Benepali 25 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Benepali 25 mg solution for injection in pre-filled syringe

etanercept

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

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

Leaflet contents

1. What Benepali is 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 (see reverse)

1. What Benepali is and what it is used for

Benepali contains the active substance etanercept.

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

Benepali can be used in adults aged 18 years and older for:

• the treatment of moderate to severe rheumatoid arthritis;
• psoriatic arthritis;
• severe axial spondyloarthritis, including ankylosing spondylitis;
• moderate to severe plaque psoriasis.

Usually, depending on the individual case, Benepali is used when other treatments have not been sufficiently effective or are not suitable for you.

In the treatment of rheumatoid arthritis, Benepali is usually used in combination with methotrexate, although it may also be used as a single medicine if treatment with methotrexate is not suitable for you. Benepali can slow down joint damage caused by rheumatoid arthritis and improve your ability to carry out daily activities, whether used alone or in combination with methotrexate.

In patients with psoriatic arthritis affecting multiple joints, Benepali may improve your ability to perform normal daily activities.

In patients with multiple, swollen or painful symmetric joints (for example, in the hands, wrists and feet), Benepali may delay the progression of structural damage to these joints caused by the disease.

Benepali is also indicated for treatment in children and adolescents with the following conditions:

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

• Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients from 2 years of age and weighing 62.5 kg or more.

• Psoriatic arthritis in patients from 12 years of age and weighing 62.5 kg or more.

• Enthesitis-related arthritis in patients from 12 years of age and weighing 62.5 kg or more, when other commonly used treatments have not worked adequately or are not suitable.

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

2. What you need to know before using Benepali

Do not use Benepali

• if you or the child under your care are allergic to etanercept or to any of the other components of this medicine (listed in section 6). If you or the child experience allergic reactions such as chest tightness, wheezing, dizziness, or rash, do not inject any more Benepali and contact your doctor immediately.
• if you or the child are at risk of developing a serious blood infection called sepsis. If you are unsure, consult your doctor.
• if you or the child have any type of infection. If you are unsure, consult your doctor.

Warnings and precautions

Talk to your doctor before starting to use Benepali.

• Allergic reactions: If you or the child experience allergic reactions such as chest tightness, wheezing, dizziness, or 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 major surgery, your doctor may consider monitoring or adjusting treatment with Benepali.
• Infections/diabetes: Inform your doctor if you or the child have a history of recurrent infections or if you have diabetes or other disorders that increase the risk of infection.
• Infections/monitoring: Inform your doctor about any recent travel outside the European region. If you or the child develop symptoms of infection such as fever, chills, or cough, notify your doctor immediately. Your doctor should decide whether continued monitoring for infections is needed after you or the child stop treatment with Benepali.
• Tuberculosis: Cases of tuberculosis have been reported in patients treated with Benepali. Your doctor will check for signs and symptoms of tuberculosis before starting Benepali. This may include a thorough medical history, chest X-ray, and a tuberculosis test. Completion of these assessments must be recorded on the Patient Information Card. It is very important that you tell your doctor if you or the child have had tuberculosis or have been in close contact with someone who has had tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, fatigue, low-grade fever) or any other infection appear during or after treatment, inform your doctor immediately.
• Hepatitis B: Inform your doctor if you or the child have or have had hepatitis B. Your doctor should test you for hepatitis B before starting treatment with Benepali. Treatment with Benepali may reactivate hepatitis B in patients previously infected with the hepatitis B virus. If this occurs, you must stop using Benepali.
• Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may wish to monitor treatment with Benepali in case the infection worsens.
• Blood disorders: Inform your doctor immediately if you or the child experience signs or symptoms such as persistent fever, sore throat, bruising, bleeding, or paleness. These symptoms may indicate a serious blood disorder that may require discontinuation of Benepali treatment.
• Nervous system and vision disorders: Inform your doctor if you or the child have multiple sclerosis, optic neuritis (inflammation of the optic nerves), or transverse myelitis (inflammation of the spinal cord). Your doctor will decide whether Benepali is an appropriate treatment.
• Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure, as Benepali must be used with caution in such cases.
• Cancer: Inform your doctor if you have or have had lymphoma (a type of blood cancer) or any other cancer before being given Benepali. Patients with severe rheumatoid arthritis who have had the disease for a long time may have a higher than average risk of developing lymphoma. Children and adults taking Benepali may have an increased risk of developing lymphoma or other cancers. Some adolescent and pediatric patients who have received etanercept or other medicines that work similarly to etanercept have developed cancers, including unusual types, some of which have been fatal. Some patients receiving Benepali have developed skin cancers. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
• Chickenpox (varicella): Inform your doctor if you or the child are exposed to chickenpox while using Benepali. Your doctor will determine whether preventive treatment for chickenpox is appropriate.
• Alcoholism: Benepali must not be used to treat hepatitis related to alcoholism. Please inform your doctor if you or the child under your care have a history of alcoholism.
• Granulomatosis with polyangiitis (Wegener’s granulomatosis): Benepali is not recommended for the treatment of granulomatosis with polyangiitis, a rare inflammatory disease. If you or the child under your care have granulomatosis with polyangiitis, discuss this with your doctor.
• Antidiabetic medicines: Inform your doctor if you or the child have diabetes or are taking medicines to treat diabetes. Your doctor may decide that you or the child need a lower dose of antidiabetic medicine while taking Benepali.
• Vaccines: Some vaccines, such as oral polio vaccine, must not be given while using 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 below 62.5 kg.

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

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

Using Benepali with other medicines

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

Do not use Benepali together with medicines containing the active substance anakinra or abatacept.

Pregnancy and breastfeeding

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

Women of childbearing potential should be advised to use adequate contraception to prevent pregnancy during treatment with Benepali and for 3 weeks after stopping treatment.

Benepali should only be used during pregnancy if clearly necessary.

If you have received Benepali during pregnancy, your baby may have an increased risk of infection. In addition, one study reported a higher number of birth defects when the mother had received etanercept during pregnancy compared to mothers who had not received etanercept or other similar medicines (TNF antagonists), but there was no consistent pattern in the types of birth defects reported. Another study found no increased risk of congenital malformations when the mother had received etanercept during pregnancy. Your doctor will help you decide whether the benefits of treatment outweigh the potential risks to your baby. Consult your doctor if you wish to breastfeed while being treated with Benepali. It is important to inform the pediatrician and other healthcare professionals about the use of Benepali during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and using machines

There is no information indicating that the use of Benepali affects the ability to drive or use machines.

Benepali contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 25 mg dose; this is essentially “sodium-free”.

3. How to use Benepali

Follow exactly the instructions for administering this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

If you think that the effect of Benepali is too strong or too weak, tell your doctor or pharmacist.

Use in adult patients (aged 18 years and older)

Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, including ankylosing spondylitis

The usual dose is 25 mg administered twice weekly or 50 mg once weekly, as a subcutaneous injection.

However, your doctor may determine an alternative injection frequency for Benepali.

Plaque psoriasis

The usual dose is 25 mg twice weekly or 50 mg once weekly.

Alternatively, 50 mg twice weekly may be administered for up to 12 weeks, followed by 25 mg twice weekly or 50 mg once weekly.

Your doctor will decide how long you should use Benepali and whether treatment should be repeated based on your response. If Benepali has no effect on your disease after 12 weeks, your doctor may instruct you to stop using this medicine.

Use in children and adolescents

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

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

Other etanercept medicines with doses appropriate for children are available.

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

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

Your doctor will give you precise instructions for preparing and calculating the correct dose.

Method and route of administration

Benepali is administered by subcutaneous injection (subcutaneous use).

Detailed instructions for injecting Benepali are included in section 7, "Instructions for use".

The Benepali solution must not be mixed with any other medicine.

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

If you use more Benepali than you should

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

If you forget to use Benepali

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

If you stop using Benepali

Your symptoms may return after stopping treatment.

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

4. Possible adverse effects

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

Allergic reactions

If you notice any of the following reactions, do not inject any more Benepali. Contact your doctor immediately or go to the nearest hospital Emergency Department.

• Difficulty swallowing or breathing
• Swelling of the face, throat, hands, and feet
• Feeling nervous or anxious, palpitations, sudden redness of the skin and/or sensation of warmth
• Severe rash, itching, or hives (prominent, red or pale skin welts, often accompanied by itching)

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

Serious adverse effects

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

• Signs of serious infections (including pneumonia, non-superficial skin infections, joint infections, and blood infection), such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a painful, tender, red, and warm area on the skin or joints;
• Signs of blood disorders, such as bleeding, bruising, or paleness;
• Signs of disorders of the nervous system, such as numbness or tingling, vision changes, eye pain, or sudden weakness in an arm or leg;
• Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath during activity, swelling of the ankles, feeling of fullness in the neck or abdomen, shortness of breath at night, cough, or bluish discoloration of the nails or around the lips;
• Signs of cancer: cancer can affect any part of the body, including the skin and blood, and possible signs depend on the type and location of the cancer. These may include weight loss, fever, swelling (with or without pain), persistent cough, or lumps or thickening of the skin;
• Signs of autoimmune reactions (in which antibodies develop that may damage normal body tissues), such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision;
• Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, muscle or joint pain, or fatigue;
• Signs of inflammation of blood vessels, such as pain, fever, redness or warmth of the skin, or itching.

These adverse effects are rare or uncommon, but are serious conditions (some of which, rarely, may be fatal). If any of these occur, inform your doctor immediately or go to the nearest hospital Emergency Department.

Other adverse effects

The following is a list of known adverse effects of Benepali, grouped in decreasing order of frequency:

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

Infections (including common cold, sinusitis, bronchitis, urinary tract infections, and skin infections); injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling) (these occur less frequently after the first month of treatment; some patients have developed injection site reactions at a site recently used); and headache.

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

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

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

Serious infections (including pneumonia, non-superficial skin infections, joint infections, blood infection, and systemic infections); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); low platelet count; skin cancer (excluding melanoma); localized swelling of the skin (angioedema); hives (prominent, red or pale skin welts, often accompanied by itching); eye inflammation; psoriasis (new onset or worsening); inflammation of blood vessels affecting multiple organs; increased liver enzymes in blood tests (in patients also receiving methotrexate, increased liver enzymes are common); abdominal cramps and pain, diarrhea, weight loss, or blood in the stool (signs of intestinal problems).

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

Severe allergic reactions (including severe localized swelling of the skin and wheezing); lymphoma (a type of blood cancer); leukemia (cancer affecting blood and bone marrow); melanoma (a type of skin cancer); combined low counts of red blood cells, white blood cells, and platelets; nervous system disorders (with severe muscle weakness and signs and symptoms similar to multiple sclerosis or inflammation of the optic nerves or spinal cord); tuberculosis; new-onset congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include persistent rash, fever, joint pain, and fatigue); skin rash, which may lead to severe blistering and peeling of the skin; liver inflammation caused by the immune system (autoimmune hepatitis; in patients also receiving methotrexate, frequency is uncommon); an immune disorder that may affect the lungs, skin, and lymph nodes (sarcoidosis); lung inflammation or scarring (in patients also receiving methotrexate, frequency of lung inflammation or scarring is uncommon); lichenoid reactions (pruritic reddish-purple skin rash and/or thick whitish-grey lines on mucous membranes); opportunistic infections (such as tuberculosis and other infections that occur when disease resistance is reduced); erythema multiforme (inflammatory rash); cutaneous vasculitis (inflammation of blood vessels in the skin); nerve damage, including Guillain-Barré syndrome (a serious illness that may affect breathing and damage organs); damage to the small filters in the kidneys, leading to impaired 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 life-threatening skin condition).

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

Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma (a rare cancer associated with human herpesvirus 8 infection; Kaposi's sarcoma usually presents more commonly as purplish skin lesions); 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 (inflammation and weakness of muscles accompanied by skin rash); listeriosis (a bacterial infection).

Adverse effects in children and adolescents

Adverse effects observed in children and adolescents, as well as their frequencies, are similar to those described above.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 packaging and on the label of the pre-filled syringe after “CAD/EXP”. The expiry date refers to the last day of the month indicated.

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

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

After removing the syringe from the refrigerator, wait approximately 30 minutes for the Benepali solution in the syringe to reach room temperature. Do not heat it in any other way. Immediate use is then recommended.

Benepali may be stored outside the refrigerator at a maximum temperature of 30°C for a single period of up to 31 days; after this period, the medicine must not be refrigerated again. Benepali must be discarded if it has not been used within 31 days of removal from the refrigerator. It is advisable to record the date when Benepali was removed from the refrigerator and the date by which Benepali must be discarded (no later than 31 days after removal from the refrigerator).

Inspect the solution in the syringe. It should be from transparent 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 the solution appears more yellowish or cloudy, or if it contains particles different from those described above. If you are concerned about the appearance of the solution, contact your pharmacist for any assistance you may need.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Benepali

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

Appearance of the product and contents of the pack

Benepali is presented as a pre-filled syringe containing a solution for injection that is clear to slightly opalescent, colourless or pale yellow (injectable).

Benepali is available in packs containing 4 pre-filled syringes, multiple packs containing 2 boxes with 4 pre-filled syringes each, and multiple packs containing 6 boxes with 4 pre-filled syringes each. Only certain pack sizes may be marketed.

Marketing Authorization 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

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

1. Instructions for use

Read the instructions for use before starting Benepali and each time you are prescribed it again. They may contain new information.

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

One pre-filled syringe for single use contains a 25 mg dose of Benepali.

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

• One new Benepali pre-filled syringe

• Do not shake the pre-filled syringe.

The pack does not include:

• 1 alcohol wipe, gauze, and plaster

• Sharps disposal container

1. Before you start

2. Inspect the pre-filled syringe:

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

• Do not use the pre-filled syringe after the expiry date.
• Do not use the pre-filled syringe if it has been dropped on a hard surface. The internal components may be damaged.
• Do not use the pre-filled syringe if the needle cap is missing or not firmly attached.

1. Check the solution:

Look at the medicine inside the pre-filled syringe.

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

• Do not use the solution if it appears more yellowish, cloudy, or if it contains particles different from those described above.

1. Allow the medicine to reach room temperature:

Remove one pre-filled syringe from the refrigerator and let it sit at room temperature for at least 30 minutes before injecting the solution.

This makes the injection easier and more comfortable for you.

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

1. Choose an injection site:

The Benepali pre-filled syringe is intended for subcutaneous injection. It should be injected into the thigh, abdomen, or upper back of the arm (see the image on the left).

A different site must be used for each new injection.

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

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

1. Injection steps

1. Care at the injection site

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

• Do not rub the injection site.

If necessary, you may cover the injection site with a bandage.