed when the mother had received Enbrel during pregnancy, compared to mothers who had not received Enbrel or other similar medicines (TNF antagonists), but there was no pattern in the types of birth defects reported. Another study did not find a higher risk of congenital defects when the mother had received Enbrel during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risk to your baby.

Consult your doctor if you want to breastfeed while being treated with Enbrel. It is important that you inform the pediatrician and other healthcare professionals about the use of Enbrel during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and using machines

It is not expected that the use of Enbrel will affect your ability to drive and use machines.

3. How to use Enbrel

Use in children and adolescents

Follow exactly the instructions for administration of this medicine given by your doctor. If you are not sure, consult your doctor or pharmacist again.

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

The suitable dose and frequency of dosing will depend on the child's or adolescent's body weight and disease. Your doctor will tell you how to prepare and measure the suitable dose.

The 10 mg vial is for children who have been prescribed a dose of 10 mg or less. Each vial is for single use only and for one patient only; any remaining solution in the vial should be discarded.

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) 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 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) once a week. If Enbrel does not have an effect on the child's disease after 12 weeks, your doctor may tell you to stop using this medicine.

Form and route of administration

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

Enbrel can be administered with or without food or drink.

The powder must be dissolved before use. In section 7, "Instructions for use", you will find detailed instructions for the preparation and injection of Enbrel.The Enbrel solution must not be mixed with any other medicine.

To help you remember, it may be useful to note down in a diary which days of the week you should use Enbrel.

If you use more Enbrel than you should

If you use more Enbrel than you should (either by injecting too much at one time or by using it too often), you should talk to a doctor or pharmacist immediately. Always take the medicine package with you, even if it is empty.

If you forget to inject Enbrel

If you forget a dose, you should inject it as soon as you remember, unless the next dose is scheduled for the next day, in which case you should omit the missed dose. Then, continue injecting the medicine on the usual day(s). If you do not remember until the day you are due to have the next dose, do not give the child a double dose (2 doses on the same day) to make up for the missed dose.

If you stop treatment with Enbrel

Your symptoms may return after stopping treatment.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Allergic Reactions

If you observe any of the following reactions in the child, do not administer more Enbrel to the child. Inform your doctor immediately or take the child to the Emergency Service of the nearest hospital.

• Difficulty swallowing or breathing.
• Swelling of the face, throat, hands, and feet.
• Feeling of nervousness or anxiety, palpitations, sudden reddening of the skin, and/or feeling of heat.
• Severe rash, itching, or urticaria (prominent skin rashes, reddened or pale, often accompanied by itching).

Severe allergic reactions are rare. If the child presents any of the above symptoms, it may be due to an allergic reaction to Enbrel, so you should seek immediate emergency medical attention.

Severe Adverse Effects

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

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

These adverse effects are rare or infrequent, but they are serious conditions (some of which can be life-threatening in rare cases). If these signs occur, inform your doctor immediately or go to the Emergency Service of the nearest hospital.

The following are the known adverse effects of Enbrel, grouped in decreasing order of frequency:

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

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

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

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

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

Severe infections (including pneumonia, non-superficial skin infections, joint infections, blood infections, and generalized infections); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); low platelet count; skin cancer (excluding melanoma); localized skin swelling (angioedema); urticaria (prominent skin rashes, reddened or pale, often accompanied by itching); eye inflammation; psoriasis (new or worsening); inflammation of blood vessels affecting multiple organs; increased liver enzymes in blood tests (in patients who also receive treatment with methotrexate, the increase in liver enzymes is frequent); abdominal cramps and pain, diarrhea, weight loss, or blood in the stool (signs of intestinal problems).

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

Severe allergic reactions (including severe localized skin swelling and wheezing); lymphoma (a type of blood cancer); leukemia (cancer that affects the blood and bone marrow); melanoma (a type of skin cancer); combined low count of red blood cells, white blood cells, and platelets; nervous system disorders (with severe muscle weakness and symptoms similar to those of multiple sclerosis or inflammation of the optic nerves or spinal cord); tuberculosis; new-onset congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain, and fatigue); skin rash that can lead to severe blistering and peeling of the skin; lichenoid reactions (itchy reddish-purple skin rash and/or thick white-gray lines on the mucous membranes); autoimmune hepatitis (in patients who also receive treatment with methotrexate, the frequency is uncommon); sarcoidosis (an immune disorder that can affect the lungs, skin, and lymph nodes); lung inflammation or scarring (in patients who also receive treatment with methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the small filters within the kidneys, leading to impaired kidney function (glomerulonephritis).

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

Failure of the bone marrow to produce crucial blood cells.

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

Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma, a rare cancer related to human herpesvirus 8 infection. Kaposi's sarcoma usually manifests more frequently as purple skin lesions; excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a disease called dermatomyositis (inflammation and weakness of the muscles accompanied by skin rash).

Other Adverse Effects in Children and Adolescents

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

Reporting of Adverse Effects

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

5. Storage of Enbrel

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

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

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

Before preparing the Enbrel solution, it can be stored outside the refrigerator at a maximum temperature of 25°C, and for a single period of up to 4 weeks; after which, the medicine cannot be refrigerated again. Enbrel should be discarded if it has not been used within 4 weeks of being removed from the refrigerator. It is recommended that you note the date on which Enbrel was removed from the refrigerator and the date from which Enbrel should be discarded (not exceeding 4 weeks from the removal of the packaging from the refrigerator). This new date should not exceed the expiration date that appears on the packaging.

After preparing the Enbrel solution, it is recommended to use it immediately. However, the solution can be used for up to 6 hours if stored at a maximum temperature of 25°C.

Do not use this medicine if you observe that the solution is not transparent or contains particles. The solution should be transparent, colorless to pale yellow or pale brown, without lumps, scales, or particles.

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

6. Container Contents and Additional Information

Composition of Enbrel

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

The other components are:

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

Solvent: Water for injectable preparations.

Appearance of the Product and Container Contents

Enbrel 10 mg powder and solvent for solution for injection for pediatric use is presented as a white powder with a solvent for solution for injection (powder for injectable). Each container contains 4 vials, 4 pre-filled syringes of water for injectable preparations, 4 needles, 4 vial adapters, and 8 alcohol swabs.

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Spain

Pfizer, S.L.

Phone: +34 91 490 99 00

Date of the Last Revision of this Prospectus:

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

1. Instructions for Use

This section is divided into the following subsections:

• Introduction

• Prepare for Injection

• Prepare the Enbrel Dose for Injection

• Add the Solvent

• Extract the Enbrel Solution from the Vial

• Place the Needle on the Syringe

• Choose an Injection Site

• Prepare the Injection Site and Inject the Enbrel Solution

• Dispose of Materials

• Introduction

The following instructions explain how to prepare and inject Enbrel. Read the instructions carefully and follow them step by step. The child's doctor or nurse will teach you the proper technique for administering an injection and the amount to be administered to the child. Do not attempt to administer the injection to the child until you are sure you understand how to prepare and administer the injection.

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

• Prepare for Injection

• Wash your hands thoroughly.
• Choose a flat, clean, and well-lit work surface.
• The tray should contain all the items listed below. (If any of the items mentioned are not found on the tray, do not use the tray and consult your pharmacist). Use only the listed items. DO NOTuse any other syringe.

1 Enbrel Vial

1 Pre-filled Syringe containing a clear and colorless solvent (water for injectable preparations)

1 Needle

1 Vial Adapter

2 Alcohol Swabs

• Check the expiration date on the labels of the vial and syringe. They should not be used after the month and year indicated on them.

• Prepare the Enbrel Dose for Injection

• Remove the contents of the tray.
• Remove the plastic cap from the Enbrel vial (see Figure 1). DO NOTremove the gray stopper or the aluminum ring that surrounds the top of the vial.

Figure 1

• Use a new alcohol swab to clean the gray stopper of the Enbrel vial. After cleaning, do not touch the stopper with your hands and avoid touching it to any surface.
• Place the vial upright on a flat and clean surface.
• Remove the paper covering the vial adapter package.
• While still in the plastic package, place the vial adapter over the top of the Enbrel vial, so that the adapter's spike is centered within the circle on the top of the vial stopper (see Figure 2).

• Hold the vial firmly with one hand on a flat surface. With the other hand, push the adapter package firmly IN A STRAIGHT LINEuntil you feel the adapter's spike penetrate the vial stopper and UNTIL YOU FEEL AND HEAR THE ADAPTER EDGE CLICK INTO PLACE(see Figure 3). DO NOTpush the adapter at an angle (see Figure 4). It is essential that the adapter's spike penetrates the vial stopper completely.

• While holding the vial in one hand, remove the plastic package from the vial adapter (see Figure 5).

Figure 5

• Remove the protective cover from the syringe tip by breaking the white cap along the perforation. This is done by holding the white cap ring while holding the syringe tip with the other hand and bending it up and down until it breaks (see Figure 6). DO NOTremove the white ring that remains attached to the syringe.

Figure 6

• Do not use the syringe if the perforation between the tip and the cap ring is already broken. Start again with another dose tray.
• Holding the glass body of the syringe (not the white ring) in one hand and the vial adapter (not the vial) in the other hand, attach the syringe to the vial adapter by inserting the tip into the opening and turning it clockwise until it is fully secured (see Figure 7).

Figure 7

• Add the Solvent

• While holding the vial upright on a flat surface, push the plunger VERY SLOWLYuntil all the solvent enters the vial. This will help reduce foam formation (many bubbles) (see Figure 8).
• Once the solvent has been added to Enbrel, the plunger may move on its own. This is due to air pressure and is not a cause for concern.

Figure 8

• With the syringe still inserted, slowly move the vial in circles a few times to dissolve the powder (see Figure 9). DO NOTshake the vial. Wait until all the powder has dissolved (usually less than 10 minutes). The solution should be clear and colorless to pale yellow or pale brown, without lumps, scales, or particles. It is normal for white foam residue to remain in the vial. DO NOTuse Enbrel if all the powder in the vial has not dissolved within 10 minutes. Start again with another dose tray.

Figure 9

• Extract the Enbrel Solution from the Vial

• The doctor or nurse will have indicated the appropriate amount of solution to be extracted from the vial. If the doctor has not provided these instructions, please contact them.
• With the syringe still inserted in the vial and its adapter, hold the inverted vial at eye level. Push the plunger completely into the syringe (see Figure 10).

Figure 10

• Then, slowly pull the plunger back to extract the liquid into the syringe (see Figure 11). Extract only the portion of liquid that the child's doctor has indicated. After extracting Enbrel from the vial, you may find some air in the syringe. Do not worry, as the air will be removed in a later stage.

Figure 11

• Hold the inverted vial and separate the syringe from the vial adapter by turning it counterclockwise (see Figure 12).

Figure 12

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

• Place the Needle on the Syringe

• The needle is included in a plastic package to keep it sterile.
• To open the plastic package, hold the shorter and wider part in one hand. Place the other hand over the longer part of the package.
• To break the seal, bend the larger end up and down until it breaks (see Figure 13).

Figure 13

• Once the seal is broken, remove the shorter and wider part of the plastic package.
• The needle will remain in the longer part of the package.
• While holding the needle and package in one hand, take the syringe and insert its tip into the needle opening.
• Insert the syringe into the needle by turning it clockwise until it is fully secured (see Figure 14).

Figure 14

• Remove the needle cap from the syringe by pulling it firmly, being careful not to touch the needle and avoiding touching the needle to any surface (see Figure 15). Be careful not to bend or twist the cap while removing it to avoid damaging the needle.

Figure 15

• While holding the syringe in a vertical position, eliminate the bubbles by slowly pushing the plunger until the air is removed (see Figure 16).

Figure 16

• Choose an Injection Site

• The three recommended injection sites for Enbrel include: (1) the middle front of the thighs; (2) the abdomen, except for the area 5 cm around the navel; and (3) the upper outer part of the arms (see Figure 17). If the child self-injects, they should not inject into the upper outer part of the arms.

Figure 17

• A different site should be used for each new injection. Each new injection should be placed at least 3 cm away from the previous injection site. DO NOTinject into sensitive, bruised, red, or hardened skin areas. Avoid areas with scars or stretch marks. (It may be helpful to note the previous injection sites).
• If the child has psoriasis, try not to inject directly into any area of thickened, red, or scaly skin ("psoriatic skin lesions").

• Prepare the Injection Site and Inject the Enbrel Solution

• Clean the injection site where you will inject Enbrel with a new alcohol swab, using a circular motion. DO NOTtouch this area again until the injection has been administered.

• When the previously cleaned skin area has dried, with one hand, pinch the skin firmly and hold it. With the other hand, hold the syringe like a pencil.
• With a quick and short movement, push the needle all the way in, penetrating the skin at an angle between 45º and 90º (see Figure 18). With practice, you will find the angle that is most comfortable for the child. Be careful not to push the needle into the skin too slowly or with too much force.

Figure 18

• When the needle is completely inserted into the skin, release the skin that you are holding. With your free hand, hold the needle near its base to stabilize it. Then, push the plunger to inject the entire solution at a SLOWand steady speed (see Figure 19).

Figure 19

• When the syringe is empty, remove the needle from the skin; be careful to keep the syringe at the same angle it was when inserted.

• Press a cotton ball over the injection site for 10 seconds. There may be slight bleeding. DO NOTrub the injection site. If desired, a band-aid or bandage can be applied.

• Dispose of Materials

• The syringe and needle SHOULD NEVERbe reused. Dispose of the needle and syringe following the instructions of your doctor, nurse, or pharmacist.

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