Eprex 2000 IU/0.5 ml solution for injection in pre-filled syringes

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

EPREX 1,000 IU/0.5ml solution for injection in pre-filled syringe

EPREX 2,000 IU/0.5ml solution for injection in pre-filled syringe

EPREX 3,000 IU/0.3ml solution for injection in pre-filled syringe

EPREX 4,000 IU/0.4ml solution for injection in pre-filled syringe

EPREX 10,000 IU/ml solution for injection in pre-filled syringe

EPREX 40,000 IU/ml solution for injection in pre-filled syringe

(epoetin alfa)

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.
• If you have any questions, ask your doctor, nurse or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What EPREX is and what it is used for

EPREX contains the active substance epoetin alfa, a protein that stimulates the bone marrow to produce more red blood cells, which carry haemoglobin (a substance that in turn carries oxygen). Epoetin alfa is a copy of human erythropoietin and acts in the same way.

• EPREX is used to treat symptomatic anaemia due to kidney disease
  • in children on haemodialysis,
  • in adults on haemodialysis or peritoneal dialysis,
  • in adults with severe anaemia who are not yet on dialysis.

If you have kidney disease and your kidneys do not produce enough erythropoietin (needed for red blood cell formation), you may develop anaemia. EPREX is prescribed to stimulate your bone marrow to produce more red blood cells.

• EPREX is used to treat anaemia in adults who are receiving chemotherapy for solid tumours, malignant lymphoma or multiple myeloma (cancer of the bone marrow) requiring blood transfusion. EPREX may reduce the need for blood transfusions in these patients.

• EPREX is used in adults with moderate anaemia who are donating part of their blood before surgery so that it can be re-transfused during or after the operation. As EPREX stimulates red blood cell production, doctors can collect more blood from these individuals.

• EPREX is used in adults with moderate anaemia who are undergoing elective major orthopaedic surgery (e.g., knee or hip replacement surgery), to reduce the potential need for blood transfusions.

EPREX is used to treat anaemia in adults with a bone marrow disorder causing a serious disturbance in blood cell production (myelodysplastic syndromes). EPREX may reduce the need for blood transfusions.

2. What you need to know before using EPREX

Do not use EPREX

• If you are allergic to epoetin alfa or to any of the other ingredients of this medicine (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 erythropoiesis-stimulating agent (including EPREX). See section 4, Possible side effects.

• If you have uncontrolled high blood pressure that is not adequately managed with medication.

• To stimulate red blood cell production (so that your doctor can collect more of your blood) if you cannot receive transfusions of your own blood during or after surgery.

• If you are scheduled to undergo major elective orthopedic surgery (such as knee or hip replacement) and:

  • you have severe heart disease
  • you have serious problems with veins and arteries
  • you recently had a heart attack or stroke
  • you cannot take blood-thinning medications.

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 clots. If you cannot take medications that prevent blood clotting, you must not use EPREX.

Warnings and precautions

Take special care with EPREX

EPREX and other erythropoiesis-stimulating agents may increase the risk of blood clots in all patients. This risk may be higher if you have other risk factors for developing blood clots (for example, if you have previously had a blood clot, or if you are overweight, have diabetes, have heart disease, or are immobile for long periods due to surgery or illness). Please discuss this with your doctor. Your doctor will help you decide whether EPREX is appropriate for you.

It is important that you inform your doctor if any of the following apply to you. You may still be able to use EPREX, but consult your doctor first.

• If you know you have or have had:

  • high blood pressure;
  • seizures or epileptic fits
  • liver disease
  • anemia due to other causes
  • porphyria (a rare blood disorder)
  • a latex allergy. The needle cap of this medicine contains latex rubber, which may 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 failure, and especially if you do not respond adequately to treatment with EPREX, your doctor will review your EPREX dose, as repeated increases in the dose of EPREX when there is no response to treatment may increase the risk of heart or blood vessel problems and may increase the risk of heart attack, stroke, and death.

• If you are a cancer patient, you should know that erythropoiesis-stimulating agents (such as EPREX) may act as a growth factor and, in theory, could affect the progression of your cancer. Depending on your individual situation, a blood transfusion may be preferable. Discuss this with your doctor.

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

• Serious skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been observed with the administration of epoetins.

SJS/TEN may initially appear as red, target-like spots or circular red patches, often with central blisters on the trunk. Sores may also develop in the mouth, throat, nose, genitals, and eyes (eye irritation and swelling). These severe skin rashes are often preceded by fever or flu-like symptoms. The skin rash may progress to widespread skin peeling and potentially life-threatening complications.

If you develop a severe skin rash or any of these other skin symptoms, stop taking EPREX and contact your doctor or seek immediate medical attention.

Take special care with other erythropoiesis-stimulating agents:

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

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

Other medicines and EPREX

Tell your doctor if you are taking, have recently taken, or might need to take any other medicine.

If you are taking a drug called cyclosporine (used, for example, after kidney transplants), your doctor may order blood tests to monitor cyclosporine levels while you are taking EPREX.

Iron supplements and other blood stimulants may enhance the effectiveness of EPREX. Your doctor will decide whether it is appropriate for you to take them.

If you go to a hospital, clinic, or primary care physician, inform them that you are receiving treatment with EPREX. It may affect other treatments or test results.

Pregnancy and breastfeeding

It is important that you inform your doctor if any of the following apply to you. You may still be able to continue using EPREX, but discuss it with your doctor first.

• If you are pregnant or think you might be pregnant.
• If you are breastfeeding.

EPREX contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; hence, it is essentially "sodium-free".

EPREX contains polysorbate 80

This medicine contains up to 0.30 mg of polysorbate 80 per syringe, equivalent to a concentration of 0.30 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you or your child has any known allergies.

3. How to use EPREX

Follow exactly your doctor's instructions on how to take this medicine. If in doubt, consult your doctor again.

Your doctor has performed blood tests and has decided that you need EPREX.

EPREX may be administered by injection:

• Either into a vein or a tube inserted into a vein (intravenous)
• Or under the skin (subcutaneous).

Your doctor will decide how EPREX should be administered. Usually, injections are given by a doctor, nurse, or other healthcare professional. Some people, depending on why they need EPREX, may later learn to self-administer the subcutaneous injection: see Instructions for self-administering EPREX.

EPREX must not be used:

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

Your dose of EPREX is based on your body weight expressed in kilograms. The cause of your anemia is also a factor your doctor will consider when determining the correct dose.

Your doctor will monitor your blood pressure regularly while you are using EPREX.

Patients with kidney disease

• Your doctor will keep your hemoglobin levels between 10 and 12 grams/decilitre, as high hemoglobin levels may increase the risk of blood clots and death. In children, hemoglobin levels should be maintained between 9.5 and 11 grams/decilitre.
• The usual initial dose of EPREX in adults and children is 50 International Units (IU) per kilogram (/kg) body weight three times a week.
• In patients undergoing peritoneal dialysis, EPREX may be administered twice a week.
• In adults and children, EPREX is administered by 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 those not yet on dialysis.
• Your doctor will request regular blood tests to monitor your response to anemia and adjust the dose accordingly, usually no more frequently than every four weeks. An increase in hemoglobin greater than 2 grams/decilitre within a four-week period should be avoided.
• After correcting anemia, your doctor will continue to monitor your blood regularly. Further adjustments to the dose and frequency of EPREX administration may be made 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 a change in your EPREX dose is needed.
• If you are on a wider dosing interval of EPREX (less than once a week), you may not maintain adequate hemoglobin levels and may require an increase in dose or frequency of EPREX administration.
• You may receive iron supplements before and during EPREX treatment to enhance its effectiveness.
• If you are undergoing dialysis at the time of starting EPREX treatment, your dialysis regimen may need adjustment. This will be decided by your doctor.

Adults receiving chemotherapy

• Your doctor may start EPREX treatment if your hemoglobin is 10 grams/decilitre or lower.
• Your doctor will keep your hemoglobin levels between 10 and 12 grams/decilitre, as high hemoglobin levels may increase the risk of blood clots and death.
• The initial dose is either 150 IU per kilogram body weight three times a week or 450 IU per kilogram body weight once a week.
• EPREX is administered by subcutaneous injection.
• Your doctor will request blood tests and may adjust the dose depending on your anemia's response to EPREX treatment.
• You may receive iron supplements before and during EPREX treatment to enhance its effectiveness.
• EPREX treatment usually continues for one month after chemotherapy ends.

Adults donating blood for autologous transfusion

• The usual dose is 600 IU per kilogram body weight twice a week.
• EPREX is administered as an intravenous injection immediately after blood donation during the 3 weeks prior to surgery.
• You may receive iron supplements before and during EPREX treatment to enhance its effectiveness.

Patients undergoing major orthopedic surgery

• The recommended dose is 600 IU per kilogram body weight once a week.
• EPREX is administered as a subcutaneous injection each week for three weeks prior to surgery and on the day of surgery.
• If medically necessary to shorten the interval before surgery, you will receive a daily dose of 300 IU/kg for up to ten days before surgery, on the day of surgery, and for the four days immediately following surgery.
• Treatment will be stopped if blood tests indicate that hemoglobin levels are too high before surgery.
• You may receive iron supplements before and during EPREX treatment to enhance its effectiveness.

Adults with myelodysplastic syndrome

• Your doctor may start EPREX treatment if your hemoglobin is less than or equal to 10 grams/decilitre. The goal of treatment is to maintain your hemoglobin levels between 10 and 12 grams/decilitre, as higher hemoglobin levels may increase the risk of blood clots and death.
• EPREX is administered by subcutaneous injection.
• The initial dose is 450 IU per kilogram body weight once a week.
• Your doctor will request blood tests and may adjust the dose depending on your anemia's response to EPREX treatment.

Instructions for self-injection of EPREX

When treatment begins, EPREX is usually administered by medical or nursing staff. Later, your doctor may suggest that you or a caregiver learn to inject EPREX under the skin (subcutaneously).

• Do not attempt to inject the medicine yourself unless trained by a doctor or nurse.
• 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.
• Before use, allow the EPREX syringe to reach room temperature. This usually takes 15–30 minutes.

Draw only one dose of EPREX from each syringe.

When EPREX is injected under the skin (subcutaneous injection), the amount administered per injection is usually no more than one millilitre (1 ml).

EPREX is administered alone and must not be mixed with other injectable liquids.

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

How to self-inject subcutaneously using a pre-filled syringe:

Pre-filled syringes are equipped with a PROTECS™ needle protection device to help prevent needlestick injuries after use. This is indicated on the box.

• Remove one syringe from the refrigerator. Allow the liquid to reach room temperature. Do not remove the needle cap from the syringe while it is warming.
• Check the syringe to ensure the dose is correct, the expiry date has not passed, the syringe is undamaged, and the liquid is clear and has not been frozen.
• Remove the peel-off part of the syringe label. If you cannot see the graduation marks through the viewing window, hold the syringe body and gently rotate the syringe by the needle cap to align the graduation marks with the viewing window.
• Choose the injection site. Suitable sites are the upper thigh and the area around the abdomen (stomach), but away from the navel. Change the site daily.
• Wash your hands. Apply an antiseptic swab to the injection site to disinfect it.
• Hold the pre-filled syringe by the body with the covered needle pointing upward.
• Do not hold it by the plunger head, plunger, needle shield wings, or needle cap.
• Do not pull the plunger at any time.
• Do not remove the needle cap from the pre-filled syringe until you are ready to inject EPREX.
• Remove the cap from the syringe by holding the body and carefully pulling off the needle cap without twisting. Do not touch the needle or shake the syringe.
• Remove the air bubble by holding the syringe with the needle pointing upward and gently pressing the plunger until a drop of liquid appears at the needle tip.
• If you need only a partial dose from the syringe as instructed by your doctor, press the plunger to the desired numbered graduation mark to expel the unused liquid before injection.
• Do not touch the wings of the needle shield to prevent premature covering of the needle by the needle shield.
• Pinch a fold of skin between your thumb and index finger. Do not squeeze tightly.
• Insert the entire needle. Your doctor or nurse will have shown you how to do this.
• Push the plunger with your thumb all the way to inject the full amount of liquid. Do this slowly and steadily, keeping the skin fold pinched. The PROTECS™ needle shield will not activate unless the full dose is administered. You should hear a click when the PROTECS™ needle shield has activated.
• After fully depressing the plunger, withdraw the needle and release the skin fold.
• Slowly remove your thumb from the plunger to allow the syringe to move until the entire needle is covered by the PROTECS™ needle shield.
• After removing the needle from your skin, there may be slight bleeding at the injection site. This is normal. You may press the injection site for several seconds with an antiseptic swab after the injection.
• Dispose of the used syringe in 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 think you have injected too much EPREX. Adverse effects due to an overdose of EPREX are unlikely.

If you forget to use EPREX

Take the next injection as soon as possible. If less than 24 hours remain until the next scheduled injection, skip the missed dose and continue with your regular schedule. Do not double the dose to make up for a missed injection.

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

You should consult your doctor, as the combination of epoetin alfa with interferon and ribavirin has led to rare cases of loss of efficacy and the development of a disorder 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 further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Tell your doctor or nurse immediately if you notice any of the effects listed below.

Severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been observed with epoetins. These reactions may appear as macules or red circular rash-like patches, often 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 immediate medical attention. See also section 2.

Very common adverse effects

These may affect more than 1 in 10 people

• Diarrhea
• Stomach discomfort
• Vomiting
• Fever
• Respiratory tract congestion, such as stuffy nose and sore throat, has been reported in patients with kidney disease not yet on dialysis.

Common adverse effects

These may affect up to 1 in 10 people

• Increased blood pressure. Headaches, especially if they are migraine-type, sharp, and sudden, confusion or seizures may be signs of a sudden rise in 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. Symptoms may include chest pain, difficulty breathing, and painful swelling and redness, usually in one leg.
• Cough
• Skin rashes, which may be signs of an allergic reaction.
• Bone or muscle pain
• Flu-like symptoms, such as headache, joint pain and aching, weakness, chills, fatigue, and dizziness. These may be more common at the beginning of treatment. If you experience these symptoms during intravenous injection, a slower injection rate 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

Uncommon adverse effects

These may affect up to 1 in 100 people

• High levels of potassium in the blood, which may cause heart rhythm abnormalities (this is a very common adverse effect in patients undergoing dialysis).
• Seizures
• Nasal or respiratory tract congestion
• Allergic reaction
• Hives

Rare adverse 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 can lead to sudden and severe anemia. Symptoms include:

• Unusual tiredness,
• Dizziness,
• Shortness of breath.

Very rare cases of PRCA have been reported, mainly in patients with kidney disease after several months or years of treatment with EPREX and other erythropoiesis-stimulating agents.

• An increase in the number of small blood cells (called platelets) that normally participate in blood clotting may occur, especially when treatment is started. Your doctor will monitor this.

• Severe allergic reactions that may include:

  • Swelling of the face, lips, mouth, tongue, or throat
  • Difficulty swallowing or breathing
  • Itchy rash (hives)

• A blood disorder that may cause pain, dark-colored urine, or increased skin sensitivity to sunlight (porphyria).

If you are receiving hemodialysis:

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

• Blood clots may also form in your hemodialysis system. Your doctor may decide to increase your heparin dose during dialysis.

If you experience any of these effects or notice any other effects while being treated with EPREX, inform your doctor or nurse immediately.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of EPREX

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

Do not use this medicine after the expiry date stated on the label and the carton, following the letters EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C). You may remove EPREX from the refrigerator and keep it at room temperature (up to 25 °C) for up to 3 days. Once the syringe has been removed from the refrigerator and has reached room temperature (up to 25 °C), it must be used within the following 3 days; otherwise, it must be discarded.

Do not freeze or shake.

Keep in the original packaging to protect from light.

Do not use this medicine if you notice that the seal is broken or if the liquid shows discoloration or particles in suspension. If you observe any of these, discard the medicine.

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 EPREX:

The active substance is: epoetin alfa (see amounts in the table).

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

Appearance of EPREX and pack contents

EPREX is presented as a solution for injection in a pre-filled syringe. The pre-filled syringes are equipped with a PROTECS™ needle protection device (see table below). EPREX is a clear, colourless solution.

Presentation	Equivalent presentations in quantity/volume for each concentration	Amount of epoetin alfa
Package containing 6 pre-filled syringes with a needle protection device PROTECS™	1,000 IU/0.5 milliliters 2,000 IU/0.5 milliliters 3,000 IU/0.3 milliliters 4,000 IU/0.4 milliliters 5,000 IU/0.5 milliliters 6,000 IU/0.6 milliliters 8,000 IU/0.8 milliliters 10,000 IU/1 milliliter	8.4 micrograms 16.8 micrograms 25.2 micrograms 33.6 micrograms 42.0 micrograms 50.4 micrograms 67.2 micrograms 84.0 micrograms
Package containing 1 pre-filled syringe with a needle protection device PROTECS™	20,000 IU/0.5 milliliter 30,000 IU/0.75 milliliter 40,000 IU/1 milliliter	168 micrograms 252 micrograms 336 micrograms
Package containing 4 pre-filled syringes with a needle protection device PROTECS™	20,000 IU/0.5 milliliter 30,000 IU/0.75 milliliter 40,000 IU/1 milliliter	168 micrograms 252 micrograms 336 micrograms
Package containing 6 pre-filled syringes with a needle protection device PROTECS™	20,000 IU/0.5 milliliter 30,000 IU/0.75 milliliter 40,000 IU/1 milliliter	168 micrograms 252 micrograms 336 micrograms

Some pack sizes may not be marketed.

Marketing Authorization Holder:

Janssen-Cilag, S.A.

Paseo del Club Deportivo 1, Edificio 16

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer:

Janssen Biologics BV

Einsteinweg 101

2333 CB

Leiden

The Netherlands

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

Austria: ERYPO®

Belgium: EPREX®

Germany: ERYPO®

Greece: EPREX®

France: EPREX®

Italy: EPREX®

Luxembourg: EPREX®

The Netherlands: EPREX®

Portugal: EPREX®

Spain: EPREX®

United Kingdom (Northern Ireland): EPREX®

This leaflet was approved in: January 2025.

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).