Eprex

Package leaflet: Information for the user

EPREX 2,000 IU/ml, 4,000 IU/ml, 10,000 IU/ml and 40,000 IU/ml

INJECTABLE SOLUTION IN PRE-FILLED SYRINGES
(epoetin alfa)
Please read this leaflet carefully before using this medicine because it contains important
information for you.

• Keep this leaflet. 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 give it to others, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, nurse or pharmacist. See section 4.

Contents of this leaflet
1. What EPREX is and what it is used for
2. What you need to know before using 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 capable of transporting oxygen). Epoetin alfa is a copy of human erythropoietin and acts in the same way.

• EPREX is used to treat symptomatic anaemia caused by renal failure.
  • in children on haemodialysis
  • in adults on haemodialysis or peritoneal dialysis
  • in adults with severe anaemia not yet undergoing dialysis.

If you suffer from renal failure and your kidneys do not produce enough erythropoietin (necessary for red blood cell production), you may have a low number of circulating red blood cells. EPREX is prescribed to stimulate the bone marrow to produce more red blood cells.

• EPREX is used to treat anaemia in adults undergoing chemotherapy for solid tumours, malignant lymphoma or multiple myeloma (a tumour of bone marrow cells), conditions that may require blood transfusions. EPREX may reduce the need for transfusions in these patients.
• EPREX is used to treat moderately anaemic adults who are eligible to donate their own blood prior to surgery, so that it can be re-transfused to them during or after the operation. Since EPREX stimulates red blood cell production, a larger amount of blood can be collected from these individuals.
• EPREX is used to treat moderately anaemic adults who are to undergo major orthopaedic surgery (e.g. hip or knee prosthesis), to reduce the need for potential blood transfusions.
• EPREX is used to treat anaemia in adults with a bone marrow disorder causing severe impairment 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 excipients of this medicine (listed in section 6);
• If you have been diagnosed with Pure Red Cell Aplasia (the bone marrow fails to produce enough red blood cells) after previous treatment with any substance able to stimulate red blood cell production (including EPREX). See section 4, Possible side effects.
• If you have uncontrolled high blood pressure not managed by medications.
• To stimulate red blood cell production (so that more of your blood can be collected) if you cannot receive transfusions of your own blood during or after surgery.
• If you are scheduled for elective major orthopedic surgery (e.g., hip or knee replacement) and you:
  • have severe heart disease
  • have serious problems affecting veins and arteries
  • have recently had a heart attack or stroke
  • cannot take blood-thinning medications.

EPREX may not be suitable for you. Discuss this with your doctor. During treatment with EPREX,
some people may require medications to reduce the risk of blood clots. If you cannot take
anticoagulant medicines, you must not take EPREX.
Warnings and precautions
Take special care with EPREX
EPREX and other agents that stimulate red blood cell production may increase the risk of
developing blood clots in all patients. This risk may be higher if you also have other risk factors
for blood clots (for example, if you have had a blood clot in the past, are overweight, have diabetes,
heart disease, or have been immobilized for a long time due to surgery or illness). Inform your doctor
if you have any of these conditions. Your doctor will determine whether EPREX is suitable for you.
It is important that you speak with your doctor if any of the following apply to you.
You may still use EPREX, but you should discuss it with your doctor first.

• If you know or have had:
  • high blood pressure (arterial hypertension);
  • seizures or convulsions;
  • liver disease;
  • anemia due to other causes;
  • porphyria (a rare blood disorder);
  • an allergy to latex. The protective cap of the needle in this medicine contains rubber latex, which may cause severe allergic reactions in latex-sensitive individuals. 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 EPREX, your doctor will monitor the dose of EPREX you are taking, because repeatedly increasing the dose when you do not respond to treatment may increase the risk of heart or blood vessel problems, and may increase the risk of myocardial infarction, stroke, and death.
• If you have cancer, you should know that substances that stimulate red blood cell production (such as EPREX) may act as growth factors and could theoretically influence tumor progression. Depending on your individual condition, a blood transfusion may be preferable. Discuss this with your doctor.
• If you have cancer, you should know that the use of EPREX has been associated with shorter survival and higher mortality rates in patients with head/neck cancer and metastatic breast cancer who are receiving chemotherapy.
• Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with epoetin treatment. Stevens-Johnson syndrome and toxic epidermal necrolysis may initially appear as red, target-like spots or circular patches, often with central blisters, on the trunk. Mouth, throat, nose, genital, and eye ulcers (red and swollen eyes) may also occur. These severe skin rashes are often preceded by fever and/or flu-like symptoms. The rashes may progress to skin peeling and life-threatening complications. If you develop a severe rash or any of these skin symptoms, stop taking EPREX and contact your doctor immediately.

Take special care with agents that stimulate red blood cell production.
EPREX belongs to a group of substances that stimulate red blood cell production, similar to human
erythropoietic factors. Your doctor will always record the exact name of the product you are using.
If during treatment you are given a substance from the same group but different from EPREX, consult
your doctor or pharmacist before use.
Other medicines and EPREX
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
If you are taking a medicine called cyclosporine (used, for example, after kidney transplantation),
your doctor may require blood tests to monitor cyclosporine levels during treatment with EPREX.
Iron supplements and other antianemic agents may enhance the effectiveness of EPREX. Your doctor
will decide whether you should take them.
If you are admitted to hospital or visit a doctor, inform them that you are being treated with EPREX.
This may affect other treatments or test results.
Pregnancy and breastfeeding
It is important to inform your doctor if any of the following apply to you. You may still use EPREX,
but discuss it with your doctor first.

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

EPREX contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially "sodium-free".
EPREX contains polysorbate 80
This medicine contains up to 0.30 mg of polysorbate 80 in each syringe, equivalent to a concentration of 0.30 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have any type of allergy.

3. How to use EPREX

Always use this medicine exactly as explained by your doctor. Check with your doctor
if you are unsure.
Based on your blood tests, your doctor has determined that you need EPREX.
EPREX may be administered by injection:

• into a vein or via an intravenous access (intravenous route)
• or under the skin (subcutaneous route).

Your doctor will decide how EPREX should be administered. Injections are usually performed
by a doctor, nurse, or other healthcare professional; however, some patients may learn to
self-administer the drug subcutaneously depending on the reason for EPREX treatment: see Instructions for self-injection of EPREX.
EPREX must not be used:

• after the expiry date stated on the label and outer packaging
• if you know or suspect the medicine may have been accidentally frozen, or
• if there has been a refrigerator malfunction

The dose of EPREX is based on body weight in kilograms and will be determined by your doctor according to
the cause of the anemia.
Your doctor will regularly monitor your blood pressure during treatment with EPREX.

Patients with renal failure

• Your hemoglobin level will be maintained between 10 and 12 g/dL, as higher hemoglobin levels may increase the risk of thrombosis and death. In children, hemoglobin levels should be maintained between 9.5 and 11 g/dL.
• The usual starting dose of EPREX for adults or children is 50 International Units (IU) per kilogram (/kg) of body weight, administered three times a week.
• In patients undergoing peritoneal dialysis, administration may be performed twice weekly.
• EPREX is administered intravenously (into a vein or venous line) to adults and children. When intravenous access (vein or venous line) is not readily available, your doctor may decide to inject EPREX under the skin (subcutaneous route). This applies to both dialysis patients and patients not yet on dialysis.
• Your doctor will regularly perform blood tests to monitor your response to EPREX treatment and may adjust the dose, usually no more frequently than once every 4 weeks. An increase in hemoglobin greater than 2 g/dL over a four-week period should be avoided.
• Once anemia is corrected, your doctor will continue to monitor blood tests regularly. The dose and frequency of EPREX administration will be further adjusted to maintain treatment response. Your doctor will use the lowest effective dose to control anemia symptoms.
• If you do not respond adequately to treatment, your doctor will review your EPREX dose and inform you if adjustment is needed.
• If you are receiving EPREX at extended dosing intervals (less than once weekly), you may not maintain adequate hemoglobin levels and may require an increase in EPREX dose or frequency.
• Iron supplements may be beneficial before and during EPREX treatment to enhance treatment effectiveness.
• If you are on hemodialysis when starting EPREX treatment, your dialysis regimen may need adjustment. Your doctor will decide this.

Adult patients undergoing chemotherapy

• Your doctor may start EPREX treatment if your hemoglobin level is ≤10 g/dL.
• Your hemoglobin level will be maintained between 10 and 12 g/dL, as higher levels may increase the risk of thrombosis and death.
• The starting dose is 150 IU per kg of body weight three times weekly, or 450 IU per kg of body weight once weekly.
• EPREX is administered by subcutaneous injection.
• Your doctor will perform regular blood tests and may adjust the dose based on your response to EPREX treatment.
• Iron supplementation before and during EPREX treatment may be beneficial to enhance treatment effectiveness.
• EPREX treatment is usually continued for 1 month after completion of chemotherapy.

Adult patients donating their own blood

• The usual dose is 600 IU per kg of body weight twice weekly.
• EPREX is administered intravenously immediately after blood donation for 3 weeks prior to surgery.
• Iron supplementation before and during EPREX treatment may be beneficial to enhance treatment effectiveness.

Adult patients scheduled for major orthopedic surgery

• The recommended dose is 600 IU per kg of body weight once weekly.
• EPREX is administered by subcutaneous injection weekly for 3 weeks before surgery and on the day of surgery.
• If the time before surgery needs to be shortened, a daily dose of 300 IU/kg will be administered for 10 days before surgery, on the day of surgery, and for 4 days after surgery.
• If preoperative blood tests reveal hemoglobin levels that are too high, treatment will be discontinued.
• Iron supplementation before and during EPREX treatment may be beneficial to enhance treatment effectiveness.

Adults with myelodysplastic syndrome

• If hemoglobin is ≤10 g/dL, your doctor may initiate EPREX treatment. The goal of treatment is to maintain your hemoglobin level between 10 and 12 g/dL, as higher levels may increase the risk of blood clots and death.
• EPREX is administered by subcutaneous injection.
• The starting dose is 450 IU per kg of body weight once weekly.
• Your doctor will order blood tests and may adjust the dose based on your response to EPREX treatment.

Instructions for self-injection of EPREX
At the beginning of treatment, EPREX is usually administered by a doctor or nurse.
Later, your doctor may suggest that you (or your caregiver) learn to perform the injection
(subcutaneous).

• Do not attempt self-injection unless your doctor or nurse has properly instructed you how to do so.
• Always follow the instructions provided by your doctor or nurse.
• Use EPREX only if it has been stored correctly – see section 5, How to store EPREX
• Before use, remove the EPREX syringe from the refrigerator and allow it to reach room temperature. This usually takes 15–30 minutes.

Draw up a single dose of EPREX from each pre-filled syringe.
When EPREX is administered subcutaneously, the volume is normally not more than 1 millilitre (1 mL) per injection.
EPREX must be administered alone and must not be mixed with other injectable solutions.
Do not shake EPREX syringes. Prolonged vigorous shaking may damage the product.
Do not use the product if it has been vigorously shaken.

How to perform self-injection subcutaneously using a pre-filled syringe
Pre-filled syringes are equipped with a needle safety device, PROTECS™, to prevent needlestick injuries after use. This is indicated on the packaging.

• Remove the pre-filled syringe from the refrigerator. Allow the liquid to reach room temperature. Do not remove the needle protective cap while waiting for temperature equilibration.
• Inspect the pre-filled syringe to ensure it is the correct dose, has not expired, is undamaged, and the liquid is clear and unfrozen.
• Remove the detachable section of the label from the syringe. If you cannot see the numbered graduations through the viewing window, hold the syringe barrel and gently rotate the syringe from the needle cap to align the numbered graduations with the viewing window.
• Choose the injection site. Suitable sites include the upper thigh and abdomen, except the area around the navel. Rotate injection sites with each use.
• Wash your hands. Use an antiseptic swab to disinfect the injection site.
• Hold the pre-filled syringe by the barrel with the covered needle pointing upward.
• Do not hold the syringe by the plunger head, plunger, needle safety wing, or needle protective cap.
• Never pull back the plunger.
• Do not remove the needle cap from the pre-filled syringe until you are ready to administer EPREX.
• Remove the needle protective cap by holding the syringe barrel and carefully pulling off the protective cap without twisting. Do not touch the needle or shake the syringe.
• Remove air bubbles 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 a partial dose from the syringe is required as directed by your doctor, push the plunger to the desired numbered graduation mark to expel the unwanted liquid before injection.
• Do not touch the needle safety wings to prevent premature activation of the needle safety device.
• Pinch the skin between your thumb and index finger without excessive pressure.
• Insert the needle fully. Your doctor or nurse will have shown you how to do this.
• Push the plunger with your thumb to inject the full amount of liquid corresponding to the correct dose. Push slowly and steadily, keeping the skin pinched.

The PROTECS needle safety device will not activate until the full dose has been administered. You may hear a "click" when the PROTECS needle safety device is activated.

• When the plunger reaches the end of its travel, withdraw the needle and release the skin.
• Slowly move your thumb away from the plunger to allow the needle to be fully covered by the safety device.
• After injection, minor bleeding at the injection site may occur. This is normal. You may disinfect the injection site by pressing the antiseptic swab against it for several seconds.
• Dispose of used syringes in a safe container – see section 5, How to store EPREX.

If you use more EPREX than you should
Inform your doctor or nurse immediately if you think you have used too much EPREX. Adverse effects from overdose are unlikely.
If you forget to inject EPREX
Administer the missed dose as soon as you remember. If the next scheduled dose is within one day, skip the missed dose and continue with your regular dosing 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 must consult your doctor because the combination of epoetin alfa with interferon and ribavirin has, in rare cases, led to loss of response and the development of a severe form of anemia called pure red cell aplasia (PRCA). EPREX is not approved for the treatment of anemia associated with hepatitis C.
If you have any questions about the use of this product, consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor or nurse immediately if you experience any of the side effects listed below.
Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with epoetin treatment. These may appear as red, target-like spots or circular patches, often with central blisters on the trunk, skin peeling, mouth, throat, nose, genital or eye ulcers, and may be preceded by fever and flu-like symptoms. Stop using EPREX if you develop any of these symptoms and contact your doctor immediately or go to the emergency department. See also section 2.

Very common side effects
Occur in more than 1 in 10 patients

• Diarrhea
• Nausea
• Vomiting
• Fever
• Respiratory tract congestion, such as nasal congestion and sore throat, has been reported in patients with kidney disease not yet undergoing dialysis.

Common side effects
Occur in up to 1 in 10 patients

• Increased blood pressure. Headache (especially if sudden, severe and migraine-like), confusion, or seizures: these may be signs of a sudden increase in blood pressure, which requires immediate treatment. Increased blood pressure may require treatment with medication (or adjustment of the dose of medicines already being taken for high blood pressure).
• Blood clots (including deep vein thrombosis and embolism), which may require urgent treatment. Symptoms may include chest pain, shortness of breath, painful swelling and redness, usually in the lower limbs.
• Cough.
• Skin irritation which may be due to an allergic reaction.
• Bone or muscle pain.
• Flu-like symptoms, such as headache, joint stiffness and pain, weakness, chills, fatigue and dizziness. These reactions are more common at the beginning of treatment. If you experience these symptoms during intravenous injection, a slower administration may help prevent them in the future.
• Redness, burning, and pain at the injection site.
• Swelling of the ankles, feet or fingers.
• Pain in arms or legs.

Uncommon side effects
Occur in up to 1 in 100 patients

• High levels of potassium in the blood, which may cause an abnormal heart rhythm (this is a very common side effect in patients on dialysis).
• Seizures.
• Nasal or airway congestion.
• Allergic reaction
• Hives (urticaria)

Rare side effects
Occur in up to 1 in 1,000 patients

• Symptoms of Pure Red Cell Aplasia (PRCA). PRCA means the bone marrow is unable to produce enough red blood cells. PRCA causes severe and sudden anemia, with symptoms including:
• unusual tiredness,
• dizziness,
• shortness of breath. PRCA has been reported very rarely, particularly in patients with kidney disease after months or years of treatment with EPREX and other substances that stimulate red blood cell production.
• An increase in the level of small blood cells (called platelets), normally involved in blood clotting, may occur, especially at the beginning of treatment. Your doctor will monitor this.
• Severe allergic reaction may include:

o swelling of the face, lips, mouth, tongue or throat
o difficulty swallowing or breathing
o itching (skin rash)

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

If you are on hemodialysis:

• Blood clots (thrombosis) may form in the dialysis shunt. This may occur more easily in case of low blood pressure (hypotension) or if there are problems with the fistula.
• Blood clots may also form in the hemodialysis system. Your doctor may decide to increase the dose of heparin during dialysis.

Tell your doctor or nurse immediately if you notice any of these side effects, or any other side effects during treatment with EPREX.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.
For individuals engaged in sports: using the medicine without a therapeutic need constitutes doping and may lead to a positive anti-doping test.

5. How to store EPREX

Keep out of the sight and reach of children.
Do not use this medicinal product after the expiry date which is stated on the carton and label after the letters EXP. The expiry date refers to the last day of the month indicated.
EPREX must be stored in a refrigerator (2°C - 8°C).
EPREX may be removed from the refrigerator and stored at room temperature (not above 25°C) for up to a maximum of 3 days. Once the syringe has been removed from the refrigerator and has reached room temperature (not above 25°C), it must be used within 3 days or discarded.
Do not freeze or shake.
Keep in the original packaging to protect from light.
Do not use this medicinal product if the seal is broken or if the solution is discoloured or contains particles in suspension. If any of these conditions are observed, discard the medicinal product.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What EPREX contains
The active substance is: epoetin alfa (for the amount, refer to the table below).
The other components are: polysorbate 80 (E 433), sodium chloride, sodium dihydrogen phosphate dihydrate,
disodium hydrogen phosphate dihydrate, glycine and water for injections.
Description of the appearance of EPREX and contents of the pack
EPREX is an injectable solution in pre-filled syringes. The pre-filled syringes are equipped with a needle safety device PROTECS™ (see the table below). EPREX is a clear, colourless solution.

It is possible that not all pack sizes are marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Janssen-Cilag SpA
Viale Fulvio Testi, 280/6
20126 Milano MI
Manufacturer:
Janssen Biologics B.V.
Einsteinweg 101
2333 CB
Leiden
The Netherlands
This medicinal product is authorized in the European Union Member States 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
United Kingdom (Northern Ireland): EPREX
Spain: EPREX