NepeXto 50 mg solution for injection in pre-filled pen

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Nepexto 50 mg solution for injection in a pre-filled pen

etanercept

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

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

Contents of the package leaflet

1. What Nepexto is and what it is used for
2. What you need to know before using Nepexto
3. How to use Nepexto
4. Possible side effects
5. How to store Nepexto
6. Contents of the pack and other information
7. Instructions for use

1. What Nepexto is and what it is used for

Nepexto contains the active substance etanercept.

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

Nepexto can be used in adults (from 18 years of age) for:

• Rheumatoid arthritis (an autoimmune disorder that primarily affects the joints), moderate to severe.
• Psoriatic arthritis (a type of inflammatory arthritis that can affect any joint in the body).
• Severe axial spondyloarthritis (a type of chronic inflammatory arthritis affecting the spine or sacroiliac joints), including ankylosing spondylitis (a type of arthritis that affects the spine).
• Psoriasis (raised, red, scaly skin patches), mild to moderate.

Nepexto may be used when commonly used treatments have not worked adequately, or when these treatments are not suitable.

In the treatment of rheumatoid arthritis, this medicine is usually used in combination with methotrexate, although it may also be used alone if treatment with methotrexate is not appropriate for you. Nepexto 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, this medicine can improve your ability to perform daily activities.

In patients with multiple, symmetric, swollen or painful joints (e.g., hands, wrists, and feet), this medicine may delay the progression of structural joint damage caused by the disease.

Nepexto 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 when methotrexate is not suitable:

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

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

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

• Severe psoriasis in patients from 6 years of age and weighing 62.5 kg 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 Nepexto

Do not use Nepexto

• If you or the child under your care are allergic to etanercept or to any of the other components of Nepexto (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 Nepexto and contact your doctor immediately.
• If you or the child have or are at risk of developing a serious blood infection known as 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 Nepexto.

• Allergic reactions: If you or the child experience allergic reactions such as chest tightness, wheezing, dizziness, or rash, stop using this medicine 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 need to monitor treatment with this medicine.
• 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 an 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 Nepexto.
• Tuberculosis: Cases of tuberculosis have been reported in patients treated with Nepexto. Your doctor will check for signs and symptoms of tuberculosis before starting this medicine. This may include a thorough medical history, chest X-ray, and a tuberculosis test. These assessments must be recorded in the Patient Card. It is very important to 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, lethargy, 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 previously had hepatitis B. Your doctor should test for hepatitis B before you or the child start treatment with this medicine. Treatment with Nepexto may reactivate hepatitis B in patients previously infected with the hepatitis B virus. If this occurs, you must stop using this medicine.
• Hepatitis C: Inform your doctor if you or the child have hepatitis C. Your doctor may want to monitor treatment with this medicine in case the infection worsens.
• Blood disorders: Inform your doctor immediately if you or the child have 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 treatment with Nepexto.
• 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 this medicine is an appropriate treatment.
• Congestive heart failure: Inform your doctor if you or the child have a history of congestive heart failure (the heart muscle does not pump blood properly), as this medicine should be used with caution in such cases.
• Cancer: Inform your doctor if you have or have previously had lymphoma (a type of blood cancer) or any other cancer before receiving this medicine. 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 this medicine 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, which sometimes resulted in death. Some patients receiving Nepexto have developed skin cancer. Inform your doctor if you or the child develop any changes in the appearance of the skin or skin growths.
• Chickenpox: Inform your doctor if you or the child are exposed to chickenpox while using this medicine. Your doctor will determine whether preventive treatment for chickenpox is appropriate.
• Alcoholism: Do not use this medicine to treat hepatitis related to alcoholism. Inform your doctor if you or the child under your care have a history of alcoholism.
• This medicine is not recommended for the treatment of Wegener's granulomatosis, a rare inflammatory disease. Inform your doctor if you or the child under your care have Wegener's granulomatosis.
• 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 this medicine.

Children and adolescents

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

Nepexto must not be used in children and adolescents weighing less than 62.5 kg.

Nepexto must not be used in children under 2 years of age with polyarticular or extended oligoarticular juvenile idiopathic arthritis, in children under 12 years of age with enthesitis-related arthritis or psoriatic arthritis, or in children under 6 years of age with psoriasis.

Using Nepexto 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 sulfasalazine), even those not prescribed by your doctor.

You or the child must not use Nepexto together with medicines containing the active substances anakinra or abatacept.

Pregnancy and breastfeeding

Nepexto should only be used during pregnancy if clearly necessary. Consult your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant.

If you have received Nepexto during pregnancy, your baby may have an increased risk of developing an infection. In addition, one study observed more birth defects when the mother had received etanercept during pregnancy compared to mothers who had not received this medicine or 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 Nepexto. It is important to inform the pediatrician and other healthcare professionals about the use of Nepexto during pregnancy and breastfeeding before your baby receives any vaccine.

Driving and using machines

Nepexto is not expected to affect the ability to drive or use machines.

Nepexto contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially "sodium-free".

3. How to use Nepexto

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

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

Use in adults

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

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

However, your doctor may determine an alternative dosing frequency for Nepexto.

Plaque psoriasis

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

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

Your doctor will decide how long you should use Nepexto and whether you need a repeat of the treatment based on your response. If Nepexto 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 appropriate dose and dosing frequency will depend on the child's or adolescent's body weight and condition.

Your doctor will advise you on how to prepare and measure the appropriate dose of etanercept for the child.

Nepexto should not be used in children and adolescents weighing less than 62.5 kg.

Other etanercept-containing medicines with formulations suitable for children are available.

For polyarticular or extended oligoarticular juvenile idiopathic arthritis in patients aged 2 years and older, or enthesitis-related arthritis or psoriatic arthritis in patients aged 12 years and older, the usual dose is 0.4 mg of etanercept per kg of body weight (up to a maximum of 25 mg) twice a week, or 0.8 mg of etanercept per kg of body weight (up to a maximum of 50 mg) once a week.

For psoriasis in patients aged 6 years and older, the usual dose is 0.8 mg of etanercept per kg of body weight (up to a maximum of 50 mg) once a week. If Nepexto has no effect on the child's disease after 12 weeks, your doctor may instruct you to stop using this medicine.

Method and route of administration

Nepexto is administered by subcutaneous injection.

Detailed instructions for the preparation and injection of Nepexto are provided in section 7: "Instructions for use".

The solution must not be mixed with any other medicine.

To help you remember, it may be useful to record in a diary the days of the week on which you should use Nepexto.

If you use more Nepexto than you should

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

If you forget to inject Nepexto

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 you are due to take the next dose, do not inject a double dose (two doses on the same day) to make up for the missed dose.

If you stop using Nepexto

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 experiences them.

Allergic reactions

If you notice any of the following reactions, do not inject any more Nepexto**. 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 welts on the skin, often accompanied by itching).

Severe allergic reactions are rare. However, any of the above symptoms may indicate an allergic reaction to this medicine, 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, such as high fever which may be accompanied by cough, shortness of breath, chills, weakness, or a painful, tender, red area with a sensation of warmth on the skin or joints.
• Signs of blood disorders, such as bleeding, bruising, or paleness.
• Signs of nervous system disorders, such as numbness or tingling, vision disturbances, 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, a 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 signs may include, among others, weight loss, fever, swelling (with or without pain), persistent cough, or lumps or thickening in 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 they represent serious conditions (some of which may, in rare cases, be fatal). If any of the above occur, contact your doctor immediately or go to the nearest hospital Emergency Department.

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

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

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

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

Allergic reactions; fever; 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 generalized infections); worsening of congestive heart failure; low red blood cell count, low white blood cell count, low neutrophil count (a type of white blood cell); low platelet count; skin cancer (excluding melanoma); localized swelling of the skin (angioedema); hives (prominent red or pale welts on the skin, 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); cramps and abdominal pain, diarrhea, weight loss, or blood in stools (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 (a 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 that may lead to severe blistering and peeling of the skin; lichenoid reactions (itchy red-purple skin rash and/or thick whitish-gray lines on mucous membranes); liver inflammation caused by the immune system (autoimmune hepatitis; in patients also receiving methotrexate, the frequency is uncommon); an immune disorder that may affect the lungs, skin, and lymph nodes (sarcoidosis); inflammation or scarring of the lungs (in patients also receiving methotrexate, the frequency of lung inflammation or scarring is uncommon); damage to the small filters within the kidneys, leading to impaired kidney function (glomerulonephritis).

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

Bone marrow failure to produce essential blood cells.

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

Merkel cell carcinoma (a type of skin cancer); Kaposi's sarcoma, an uncommon 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).

Other adverse effects in children and adolescents

The 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 adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: included in Annex V.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Nepexto

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

Do not use this medicine after the expiry date stated on the packaging and on the pre-filled pen after "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 pens in their outer packaging to protect them from light.

After removing the pre-filled pen from the refrigerator, wait approximately 30 minutes for the Nepexto solution in the pre-filled pen to reach room temperature. Do not heat it in any other way. Use it immediately.

Nepexto may be stored outside the refrigerator at a maximum temperature of 25 °C for a single period of up to four weeks; after this period, the medicine must not be refrigerated again. Nepexto must be discarded if not used within four weeks of being removed from the refrigerator. It is advisable to record the date on which Nepexto was removed from the refrigerator and the date by which Nepexto must be discarded (no later than four weeks after removal from the refrigerator packaging).

Inspect the solution in the pen. It should be from clear to opalescent, colourless or yellowish, and may contain small white or almost transparent protein particles. This is the normal appearance of Nepexto. Do not use the solution if it is discoloured 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.

Medicines must 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. Contents of the pack and other information

Composition of Nepexto

• The active substance is etanercept. Each pre-filled pen contains 50 mg of etanercept.
• The other components are sodium citrate, sodium dihydrogen phosphate dihydrate, glycine, sucrose, sodium chloride, and water for injection.

Presentation of the product and contents of the pack

Nepexto is presented as a pre-filled pen containing a solution that is transparent to opalescent, colourless or yellowish, for injection.

Nepexto is available in packs containing 4 or 12 pre-filled pens. Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Biosimilar Collaborations Ireland Limited
Unit 35/36
Grange Parade,
Baldoyle Industrial Estate,
Dublin 13
DUBLIN
Ireland
D13 R20R

Manufacturer responsible for batch release

Biosimilar Collaborations Ireland Limited
Block B, The Crescent Building, Santry Demesne
Dublin
D09 C6X8
Ireland

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

Date of the last review of this leaflet:

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

1. Instructions for use

Read the instructions for use before starting to use Nepexto and each time you receive a refill of your prescription. It may contain new information.

• Do not attempt to self-inject unless your doctor or nurse has shown you how to do so.

The pack does not include:

• Alcohol-impregnated wipe
• Gauze and plasters
• Sharps disposal container

Parts of the device

1. Preparation for injection

Find a clean, flat, and well-lit surface and gather all necessary items.

1. Steps for injection

1. Care of 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, cover the injection site with a plaster.

If you have any doubts or need further information, contact your doctor, nurse, or pharmacist.