BENEPALI 50 mg Инъекционный Раствор

Содержание инструкции

1. Benepali 25 mg injectable solution in pre-filled syringe
   1. What is Benepali and what it is used for
   2. What you need to know before using Benepali
   3. How to use Benepali
   4. Possible side effects
   5. How to store Benepali
   6. Contents of the pack and other information
   7. Instructions for Use
   8. Inspect the prefilled syringe:
   9. Inspect the solution:
   10. Wait for the medicine to reach room temperature:
   11. Injection Site Selection:
2. Benepali 50 mg injectable solution in pre-filled syringe
   1. What is Benepali and what it is used for
   2. What you need to know before using Benepali
   3. How to use Benepali
   4. Possible side effects
   5. How to store Benepali
   6. Package contents and other information
   7. Instructions for Use
   8. Inspect the prefilled syringe:
   9. Inspect the solution:
   10. Wait for the medicine to reach room temperature:
   11. Choice of injection site:
3. Benepali 50 mg injectable solution in pre-filled pen
   1. What is Benepali and what it is used for
   2. What you need to know before using Benepali
   3. How to use Benepali
   4. Possible side effects
   5. How to store Benepali
   6. Contents of the pack and other information
   7. Instructions for Use
   8. Inspect the pre-filled pen:
   9. Inspect the solution:
   10. Wait for the medicine to reach room temperature:
   11. Choice of injection site:

Benepali 25 mg injectable solution in pre-filled syringe

etanercept

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with the Patient Card which contains 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 for your child only. Do not pass it on to others, even if their symptoms are the same as yours or your child's, as it could be harmful.
• If any side effects occur, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Benepali is and what it is used for
• 2. What you need to know before you use Benepali
• 3. How to use Benepali
• 4. Possible side effects
• 5. How to store Benepali
• 6. Contents of the pack and other information
• 7. Instructions for use (see on the back)

1. What is Benepali and what it is used for

Benepali contains the active ingredient 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 the inflammation
associated with certain diseases.
In adults (aged 18 years and over), Benepali can be used for the treatment:

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

For rheumatoid arthritis, Benepali is usually used in combination with methotrexate, although
it can also be used alone if treatment with methotrexate is not suitable for you. Whether
used alone or in combination with methotrexate, Benepali can slow down the damage to the
joints caused by rheumatoid arthritis and improves the ability to perform normal daily
activities.
For patients with psoriatic arthritiswith involvement of multiple joints, Benepali can
improve the ability to perform daily activities.
For patients with multiple symmetrical painful or swollen joints(e.g. hands, wrists and
feet), Benepali can slow down the 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 given a sufficiently good response or is not appropriate:
• - Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients aged 2 years and over, with a body weight of 62.5 kg or more.
• - Psoriatic arthritis in patients aged 12 years and over, with a body weight of 62.5 kg or more.
• - For arthritis related to enthesitis in patients aged 12 years and over, with a body weight of 62.5 kg or more, when other widely used treatments have not given a sufficiently good response or are not appropriate.
• - Severe plaque psoriasis in patients starting from 6 years of age, with a body weight of 62.5 kg or more, who have had an inadequate response to (or cannot take) phototherapies or other systemic therapies.

2. What you need to know before using Benepali

Do not use Benepali

• - if you, or the child, are allergic to etanerceptor to any of the other ingredients ofthis medicine(listed in section 6). If you or the child experience allergic reactions such as tightness in the chest, wheezing, 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 infectioncalled sepsis. If you have any doubts, contact your doctor.
• - if you, or the child, have an infection of any kind.If you have any doubts, talk to your doctor.

Warnings and precautions
Talk to your doctor before taking Benepali.

• Allergic reactions:If you, or the child, experience allergic reactions such as tightness in the chest, wheezing, 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 want to check your treatment with Benepali.
• Infections/diabetes:Tell 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:Tell your doctor about any recent travel outside of 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:Because 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 review of your medical history, chest X-rays and a tuberculin test. The results of these tests should be reported on your Patient Card. It is very important that you tell your doctor if you or the child has ever had tuberculosis or has been in close contact with someone with tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, mild fever) or any other infection appear during or after therapy, tell your doctor immediately.
• Hepatitis B:Tell your doctor if you or the child has or has had hepatitis B. The

doctor must test for hepatitis B before you or the child start treatment
with Benepali. Treatment with Benepali may cause reactivation of hepatitis B in patients
with a previous hepatitis B virus infection. In this case, you must stop using Benepali.

• Hepatitis C:Tell your doctor if you or the child has hepatitis C. The 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 sign or symptom such as persistent fever, sore throat, bruising, bleeding or paleness. These symptoms may indicate the presence of blood disorders that are potentially life-threatening and may require discontinuation of treatment with Benepali.
• Nervous system and eye disorders:Tell 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). The doctor will assess whether Benepali is an appropriate treatment.
• Congestive heart failure:Tell your doctor if you or the child has a history of congestive heart failure, as Benepali must be used with caution in these circumstances.
• Cancer:Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer, before taking Benepali. Patients with severe, long-standing rheumatoid arthritis may be at a higher than average risk of developing lymphoma. Children and adults taking Benepali may have an increased risk of developing lymphoma or another cancer. Some children and adolescent patients who have been treated with etanercept or other medicines that act like etanercept have developed cancers, sometimes rare, sometimes fatal. Some patients receiving Benepali have developed skin cancers. Tell your doctor if you or the child develops any changes in the appearance of the skin or growths on the skin.
• Chickenpox:Tell your doctor if you or the child is exposed to chickenpox while using Benepali. The doctor will assess whether preventive treatment for chickenpox is appropriate.
• Alcohol abuse:Benepali should not be used to treat hepatitis related to alcohol abuse. Tell your doctor if you or the child you are caring for 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 you are caring for has Wegener's granulomatosis, consult your doctor.
• Anti-diabetic medicines:Tell your doctor if you or the child suffers from diabetes or is taking medicines to treat diabetes. The doctor may decide whether you or the child needs to receive less anti-diabetic medicine while taking Benepali.
• - Vaccinations:Some vaccines, such as oral polio vaccine, should not be administered during therapy 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 a body weight of less than 62.5 kg.

• - Vaccinations: If possible, before using Benepali, children should be up to date with all vaccinations. Some vaccines, such as oral polio vaccine, should not be given while taking Benepali. Consult your doctor before you or the child receive any vaccine.

As a rule, Benepali should not be used in children with polyarticular or extended oligoarticular arthritis under the age of 2 years or with a body weight of less than 62.5 kg, or in children with enthesitis-related arthritis or psoriatic arthritis under the age of 12 years or with a body weight of less than 62.5 kg, or in children with psoriasis under the age of 6 years or with a body weight of less than 62.5 kg.

Other medicines and Benepali
Tell your doctor or pharmacist if you or the child is taking, has recently taken or
may take any other medicine (including anakinra, abatacept or sulfasalazine).
You or the child must not useBenepali with medicines containing the active ingredients anakinra or
abatacept.

Pregnancy and breastfeeding
If you are pregnant, suspect you are 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 appropriate contraception to avoid pregnancy
during therapy with Benepali and for three weeks after stopping therapy.
Benepali should only be used during pregnancy if clearly necessary.
If you have received Benepali during pregnancy, the newborn may be at increased risk of
infection. In addition, one study indicated that there was 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 particular type of birth defect emerged among the reported birth defects. 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 while taking Benepali. It is important
to inform the child's paediatricians 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 the use of Benepali affects the ability to drive
vehicles or use machines.

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 following the instructions of your doctor exactly. 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 or older)
Rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 25 mg twice a week or 50 mg once a week by subcutaneous
injection.
In any case, the doctor may establish a different frequency with which to inject Benepali.
Plaque psoriasis
The usual dose is 25 mg twice a week or 50 mg once a week.
Alternatively, a dose of 50 mg twice a week may be administered for up to
12 weeks, followed by a dose of 25 mg twice a week or 50 mg once a
week.
The doctor will decide how long you should use Benepali and whether, based on your response, a
new treatment is necessary. If, after 12 weeks, Benepali has no effect on your
condition, your doctor may tell you to stop treatment.

Use in children and adolescents
The dose and frequency of dosage for the child or adolescent will depend on body weight and
the disease. The doctor will establish the correct dose for the child and prescribe an appropriate
dosage of etanercept.
Paediatric patients with a body weight of 62.5 kg or more may receive 25 mg twice a
week or 50 mg once a week using either the prefilled syringe or the prefilled fixed-dose pen.
Other products containing etanercept with a dosage suitable for children are available.
For polyarthritis or extended oligoarthritis in patients starting from 2 years of age, with a body weight of or
greater than 62.5 kg, or enthesitis-related arthritis or psoriatic arthritis in patients starting from 12 years
of age, with a body weight of or greater than 62.5 kg, the usual dose is 25 mg twice a week or
50 mg once a week.
For psoriasis in patients starting from 6 years of age, with a body weight of or greater than 62.5 kg, the
usual dose is 50 mg and must be administered once a week. If Benepali has no effect
on the child's condition after 12 weeks, the doctor may tell you to stop the
treatment with this medicine.
The doctor will provide you with detailed information on how to prepare and measure the appropriate dosage.

Route of administration and how to administer
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 useful to write in an agenda 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 on a single occasion or
using it too frequently), speak to a doctor or pharmacist immediately. Always keep the medicine
pack with you, even if it is empty.

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

If you stop using Benepali
Following discontinuation of treatment, the symptoms of the disease may return.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions
If any of the following side effects occur, do not inject Benepali anymore. Inform your doctor immediately, or go to the emergency room of the nearest hospital.

• - Difficulty swallowing or breathing
• - Swelling of the face, throat, hands or feet
• - Feeling of nervousness or anxiety, palpitations, sudden redness of the skin and/or feeling of warmth
• - Severe skin rash, itching, hives (raised, red or pale patches of skin that often itch)

Severe allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Benepali; therefore, you should seek immediate medical attention.

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

• - 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 disorders, such as numbness or tingling, changes in vision, eye pain or onset of weakness in an arm or leg;
• - Symptoms of heart failureor worsening of heart failure, such as fatigue or shortness of breath during activity, swelling of the ankles, a feeling of swelling in the neck or abdomen, shortness of breath at night or cough, bluish colour of the nails or lips;
• - Symptoms of tumours:tumours can affect any part of the body, including skin and blood, and the 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 growths on the skin;
• - Symptoms of autoimmune reactions(where antibodies are created that can damage normal body tissues), such as pain, itching, weakness, abnormalities in breathing, thinking, sensations 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 blood vessel inflammation, such as pain, fever, redness or overheating of the skin or itching.

These side effects are rare or uncommon, but are serious conditions (some of which can rarely cause death). If any of these symptoms occur, inform your doctor immediately, or go to the emergency room of the nearest hospital.
Other side effects
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 cold, sinusitis, bronchitis, urinary tract infections and skin infections); reactions at the injection site (including bleeding, bruising, redness, itching, pain and swelling) (these do not occur as often 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 in various sites); worsening of congestive heart failure; low number of red blood cells, low number of white blood cells, low number of neutrophils (a type of white blood cells); reduced number of platelets in the blood; skin tumour (excluding melanoma); localised swelling of the skin (angioedema); hives (raised, red or pale patches of skin that often itch); inflammation of the eyes; psoriasis (first appearance or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood (in patients also 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 bowel problems).
• Rare(may affect up to 1 in 1,000 people) Severe allergic reactions (including severe localised swelling of the skin and difficulty breathing); lymphoma (a type of blood cancer); leukaemia (a cancer affecting the blood and bone marrow); melanoma (a type of skin cancer); combined reduction in the number of platelets, red blood cells and white blood cells; changes in the nervous system (with severe muscle weakness and signs and symptoms similar to those of multiple sclerosis or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; convulsions; lupus or lupus-like syndrome (symptoms may include a persistent rash, fever, joint pain and fatigue); skin rash that can lead to severe blistering and peeling of the skin; inflammation of the liver caused by your immune system (autoimmune hepatitis; in patients also treated with methotrexate, the frequency is uncommon); immune disorder that can affect the lungs, skin and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also treated with methotrexate, the frequency of inflammation or scarring of the lungs is uncommon); lichenoid reactions (itchy reddish/purple rash and/or whitish-greyish filamentous lines on mucous membranes); opportunistic infections (including tuberculosis and other infections that occur when resistance to disease is reduced); erythema multiforme (inflammatory skin rash); cutaneous vasculitis (inflammation of the skin blood vessels); nerve damage, including Guillain-Barré syndrome (a serious illness that can impair breathing and damage organs); damage to the tiny filters inside the kidneys causing reduced kidney function (glomerulonephritis).
• Very rare(may affect up to 1 in 10,000 people) Inability of the bone marrow to produce essential blood cells; toxic epidermal necrolysis (a potentially life-threatening skin disease).
• Not known (frequency cannot be estimated based on available data) Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma (a rare form of cancer related to human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness, accompanied by a rash); listeriosis (a bacterial infection).

Side effects in children and adolescents
Side effects and their frequency observed in children and adolescents are similar to those described above.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system reported 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
pre-filled syringe after Expiry/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 pre-filled syringes in the outer packaging to protect the medicine from light.
After taking a syringe from the refrigerator, wait approximately 30 minutes to allow the
solution of Benepali in the syringe to reach room temperature.Do not heat it in any
other way. Immediate use is then recommended.
Benepali can be stored at a maximum temperature of 30°C for up to 31 days, for one time only; after this
period it cannot be returned to the refrigerator. If not used within 31 days
outside the refrigerator, Benepali must be discarded. It is recommended to note the date on which Benepali is removed
from the refrigerator and the date by which Benepali must be disposed of (no more than 31 days outside the
refrigerator).
Inspect the solution inside the syringe. The solution should be from clear to slightly
opalescent, colourless or pale 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 that the solution
presents colour changes or appears cloudy or if particles other than those
described are visible. If you have any doubts regarding the appearance of the solution, contact your pharmacist for assistance.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Benepali contains

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

Description of Benepali and contents of the pack
Benepali is supplied as a pre-filled syringe containing an injectable solution
(injectable preparation) from clear to slightly opalescent, colourless or pale yellow.
Benepali is available in packs containing 4 pre-filled syringes, multi-packs
comprising 2 boxes each containing 4 pre-filled syringes, and multi-packs comprising
6 boxes each containing 4 pre-filled syringes. 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, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Biogen Belgium NV/S.A
Tél/Tel: + 32 (0)2 808 5947

Lietuva
Biogen Lithuania UAB
Tel: +370 52 07 91 38

България
Ewopharma AG Representative Office
Тел.: + 359 249 176 81

Luxembourg/Luxemburg
Biogen Belgium NV/SA
Tél/Tel: +35 227 772 038

Česká republika
Biogen (Czech Republic) s.r.o.
Tel: + 420 228 884 152

Magyarország
Biogen Hungary Kft.
Tel.: + 36 1 848 04 64

Danmark
Biogen (Denmark) A/S
Tlf.: + 45 78 79 37 53

Malta
Pharma.MT Ltd
Tel: + 356 27 78 15 79

Deutschland
Biogen GmbH
Tel: + 49 (0)89 996 177 00

Nederland
Biogen Netherlands B.V.
Tel: + 31 (0)20 808 02 70

Eesti
Biogen Estonia OÜ
Tel: + 372 6 68 30 56

Norge
Biogen Norway AS
Tlf: + 47 21 93 95 87

Ελλάδα
Genesis Pharma S.A.
Τηλ: + 30 211 176 8555

Ö sterreich
Biogen Austria GmbH
Tel: + 43 (0)1 267 51 42

España
Biogen Spain, S.L.
Tel: + 34 91 310 7110

Polska
Biogen Poland Sp. z o.o.
Tel.: + 48 22 116 86 94

France
Biogen France SAS
Tél: + 33 (0)1 776 968 14

Portugal
Biogen Portugal Sociedade Farmacêutica,
Unipessoal, Lda
Tel: + 351 308 800 792

Hrvatska
Ewopharma d.o.o
Tel: + 385 (0)1 777 64 37

România
Ewopharma România SRL
Tel: + 40 212 601 407

Ireland
Biogen Idec (Ireland) Ltd.
Tel: +353 (0)1 513 33 33

Slovenija
Biogen Pharma d.o.o.
Tel: + 386 (0)1 888 81 07

Ísland
Icepharma hf.
Sími: + 354 800 9836

Slovenská republika
Biogen Slovakia s.r.o.
Tel: + 421 (0)2 333 257 10

Italia
Biogen Italia s.r.l.
Tel: + 39 (0)6 899 701 50

Suomi/Finland
Biogen Finland Oy
Puh/Tel: + 358 (0)9 427 041 08

Κύπρος
Genesis Pharma (Cyprus) Ltd
Τηλ: + 357 22 00 04 93

Sverige
Biogen Sweden AB
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 website of the European
Medicines Agency: http://www.ema.europa.eu .

7. Instructions for Use

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

• - Do notattempt self-injection before the doctor or nurse has explained how to do it.

A pre-filled syringe for single use contains a dose of 25 mg of Benepali.
Choose a well-lit and clean work surface and have everything you need within reach:

• - A new pre-filled syringe of Benepali

o Do notshake the pre-filled syringe.

Not included in the package:

• - 1 alcohol swab, gauze and plaster

• - Sharps container

• A. Before you begin

1. Inspect the prefilled syringe:

Check the expiration date reported on the syringe label.

• - Do notuse the prefilled syringe after the expiration date.
• - Do notuse the prefilled syringe if it has fallen onto a hard surface. The components inside the prefilled syringe may have been broken.
• - Do notuse the prefilled syringe if the needle cap is missing or if it is 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 light yellow and may
contain small, white or almost transparent protein particles.

• - Do notuse the solution if it presents color changes or appears cloudy or if particles different from those described are visible.

3. Wait for the medicine to reach room temperature:

Take a pre-filled syringe from the refrigerator and leave it at room temperature for
at least 30 minutes before performing the injection.
This is important to make the injection easier and more comfortably.

• - Do notremove the needle cap until you are ready for the injection.
• - Do notuse heat sources such as a microwave oven or boiling water to heat Benepali.

4. Injection Site Selection:

The pre-filled syringe of Benepali is intended for subcutaneous injection. The injection must
be administered to the thigh, abdomen, or the back of the arm(see figure on the
left).

Make each new injection at a different site.
If you inject into the abdomen, choose a site at least 5 cm away from the navel.

• - Do notinject into areas that are red, hardened, bruised, or sensitive.
• - Do notinject into scars or stretch marks.
• - If you have psoriasis, do notinject into swollen, thickened, red, or scaly areas of the skin or into damaged areas.
• B. Injection Steps

Step 1:

Wash your hands with soap and water.
Step 2:

Disinfect the skin at the injection site
with an alcohol-soaked swab.
See “Injection Site Selection” for advice on choosing the
injection site.

• - Do nottouch this area again before administering the injection.

Step 3:

Remove the needle cap by holding it straight and
dispose of it in household waste or a sharps container.
See “Injection Site Selection” for advice on choosing the
injection site.

• - Do nottwist or bend the needle cap when removing it, as this could damage the needle.
• - Do nottouch the plunger rod when removing the needle cap.
• - Never recap the needle.

Step 4:

Carefully form a skin fold at the injection site.
Hold the pre-filled syringe at a 45-degree angle to the
skin. Insert the needle fully into the skin with a
quick motion, as if throwing a dart.
After the needle has been inserted completely, you can release
the skin fold.

Step 5:

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

When the syringe is empty, remove the needle from the skin
keeping it at the same angle it was inserted.

• - Neverrecap the needle. Otherwise, you risk pricking yourself.

Disposal:

Dispose of the entire syringe in a designated sharps
container.
Ask healthcare professionals for instructions on how to properly dispose of the sharps container when
it is full. Sharps containers can be purchased at pharmacies.

• - Do notdispose of the sharps container in household waste.
• - Do notrecycle it.
• - Do notreuse the pre-filled Benepali syringe.
• - Always keep the container out of sight and reach of children.
• C. Dressing the Injection Site

If there is bleeding at the injection site, press gauze onto the injection site.

• - Do notrub the injection site.

If necessary, cover the injection site with a bandage.

Benepali 50 mg injectable solution in pre-filled syringe

etanercept

Read this leaflet carefully before using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with the Patient Card which contains 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 only for you or for your child. Do not give it to other people, even if their symptoms are the same as yours or your child's, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Benepali is and what it is used for
• 2. What you need to know before you use Benepali
• 3. How to use Benepali
• 4. Possible side effects
• 5. How to store Benepali
• 6. Contents of the pack and other information
• 7. Instructions for use (see on the back)

1. What is Benepali 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 the inflammation
associated with certain diseases.
In adults (aged 18 years or older), Benepali can be used for the treatment:

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

For rheumatoid arthritis, Benepali is usually used in combination with methotrexate, although
it can also be used alone if treatment with methotrexate is not suitable for you. Both
when used alone or in combination with methotrexate, Benepali can slow down the damage to the
joints caused by rheumatoid arthritis and improves the ability to perform normal daily
activities.
For patients with psoriatic arthritiswith involvement of multiple joints, Benepali can
improve the ability to perform daily activities.
For patients with multiple symmetrical painful or swollen joints(e.g. hands, wrists and
feet), Benepali can slow down the 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 given a sufficiently good response or is not appropriate:
• - Polyarthritis (positive or negative for rheumatoid factor) and extended oligoarthritis in patients aged 2 years or older, with a body weight of 62.5 kg or more.
• - Psoriatic arthritis in patients aged 12 years or older, with a body weight of 62.5 kg or more.
• - For arthritis related to enthesitis in patients aged 12 years or older, with a body weight of 62.5 kg or more, when other widely used treatments have not given a sufficiently good response or are not appropriate.
• - Severe plaque psoriasis in patients starting from 6 years of age, with a body weight of 62.5 kg or more, who have had an inadequate response with (or cannot take) phototherapies or other systemic therapies.

2. What you need to know before using Benepali

Do not use Benepali

• - if you, or the child, are allergic to etanerceptor to any of the other ingredients ofthis medicine(listed in section 6). If you or the child experience allergic reactions such as tightness in the chest, wheezing, 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 severe blood infectioncalled sepsis. If you have any doubts, contact your doctor.
• - if you, or the child, have an infection of any kind.If you have any doubts, talk to your doctor.

Warnings and precautions
Talk to your doctor before taking Benepali.

• Allergic reactions:If you, or the child, experience allergic reactions such as tightness in the chest, wheezing, 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 surgery. Your doctor may want to check your treatment with Benepali.
• Infections/diabetes:Tell 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:Tell your doctor about any recent travel outside of Europe. If you, or the child, develop symptoms of an infection such as fever, chills or cough, inform your doctor immediately. The doctor may decide to continue monitoring you or the child for infections after you have stopped taking Benepali.
• Tuberculosis:Because 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 review of your medical history, chest X-rays and a tuberculin test. The results of these tests should be reported on the Patient Card. It is very important that you tell your doctor if you or the child has ever had tuberculosis or has been in close contact with someone with tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, mild fever) or any other infection appear during or after therapy, tell your doctor immediately.
• Hepatitis B:Tell your doctor if you or the child have or have had hepatitis B. Your doctor should test for hepatitis B before you or the child start treatment with Benepali. Treatment with Benepali may cause reactivation of hepatitis B in patients with a previous hepatitis B virus infection. If this happens, you must stop using Benepali.
• Hepatitis C:Tell your doctor if you or the child have hepatitis C. Your doctor may consider monitoring your treatment with Benepali if the infection worsens.
• Blood disorders:Seek immediate medical attention if you or the child have any signs or symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. These symptoms may indicate the presence of blood disorders that are potentially life-threatening and may require discontinuation of treatment with Benepali.
• Nervous system and eye disorders:Tell 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). The doctor will assess whether Benepali is an appropriate treatment.
• Congestive heart failure:Tell 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:Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer, before taking Benepali. Patients with severe rheumatoid arthritis for a long time may be at a higher than average risk of developing lymphoma. Children and adults taking Benepali may have an increased risk of developing lymphoma or another cancer. Some children and adolescent patients who have been treated with etanercept or other medicines that act like etanercept have developed tumors, sometimes unusual and sometimes fatal. Some patients receiving Benepali have developed skin tumors. Tell your doctor if you or the child develops any changes in the appearance of the skin or growths on the skin.
• Chickenpox:Tell your doctor if you or the child are exposed to chickenpox while using Benepali. The doctor will assess whether preventive treatment for chickenpox is appropriate.
• Alcohol abuse:Benepali should not be used to treat hepatitis related to alcohol abuse. Tell your doctor if you or the child you are caring for 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 you are caring for has Wegener's granulomatosis, consult your doctor.
• Anti-diabetic medicines:Tell your doctor if you or the child suffer from diabetes or are taking medicines to treat diabetes. The doctor may decide whether you or the child need to receive less anti-diabetic medicine while taking Benepali.
• - Vaccinations: Some vaccines, such as the oral polio vaccine, should not be given during therapy 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 a body weight of less than 62.5 kg.

• - Vaccinations: If possible, before using Benepali, children should be up to date with all vaccinations. Some vaccines, such as the oral polio vaccine, should not be given while taking Benepali. Consult your doctor before you or the child receive any vaccine.

Generally Benepali should not be used in children with polyarticular or extended oligoarticular arthritis under the age of
2 years or with a body weight of less than 62.5 kg, or in children with arthritis related to
enthesitis or psoriatic arthritis under the age of 12 years or with a body weight of less than 62.5 kg, or in
children with psoriasis under the age of 6 years or with a body weight of less than 62.5 kg.

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

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant or 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 avoid pregnancy
during therapy with Benepali and for three weeks after the end of therapy.
Benepali should only be used during pregnancy if clearly necessary.
If you have received Benepali during pregnancy, the newborn may be at increased risk of
infection. In addition, one study has shown that there was 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 particular type of birth defect emerged among the reported birth defects. 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.

Contact your doctor if you wish to breastfeed while taking Benepali. It is important
to inform the child's pediatricians 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 indicate that the use of Benepali affects the ability to drive vehicles
or use machines.

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

3. How to use Benepali

Use this medicine following the instructions of your doctor exactly. If you have any doubts, ask 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 or older)
Rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, including ankylosing spondylitis
The usual dose is 50 mg once a week by subcutaneous injection.
In any case, the doctor may establish a different frequency with which to inject Benepali.
Plaque psoriasis
The usual dose is 50 mg administered once a week.
Alternatively, a dose of 50 mg can be administered twice a week for a maximum of
12 weeks, followed by a dose of 50 mg administered once a week.
The doctor will decide how long you should use Benepali and whether, based on your response, a
new treatment is necessary. If, after 12 weeks, Benepali has no effect on your
disease, your doctor may tell you to stop treatment.

Use in children and adolescents
The dose and frequency of dosage for the child or adolescent will depend on body weight and
the disease. The doctor will establish the correct dose for the child and prescribe an appropriate
dosage of etanercept.
Paediatric patients with a body weight of 62.5 kg or more may receive 25 mg twice a
week or 50 mg once a week using either the pre-filled syringe or the pre-filled fixed-dose pen.
Other products containing etanercept with a dosage suitable for children are available.
For polyarticular or extended oligoarticular arthritis in patients starting from 2 years of age, with a body weight of
62.5 kg or more, or arthritis related to enthesitis or psoriatic arthritis in patients starting from 12 years
of age, with a body weight of 62.5 kg or more, the usual dose is 25 mg twice a week or
50 mg once a week.
For psoriasis in patients starting from 6 years of age, with a body weight of 62.5 kg or more, the
usual dose is 50 mg and must be administered once a week. If Benepali has no effect
on the child's condition after 12 weeks, the doctor may tell you to stop
treatment with this medicine.
The doctor will provide you with detailed information on how to prepare and measure the appropriate dosage.

Route of administration and how to administer
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 useful to write in an agenda 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 on a single occasion or
using it too frequently), speak to a doctor or pharmacist immediately. Always keep the medicine
pack with you, even if it is empty.

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

If you stop using Benepali
Following discontinuation of treatment, the symptoms of the disease may return.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions
If any of the following side effects occur, do not inject Benepali anymore. Inform your doctor immediately, or go to the nearest hospital emergency room.

• - Difficulty swallowing or breathing
• - Swelling of the face, throat, hands or feet
• - Feeling of nervousness or anxiety, palpitations, sudden redness of the skin and/or feeling of warmth
• - Severe skin rash, itching, hives (raised, red or pale patches of skin that often itch)

Severe allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to Benepali; therefore, you should seek immediate medical attention.

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

• - 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 disorders, such as numbness or tingling, changes in vision, eye pain or onset of weakness in an arm or leg;
• - Symptoms of heart failureor worsening of heart failure, such as fatigue or shortness of breath during activity, swelling of the ankles, a feeling of swelling in the neck or abdomen, shortness of breath at night or coughing, bluish colour of the nails or lips;
• - Symptoms of tumours:tumours can affect any part of the body, including the skin and blood, and the 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 growths on the skin;
• - Symptoms of autoimmune reactions(where antibodies are created that can damage normal body tissues), such as pain, itching, weakness, abnormalities in breathing, thinking, sensations or vision;
• - Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, pain in joints or muscles, or fatigue;
• - Symptoms of blood vessel inflammation, such as pain, fever, redness or overheating of the skin or itching.

These side effects are rare or uncommon, but are serious conditions (some of which can rarely be fatal). If any of these symptoms occur, inform your doctor immediately, or go to the nearest hospital emergency room.
Other side effects
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 cold, sinusitis, bronchitis, urinary tract infections and skin infections); reactions at the injection site (including bleeding, bruising, redness, itching, pain and swelling) (these do not occur as often 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; itching; antibodies directed against normal tissue (autoantibody formation).
• Uncommon(may affect up to 1 in 100 people) Serious infections (including pneumonia, deep skin infections, joint infections, blood infections and infections in various sites); worsening of congestive heart failure; low number of red blood cells, low number of white blood cells, low number of neutrophils (a type of white blood cells); reduced number of platelets in the blood; skin tumour (excluding melanoma); localised swelling of the skin (angioedema); hives (raised, red or pale patches of skin that often itch); eye inflammation; psoriasis (first occurrence or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood (in patients also receiving 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 bowel problems).
• Rare(may affect up to 1 in 1,000 people) Severe allergic reactions (including severe localised swelling of the skin and difficulty breathing); lymphoma (a type of blood cancer); leukaemia (a cancer affecting the blood and bone marrow); melanoma (a type of skin cancer); combined reduction in the number of platelets, red blood cells and white blood cells; changes in the nervous system (with severe muscle weakness and signs and symptoms similar to those of multiple sclerosis or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include a persistent rash, fever, joint pain and fatigue); skin rash that can lead to severe blistering and peeling of the skin; inflammation of the liver caused by your immune system (autoimmune hepatitis; in patients also receiving methotrexate, the frequency is uncommon); immune disorder that can 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); lichenoid reactions (itchy reddish/purple rash and/or whitish-greyish linear streaks on mucous membranes); opportunistic infections (including tuberculosis and other infections that occur when resistance to disease is reduced); erythema multiforme (inflammatory skin rash); cutaneous vasculitis (inflammation of the skin blood vessels); nerve damage, including Guillain-Barré syndrome (a serious illness that can impair breathing and damage organs); damage to the tiny filters inside the kidneys resulting in reduced kidney function (glomerulonephritis).
• Very rare(may affect up to 1 in 10,000 people) Bone marrow failure 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 related to human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); reactivation of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness, accompanied by a 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 get any side effects, talk to your doctor or pharmacist. You can also report side effects directly through 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 pack and on the label of the
pre-filled syringe after Expiry/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 pre-filled syringes in the outer packaging to protect the medicine from light.
After taking a syringe from the refrigerator, wait approximately 30 minutes to allow the
solution of Benepali in the syringe to reach room temperature.Do not heat it in any
other way. Immediate use is then recommended.
Benepali can be stored at a maximum temperature of 30°C for up to 31 days, for single use only; after this
period it cannot be returned to the refrigerator. If not used within 31 days
outside the refrigerator, Benepali must be discarded. It is recommended to note the date on which Benepali is removed
from the refrigerator and the date by which Benepali must be disposed of (no more than 31 days outside the
refrigerator).
Inspect the solution inside the syringe. The solution should be from clear to slightly
opalescent, colourless or pale 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 that the solution
presents colour changes or appears cloudy or if particles other than those
described are visible. If you have any doubts regarding the appearance of the solution, contact your pharmacist for assistance.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer 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 50 mg of etanercept.
• The other ingredients are sucrose, sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate heptahydrate and water for injections (see section 2 “Benepali contains sodium”).

Description of Benepali and package contents
Benepali is supplied as a pre-filled syringe containing an injectable solution
(injectable preparation) that is clear to slightly opalescent, colourless or pale yellow.
Benepali is available in packs containing 4 pre-filled syringes and in multiple packs
consisting of 3 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
Netherlands

Manufacturer
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 on this medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Biogen Belgium NV/S.A
Tél/Tel: + 32 (0)2 808 5947

Lietuva
Biogen Lithuania UAB
Tel: +370 52 07 91 38

България
Ewopharma AG Representative Office
Тел.: + 359 249 176 81

Luxembourg/Luxemburg
Biogen Belgium NV/SA
Tél/Tel: +35 227 772 038

Česká republika
Biogen (Czech Republic) s.r.o.
Tel: + 420 228 884 152

Magyarország
Biogen Hungary Kft.
Tel.: + 36 1 848 04 64

Danmark
Biogen (Denmark) A/S
Tlf.: + 45 78 79 37 53

Malta
Pharma.MT Ltd
Tel: + 356 27 78 15 79

Deutschland
Biogen GmbH
Tel: + 49 (0)89 996 177 00

Nederland
Biogen Netherlands B.V.
Tel: + 31 (0)20 808 02 70

Eesti
Biogen Estonia OÜ
Tel: + 372 6 68 30 56

Norge
Biogen Norway AS
Tlf: + 47 21 93 95 87

Ελλάδα
Genesis Pharma S.A.
Τηλ: + 30 211 176 8555

Ö sterreich
Biogen Austria GmbH
Tel: + 43 (0)1 267 51 42

España
Biogen Spain, S.L.
Tel: + 34 91 310 7110

Polska
Biogen Poland Sp. z o.o.
Tel.: + 48 22 116 86 94

France
Biogen France SAS
Tél: + 33 (0)1 776 968 14

Portugal
Biogen Portugal Sociedade Farmacêutica,
Unipessoal, Lda
Tel: + 351 308 800 792

Hrvatska
Ewopharma d.o.o
Tel: + 385 (0)1 777 64 37

România
Ewopharma România SRL
Tel: + 40 212 601 407

Ireland
Biogen Idec (Ireland) Ltd.
Tel: +353 (0)1 513 33 33

Slovenija
Biogen Pharma d.o.o.
Tel: + 386 (0)1 888 81 07

Ísland
Icepharma hf.
Sími: + 354 800 9836

Slovenská republika
Biogen Slovakia s.r.o.
Tel: + 421 (0)2 333 257 10

Italia
Biogen Italia s.r.l.
Tel: + 39 (0)6 899 701 50

Suomi/Finland
Biogen Finland Oy
Puh/Tel: + 358 (0)9 427 041 08

Κύπρος
Genesis Pharma (Cyprus) Ltd
Τηλ: + 357 22 00 04 93

Sverige
Biogen Sweden AB
Tel: +46 (0)8 525 038 36

Latvija
Biogen Latvia SIA
Tel: + 371 66 16 40 32
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu .

7. Instructions for Use

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

• - Donot attempt self-injection before the doctor or nurse has explained how to do it.

A pre-filled single-use syringe contains a 50 mg dose of Benepali.
Choose a well-lit and clean work surface and keep everything you need within reach:

• - A new pre-filled syringe of Benepali

o Donot shake the pre-filled syringe.

Not included in the package:

• - 1 alcohol swab, gauze and plaster

• - Sharps container

• A. Before you begin

1. Inspect the prefilled syringe:

Check the expiration date reported on the syringe label.

• - Do notuse the prefilled syringe after the expiration date.
• - Do notuse the prefilled syringe if it has fallen onto a hard surface. The components inside the prefilled syringe may have been broken.
• - Do notuse the prefilled syringe if the needle cap is missing or if it is not securely closed.

2. Inspect the solution:

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

• - Do notuse the solution if it presents colour changes or appears cloudy or if particles different from those described are visible.

3. Wait for the medicine to reach room temperature:

Remove a pre-filled syringe from the refrigerator and leave it at room temperature for
at least 30 minutes before performing the injection.
This is important to make the injection easier and more comfortable.

• - Do notremove the needle cap until you are ready for the injection.
• - Do notuse heat sources such as a microwave oven or boiling water to warm Benepali.

4. Choice of injection site:

The pre-filled syringe of Benepali is intended for subcutaneous injection. The injection must
be performed in the thigh, abdomen, or the back of the arm(see figure on the
left).

Make each new injection at a different site.
If you inject into the abdomen, choose a site at least 5 cm away from the navel.

• - Do notinject into areas that are red, hardened, bruised, or sensitive.
• - Do notinject into scars or stretch marks.
• - If you have psoriasis, do notinject into areas of swollen, thickened, red, or scaly skin or into damaged areas.
• B. Injection steps

Step 1:

Wash your hands with soap and water.
Step 2:

Disinfect the skin at the injection site
with an alcohol-soaked swab.
See “Choice of injection site” for advice on choosing the
injection site.

• - Do nottouch this area again before performing the injection.

Step 3:

Pull off the needle cap, keeping it straight and
dispose of it in household waste or a sharps container.
See “Choice of injection site” for advice on choosing the
injection site.

• - Do nottwist or bend the needle cap when removing it, as this could damage the needle.
• - Do nottouch the plunger rod when removing the needle cap.
• - Nevercover the needle with the cap.

Step 4:

Carefully form a skin fold at the injection site.
Hold the pre-filled syringe at a 45-degree angle to the
skin. Insert the needle fully into the skin with a
quick motion, as if throwing a dart.
After the needle has been inserted completely, you can release
the skin fold.

Step 5:

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

When the syringe is empty, remove the needle from the skin
keeping it at the same angle it was
inserted.

• - Nevercover the needle with the cap. Otherwise, you risk pricking yourself.

Disposal:

Dispose of the entire syringe in a designated sharps container.
Ask healthcare professionals for instructions on how to properly dispose of the sharps container when
it is full. Sharps containers can be purchased at a
pharmacy.

• - Do notthrow the sharps container in household waste.
• - Do notrecycle it.
• - Do notreuse the pre-filled Benepali syringe.
• - Always keep the container out of sight and reach of children.
• C. Dressing the injection site

If there is bleeding at the injection site, press gauze onto the injection site.

• - Do notrub the injection site.

If necessary, cover the injection site with a bandage.

Benepali 50 mg injectable solution in pre-filled pen

etanercept

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with the Patient Card which contains 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 for your child only. Do not pass it on to others, even if their symptoms are the same as yours or your child’s, as it could be harmful.
• If any side effects occur, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Benepali is and what it is used for
• 2. What you need to know before you use Benepali
• 3. How to use Benepali
• 4. Possible side effects
• 5. How to store Benepali
• 6. Contents of the pack and other information
• 7. Instructions for use (see on the back)

1. What is Benepali 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 the inflammation
associated with certain diseases.
In adults (aged 18 years and over), Benepali can be used for the treatment:

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

For rheumatoid arthritis, Benepali is usually used in combination with methotrexate, although
it can also be used alone if treatment with methotrexate is not suitable for you. Both
when used alone or in combination with methotrexate, Benepali can slow down the damage to the
joints caused by rheumatoid arthritis and improves the ability to perform normal daily
activities.
For patients with psoriatic arthritiswith involvement of multiple joints, Benepali can
improve the ability to perform daily activities.
For patients with multiple symmetrical painful or swollen joints(e.g. hands, wrists and
feet), Benepali can slow down the 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 given a sufficiently good response or is not appropriate:
• - Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients aged 2 years and over, with a body weight of 62.5 kg or more.
• - Psoriatic arthritis in patients aged 12 years and over, with a body weight of 62.5 kg or more.
• - For arthritis related to enthesitis in patients aged 12 years and over, with a body weight of 62.5 kg or more, when other widely used treatments have not given a sufficiently good response or are not appropriate.
• - Severe plaque psoriasis in patients starting from 6 years of age, with a body weight of 62.5 kg or more, who have had an inadequate response with (or cannot take) phototherapy or other systemic therapies.

2. What you need to know before using Benepali

Do not use Benepali

• - if you, or the child, are allergic to etanerceptor to any of the other ingredients ofthis medicine(listed in section 6). If you or the child experience allergic reactions such as tightness in the chest, wheezing, 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 infectioncalled sepsis. If you have any doubts, contact your doctor.
• - if you, or the child, have an infection of any kind.If you have any doubts, talk to your doctor.

Warnings and precautions
Talk to your doctor before taking Benepali.

• - Allergic reactions:If you, or the child, experience allergic reactions such as tightness in the chest, wheezing, 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 want to check your treatment with Benepali.
• - Infections/diabetes: Tell 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:Tell your doctor about any recent travel outside of 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:Because 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 review of your medical history, chest X-rays and a tuberculin test. The results of these tests should be reported on the Patient Card. It is very important that you tell your doctor if you or the child has ever had tuberculosis or has been in close contact with someone with tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, weakness, low-grade fever) or any other infection appear during or after therapy, report them to your doctor immediately.
• - Hepatitis B:Tell your doctor if you or the child has or has had hepatitis B. Your doctor should test for hepatitis B before you or the child start treatment with Benepali. Treatment with Benepali may cause reactivation of hepatitis B in patients with a previous hepatitis B virus infection. If this happens, you must stop using Benepali.
• - Hepatitis C:Tell your doctor if you or the child has hepatitis C. Your doctor may consider monitoring the treatment with Benepali if the infection worsens.
• - Blood disorders:Seek immediate medical attention if you or the child has any sign or symptom such as persistent fever, sore throat, bruising, bleeding or paleness. These symptoms may indicate the presence of blood disorders that are potentially life-threatening and may require discontinuation of treatment with Benepali.
• - Nervous system and eye disorders:Tell 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). The doctor will assess whether Benepali is an appropriate treatment.
• - Congestive heart failure:Tell your doctor if you or the child has a history of congestive heart failure, as Benepali should be used with caution in these circumstances.
• - Cancer:Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer, before taking Benepali. Patients with long-standing severe rheumatoid arthritis may be at a higher than average risk of developing lymphoma. Children and adults taking Benepali may have an increased risk of developing lymphoma or another cancer. Some children and adolescent patients who have been treated with etanercept or other medicines that act like etanercept have developed tumors, sometimes unusual, and sometimes fatal. Some patients receiving Benepali have developed skin tumors. Tell your doctor if you or the child develops any changes in the appearance of the skin or growths on the skin.
• - Chickenpox:Tell your doctor if you or the child is exposed to chickenpox while using Benepali. The doctor will assess whether preventive treatment for chickenpox is appropriate.
• - Alcohol abuse:Benepali should not be used to treat hepatitis related to alcohol abuse. Tell your doctor if you or the child you are caring for 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 you are caring for has Wegener's granulomatosis, consult your doctor.
• - Anti-diabetic medicines:Tell your doctor if you or the child suffers from diabetes or is taking medicines to treat diabetes. The doctor may decide whether you or the child needs to receive less anti-diabetic medicine while taking Benepali.
• - Vaccinations:Some vaccines, such as oral polio vaccine, should not be administered during therapy 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 a body weight less than
62.5 kg.

• - Vaccinations: If possible, before using Benepali, children should be up to date with all vaccinations. Some vaccines, such as oral polio vaccine, should not be given while taking Benepali. Consult your doctor before you or the child receive any vaccine.

As a rule, Benepali should not be used in children with polyarticular or extended oligoarticular arthritis under the age of
2 years or with a body weight less than 62.5 kg, or in children with arthritis related to
enthesitis or psoriatic arthritis under the age of 12 years or with a body weight less than 62.5 kg, or in
children with psoriasis under the age of 6 years or with a body weight less than 62.5 kg.

Other medicines and Benepali
Tell your doctor or pharmacist if you or the child is taking, has recently taken or
may take any other medicine (including anakinra, abatacept or sulfasalazine).
You or the child must not useBenepali with medicines containing the active ingredients anakinra or
abatacept.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding,
ask your doctor or pharmacist for advice before taking this medicine.
Women of childbearing potential should be advised to use appropriate contraception to avoid pregnancy
during therapy with Benepali and for three weeks after the end of therapy.
Benepali should only be used in pregnancy if clearly necessary.
If you have received Benepali during pregnancy, the newborn may be at increased risk of
infection. In addition, one study has indicated that there was 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 particular type of birth defect emerged among those reported. 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.
Talk to your doctor if you wish to breastfeed while taking Benepali. It is important
to inform the child's pediatricians 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 the use of Benepali affects the ability to drive vehicles
or use machines.

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

3. How to use Benepali

Use this medicine following exactly the instructions of your doctor. If you have any doubts, ask 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 or over)
Rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis
The usual dose is 50 mg once a week by subcutaneous injection.
In any case, the doctor may establish a different frequency with which to inject Benepali.
Plaque psoriasis
The usual dose is 50 mg administered once a week.
Alternatively, a dose of 50 mg can be administered twice a week for a maximum of 12 weeks, followed by a
dose of 50 mg administered once a week.
The doctor will decide how long you should use Benepali and whether, based on your response, a new
treatment is necessary. If, after 12 weeks, Benepali has no effect on your disease, your doctor may tell you to
discontinue treatment.

Use in children and adolescents
The dose and frequency of dosage for the child or adolescent will depend on body weight and
disease. The doctor will establish the correct dose for the child and prescribe an appropriate
dosage of etanercept.
Paediatric patients with a body weight of 62.5 kg or more may receive 25 mg twice a week or 50 mg once a
week using either the pre-filled syringe or the pre-filled fixed-dose pen.
Other products containing etanercept with a dosage suitable for children are available.
For polyarthritis or extended oligoarthritis in patients starting from 2 years of age, with a body weight of
62.5 kg or more, or arthritis related to enthesitis or psoriatic arthritis in patients starting from 12 years
of age, with a body weight of 62.5 kg or more, the usual dose is 25 mg twice a week or 50 mg once a
week.
For psoriasis in patients starting from 6 years of age, with a body weight of 62.5 kg or more, the
usual dose is 50 mg and must be administered once a week. If Benepali has no effect on the child's
condition after 12 weeks, the doctor may tell you to stop treatment with this medicine.
The doctor will provide you with detailed information on how to prepare and measure the appropriate
dosage.

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 useful to write in an agenda 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 on a single occasion or
using it too frequently), speak to a doctor or pharmacist immediately. Always keep the medicine
pack with you, even if it is empty.

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

If you stop using Benepali
Following discontinuation of treatment, the symptoms of the disease may return.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
li manifestino.

Allergic reactions
If any of the following side effects occur, do not inject Benepali anymore. Inform your doctor
immediately, or go to the nearest hospital emergency room.

• - Difficulty swallowing or breathing
• - Swelling of the face, throat, hands or feet
• - Feeling of nervousness or anxiety, palpitations, sudden flushing of the skin and/or feeling of warmth
• - Severe rash, itching, hives (raised, red or pale patches of skin that often itch)

Severe allergic reactions are rare. However, any of the above symptoms may indicate
an allergic reaction to Benepali; therefore, you should 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 disorders, such as numbness or tingling, changes in vision, eye pain or onset of weakness in an arm or leg;
• - Symptoms of heart failureor worsening of 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 coughing, bluish discoloration of the nails or lips;
• - Symptoms of tumors:tumors can affect any part of the body, including skin and blood, and the possible symptoms depend on the type and location of the tumor. These symptoms may include weight loss, fever, swelling (with or without pain), persistent cough, presence of cysts or growths on the skin;
• - Symptoms of autoimmune reactions(where antibodies are created that can damage normal tissues of the body), such as pain, itching, weakness, abnormalities in breathing, thinking, sensations or vision;
• - Symptoms of lupus or lupus-like syndrome, such as changes in body weight, persistent rash, fever, pain in joints or muscles, or fatigue;
• - Symptoms of blood vessel inflammation, such as pain, fever, redness or overheating of the skin or itching.

These side effects are rare or uncommon, but are serious conditions (some of which
can rarely be fatal). If any of these symptoms occur, inform your doctor
immediately, or go to the nearest hospital emergency room.
Other side effects
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); reactions at the injection site (including bleeding, bruising, redness, itching, pain and swelling) (these are less common after the first month of treatment; some patients have developed a reaction recently used); headache.
• - Common(may affect up to 1 in 10 people)

Allergic reactions; fever; rash; 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 in various sites); worsening of congestive heart failure; low number of red blood cells, low number of white blood cells, low number of neutrophils (a type of white blood cells); reduced number of platelets in the blood; skin tumor (excluding melanoma); localized swelling of the skin (angioedema); hives (raised, red or pale patches of skin that often itch); eye inflammation; psoriasis (first appearance or worsening); inflammation of blood vessels affecting more than one organ; elevated liver enzymes in the blood (in patients also treated with methotrexate, the frequency of increased liver enzymes in the blood is common); abdominal pain and cramps, diarrhea, weight loss or blood in the stool (symptoms of bowel problems).
• - Rare(may affect up to 1 in 1,000 people) Severe allergic reactions (including severe localized swelling of the skin and difficulty breathing); lymphoma (a type of blood cancer); leukemia (a cancer that affects the blood and bone marrow); melanoma (a type of skin cancer); joint reduction in the number of platelets, red blood cells and white blood cells; changes in the nervous system (with severe muscle weakness and signs and symptoms similar to those of multiple sclerosis or inflammation of the nerves of the eye or spinal cord); tuberculosis; new onset of congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include a persistent rash, fever, joint pain and fatigue); rash that can lead to blisters and severe skin peeling; inflammation of the liver caused by your immune system (autoimmune hepatitis; in patients also treated with methotrexate, the frequency is uncommon); immune disorder that can affect the lungs, skin and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also treated with methotrexate, the frequency of inflammation or scarring of the lungs is uncommon); lichenoid reactions (itchy reddish/purple rash and/or whitish-grayish filamentous lines on mucous membranes); opportunistic infections (including tuberculosis and other infections that occur when resistance to disease is reduced); erythema multiforme (inflammatory skin rash); cutaneous vasculitis (inflammation of the skin blood vessels); nerve damage, including Guillain-Barré syndrome (a serious illness that can impair breathing and damage organs); damage to the tiny filters inside the kidneys that causes reduced kidney function (glomerulonephritis).
• - Very rare(may affect up to 1 in 10,000 people) Inability of the bone marrow to produce essential blood cells; toxic epidermal necrolysis (a potentially fatal skin disease).
• - Not known (frequency cannot be estimated based on available data) Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma (a rare form of cancer related to human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin); excessive activation of white blood cells associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a liver infection); worsening of a condition called dermatomyositis (muscle inflammation and weakness, accompanied by a rash); listeriosis (a bacterial infection).

Side effects in children and adolescents
Side effects and their frequency observed in children and adolescents are similar to those
described above.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through 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 pack and on the label of the
pre-filled pen 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 pre-filled pens in the outer packaging to protect the medicine from light.
After taking a pre-filled pen out of the refrigerator, wait approximately 30 minutes to allow
the Benepali solution in the pen to reach room temperature.Do not heat it in
any other way. Immediate use is then recommended.
Benepali can be stored at a maximum temperature of 30°C for up to 31 days, for single
use 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 note the date on which 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 inside the pen by looking through the transparent inspection window.
The solution should be from clear to slightly opalescent, colourless or pale 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 that the solution has a change in colour or appears
cloudy, or if particles other than those described are visible. If you have any doubts about the appearance
of the solution, contact your pharmacist for assistance.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Benepali contains

• The active substance is etanercept. Each pre-filled pen 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”).

Description of Benepali and contents of the pack
Benepali is supplied as an injectable solution in a pre-filled pen (injectable solution). The pen contains an injectable solution (injectable preparation) that is clear to slightly opalescent, colourless or pale yellow.
Benepali is available in packs containing 4 pre-filled pens and in multiple packs consisting
of 3 boxes containing 4 pre-filled pens 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, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Biogen Belgium NV/S.A
Tél/Tel: + 32 (0)2 808 5947

Lietuva
Biogen Lithuania UAB
Tel: +370 52 07 91 38

България
Ewopharma AG Representative Office
Тел.: + 359 249 176 81

Luxembourg/Luxemburg
Biogen Belgium NV/SA
Tél/Tel: +35 227 772 038

Česká republika
Biogen (Czech Republic) s.r.o.
Tel: + 420 228 884 152

Magyarország
Biogen Hungary Kft.
Tel.: + 36 1 848 04 64

Danmark
Biogen (Denmark) A/S
Tlf.: + 45 78 79 37 53

Malta
Pharma.MT Ltd
Tel: + 356 27 78 15 79

Deutschland
Biogen GmbH
Tel: + 49 (0)89 996 177 00

Nederland
Biogen Netherlands B.V.
Tel: + 31 (0)20 808 02 70

Eesti
Biogen Estonia OÜ
Tel: + 372 6 68 30 56

Norge
Biogen Norway AS
Tlf: + 47 21 93 95 87

Ελλάδα
Genesis Pharma S.A.
Τηλ: + 30 211 176 8555

Ö sterreich
Biogen Austria GmbH
Tel: + 43 (0)1 267 51 42

España
Biogen Spain, S.L.
Tel: + 34 91 310 7110

Polska
Biogen Poland Sp. z o.o.
Tel.: + 48 22 116 86 94

France
Biogen France SAS
Tél: + 33 (0)1 776 968 14

Portugal
Biogen Portugal Sociedade Farmacêutica,
Unipessoal, Lda
Tel: + 351 308 800 792

Hrvatska
Ewopharma d.o.o
Tel: + 385 (0)1 777 64 37

România
Ewopharma România SRL
Tel: + 40 212 601 407

Ireland
Biogen Idec (Ireland) Ltd.
Tel: +353 (0)1 513 33 33

Slovenija
Biogen Pharma d.o.o.
Tel: + 386 (0)1 888 81 07

Ísland
Icepharma hf.
Sími: + 354 800 9836

Slovenská republika
Biogen Slovakia s.r.o.
Tel: + 421 (0)2 333 257 10

Italia
Biogen Italia s.r.l.
Tel: + 39 (0)6 899 701 50

Suomi/Finland
Biogen Finland Oy
Puh/Tel: + 358 (0)9 427 041 08

Κύπρος
Genesis Pharma (Cyprus) Ltd
Τηλ: + 357 22 00 04 93

Sverige
Biogen Sweden AB
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 website of the European
Medicines Agency: http://www.ema.europa.eu .

7. Instructions for Use

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

• - Do notattempt self-injection before the doctor or nurse has explained how to do it.

A single-use pre-filled pen contains a dose of 50 mg of Benepali.
Choose a well-lit and clean work surface and keep everything you need within reach:

• A new pre-filled Benepali pen

o Do notshake the pre-filled pen.

Not included in the package:

• - 1 alcohol swab, gauze and adhesive bandage

• - Sharps container

• A. Before you begin

1. Inspect the pre-filled pen:

Check the expiration date reported on the label of the pre-filled pen.

• - Do notuse the pre-filled pen after the expiration date.
• - Do notuse the pre-filled pen if it has fallen onto a hard surface. The components inside the pre-filled pen may be broken.
• - Do notuse the pre-filled pen if the needle cap is missing or if it is not well closed.

2. Inspect the solution:

Inspect the medicine through the inspection window.
The medicine should be from clear to slightly opalescent, colorless or light yellow and may
contain small white or almost transparent protein particles.

• - Do not use the solution if it presents color changes or appears cloudy or ifparticles other than those described arevisible.

3. Wait for the medicine to reach room temperature:

Remove a pre-filled pen from the refrigerated carton and leave it at
room temperature for at least 30 minutes before performing the injection.
This is important to make the injection easier and more comfortable.

• - Do notremove the needle cap until you are ready for the injection.
• - Do notuse heat sources such as a microwave oven or boiling water to warm Benepali.

4. Choice of injection site:

The pre-filled pen of Benepali is intended for subcutaneous injection. The injection must
be administered in the thigh, abdomen, or back of the arm(see figure on the
left).

Make each new injection at a different site.
If you inject into the abdomen, choose a site at least 5 cm away from the navel.

• - Do notinject into areas that are red, hardened, bruised, or sensitive.
• - Do notinject into scars or stretch marks.
• - If you have psoriasis, do notinject into areas of swollen, thickened, red, or scaly skin or into lesioned areas.
• B. Injection steps

Step 1:

Wash your hands with soap and water.
Step 2:

Disinfect the skin at the injection site
with a swab soaked in alcohol.
See “Choice of injection site” for advice on choosing the
injection site.

• - Do nottouch this area again before administering the injection.

Step 3:

Pull off the needle cap, keeping it straight and
dispose of it in household waste or a sharps container.

• - Do nottwist or bend the needle cap when removing it, as this could damage the needle. Do not recap the needle.
• - Never recap the needle.

Step 4:

Gently stretch the skin at the cleaned injection site. Hold the pen at an
angle of approximately 90 degrees to the skin.

• - Do notpinch the skin between your fingers.
• - Stretching the skin creates a stable surface.

Step 5:

Press the pre-filled pen firmly into the injection site to begin the injection.
You will feel a click of the device when the injection starts.

Continue to hold the pre-filled pen firmly
pressed into the injection site.
You will feel a second click.

Step 6:

After the second click, slowly count to 15 to
complete the injection.

• - Do notrelease pressure on the injection site until the injection is complete.
• - Do notmove the pre-filled pen during the injection.

Step 7:

Remove the empty pen from the skin.
The special protective shield will completely cover the needle.

Check that the yellow plunger rod is visible in the
window to confirm the release of the entire dose.
Disposal:

Dispose of the empty pen in a suitable sharps container.
Ask healthcare professionals for instructions on how to properly dispose of the sharps container when
it is full. Sharps containers are available at pharmacies.

• - Do notthrow the sharps container into household waste.
• - Do notrecycle it.
• - Always keep the container out of sight and reach of children.
• C. Injection site dressing

If there is bleeding at the injection site, press gauze onto the injection site.

• - Do notrub the injection site.

If necessary, cover the injection site with a bandage.