Label: information for the user

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

etanercept

The information inthislabel is organizedinthe following 7 sections:

1.What Enbrel is and what it is used for

2.What you need to know before starting to use Enbrel

3.How to use Enbrel

1. Possible side effects
2. Storage of Enbrel
3. Contents of the pack and additional information
4. Instructions for use

Enbrel is a medication made from two human proteins. It blocks the activity of another protein found in the body that produces inflammation. Enbrel acts by reducing the inflammation associated with certain diseases.

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

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

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

• For arthritis associated with enthesitis in patients aged 12 years or older for whom the use of other commonly used treatments has not worked adequately, or such treatments are not suitable for them.
• Severe psoriasis in patients aged 6 years or older who have had an inadequate response to (or are unable to take) phototherapy or other systemic therapies.

No use Enbrel

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

• if the child has or is at risk of developing a severe blood infection, known as sepsis. If unsure, consult your doctor.

• if the child has any type of infection. If unsure, consult your doctor.

Warnings and Precautions

Consult your doctor before starting to use Enbrel.

• Allergic Reactions:If the child experiences allergic reactions such as chest tightness, rapid breathing, dizziness, or rash, do not administer more Enbrel and immediately contact your doctor.
• Latex:The syringe cap is made of latex (natural dried rubber). Contact your doctor before using Enbrel if the syringe will be handled by, or if Enbrel will be administered to, someone with known or possible latex hypersensitivity.
• Infections/Surgery:If the child develops a new infection or is about to undergo major surgery, your doctor may be interested in controlling the child's Enbrel treatment.
• Infections/Diabetes:Inform your doctor if the child has a history of recurrent infections or has diabetes or other conditions 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 if the child should continue to be monitored for the presence of infections after the child stops Enbrel treatment.
• Tuberculosis:Since cases of tuberculosis have been reported in patients treated with Enbrel, your doctor will examine the child for signs and symptoms of tuberculosis before starting Enbrel. This may include a thorough medical history, chest X-ray, and tuberculosis test. The results of these tests should be recorded in the Patient Information Card. It is very important to inform your doctor if the child has had tuberculosis, or if they have been in direct contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, apathy, 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 at any time. Your doctor should perform a hepatitis B test before the child starts Enbrel treatment. Enbrel treatment may reactivate hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, stop using Enbrel.
• Hepatitis C:Inform your doctor if the child has hepatitis C. Your doctor may want to monitor Enbrel treatment in case the infection worsens.

• Blood Disorders:Inform your doctor immediately if the child experiences symptoms such as persistent fever, sore throat, bruises, bleeding, or paleness. These symptoms may indicate a severe blood disorder that requires stopping Enbrel treatment.
• Nervous System and Vision Disorders:Inform your doctor if the child experiences multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will decide if Enbrel is an appropriate treatment.
• Heart Failure:Inform your doctor if the child has a history of congestive heart failure, as Enbrel should be used with caution in such cases.
• 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 higher risk of developing lymphoma.

Children and adults taking Enbrel may be at increased risk of developing lymphoma or other cancers.

Some adolescent and child patients who have received Enbrel or other medications that work in the same way as Enbrel have developed cancers, including rare types, which sometimes resulted in death.

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

• Chickenpox:Inform your doctor if the child is exposed to chickenpox while using Enbrel. Your doctor will determine if 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 it with your doctor.
• Antidiabetic Medications:Inform your doctor if the child has diabetes or is taking medications to treat diabetes. Your doctor may decide if the child needs less antidiabetic medication while taking Enbrel.

Children and Adolescents

Vaccinations:If possible, children should have all vaccinations updated before using Enbrel. Some vaccines, such as the oral polio vaccine, should not be administered while using Enbrel. Consult the child's doctor before administering any vaccine.

Enbrel should not normally be used in children under 2 years with polyarthritis or oligoarthritis, in children under 12 years with arthritis related to enthesitis or psoriatic arthritis, or in children under 6 years with psoriasis.

Other Medications and Enbrel

Inform your doctor or pharmacist if the child is using, has used recently, or may need to use any other medication (including anakinra, abatacept, or sulfasalazine), even those not prescribed by the child's doctor. The child should not use Enbrel with medications containing 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 be at increased risk of 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 similar medications (TNF antagonists), but no pattern was observed in the types of birth defects reported. Another study found no increased risk of congenital defects when the mother had received Enbrel during pregnancy. Your doctor will help you decide if the benefits of treatment outweigh the potential risk to your baby.

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

Driving and Operating Machinery

It is not expected that Enbrel use will affect your ability to drive and operate machinery.

Use in Children and Adolescents

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

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

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

The 10 mg vial is for children who have been prescribed a dose equal to or less than 10 mg. Each vial is for single use and for a single patient, and any remaining solution in the vial should be discarded.

For extended polyarthritis or oligoarthritis in patients aged 2 years or older, or psoriatic arthritis related to enthesitis or psoriatic arthritis in patients aged 12 years or 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 or 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 medication.

Form and Route of Administration

Enbrel is administered by subcutaneous injection under the skin.

Enbrel can be administered with or without food or beverages.

The powder must be dissolved before use.In Section 7, “Instructions for Use”, detailed instructions for preparing and injecting Enbrel are included.Enbrel solution should not be mixed with any other medication.

It may be helpful to note in a diary what 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 a large amount at one time or by using it too frequently), you should speak with a doctor or pharmacist immediately. Always carry the medication packaging 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 due the following day, in which case you should omit the missed dose. Then, continue injecting the medication on the usual days. If you do not remember until the day you are due to administer the next dose, do not administer a double dose (2 doses on the same day) to compensate for the missed dose.

If You Interrupt Treatment with Enbrel

Your symptoms may return after treatment is interrupted.

If you have any other questions about using this medication, ask your doctor or pharmacist.

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

Allergic reactions

If you notice any of the following reactions in the child, do not administer Enbrel to the child again. Inform your doctor immediately or take the child to the nearest hospital emergency department.

• Difficulty swallowing or breathing.
• Swelling of the face, throat, hands, and feet.
• Feeling of nervousness or anxiety, palpitations, sudden redness of the skin, and/or feeling of heat.
• Severe rash, itching, or urticaria (prominent skin rashes, red 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 must seek urgent medical attention immediately.

Severe side effects

If you notice any of the following side effects, the child may need emergency 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, red, and warm area on the skin or joints of the child.
• Signs of blood disorders, such as bleeding, bruises, or paleness.
• Signs of nervous system disorders, such as numbness or tingling, visual disturbances, eye pain, or weakness in one arm or leg.
• Signs of heart failure or worsening 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 nails or around the child's lips.
• Signs of cancer: cancer can affect any part of the body, including the skin and blood, and the possible signs will depend on the type and location of the cancer. These signs may include weight loss, fever, swelling (with or without pain), persistent cough, presence of lumps or thickening in the skin.
• Signs of autoimmune reactions (in which antibodies may damage normal body tissues) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision.
• Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or muscle pain, or fatigue.
• Signs of inflammation of 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 be fatal in rare cases). If these signs occur, inform your doctor immediately or go to the nearest hospital emergency department.

The following are known side effects of Enbrel, 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); reactions at the injection site (including bleeding, bruising, redness, itching, pain, and swelling) (do not occur as frequently after the first month of treatment; some patients have developed a reaction at the injection site that they had recently used); and headache.

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

Allergic reactions; fever; rash; itching; and autoantibodies 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, red 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 also receiving methotrexate, the increase in liver enzymes is common); 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 localized severe skin swelling and labored breathing); lymphoma (a type of blood cancer); leukemia (cancer affecting the blood and bone marrow); melanoma (a type of skin cancer); combined low red blood cell, white blood cell, and platelet count; nervous system disorders (with severe muscle weakness and symptoms and signs similar to multiple sclerosis or inflammation of the optic nerves or spinal cord); tuberculosis; congestive heart failure of new onset; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint or muscle pain, or fatigue); skin eruption, which may lead to severe blistering and peeling of the skin; lymphoid reactions (skin eruption, pruritic, red-brown, and/or white-gray lines on mucous membranes); autoimmune hepatitis caused by the immune system (in patients also receiving methotrexate, the frequency is uncommon); immunological disorder that may affect the lungs, skin, and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also receiving methotrexate, the frequency of inflammation or scarring of the lungs 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 critical blood cells.

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

Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma, a rare cancer related to human herpes virus 8 infection. Kaposi's sarcoma usually manifests 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 side effects in children and adolescents

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

Reporting side effects

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

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

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

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

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

After preparing the Enbrel solution, immediate use is recommended. However, the solution can be used within 6 hours if stored at a maximum temperature of 25 °C.

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

Medications must not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Enbrel Composition

The active ingredient of Enbrel is etanercept. Each vial of Enbrel 10 mg powder and diluent for injectable solution 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 tromethamine.

Diluent: Water for injection.

Appearance of the product and content of the container

Enbrel 10 mg powder and diluent for injectable solution for pediatric use is presented as a white powder with a diluent for injectable solution (powder for injection). Each container contains 4 vials, 4 preloaded syringes of water for injection, 4 needles, 4 vial adapters, and 8 alcohol wipes.

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Spain

Pfizer, S.L.

Tel: +34 91 490 99 00

Last review date of this leaflet:

The detailed information about this medicine 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 for the injection

c.Preparing the Enbrel dose for injection

d.Adding the diluent

e.Extracting the Enbrel solution from the vial

f.Placing the needle in 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 these 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 administer to the child. Do not attempt to administer an 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 medicine. See section 5 for instructions on how to store Enbrel.

b.Preparing for the injection

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

1 Enbrel vial

1 Preloaded syringe containing a transparent and colorless diluent (water for injection)

1 Needle

1 Vial adapter

2 Alcohol wipes

• Examine the expiration date on the labels of the vial and syringe. Do not use them 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 NOTremove the gray stopper or the aluminum ring surrounding the top of the vial.

Figure 1

• Use a new alcohol wipe to clean the gray stopper of the Enbrel vial. After cleaning it, do not touch the stopper with your hands and avoid having it touch any surface.
• Place the vial upright on a flat and clean surface.
• Remove the paper covering the container of the vial adapter.
• Placing the vial adapter on top of the Enbrel vial, with the needle of the adapter centered within the circle on the top of the vial stopper (see Figure 2).

• Hold the vial firmly with one hand on the flat surface. With the other hand, push the vial adapter firmly in a straight line until you feel the needle penetrate the vial stopper and you hear the adapter's edge engage in its place (see Figure 3).DO NOTpush the adapter at an angle (see Figure 4). It is essential that the needle of the vial adapter penetrates the vial stopper completely.

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

Figure 5

• Remove the protective covering from the end of the syringe by breaking the white capsule along the perforation. This is done by holding the ring of the white capsule while grasping the end of the capsule 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 end and the ring of the capsule is already broken. Start again with a new dose tray.
• Hold the glass body of the syringe (not the white ring) in one hand and the vial adapter (not the vial) in the other hand, connect the syringe to the vial adapter by inserting the end into the opening and turning it clockwise until it is securely attached (see Figure 7).

Figure 7

d.Adding the diluent

• While holding the vial upright on a flat surface, slowly push the plunger until all the diluent enters the vial. This will help reduce foam formation (many bubbles) (see Figure 8).
• Once the diluent 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 attached, slowly move the vial in a circular motion 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 transparent and colorless to pale yellow or pale brown, without lumps, scales, or particles. It is normal for there to be white foam in the vial.DO NOTuse Enbrel if the powder has not dissolved in 10 minutes. Start again with a new dose tray.

Figure 9

e.Extracting the Enbrel solution from the vial

• The doctor or nurse will have indicated the correct amount of solution to extract from the vial. If your doctor has not provided these instructions, please contact them.
• While holding the vial upright and the syringe still attached, push the plunger completely into the syringe (see Figure 10).

Figure 10

• Then, slowly pull the plunger back to extract the liquid from the syringe (see Figure 11). Extract only the amount of liquid indicated by the child's doctor. After extracting Enbrel from the vial, you may find some air in the syringe. Do not worry, as the air will be eliminated in the final step.

Figure 11

• Hold the vial upright 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 end does not touch anything. Be careful not to push the plunger down.

f.Placing the needle in the syringe

• The needle is included in a plastic container to keep it sterile.
• To open the plastic container, hold the shorter and wider part in one hand. Place the other hand on the longer part of the container.
• To break the seal, bend the longer 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 container.
• The needle will remain in the longer part of the container.
• While holding the needle and container in one hand, pick up the syringe and insert its end into the opening of the needle.
• Insert the syringe into the needle by turning it clockwise until it is securely attached (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 having it touch 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 upright, eliminate the bubbles by slowly pushing the plunger until the air is extracted (see Figure 16).

Figure 16

g.Choosing an injection site

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

Figure 17

• A different site should be used for each new injection. Each new injection should be 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”).

h..Preparing the injection site and injecting the Enbrel solution

• Clean the injection site with a new alcohol wipe, moving in 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 it and hold it firmly. With the other hand, hold the syringe like a pencil.
• With a quick and short motion, push the needle until it reaches the end, penetrating the skin at an angle between 45° and 90° (see Figure 18). With practice, you will find the angle that is most comfortable for the child. Be careful not to push the needle too slowly or with too much force.

Figure 18

• When the needle is fully inserted into the skin, release the skin 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 slow and steady pace (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 or gauze over the injection site for 10 seconds. A slight bleeding may occur.DO NOTrub the injection site. If desired, you can apply a bandage or dressing.

i.Disposal of materials

• The syringe and needle NEVERshould be reused. Dispose of the needle and syringe according to 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.