Package Leaflet: Information for the User

EPREX 1,000 UI/0.5ml injectable solution in pre-filled syringe

EPREX 2,000 UI/0.5ml injectable solution in pre-filled syringe

EPREX 3,000 UI/0.3ml injectable solution in pre-filled syringe

EPREX 4,000 UI/0.4ml injectable solution in pre-filled syringe

EPREX 10,000 UI/ml injectable solution in pre-filled syringe

EPREX 40,000 UI/ml injectable solution in pre-filled syringe

(epoetin alfa)

Read 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.
• If you have any questions, ask your doctor, nurse or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have similar symptoms. It may harm them.
• If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, pharmacist or nurse. See section 4.

1.What EPREX is and what it is used for

2.What you need to know before you start using EPREX

3.How to use EPREX

4.Possible side effects

5.Storage of EPREX

6.Contents of the pack and additional information

EPREX contains the active ingredient epoetina alfa, a protein that stimulates the bone marrow to produce more red blood cells, which transport hemoglobin (a substance that in turn transports oxygen).Epoetina alfa is a copy of human erythropoietin and acts in the same way.

• EPREX is used to treat symptomatic anemia due to kidney disease
• • in children undergoing hemodialysis,
  • in adults undergoing hemodialysis or peritoneal dialysis,
  • in adults with severe anemia not yet undergoing dialysis.

If you have kidney disease and your kidney does not produce enougherythropoietin(necessary for the formation of red blood cells) you may have anemia.EPREX is prescribed to stimulate your bone marrow to produce more red blood cells.

• EPREX is used to treat anemia in adults receiving chemotherapy for solid tumors, malignant lymphoma or multiple myeloma (bone marrow cancer) that requires a blood transfusion.EPREX may reduce the need for blood transfusions in these patients.

• EPREX is used in adults with moderate anemia who donate part of their blood before a surgical procedureso that they can be re-transfused during the operation or after it.As EPREX stimulates the production of red blood cells, doctors can extract more blood from these individuals.

• EPREX is used in adults with moderate anemia who are about to undergo major elective orthopedic surgery(for example, knee or hip replacement operations),to reduce the possible need for blood transfusions.

EPREX is used to treat anemia in adults with a bone marrow disorder that causes a severe alteration in the creation of blood cells (myelodysplastic syndromes).EPREX may reduce the need for blood transfusions.

No use EPREX

• If you are allergicto epoetina alfa or to any of the other components ofthis medication(listed in section 6).

• If you have been diagnosed with Pure Red Cell Aplasia(the bone marrow cannot produce enough red blood cells) after previous treatment with any product that stimulates red blood cell production, (including EPREX).See section 4,Possible side effects.

• If you have high blood pressureand it is not adequately controlled with medication.

• To stimulate red blood cell production (so that your doctor can take more blood)if you cannot receive blood transfusions from your own bloodduring surgery or after it.

• If you are planning to undergo major elective orthopedic surgery(such as a knee or hip replacement) and:
• you have severe heart disease

• you have severe vein and artery problems
• you have recently had a heart attack or stroke
• you cannot take medications to thin the blood.

EPREX may not be suitable for you.Consult your doctor.While receiving EPREX, some people need to take medications to reduce the risk of blood clotting.If you cannot take medications that prevent blood clotting, do not use EPREX.

Warnings and precautions

Be especially careful with EPREX

EPREX and other products that stimulate red blood cell production may increase the risk of blood clots in all patients.This risk may be higher if you have other risk factorsfor blood clots (for example, if you have had a blood clot in the past or if you are overweight, if you have diabetes, if you have heart disease, or if you have been bedridden for a long time due to an operation or illness).Please discuss this with your doctor. Your doctor will help you decide if EPREX is suitable for you.

It is essential that you inform your doctorif you experience any of the following circumstances.You may still be able to use EPREX, but please consult your doctor first.

• If you know that you haveor have had:

• high blood pressure;;
• seizuresor epilepsy
• liver disease
• anemia due to other causes
• porphyria (a rare blood disorder)
• latex allergy. The cap of the needle of this medication contains latex, which can cause severe allergic reactions in people sensitive to latex. See section 4 for signs of an allergic reaction.

• If you are a patient with chronic kidney disease, and especially if you do not respond adequately to EPREX treatment, your doctor will review your EPREX dose as repeated increases in the EPREX dose when not responding to treatment may increase the risk of heart problems or vascular problems and may increase the risk of myocardial infarction, stroke, and death.

• If you are a cancer patient, you should know that products that stimulate red blood cell production (such as EPREX) may act as a growth factor and, in theory, could affect the progression of your cancer.Depending on your individual situation, it may be preferable to have a blood transfusion.Consult this with your doctor.

• If you are a cancer patient, you should know that the use of EPREX may be associated with lower survival rates and higher mortality rates in patients with head and neck cancer, metastatic breast cancer, who receive chemotherapy.

• Severe skin reactionssuch as Stevens-Johnson syndrome (SSJ) and toxic epidermal necrolysis (TEN) have been observed with the administration of epoetins.

SSJ/TEN may initially appear as circular, red, scaly patches on the trunk, often with central blisters. They may also appear on the mouth, throat, nose, genitals, and eyes (eye irritation and swelling). These severe skin reactions are often preceded by fever or flu-like symptoms. The skin reaction may progress to widespread skin peeling and potentially life-threatening complications.

If you experience a severe skin reaction or any of these other skin symptoms, stop taking EPREX and seek medical attention immediately.

Be especially careful with other products that stimulate red blood cell production:

EPREX belongs to a group of products that stimulate red blood cell production like human erythropoietin.Your doctor will always record the exact name of the product you are using.

If during your treatment you are given a product from this group other than EPREX, inform your doctor or pharmacist before using it.

Other medications and EPREX

Inform your doctor if you are taking, have taken recently, or may need to take any other medication.

If you are taking a medication called ciclosporin(which is used, for example, after kidney transplants), your doctor may ask you to have blood tests to determine ciclosporin levels while taking EPREX.

Iron supplements and other blood stimulantsmay increase the effectiveness of EPREX.Your doctor will decide if it is suitable for you to take them.

If you visit a hospital, clinic, or primary care doctor, inform them that you are receiving EPREX treatment.This may affect other treatments or the results of some tests.

Pregnancy and breastfeeding

It is essential that you inform your doctorif any of the following apply to you. You will probably be able to continue using EPREX, but please discuss this with your doctor first.

• If you are pregnant, or think you may be.
• If you are breastfeeding.

EPREX contains sodium

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

EPREX contains polisorbate 80

This medication contains a maximum of 0.30 mg of polisorbate 80 in each syringe, equivalent to a concentration of 0.30 mg/ml. Polisorbates can cause allergic reactions. Inform your doctor if you or your child has any known allergy.

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

Your doctor has performed blood testsand has decided that you need EPREX.

EPREX can be administered by injection:

• Eitherin a vein or a tube inserted into a vein (intravenous)
• Orunder the skin (subcutaneous).

Your doctor will decide how to administer EPREX.Usually, injections will be given by a doctor, nurse, or other healthcare professional.Some people, depending on the reason they need EPREX, may later learn to give themselves the injection under the skin:seeEPREX Self-Administration Instructions.

EPREX should not be used:

• after the expiration date on the label and the outer packaging
• if you know or suspect it has been accidentally frozen, or
• if the refrigerator has malfunctioned.

The dose of EPREX you will receive is based on your body weight expressed in kilograms.The cause of your anemia is also a factor that your doctor will take into account when deciding on the correct dose.

Your doctor will monitor your blood pressureregularly while using EPREX.

People with kidney disease

• Your doctor will keep your hemoglobin levels between 10 and 12 grams per deciliter since high levels of hemoglobin can increase the risk of blood clots and death. In children, hemoglobin levels should be maintained between 9.5 and 11 grams per deciliter.
• The usual initial doseof EPREX in adults and children is 50 International Units (UI) per kilogram (kg) of body weight three times a week.
• In patients undergoing peritoneal dialysis, EPREX can be administered twice a week.
• In adults and children, EPREX is administered as an injection into a vein or a tube inserted into a vein. When this access (vein or tube) is not readily available, your doctor may decide that EPREX should be injected under the skin (subcutaneous injection). This also applies to patients on dialysis and patients who are not yet on dialysis.
• Your doctor will request regular blood tests to monitor your anemia response and adjust the dose, usually not more than every four weeks.Avoid an increase in hemoglobin of more than 2 grams per deciliter in a four-week period.
• After correcting your anemia, your doctor will continue to monitor your blood regularly. It may be necessary to make new adjustments to the dose and frequency of EPREX administration to maintain your response to treatment.Your doctor will use the lowest effective dose to control your anemia symptoms.
• If you do not respond adequately to EPREX, your doctor will review your dose and inform you if it is necessary to change your EPREX doses.
• If you follow a wider dosing interval of EPREX (more than once a week), you may not maintain adequate hemoglobin levels and may need to increase the dose or frequency of EPREX administration.
• It is possible that you will receive iron supplements before and during EPREX treatment to make it more effective.
• If you are receiving dialysis at the time of starting EPREX treatment, it may be necessary to adjust your dialysis regimen.This will be decided by your doctor.

Adults receiving chemotherapy

• Su médico puede iniciar el tratamiento con EPREX si su hemoglobina es 10 gramos/ decilitro o menor.
• Su médico mantendrá sus niveles de hemoglobina entre 10 y 12 gramos/decilitro ya que los niveles altos de hemoglobina pueden aumentar el riesgo de coágulos de sangre y muerte.
• La dosis inicial es detanto150UI por kilogramo de peso corporal tres veces a la semanacomode 450 UI por kilogramo de peso corporal una vez a la semana.
• EPREX se administra mediante inyección subcutánea.
• Su médico solicitará análisis de sangre y puede ajustar la dosis, dependiendo de la respuesta de su anemia al tratamiento con EPREX.
• Cabe la posibilidad de que reciba suplementos de hierro antes y durante el tratamiento con EPREX para que sea más eficaz.
• Normalmente continuará el tratamiento con EPREX durante un mes después de que termine la quimioterapia.

Adultos que donan sangre para autotrasfusión

• Ladosis habituales de 600 UI por kilogramo de peso corporal dos veces a la semana.
• EPREX se administra como inyección intravenosa inmediatamente después de que haya donado sangre durante las 3 semanas previas a la intervención quirúrgica.
• Cabe la posibilidad de que reciba suplementos de hierro antes y durante el tratamiento con EPREX para que sea más eficaz.

Pacientes que van a someterse a una cirugía ortopédica mayor

• Ladosis recomendadaes de 600 UI por kilogramo de peso corporal una vez a la semana.
• EPREX se administra como inyección subcutánea cada semana durante las tres semanas previas a la intervención quirúrgica y el día de la operación.
• Si por motivos médicos es necesario reducir el intervalo hasta la operación, recibirá una dosis diaria de 300 UI/kg durante un periodo de hasta diez días antes de la intervención, el día de la operación y en los cuatro días inmediatamente posteriores.
• El tratamiento se interrumpirá si los análisis de sangre indican que los valores de hemoglobina son demasiado elevados antes de la operación.
• Cabe la posibilidad de que reciba suplementos de hierro antes y durante el tratamiento con EPREX para que sea más eficaz.

Adultos con síndrome mielodisplásico

• Su médico puede iniciar el tratamiento con EPREX si su hemoglobina es menor o igual a 10 gramos/ decilitro. El objetivo del tratamiento es mantener sus niveles de hemoglobina entre 10 y 12 gramos/decilitro ya que niveles más altos de hemoglobina pueden aumentar el riesgo de coágulos de sangre y muerte.
• EPREX se administra como inyección subcutánea.
• La dosisinicial es de450 UI por kilogramo de peso corporal una vez a la semana.
• Su médico solicitará análisis de sangre y puede ajustar la dosis, dependiendo de la respuesta de su anemia al tratamiento con EPREX.

Instrucciones para la autoinyección de EPREX

Cuando comienza el tratamiento, EPREX suele ser administrado por personal médico o de enfermería.Más tarde, su médico puede sugerir que usted o un cuidador aprendan a inyectar EPREX bajo la piel (por vía subcutánea).

• Do not attempt to inject the medication unless a doctor or nurse has taught you.
• Always use EPREX exactly as instructed by your doctor or nurse.
• Use EPREX only if it has been stored correctly – See section 5,Storage of EPREX.
• Wait for the EPREX syringe to reach room temperature before use.This usually takes 15‑30 minutes.

Extract only one dose of EPREX from each syringe.

When injecting EPREX under the skin (subcutaneous injection), the amount administered in each injection is usually not more than one milliliter (1 ml).

EPREX is administered alone and not mixed with other injection liquids.

Do not shake the EPREX syringes.The vigorous shaking may damage the product.Do not use the product if it has been vigorously shaken.

How to self-administer EPREX subcutaneously using a pre-filled syringe:

The pre-filled syringes have a needle protection devicePROTECS™that helps prevent needlestick injuries. This is indicated on the box.

• Remove a syringe from the refrigerator.The liquid must reach room temperature.Do not remove the needle cap from the syringe while it reaches room temperature.
• Check the syringe,to ensure that the dose is correct, has not expired, is not damaged, and the liquid is transparent and has not frozen.
• Remove the detachable label from the syringe. If you cannot see the graduation marks through the viewfinder, hold the syringe body and rotate the syringe by the needle cap to align the graduation marks with the viewfinder.
• Choose the injection site.The most suitable places are the upper thigh and around the abdomen (stomach) but away from the navel.Change the injection site from day to day.
• Wash your hands.Apply an antiseptic swab to the injection siteto disinfect it.
• Hold the pre-filled syringe by the syringe body with the needle cap covered pointing upwards.
• Do not hold it by the plunger, the plunger, the wings of the needle protector or the needle cap.
• Do not pull the plunger at any time
• Do not remove the needle cap from the syringe until you are ready to inject EPREX.
• Remove the needle capholding the syringe body and pulling the needle cap carefully, without rotating it.Do not touch the needle or shake the syringe.
• Remove the air bubble by holding the syringe with the needle pointing upwards and gently pressing the plunger until a drop of liquid comes out of the needle tip.
• If you only need a partial dose of the syringe as indicated by your doctor, press the plunger to the desired graduation mark to remove the liquid you do not need before injection.
• Do not touch the wings of the needle protector to avoid the needle being prematurely covered by the needle protector.
• Hold a fold of skinbetween your thumb and index finger.Do not pinch it.
• Insert the entire needle.Your doctor or nurse will have taught you how to do it.
• Push the plunger with your thumb until the end to inject the total amount of liquid.Do it slowly and uniformly, keeping the skin fold pinched.The needle protectorPROTECS™will not activate unless the entire dose is administered. You should hear aclickwhen the needle protector PROTECS™has been activated.
• When you have pressed the plunger to the top,remove the needle and release the skin fold.
• Slowly remove your thumb from the plungerto allow the syringe to move until the entire needle is covered by the needle protectorPROTECS™.
• When you remove the needle from your skin, you may experience some bleeding at the injection site. This is normal. You can pressthe injection site with an antiseptic swabfor several secondsafter injection.
• Dispose of the used syringein a safe container; see section 5,Storage of EPREX.

If you use more EPREX than you should

Inform your doctor or nurse immediately if you consider that you have injected an excessive amount of EPREX.It is unlikely that you will experience adverse effects as a result of an EPREX overdose.

If you forgot to use EPREX

Get the next injection as soon as possible.If there are less than 24 hours until the next injection, forget the one you missed and continue with your regular schedule.Do not duplicate injectionsto compensate for the missed doses.

If you are a patient with Hepatitis C and receive interferon and ribavirin

You should consult with your doctor since the combination of epoetina alfa with interferon and ribavirin has led to rare cases of loss of efficacy and the development of a condition called pure red cell aplasia (PRCA), a severe form of anemia. EPREX is not authorized for the management of anemia associated with hepatitis C.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines,this medicinecan cause side effects, although not everyone will experience them.

Inform your doctor or nurse immediatelyif you detect any of the side effects listed in this list.

Severe skin eruptions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been observed with the administration of epoetins. These reactions can appear as red, circular patches or spots with central blisters on the trunk, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms. Stop using EPREX if you experience these symptoms and contact your doctor or seek medical attention immediately. See section 2.

Very common side effects

These may affect more than 1 in 10 people

• Diarrhea
• Stomach discomfort
• Vomiting
• Fever
• Notified cases ofrespiratory tract congestion, such as stuffy nose and sore throat, have been reported in patients with kidney disease who have not yet undergone dialysis.

Common side effects

These may affect up to 1 in 10 people

• Increased blood pressure.Headachesespecially if they are migrainous, stabbing, and sudden,confusion or convulsionsmay be signs of a sudden increasein blood pressure. This requires urgent treatment.High blood pressure may require treatment with medication (or adjustment of some medications you are already taking for hypertension).
• Blood clots(including deep vein thrombosis and embolism) that may require urgent treatment. The symptoms you may experience arechest pain, difficulty breathing, and painful and inflamed swelling, usuallyof a leg.
• Cough
• Skin eruptions,which may be manifestations of an allergic reaction.
• Pain in bones or muscles
• Flu-like symptoms, such as headache, pinpricks, and joint pain, weakness, chills, fatigue, and dizziness. They may be more frequent at the beginning of treatment. If you experience these symptoms during intravenous injection, a slower administration of the injection may help prevent them.
• Redness, burning, and pain at the injection site
• Swelling of the ankles, feet, or fingers
• Pain in the arm or leg

Rare side effects

These may affect up to 1 in 100 people

• High levels of potassium in the bloodthat may cause heart rhythm abnormalities (this is a very common side effect in patients undergoing dialysis).
• Seizures
• Respiratory congestion or nasal congestion
• Allergic reaction
• Itching

Very rare side effects

These may affect up to 1 in 1,000 people

• Symptoms of pure red cell aplasia (PRCA).

PRCA is the inability to produce enough red blood cells in the bone marrow. PRCA may cause asevere and sudden anemia.The symptoms are:

Notified cases of PRCA have mainly been reported in patients with kidney disease after months or years of treatment with EPREX and other products that stimulate red blood cell production.

• A possible increase in the number of small blood cells (calledplatelets) that normally participate in the formation of blood clots, especially when treatment is initiated.Your doctor will check this.

• Severe allergic reactions that may include:
• • Swollen face, lips, mouth, tongue, or throat
  • Difficulty swallowing or breathing
  • Itching with a rash(itching)

• Blood disorderthat may cause pain, dark urine, or increased skin sensitivity to sunlight (porphyria).

If you are receiving hemodialysis:

• Blood clots(thrombosis)may form in the dialysis fistula(shunt).Thisis more frequent if you have low blood pressure or if your fistula has complications.

• Blood clots(thrombosis)may also form in your dialysis system.Your doctor may decide to increaseyour heparin dose during dialysis.

If you experience any of these side effects or if you notice any other side effect while taking EPREX,inform your doctor or nurse immediately.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and in the box after the letters CAD.The expiration date is the last day of the month indicated.

Store in refrigerator (between 2 °C and 8 °C). You can remove EPREX from the refrigerator and keep it at room temperature (up to 25ºC) for 3 days. Once the syringe has been removed from the refrigerator and has reached room temperature (up to 25ºC) it must be used within the 3 days that follow or it must be discarded.

Do not freeze or shake.

Store in the original container to protect it from light.

Do not use this medication if you observe that the seal is broken or if the liquid presents discoloration or particles in suspension can be observed. If you observe any of these things, discard the medication.

Medications should not be disposed of through drains or in the trash.Ask your pharmacist how to dispose of the containers and medications that you no longer need.By doing so, you will help protect the environment.

Composition of EPREX:

The active ingredient is:epoetin alfa (see quantities in the table).

The other components are:polysorbate 80 (E 433), sodium chloride,dihydrogen phosphate monobasic dihydrate, sodium phosphate dibasic dihydrate, glycine, and water for injection.

Appearance of EPREX and contents of the package

EPREX is presented as a pre-filled syringe solution. The pre-filled syringes are equipped with a needle protection device PROTECS™(see table below). EPREX is a transparent and colorless solution.

Only some package sizes may be commercially available.

Marketing Authorization Holder:

Janssen-Cilag, S.A.

Paseo de las Doce Estrellas, 5-7

28042 - Madrid

Responsible for manufacturing:

Janssen Biologics BV

Einsteinweg 101

2333 CB

Leiden

Netherlands

This medicinal product is authorized in the Member States of the EEA and in the United Kingdom (Northern Ireland) under the following names:

Austria:ERYPO?

Belgium:EPREX?

Germany:ERYPO?

Greece:EPREX?

France:EPREX?

Italy:EPREX?

Luxembourg:EPREX?

Netherlands:EPREX?

Portugal:EPREX?

Spain:EPREX?

United Kingdom (Northern Ireland):EPREX?

This leaflet was approved in:January 2025.

Further information is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).