Benepali: detailed information

Patient Information Leaflet: Information for the User

Benepali 25 mg solution for injection in pre-filled syringe

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

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

Contents of this leaflet

What Benepali is and what it is used for
What you need to know before using Benepali
How to use Benepali
Possible side effects
How to store Benepali
Contents of the pack and other information
Instructions for use (see reverse)

1. What Benepali is and what it is used for

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

In adults (aged 18 years and older), Benepali can be used to treat:

- moderate to severe rheumatoid arthritis;
- psoriatic arthritis;
- severe axial spondyloarthritis, including ankylosing spondylitis;
- moderate to severe plaque psoriasis. In each case, Benepali is usually used when other widely used treatments have not worked well enough or are not suitable for you.

For patients with psoriatic arthritis affecting multiple joints, Benepali can improve the ability to perform daily activities.

For patients with painful or swollen symmetric joints (e.g., hands, wrists, and feet), Benepali can slow down structural damage to these joints caused by the disease.

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

- The following types of juvenile idiopathic arthritis, when treatment with methotrexate has not provided a sufficient response or is not appropriate:
- Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients aged 2 years and older, with body weight equal to or greater than 62.5 kg.
- Psoriatic arthritis in patients aged 12 years and older, with body weight equal to or greater than 62.5 kg.
- Enthesitis-related arthritis in patients aged 12 years and older, with body weight equal to or greater than 62.5 kg, when other widely used treatments have not provided a sufficient response or are not appropriate.
- Severe plaque psoriasis in patients aged 6 years and older, with body weight equal to or greater than 62.5 kg, who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies.

2. What you should know before using Benepali

Do not use Benepali

- if you, or the child, are allergic to etanercept or to any of the other components of this medicine (listed in section 6). If you or the child experience allergic reactions such as chest tightness, shortness of breath, dizziness or skin rash, do not inject any more Benepali and contact your doctor immediately.
- if you, or the child, have or are at risk of developing a serious blood infection called sepsis. If in doubt, contact your doctor.
- if you, or the child, have an infection of any kind. If in doubt, speak with your doctor.

Warnings and precautions
Talk to your doctor before taking Benepali.

Allergic reactions: If you, or the child, experience allergic reactions such as chest tightness, shortness of breath, dizziness or skin rash, do not inject any more Benepali and contact your doctor immediately.
Infections/surgery: If you, or the child, develop a new infection or are about to undergo any major surgical procedure. Your doctor may wish to review treatment with Benepali.
Infections/diabetes: Inform your doctor if you or the child have a history of recurrent infections or suffer from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Inform your doctor about any recent travel outside Europe. If you, or the child, develop symptoms of an infection such as fever, chills or cough, inform your doctor immediately. Your doctor may decide to continue monitoring you or the child for infections after you have stopped taking Benepali.
Tuberculosis: Since cases of tuberculosis have been reported in patients treated with Benepali, your doctor will check you for signs and symptoms of tuberculosis before starting treatment with Benepali. This may include a thorough medical history, chest X-rays and a tuberculin skin test. The results of these tests must be recorded in the Patient Record Card. It is very important that you inform your doctor if you or the child have ever had tuberculosis or have been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection occur during or after therapy, inform your doctor immediately.
Hepatitis B: Inform your doctor if you or the child have or have had hepatitis B. Your doctor must perform a test for hepatitis B before you or the child start treatment with Benepali. Treatment with Benepali can cause reactivation of hepatitis B in patients with previous hepatitis B virus infection. In such cases, you must stop using Benepali.
Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may consider it appropriate to monitor treatment with Benepali if the infection worsens.
Blood disorders: Seek immediate medical attention if you or the child experience any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of treatment with Benepali.
Nervous system and eye disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves) or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Benepali is an appropriate treatment.
Congestive 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 such cases.
Tumours: Inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumour before taking Benepali. Patients with long-standing severe rheumatoid arthritis may be at higher than average risk of developing lymphoma. Children and adults taking Benepali may have an increased risk of developing lymphoma or other tumours. Some children and adolescent patients treated with etanercept or other medicines acting like etanercept have developed tumours, including unusual types, sometimes with fatal outcome. Some patients receiving Benepali have developed skin tumours. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
Chickenpox (varicella): Inform your doctor if you or the child are exposed to chickenpox while using Benepali. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
Alcohol abuse: Benepali must not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child in your care have a history of alcohol abuse.
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, consult your doctor.
Anti-diabetes medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide whether you or the child need to receive a lower dose of anti-diabetes medicine while taking Benepali.
- Vaccinations: Some vaccines, such as oral polio vaccine, must not be given during treatment with Benepali. Consult your doctor before you or the child receive any vaccine.

Children and adolescents
The use of Benepali is not indicated in children and adolescents with body weight below 62.5 kg.

- Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Benepali. Some vaccines, such as oral polio vaccine, must not be taken while receiving Benepali. Consult your doctor before you or the child receive any vaccine.

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

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Women of childbearing potential should be advised to use adequate contraception to prevent pregnancy during treatment with Benepali and for three weeks after stopping treatment.
Benepali should be used during pregnancy only if clearly needed.
If you received Benepali during pregnancy, the newborn may be at increased risk of infection. Furthermore, one study indicated a higher number of birth defects in mothers who received etanercept during pregnancy compared to mothers who did not receive etanercept or other similar medicines (TNF antagonists), but no specific pattern of birth defects was observed. Another study did not show an increased risk of birth defects when mothers received etanercept during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby.
Talk to your doctor if you wish to breastfeed during treatment with Benepali. It is important to inform the child's paediatrician and other healthcare professionals about the use of Benepali during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
There is no information indicating whether the use of Benepali affects the ability to drive vehicles or operate machinery.

Benepali contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 25 mg, i.e. it is practically 'sodium-free'.

3. How to use Benepali

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
If you feel that the effect of Benepali is too strong or too weak, talk to your doctor or
pharmacist.

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

Plaque psoriasis
The usual dose is 25 mg twice weekly or 50 mg once weekly.
Alternatively, a dose of 50 mg twice weekly may be administered for up to 12 weeks, followed by 25 mg twice weekly or 50 mg once weekly.
Your doctor will decide how long you should use Benepali and whether, based on your response, further treatment is needed. If after 12 weeks Benepali has no effect on your disease, your doctor may instruct you to stop treatment.

Use in children and adolescents
The dose and dosing frequency for a child or adolescent will depend on body weight and the condition being treated. Your doctor will determine the correct dose for the child and prescribe an appropriate etanercept dosage.
Paediatric patients weighing 62.5 kg or more may receive 25 mg twice weekly or 50 mg once weekly using either the pre-filled syringe or the pre-filled pen with fixed dose.
Other etanercept-containing products with paediatric-appropriate dosages are available.
For polyarticular or extended oligoarticular juvenile idiopathic arthritis in patients from 2 years of age, with body weight equal to or greater than 62.5 kg, or for enthesitis-related arthritis or psoriatic arthritis in patients from 12 years of age, with body weight equal to or greater than 62.5 kg, the usual dose is 25 mg twice weekly or 50 mg once weekly.
For psoriasis in patients from 6 years of age, with body weight equal to or greater than 62.5 kg, the usual dose is 50 mg administered once weekly. If Benepali has no effect on the child's condition after 12 weeks, the doctor may instruct you to stop treatment with this medicine.
Your doctor will provide detailed instructions on how to prepare and measure the appropriate dose.

Method and route of administration
Benepali is administered by injection under the skin (subcutaneous use).
Detailed instructions on how to inject Benepali are provided in section 7 “Instructions for use”. Do not mix the Benepali solution with other medicines.
To help you remember, it may be helpful to write in a diary on which day(s) of the week Benepali should be used.

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

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

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

4. Possible side effects

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

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

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

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

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

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

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

5. How to store Benepali

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and on the label of the
prefilled syringe after Exp./EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the prefilled syringes in their outer packaging to protect the medicine from light.
After removing a syringe from the refrigerator, wait approximately 30 minutes to allow the Benepali
solution in the syringe to reach room temperature. Do not heat it in any other way. Immediate use is therefore recommended.
Benepali may be stored at a maximum temperature of 30°C for up to 31 days, for one time only; after this period it must not be returned to the refrigerator. If not used within 31 days outside the refrigerator, Benepali must be discarded. It is recommended to record the date when Benepali is removed from the refrigerator and the date by which Benepali must be discarded (no more than 31 days outside the refrigerator).
Inspect the solution in the syringe. The solution should be from clear to slightly opalescent, colourless or slightly yellow, and may contain small white or almost transparent protein particles. This is the normal appearance of Benepali. Do not use this medicine if you notice changes in colour, if the solution appears cloudy, or if visible particles are present that differ from those described. If you have any doubts about the appearance of the solution, contact your pharmacist for advice.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Benepali contains

The active substance is etanercept. Each pre-filled syringe contains 25 mg of etanercept.
The other components are sucrose, sodium chloride, monosodium phosphate monohydrate, disodium hydrogen phosphate heptahydrate and water for injections (see section 2 “Benepali contains sodium”).

Description of the appearance of Benepali and contents of the pack
Benepali is supplied as a pre-filled syringe containing an injectable solution (injection preparation) ranging from clear to slightly opalescent, colourless or pale yellow.
Benepali is available in packs containing 4 pre-filled syringes, multiple packs comprising 2 boxes containing 4 pre-filled syringes each, and multiple packs comprising 6 boxes containing 4 pre-filled syringes each. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands

Manufacturer
Biogen Netherlands B.V.
Prins Mauritslaan 13
1171 LP Badhoevedorp
The Netherlands
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands

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

België/Belgique/Belgien Lietuva
Biogen Belgium NV/SA Biogen Lithuania UAB
Tél/Tel: + 32 (0)2 808 5947 Tel: +370 52 07 91 38
България Luxembourg/Luxemburg
Ewopharma AG Representative Office Biogen Belgium NV/SA
Teл.: + 359 249 176 81 Tél/Tel: +35 227 772 038
Česká republika Magyarország
Biogen (Czech Republic) s.r.o. Biogen Hungary Kft.
Tel: + 420 228 884 152 Tel.: + 36 1 848 04 64
Danmark Malta
Biogen (Denmark) A/S Pharma.MT Ltd
Tlf.: + 45 78 79 37 53 Tel: + 356 27 78 15 79
Deutschland Nederland
Biogen GmbH Biogen Netherlands B.V.
Tel: + 49 (0)89 996 177 00 Tel: + 31 (0)20 808 02 70
Eesti Norge
Biogen Estonia OÜ Biogen Norway AS
Tel: + 372 6 68 30 56 Tlf: + 47 21 93 95 87
Ελλάδα Österreich
Genesis Pharma S.A. Biogen Austria GmbH
Τηλ: + 30 211 176 8555 Tel: + 43 (0)1 267 51 42
España Polska
Biogen Spain, S.L. Biogen Poland Sp. z o.o.
Tel: + 34 91 310 7110 Tel.: + 48 22 116 86 94
France Portugal
Biogen France SAS Biogen Portugal Sociedade Farmacêutica,
Tél: + 33 (0)1 776 968 14 Unipessoal, Lda
Tel: + 351 308 800 792
Hrvatska România
Ewopharma d.o.o Ewopharma România SRL
Tel: + 385 (0)1 777 64 37 Tel: + 40 212 601 407
Ireland Slovenija
Biogen Idec (Ireland) Ltd. Biogen Pharma d.o.o.
Tel: +353 (0)1 513 33 33 Tel: + 386 (0)1 888 81 07
Ísland Slovenská republika
Icepharma hf. Biogen Slovakia s.r.o.
Sími: + 354 800 9836 Tel: + 421 (0)2 333 257 10
Italia Suomi/Finland
Biogen Italia s.r.l. Biogen Finland Oy
Tel: + 39 (0)6 899 701 50 Puh/Tel: + 358 (0)9 427 041 08
Κύπρος Sverige
Genesis Pharma (Cyprus) Ltd Biogen Sweden AB
Τηλ: + 357 22 00 04 93 Tel: +46 (0)8 525 038 36
Latvija
Biogen Latvia SIA
Tel: + 371 66 16 40 32

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

7. Instructions for use

Read the instructions for use before starting to use Benepali and each time your prescription is renewed. New information may be available.

- Do not attempt to perform self-injection before your doctor or nurse has shown you how to do it.

A single-use pre-filled syringe contains a 25 mg dose of Benepali.
Choose a clean, well-lit working surface and have all necessary items within easy reach:

- One new pre-filled syringe of Benepali

Diagram of a Benepali 25 mg syringe with labels indicating the needle cap

o Do not shake the pre-filled syringe.
Not included in the package:

- 1 alcohol swab, gauze, and plaster

Blue text reading 'alcohol swab soaked in'

- Sharps container

Yellow container with blue lid and black biohazard symbol in the center for disposal of hazardous medical waste

A. Before starting

1. Inspect the pre-filled syringe:

Check the expiry date shown 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 been dropped on a hard surface. The components inside the pre-filled syringe may have broken.
- Do not use the pre-filled syringe if the needle cap is missing or not securely closed.

2. Inspect the solution:

Inspect the medicine inside the pre-filled syringe.
The medicine should be from clear to slightly opalescent, colorless or pale yellow, and may
contain small white or almost transparent protein particles.

- Do not use the solution if it shows discoloration, appears cloudy, or if particles other than those described are visible.

3. Wait for the medicine to reach room temperature:

Take one prefilled syringe out of the refrigerator and allow it to sit at room temperature for
at least 30 minutes before administering the injection.
This is important to make the injection easier and more comfortable.

- Do not remove the needle cap until you are ready to administer the injection.
- Do not use heat sources such as a microwave or boiling water to warm Benepali.

4. Injection Site Selection:

Diagram of a human body showing anterior and posterior views with blue areas on abdomen, thighs, and arms indicating injection sites

The pre-filled syringe of Benepali is intended for subcutaneous injection. The injection should be administered in the thigh, abdomen, or upper outer area of the upper arm (see figure on the left).
Always use a different site for each new injection.
If injecting in the abdomen, select a site at least 5 cm away from the navel.

- Do not inject into areas that are red, hardened, bruised, or tender.
- Do not inject into scars or stretch marks.
- If you have psoriasis, do not inject into swollen, thickened, red, scaly areas of skin or into affected skin lesions.

B. Injection Steps
Step 1:

Wash your hands with soap and water.
Step 2:

One hand gently lifts a skin fold on a limb to prepare the area for injection

Disinfect the skin at the injection site using an alcohol swab.
Refer to “Injection Site Selection” for guidance on choosing the injection site.

- Do not touch this area again before administering the injection.

Step 3:

Two hands separating a syringe from a small rectangular container with a blue arrow indicating movement to the right

Remove the needle cap by pulling it straight off and dispose of it in household waste or in a sharps container.
Refer to “Injection Site Selection” for guidance on choosing the injection site.

- Do not twist or bend the needle cap when removing it, as this may damage the needle.
- Do not touch the plunger rod when removing the needle cap.
- Never recap the needle.

Step 4:

A hand holds a syringe with needle pointing downward while the

Gently pinch a fold of skin at the cleaned injection site. Hold the pre-filled syringe at a 45-degree angle to the skin. Insert the needle completely into the skin with a quick motion, similar to throwing a dart. After the needle is fully inserted, release the skin fold.
Step 5:

A hand holds a syringe with needle and white tip injecting medication into the upper thigh with a blue arrow indicating the direction of movement

Slowly press the plunger to inject the entire solution of Benepali.
Step 6:

A hand holds a syringe with needle directed toward the skin of a leg, with a blue arrow indicating movement toward the skin

Once the syringe is empty, remove the needle from the skin, maintaining the same angle used for insertion.

- Never recap the needle. This may result in a needlestick injury.

Disposal:

Yellow biological waste container with blue lid containing a needle and syringe, with biohazard symbol on the front

Dispose of the entire syringe in a designated sharps container.
Ask your healthcare provider for instructions on how to properly dispose of the sharps container when it is full. Sharps containers are available at pharmacies.

- Do not throw the sharps container into household waste.
- Do not recycle it.
- Do not reuse the pre-filled syringe of Benepali.
- Always keep the sharps container out of sight and out of reach of children.

C. Care of the Injection Site
If bleeding occurs at the injection site, apply gentle pressure with a piece of gauze.

- Do not rub the injection site.

If needed, cover the injection site with a plaster (bandage).

Patient Information Leaflet: Information for the User

Benepali 50 mg solution for injection in pre-filled syringe

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

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

Contents of this leaflet

What Benepali is and what it is used for
What you need to know before using Benepali
How to use Benepali
Possible side effects
How to store Benepali
Contents of the pack and other information
Instructions for use (see reverse side)

1. What Benepali is and what it is used for

Benepali contains the active substance etanercept.
Benepali is a medicine made by combining two human proteins. It blocks the activity of another protein that causes inflammation in the human body. Benepali works by reducing inflammation associated with certain diseases.

In adults (aged 18 years and older), Benepali can be used to treat:

- Moderate to severe rheumatoid arthritis;
- Psoriatic arthritis;
- Severe axial spondyloarthritis, including ankylosing spondylitis;
- Moderate to severe plaque psoriasis. In each case, Benepali is usually used when other widely used treatments have not worked well enough or are not suitable for you.

For patients with psoriatic arthritis affecting multiple joints, Benepali can improve the ability to perform daily activities.

For patients with painful or swollen symmetric joints (e.g., hands, wrists, and feet), Benepali can slow down structural damage to these joints caused by the disease.

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

- For the following types of juvenile idiopathic arthritis, when treatment with methotrexate has not provided an adequate response or is not appropriate:
- Polyarticular juvenile idiopathic arthritis (rheumatoid factor positive or negative) and extended oligoarticular juvenile idiopathic arthritis in patients from the age of 2 years, with body weight equal to or greater than 62.5 kg.
- Psoriatic arthritis in patients from the age of 12 years, with body weight equal to or greater than 62.5 kg.
- Enthesitis-related arthritis in patients from the age of 12 years, with body weight equal to or greater than 62.5 kg, when other widely used treatments have not provided an adequate response or are not appropriate.
- Severe plaque psoriasis in patients from the age of 6 years, with body weight equal to or greater than 62.5 kg, who have had an inadequate response to (or cannot take) phototherapy or other systemic therapies.

2. What you should know before using Benepali

Do not use Benepali

- if you or the child is allergic to etanercept or to any of the other components of this medicine (listed in section 6). If allergic reactions occur in you or the child, such as chest tightness, shortness of breath, dizziness or rash, do not inject any more Benepali and contact your doctor immediately.
- if you or the child has or is at risk of developing a serious blood infection called sepsis. If in doubt, contact your doctor.
- if you or the child has an infection of any kind. If in doubt, speak with your doctor.

Warnings and precautions
Talk to your doctor before taking Benepali.

Allergic reactions: If you or the child experiences allergic reactions such as chest tightness, shortness of breath, dizziness or rash, do not inject any more Benepali and contact your doctor immediately.
Infections/surgery: If you or the child develops a new infection or is about to undergo any major surgical procedure. Your doctor may want to review treatment with Benepali.
Infections/diabetes: Inform your doctor if you or the child has a history of recurrent infections or suffers from diabetes or other conditions that increase the risk of infection.
Infections/monitoring: Inform your doctor about any recent travel outside Europe. If you or the child develops symptoms of an infection such as fever, chills or cough, inform your doctor immediately. Your doctor may decide to continue monitoring you or the child for infections after you have stopped taking Benepali.
Tuberculosis: Since cases of tuberculosis have been reported in patients treated with Benepali, your doctor will check for signs and symptoms of tuberculosis before starting treatment with Benepali. This may include a thorough medical history, chest X-rays and tuberculin testing. The results of these tests must be recorded in the Patient Record Card. It is very important that you inform your doctor if you or the child has ever had tuberculosis or has been in close contact with someone who has tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection appear during or after therapy, inform your doctor immediately.
Hepatitis B: Inform your doctor if you or the child has or has had hepatitis B. Your doctor must perform a test for hepatitis B before you or the child starts treatment with Benepali. Treatment with Benepali can cause reactivation of hepatitis B in patients with previous infection with hepatitis B virus. In such cases, you must stop using Benepali.
Hepatitis C: Inform your doctor if you or the child has hepatitis C. Your doctor may consider it appropriate to monitor treatment with Benepali if the infection worsens.
Blood disorders: Seek immediate medical attention if you or the child has any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. These symptoms may indicate potentially life-threatening blood disorders that may require discontinuation of treatment with Benepali.
Nervous system and eye disorders: Inform your doctor if you or the child has multiple sclerosis, optic neuritis (inflammation of the optic nerves) or transverse myelitis (inflammation of the spinal cord). Your doctor will assess whether Benepali is an appropriate treatment.
Congestive heart failure: Inform your doctor if you or the child has a history of congestive heart failure, as Benepali should be used with caution in these circumstances.
Tumours: Inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other tumour before taking Benepali. Patients with long-standing severe rheumatoid arthritis may be at higher than average risk of developing lymphoma. Children and adults taking Benepali may have an increased risk of developing lymphoma or other tumours. Some children and adolescent patients treated with etanercept or other medicines acting like etanercept have developed tumours, including unusual types, sometimes with fatal outcome. Some patients receiving Benepali have developed skin tumours. Inform your doctor if you or the child develops any changes in the appearance of the skin or skin growths.
Chickenpox: Inform your doctor if you or the child is exposed to chickenpox while using Benepali. Your doctor will assess whether preventive treatment for chickenpox is appropriate.
Alcohol abuse: Benepali must not be used to treat hepatitis related to alcohol abuse. Inform your doctor if you or the child in your care has a history of alcohol abuse.
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 has Wegener’s granulomatosis, consult your doctor.
Antidiabetic medicines: Inform your doctor if you or the child has diabetes or is taking medicines to treat diabetes. Your doctor may decide whether you or the child needs to receive a lower dose of antidiabetic medicine while taking Benepali.
- Vaccinations: Some vaccines, such as oral polio vaccine, must not be administered during treatment with Benepali. Consult your doctor before you or the child receive any vaccine.

Children and adolescents
The use of Benepali is not indicated in children and adolescents weighing less than 62.5 kg.

- Vaccinations: Whenever possible, children should be up to date with all vaccinations before starting Benepali. Some vaccines, such as oral polio vaccine, must not be taken while receiving Benepali. Consult your doctor before you or the child receive any vaccine.

Benepali should normally not be used in children with polyarticular or extended oligoarticular juvenile idiopathic arthritis under 2 years of age or weighing less than 62.5 kg, or in children with enthesitis-related arthritis or psoriatic arthritis under 12 years of age or weighing less than 62.5 kg, or in children with psoriasis under 6 years of age or weighing less than 62.5 kg.

Other medicines and Benepali
Inform your doctor or pharmacist if you or the child is taking, has recently taken or might take any other medicines (including anakinra, abatacept or sulfasalazine).
You or the child must not use Benepali with medicines containing the active substances anakinra or abatacept.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Women of childbearing potential should be advised to use adequate contraception to prevent pregnancy during treatment with Benepali and for three weeks after stopping treatment.
Benepali should be used during pregnancy only if clearly necessary.
If you received Benepali during pregnancy, the newborn may be at increased risk of infection. In addition, one study indicated a higher number of birth defects in mothers who received etanercept during pregnancy compared to mothers who did not receive etanercept or other similar medicines (TNF antagonists), but no specific pattern of birth defects was identified. Another study did not show an increased risk of birth defects when mothers received etanercept 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 wish to breastfeed during treatment with Benepali. It is important to inform the child's paediatrician and other healthcare professionals about the use of Benepali during pregnancy and breastfeeding before the child receives any vaccine.

Driving and using machines
There is no information to suggest that Benepali affects the ability to drive or operate machinery.

Benepali contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 50 mg, i.e. it is practically 'sodium-free'.