Label: information for the user

Benepali 50 mg injectable solution in pre-filled syringe

etanercept

Read this label carefully before starting to use this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• Your doctor will also give you a Patient Information Leaflet, which contains important safety information that you need to know before and during treatment with Benepali.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you or the child in your care, and you must not give it to other people even if they have the same symptoms as you or the child in your care, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

Etanercept is the active principle in Benepali.

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

Benepali may be used in adults 18 years of age or older for:

• treatment ofmoderate to severe rheumatoid arthritis;
• psoriatic arthritis;
• axial spondyloarthritis, includingankylosing spondylitis;
• plaque psoriasismoderate to severe.

Benepali is usually used when other treatments have not been effective enough or are not suitable for you.

In the treatment ofrheumatoid arthritis, Benepali is typically used in combination with methotrexate, although it can also be used as a single medication if methotrexate treatment is not suitable for you. Benepali can slow down the damage caused by rheumatoid arthritis in your joints and improve your ability to perform daily activities, whether used alone or in combination with methotrexate.

In patients withpsoriatic arthritiswith multiple joint involvement, Benepali can improve your ability to perform normal daily activities.

In patients withsymmetrically multiple, swollen, or painful joints(e.g., in hands, wrists, and feet), Benepali can delay the progression of structural damage to these joints caused by the disease.

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

• For the following types of juvenile idiopathic arthritis when methotrexate treatment has not been effective enough, or is not suitable for them:

• polyarthritis (with positive or negative rheumatoid factor) and extended oligoarthritis in patients aged 2 years or older and weighing 62.5 kg or more.

• Psoriatic arthritis in patients aged 12 years or older and weighing 62.5 kg or more.

• Arthritis associated with enthesitis in patients aged 12 years or older and weighing 62.5 kg or more for whom other commonly used treatments have not been effective enough, or are not suitable for them.

• Severe plaque psoriasis in patients aged 6 years or older and weighing 62.5 kg or more who have had an inadequate response to (or are unable to take) phototherapy or other systemic therapies.

No use Benepali

• if you or the child in your care areallergic to etanerceptor to any of the othercomponents of this medication(listed in section 6). If you or the child experience allergic reactions, such as chest tightness, rapid breathing, dizziness, or rash, do not inject more Benepali and immediately contact your doctor.
• if you or the child have a risk of developing aserious blood infectioncalled sepsis. If unsure, consult your doctor.
• if you or the child have anyinfection. If unsure, consult your doctor.

Warnings and precautions

Consult your doctor before starting to use Benepali.

• Allergic reactions:If you or the child experience allergic reactions, such as chest tightness, rapid breathing, dizziness, or rash, do not inject more Benepali and immediately contact your doctor.
• Infections/surgery:If you or the child develop a new infection or are about to undergo major surgery, your doctor may be interested in controlling the treatment with Benepali.
• Infections/diabetes:Inform your doctor if you or the child have a history of recurrent infections or if you have diabetes or other conditions that increase the risk of infection.
• Infections/monitoring:Inform your doctor of any recent travel outside the European region. If you or the child develop symptoms of an infection, such as fever, chills, or cough, notify your doctor immediately. Your doctor should decide whether to continue monitoring you or the child for the presence of infections after you or the child stop treatment with Benepali.
• Tuberculosis:Since cases of tuberculosis have been reported in patients treated with Benepali, your doctor will examine the signs and symptoms of tuberculosis before starting Benepali. This may include a detailed medical history, chest X-ray, and tuberculosis test. The performance of these tests should be recorded in the Patient Information Card. It is very important to inform your doctor if you or the child have had tuberculosis or 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 you or the child have or have had hepatitis B at any time. Your doctor should perform a hepatitis B test before you or the child start treatment with Benepali. Treatment with Benepali can reactivate hepatitis B in patients who have previously been infected with the hepatitis B virus. If this occurs, you should stop using Benepali.
• Hepatitis C:Inform your doctor if you or the child have hepatitis C. Your doctor may want to monitor the treatment with Benepali if the infection worsens.
• Blood disorders:Inform your doctor immediately if you or the child experience symptoms such as persistent fever, sore throat, bruises, bleeding, or pallor. These symptoms may indicate the presence of a serious blood disorder that requires discontinuation of Benepali treatment.
• Nervous system and vision disorders:Inform your doctor if you or the child experience multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will decide if Benepali is an appropriate treatment.
• Heart failure:Inform your doctor if you or the child have a history of congestive heart failure, as Benepali should be used with caution in these circumstances.
• Cancer:Inform your doctor if you have or have had lymphoma (a type of blood cancer) or any other cancer before receiving Benepali. 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 Benepali may be at increased risk of developing lymphoma or other cancers. Some adolescent and child patients who have received etanercept or other medications that work in the same way as etanercept have developed cancers, including rare types, which sometimes had a fatal outcome. Some patients taking Benepali have developed skin cancers. Inform your doctor if you or the child develop any changes in skin appearance or growths on the skin.
• Chickenpox:Inform your doctor if you or the child are exposed to chickenpox while using Benepali. Your doctor will determine if preventive treatment for chickenpox is appropriate.
• Alcoholism: Benepali should not be used to treat alcohol-related hepatitis. Please inform your doctor if you or the child in your care have a history of alcoholism.
• Wegener's granulomatosis:Benepali 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, inform your doctor.
• Antidiabetic medications:Inform your doctor if you or the child have diabetes or are taking medications to treat diabetes. Your doctor may decide if you or the child need less antidiabetic medication while taking Benepali.
• Vaccines:Some vaccines, such as the oral polio vaccine, should not be administered while using Benepali. Consult your doctor before using any vaccine.

Children and adolescents

Benepali is not indicated for use in children and adolescents with a body weight of less than 62.5 kg.

• Vaccinations:If possible, children should have all vaccinations updated before using Benepali. Some vaccines, such as the oral polio vaccine, should not be administered while using Benepali. Consult your doctor before using any vaccine.

Benepali should not normally be used in children under 2 years or with a body weight of less than 62.5 kg with polyarthritis or oligoarthritis, in children under 12 years or with a body weight of less than 62.5 kg with arthritis related to enthesitis or psoriatic arthritis, or in children under 6 years or with a body weight of less than 62.5 kg with psoriasis.

Use of Benepali with other medications

Inform your doctor or pharmacist if you or the child are using, have used recently, or may need to use any other medication (including anakinra, abatacept, or sulfasalazine).

Do not useBenepali with medications that contain the active ingredient anakinra or abatacept.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Women of childbearing age should be advised to use effective contraceptive methods to avoid pregnancy during treatment with Benepali and for 3 weeks after stopping treatment.

Benepali should only be used during pregnancy if clearly necessary.

If you have received Benepali 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 etanercept during pregnancy, compared to mothers who had not received etanercept or similar medications (TNF antagonists), but no pattern of birth defects was reported. Another study found no increased risk of congenital defects when the mother had received etanercept 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 treatment with Benepali. It is essential to inform the pediatrician and other healthcare professionals about the use of Benepali during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and operating machinery

No information is available to indicate that the use of Benepali affects the ability to drive and operate machinery.

Benepali contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 25 mg; it is essentially "sodium-free."

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

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

Use in adult patients (18 years of age or older)

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, in the form of a subcutaneous injection.

However, your doctor may determine an alternative frequency at which to inject Benepali.

Plaque psoriasis

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

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

Your doctor will decide how long you should use Benepali and if you need a repeat of the treatment based on your response. If Benepali has no effect on your disease after 12 weeks, your doctor may instruct you to stop using this medication.

Use in children and adolescents

The dose and dosing frequency will depend on the child's or adolescent's body weight and disease. Your doctor will determine the appropriate dose for the child and prescribe the most suitable presentation of etanercept.

The dose for pediatric patients with a body weight of 62.5 kg or more is 25 mg administered twice a week or 50 mg administered once a week with a pre-filled syringe or a pre-filled pen.

Other etanercept medications are available with the appropriate doses for children.

For extended oligoarthritis or polyarthritis in patients aged 2 years or older and with a body weight of 62.5 kg or more, or psoriatic arthritis-related arthritis or psoriatic arthritis in patients aged 12 years or older and with a body weight of 62.5 kg or more, the usual dose is 25 mg administered twice a week or 50 mg administered once a week.

For plaque psoriasis in patients aged 6 years or older and with a body weight of 62.5 kg or more, the usual dose is 50 mg administered once a week. If Benepali has no effect on the child's disease after 12 weeks, your doctor may instruct you to stop using this medication.

Your doctor will give you precise instructions to prepare and calculate the correct dose.

Form and route of administration

Benepali is administered via a subcutaneous injection.

See Section 7, “Instructions for use”, for detailed instructions on injecting Benepali.

The Benepali solution should not be mixed with any other medication.

To help you remember, it may be useful to note in a diary which day(s) of the week you should use Benepali.

If you use more Benepali than you should

If you use more Benepali than you should (either by injecting a high amount at one time or by using it too frequently),you should speak with a doctor or pharmacist immediately. Always carry the medication container with you, even if it is empty.

If you forget to use Benepali

If you forget 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 omit the missed dose. Then, continue injecting the medication on the usual day(s). If you do not remember until the day when the next dose is due, do not inject a double dose (two doses on the same day) to compensate for the missed dose.

If you interrupt treatment with Benepali

Your symptoms may return after treatment interruption.

If you have any other doubts 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, do not inject Benepali again.Inform your doctor immediately or go to the nearest hospital emergency department.

• Difficulty swallowing or breathing
• Swelling of the face, throat, hands, and feet
• Sensation of nervousness or anxiety, palpitations, sudden redness of the skin, and/or sensation of heat
• Severe rash, itching, or urticaria (prominent skin rashes, red or pale, often accompanied by itching)

Severe allergic reactions are rare. However, any of the above symptoms may be a sign of an allergic reaction to Benepali, so you must seek urgent medical attention immediately.

Severe side effects

If you notice any of the following side effects, you or the child may need emergency medical attention.

• Symptoms ofserious infections(including pneumonia, non-superficial skin infections, joint infections, and blood 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;
• Symptoms ofblood disorders, such as bleeding, bruises, or paleness;
• Symptoms ofnervous system disorders, such as numbness or tingling, visual disturbances, eye pain, or weakness in an arm or leg;
• Symptoms ofheart failureorexacerbation of heart failure, such as fatigue or shortness of breath with activity, swelling of the ankles, sensation of fullness in the neck or abdomen, shortness of breath at night, or cough, blue discoloration of the nails or around the lips;
• Symptoms ofcancer:Cancer can affect any part of the body, including the skin and blood, and the possible symptoms will depend on the type and location of the cancer. These symptoms may include weight loss, fever, swelling (with or without pain), persistent cough, presence of lumps or thickening of the skin;
• Symptoms ofautoimmune reactions(in which antibodies may damage normal body tissues) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision;
• Symptoms of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint pain, or fatigue;
• Symptoms ofvasculitis, 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 any of them occur, inform your doctor immediately or go to the nearest hospital emergency department.

Other side effects

The following side effects of Benepali are listed in order of 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 antibodies directed against normal tissues (autoantibody formation).

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

Severe infections (including pneumonia, non-superficial skin infections, joint infections, blood infections, and generalized infections); exacerbation 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; elevated liver enzymes in blood tests (in patients also receiving methotrexate treatment, elevated liver enzymes are 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 pain, and fatigue); skin eruption, which may lead to severe blistering and peeling of the skin; autoimmune hepatitis caused by the immune system (autoimmune hepatitis; in patients also receiving methotrexate treatment, 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 treatment, the frequency of inflammation or scarring of the lungs is uncommon); lichenoid reactions (pruritic, red-purple skin rash and/or thick white-gray lines on mucous membranes); opportunistic infections (such as tuberculosis and other infections that occur when resistance to disease decreases); erythema multiforme (inflammatory rash); cutaneous vasculitis (inflammation of blood vessels in the skin); nerve damage, including Guillain-Barré syndrome (a serious disease that may affect breathing and damage organs); damage to small filters within the kidneys, leading to impaired kidney function (glomerulonephritis).

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

Bone marrow failure to produce crucial blood cells; toxic epidermal necrolysis (a potentially fatal skin disease).

• 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 herpesvirus 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 (liver infection); worsening of a disease called dermatomyositis (inflammation and weakness of muscles accompanied by skin rash); listeria (bacterial infection).

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 leaflet. You can also report them directly through thenational notification system included in Appendix V. 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 and the pre-filled syringe label after “CAD/EXP”. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2 °C and 8 °C). Do not freeze.

Store pre-filled syringes in the outer packaging to protect them from light.

After removing the syringe from the refrigerator,wait approximately 30 minutes for the Benepali solution in the syringe to reach room temperature.Do not heat it in any other way. Use immediately thereafter.

Benepali can be stored outside the refrigerator at a maximum temperature of 30°C, and for a single period of up to 31 days; after which, the medication cannot be refrigerated again. Benepali must be discarded if not used within 31 days following its removal from the refrigerator. It is recommended to note the date on which Benepali was removed from the refrigerator and the date from which Benepali must be discarded (not exceeding 31 days from the removal from the refrigerator packaging).

Observe the solution in the syringe. It should be between transparent and slightly opalescent, colorless or pale yellow, and may contain small white or almost transparent protein particles. This is the normal appearance of Benepali. Do not use this medication if you observe that the solution is more yellowish or turbid, or if it presents different particles. If you are concerned about the appearance of the solution, contact your pharmacist for any assistance you may need.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you do not need. This will help protect the environment.

Composition of Benepali

• The active ingredient is etanercept. Each pre-filled syringe contains 50 mg of etanercept.
• The other components are sucrose, sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate heptahydrate, and water for injections (see section 2 "Benepali contains sodium").

Appearance of the product and contents of the pack

Benepali is presented as a pre-filled syringe, containing a transparent or slightly opalescent, colourless or pale yellow injectable solution.

Benepali is available in packs containing 4 pre-filled syringes and a multiple pack containing 3 packs with 4 pre-filled syringes each. Only certain pack sizes may be marketed.

Marketing authorisation holder

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

Manufacturer responsible

Biogen Netherlands B.V.

Prins Mauritslaan 13

1171 LP Badhoevedorp

Netherlands

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of the summary of product characteristics: 03/2025

For detailed information about this medicinal product, please consult the website of the European Medicines Agency:http://www.ema.europa.eu.

7.Instructions for use

Read the instructions for use before starting treatment with Benepali and each time a new prescription is given.

They may contain new information.

• Do not attempt to administer an injection until your doctor or nurse has shown you how to do it.

Each pre-filled syringe contains a single dose of 50 mg of Benepali.

Find a well-lit and clean surface and gather the components you need:

• A new pre-filled syringe of Benepali

• Do not shake the pre-filled syringe.

The pack does not include:

• 1 alcohol wipe, gauze, and dressing

• Sharps disposal container

1. Before starting

Check the expiry date on the label of the pre-filled syringe.

• Do not use the pre-filled syringe after the expiry date.
• Do not use the pre-filled syringe if it has fallen onto a hard surface. The internal components may be broken.
• Do not use the pre-filled syringe if the needle cap is not in place or is not securely tightened.

Observe the medicine inside the pre-filled syringe.

The medicine should be between transparent and slightly opalescent, colourless or pale yellow and may contain small white or almost transparent protein particles.

• Do not use the solution if it is more yellow or cloudy, or if it contains different particles.

Take one of the pre-filled syringes out of the refrigerator and let it reach room temperature for at least 30 minutes before injecting the solution.

This makes the injection easier and more comfortable for you.

• Do not remove the needle cap until you are ready to inject.
• Do not use heat sources such as a microwave or hot water to warm Benepali.

A different site should be used for each new injection.

If injecting into the abdomen, choose a site that is at least 5 cm away from the navel.

• Do not administer the injection into areas of skin that are red, hardened, bruised, or sensitive.
• Avoid areas with scars or stretch marks.
• If you have psoriasis,do not inject the medicine into any raised, thickened, red, or scaly skin patches, or lesions.

1. Steps for the injection

1. Care of the injection site

If bleeding occurs at the injection site, press the area with a gauze.

• Do not rub the injection site.

If necessary, you can cover the injection site with a dressing.