Retacrit 40000 IU/1.0 ml solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Retacrit 1,000 IU/0.3 ml solution for injection in a pre-filled syringe

Retacrit 2,000 IU/0.6 ml solution for injection in a pre-filled syringe

Retacrit 3,000 IU/0.9 ml solution for injection in a pre-filled syringe

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

Retacrit 5,000 IU/0.5 ml solution for injection in a pre-filled syringe

Retacrit 6,000 IU/0.6 ml solution for injection in a pre-filled syringe

Retacrit 8,000 IU/0.8 ml solution for injection in a pre-filled syringe

Retacrit 10,000 IU/1 ml solution for injection in a pre-filled syringe

Retacrit 20,000 IU/0.5 ml solution for injection in a pre-filled syringe

Retacrit 30,000 IU/0.75 ml solution for injection in a pre-filled syringe

Retacrit 40,000 IU/1 ml solution for injection in a pre-filled syringe

epoetin zeta

Read the entire leaflet carefully before you start 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, 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.

What is in this leaflet

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

1. What Retacrit is and what it is used for

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

• Retacrit is indicated for the treatment of symptomatic anaemia caused by kidney disease

  • in children undergoing haemodialysis;
  • in adults undergoing haemodialysis or peritoneal dialysis;
  • in adults with severe anaemia who have not yet started dialysis.

If you have kidney disease, you may have a low number of red blood cells because your kidneys do not produce enough erythropoietin (which is necessary for red blood cell production). Retacrit is prescribed to stimulate the bone marrow to produce more red blood cells.

• Retacrit is indicated for the treatment of anaemia in adults receiving chemotherapy for solid tumours, malignant lymphoma, or multiple myeloma (a bone marrow neoplasm) who may require blood transfusion. Retacrit may reduce the need for blood transfusion in these patients.

• Retacrit is indicated in adults with moderate anaemia who are donating blood prior to undergoing surgery, so that it can be re-infused during or after the surgical procedure. Since Retacrit stimulates red blood cell production, doctors can collect more blood from these individuals.

• Retacrit is indicated in adults with moderate anaemia who are about to undergo major elective orthopaedic surgery (e.g., hip or knee replacement surgery) to reduce the potential need for blood transfusion.

• Retacrit is indicated in adult patients with anaemia due to a bone marrow disorder causing a severe impairment in blood cell formation (myelodysplastic syndromes). Retacrit may reduce the need for blood transfusion.

2. What you need to know before using Retacrit

Do not use Retacrit

• If you are allergic to epoetin zeta 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 product that stimulates red blood cell production (including Retacrit). See section 4.

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

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

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

  • have severe heart disease;
  • have serious disorders of veins or arteries;
  • have recently had a heart attack or stroke;
  • cannot take blood-thinning medications.

Retacrit may not be suitable for you. Talk to your doctor. Some people need medications to reduce the risk of blood clots during Retacrit treatment. If you cannot take medications to prevent blood clot formation, you must not take Retacrit.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Retacrit.

Take special care with Retacrit

Retacrit 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 factors for blood clot formation (for example, if you have had a blood clot in the past, or if you are overweight, have diabetes, suffer from heart disease, or are immobile for long periods due to surgery or illness). Inform your doctor about any of these conditions. Your doctor will help you decide whether Retacrit is suitable for you.

Talk to your doctor if any of the following apply to you. You may still be able to use Retacrit, but discuss it with your doctor first.

• If you know you have or have had:

  • high blood pressure;
  • epileptic seizures or convulsions;
  • liver disease;
  • anemia due to other causes;
  • porphyria (a rare blood disorder).

• If you are a patient with chronic kidney failure, and especially if you do not respond well to Retacrit, your doctor will review your Retacrit dose, because repeatedly increasing the dose of Retacrit when not responding to treatment may increase the risk of heart or blood vessel problems and could increase the risk of heart attack, stroke, and death.

• If you are a cancer patient, you should know that products that stimulate red blood cell production (such as Retacrit) may act as growth factors and, therefore, could theoretically affect cancer progression. 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 Retacrit may be associated with reduced survival and higher mortality rates in patients with head and neck cancer and metastatic breast cancer receiving chemotherapy.

• Severe skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been observed with epoetin administration.

SJS/TEN may initially appear as red, target-like spots or circular patches, often with central blisters, typically on the trunk. Mouth, throat, nose, genital, and eye ulcers (eye irritation and swelling) may also occur. These severe skin rashes are often preceded by fever or flu-like symptoms. The rashes 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 Retacrit and contact your doctor or seek immediate medical attention.

Take special care with other products that stimulate red blood cell production

Retacrit belongs to a group of products that stimulate red blood cell production in the same way as human erythropoietin protein. Your doctor must record the exact name of the product you are using.

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

Other medicines and Retacrit

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

If you are using Retacrit together with a medicine called cyclosporine (e.g., after a kidney transplant), your doctor may request blood tests to monitor cyclosporine levels.

Iron supplements and other blood stimulants may increase the effectiveness of Retacrit. Your doctor will decide whether they are suitable for you.

If you visit a hospital, clinic, or general practitioner, inform them that you are receiving treatment with Retacrit, as it may affect other treatments or test results.

Pregnancy, breastfeeding, and fertility

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

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

There are no data available on the effects of epoetin zeta on fertility.

Driving and using machines

The influence of Retacrit on the ability to drive and use machines is negligible or none.

Retacrit contains phenylalanine

Retacrit contains 0.5 mg of phenylalanine per ml.

Phenylalanine may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

Retacrit contains sodium

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

Retacrit contains polysorbate 20

This medicine contains up to 0.1 mg of polysorbate 20 per syringe, equivalent to a concentration of 0.1 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have any known allergies.

3. How to use Retacrit

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

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

Retacrit may be administered by injection:

• either into a vein or through a tube inserted into a vein (intravenously),
• or under the skin (subcutaneously).

Your doctor will decide how Retacrit will be injected. Injections are usually performed by a doctor, nurse, or other healthcare professional. Later, and depending on the reason for treatment with Retacrit, some people may learn to self-inject the medicine under the skin: see Instructions on how to self-inject Retacrit.

Retacrit must not be used:

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

The dose of Retacrit you will receive is based on your body weight 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 periodically while you are receiving treatment with Retacrit.

Patients with renal insufficiency

• Your doctor will maintain your hemoglobin level between 10 and 12 g/dl, as a high hemoglobin level may increase the risk of blood clots and death. In children, the hemoglobin level should be maintained between 9.5 and 11 g/dl.
• The usual starting dose of Retacrit for adults and children is 50 IU/kg (international units per kilogram) three times a week.
• In patients on peritoneal dialysis, Retacrit may be administered twice a week.
• In both adults and children, Retacrit is given as an injection either into a vein (intravenous route) or through a tube inserted into a vein. When venous access (via a vein or tube) is not easily achievable, your doctor may decide that Retacrit should be injected under the skin (subcutaneously). This includes patients on dialysis and those not yet on dialysis.
• Your doctor will order periodic blood tests to monitor your response to anemia treatment and may adjust the dose, usually no more frequently than every four weeks. An increase in hemoglobin greater than 2 g/dl over a four-week period should be avoided.
• Once anemia has been corrected, your doctor will continue to perform periodic blood tests. The dose and frequency of Retacrit administration may be readjusted to maintain your response to treatment. Your doctor will use the lowest effective dose to control the symptoms of anemia.
• If you do not respond well to Retacrit, your doctor will review your dose and inform you if a dose adjustment is needed.
• If you receive Retacrit at longer dosing intervals (less than once per week), you may not maintain adequate hemoglobin levels and may require an increase in the dose or frequency of Retacrit administration.
• Iron supplements may be given before and during treatment with Retacrit to enhance its effectiveness.
• If you are undergoing dialysis at the start of Retacrit treatment, your dialysis regimen may need to be adjusted. Your doctor will decide whether this is necessary.

Adults undergoing chemotherapy

• Your doctor may initiate treatment with Retacrit if your hemoglobin level is ≤10 g/dl.
• Your doctor will maintain your hemoglobin concentration between 10 and 12 g/dl, as a high hemoglobin level may increase the risk of blood clots and death.
• The starting dose is 150 IU/kg body weight three times per week or 450 IU/kg body weight once per week.
• Retacrit is administered by subcutaneous injection.
• Your doctor will request blood tests and may adjust the dose depending on how your anemia responds to Retacrit treatment.
• Iron supplements may be administered before and during treatment with Retacrit to enhance its effectiveness.
• You will usually continue receiving Retacrit treatment for one month after completion of chemotherapy.

Adult autologous blood donors

• The usual dose is 600 IU/kg body weight twice per week.
• Retacrit is administered by intravenous injection immediately after donating blood, for three weeks prior to surgery.
• Iron supplements may be administered before and during treatment with Retacrit to enhance its effectiveness.

Adults scheduled for major orthopedic surgery

• The recommended dose is 600 IU/kg body weight once per week.
• Retacrit is administered by subcutaneous injection for three weeks before surgery and on the day of surgery.
• In cases where the preoperative period needs to be shortened, you will receive a daily dose of 300 IU/kg for up to 10 days before surgery, on the day of surgery, and for four days immediately after surgery.
• If blood tests show a hemoglobin level that is too high before surgery, treatment will be discontinued.
• Iron supplements may be administered before and during treatment with Retacrit to enhance its effectiveness.

Adults with myelodysplastic syndrome

• Your doctor may initiate treatment with Retacrit if your hemoglobin concentration is ≤10 g/dl. The goal of treatment is to maintain hemoglobin levels between 10 and 12 g/dl, as higher hemoglobin levels may increase the risk of blood clots and death.
• Retacrit is administered by subcutaneous injection.
• The starting dose is 450 IU per kilogram of body weight once per week.
• Your doctor will request blood tests and may adjust the dose depending on how your anemia responds to Retacrit treatment.

Instructions on how to self-inject Retacrit

When treatment is initiated, medical or nursing staff usually administer Retacrit injections. Later, your doctor may suggest that you or your caregiver learn to self-inject Retacrit under the skin (subcutaneously).

• Do not attempt to self-inject unless your doctor or nurse has trained you how to do so.
• Follow exactly the administration instructions for Retacrit provided by your doctor or nurse.
• Only use Retacrit if it has been stored correctly; see section 5, Storage of Retacrit.
• Before use, allow the Retacrit syringe to sit at room temperature. This usually takes between 15 and 30 minutes.

Use only one dose of Retacrit from each syringe.

If Retacrit is injected subcutaneously, the injected volume should not normally exceed 1 milliliter (1 ml) per single injection. For larger volumes, more than one injection site should be used.

Retacrit is administered alone and must not be mixed with other injectable solutions.

Do not shake Retacrit syringes. Prolonged vigorous shaking may damage the product. If the product has been shaken vigorously, do not use it.

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

• Remove the package containing the pre-filled syringe from the refrigerator.
• Remove the blister containing the pre-filled syringe from the package. If the package contains multiple blisters with pre-filled syringes, cut off the blister with one pre-filled syringe along the perforated line, return the remaining blisters with pre-filled syringes to the package, and return the package to the refrigerator.
• Open the blister with the pre-filled syringe after removing it from the refrigerator. Allow the liquid to reach room temperature. Do not remove the needle cap from the syringe while allowing the pre-filled syringe to reach room temperature.

• Inspect the syringe to ensure it is the correct dose, has not expired, is undamaged, and the liquid is clear and unfrozen.
• Do not use the pre-filled syringe if:
  • The packaging is open or damaged.
  • The medicine is cloudy, has changed color, or contains floating particles.
  • Any part of the pre-filled syringe appears cracked or broken, or liquid has leaked from the syringe.
  • The pre-filled syringe has been dropped. The syringe may be broken even if the damage is not visible.
  • The needle cap is missing or not properly attached.
  • The expiry date printed on the label has passed.

In all of the above cases, discard the pre-filled syringe and use a new one.

• Choose an injection site. Suitable sites are the upper thigh and the area around the abdomen (abdomen), but away from the navel. Vary the site daily.
• Wash your hands. Use an antiseptic swab to disinfect the injection site.
• Hold the pre-filled syringe by the barrel with the needle cap pointing upward.
  • Do not hold it by the plunger head, plunger, or needle cap.
  • Do not pull back the plunger at any time.
  • Do not remove the needle cap from the pre-filled syringe until you are ready to inject your medicine.
• Remove the needle cap by holding the syringe barrel and carefully pulling the needle cap straight off and away from your body without twisting. Discard the needle cap. Do not recap the needle. Do not push the plunger, touch the needle, or shake the syringe.

• Pinch a fold of skin between your thumb and index finger. Do not compress it.
• With the other hand, hold the pre-filled syringe like a pencil. Use a quick "dart-like" motion to insert the needle into the skin at an approximate angle of 45 degrees.

• Insert the needle completely. Your doctor or nurse has shown you how to do this.
• Push the plunger with your thumb as far as possible to inject the full amount of liquid. Push slowly and steadily, keeping the skin fold pinched.
• When the plunger reaches the end, remove the needle and release the skin.
• When the needle is withdrawn from the skin, there may be slight bleeding at the injection site. This is normal. You may press an antiseptic swab over the injection site for a few seconds after injection.
• Do not attempt to recap the needle. Dispose of the used syringe in a sharps container (puncture-resistant).
• Never place used syringes in your regular household waste bin.

How to self-inject subcutaneously using a pre-filled syringe with needle protection mechanism

Your pre-filled syringe has an attached needle protection mechanism to protect you from needlestick injury.

• Remove the package containing the pre-filled syringe with needle protection mechanism from the refrigerator.
• Remove the blister with the pre-filled syringe from the package. If the package contains multiple blisters with pre-filled syringes, cut off the blister with one pre-filled syringe along the perforated line, return the remaining blisters with pre-filled syringes to the package, and return the package to the refrigerator.
• Open the blister by removing the blister lid.
• Remove the pre-filled syringe from the blister by holding it by the barrel.
  • Do not touch the grey needle cap or the plunger.

• Check the syringe to ensure the needle protection mechanism covers the body of the pre-filled syringe. Do not push the needle protection mechanism over the needle cap before injection. This may activate or block the needle protection mechanism. If the needle protection mechanism covers the needle, it means it has been activated.
• Allow the liquid to reach room temperature. Do not remove the needle cap from the syringe while allowing the pre-filled syringe to reach room temperature.

1	Needle protection mechanism
2	Needle cap
3	Medication
4	Plunger

• Check the syringe to make sure it is the correct dose, has not passed its expiry date, is not damaged, and the liquid is clear and unfrozen.

• Do not use the pre-filled syringe if:

  • The carton is open or damaged.
  • The needle shield is missing, detached, or has been activated.
  • The medicine is cloudy or has changed colour, or the liquid contains particles floating in it. Do not inspect the product through the plastic of the safety device.
  • Any part of the pre-filled syringe appears cracked or broken, or liquid has leaked from the syringe.
  • The pre-filled syringe has been dropped. The pre-filled syringe may be broken even if you cannot see the break.
  • The needle cap is missing or not properly in place.
  • The expiry date printed on the label has passed.

In all of the above cases, discard the pre-filled syringe and use a new pre-filled syringe.

• Choose an injection site. Suitable sites are the upper thigh and around the abdomen (belly), but away from the navel. Vary the site from day to day.
• Wash your hands. Use an antiseptic swab at the injection site to disinfect it.
• Hold the pre-filled syringe by the body of the needle safety device with the covered needle pointing upwards.
  • Do not hold it by the plunger head, plunger, 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 your medicine.
• Remove the needle cap by holding the body of the syringe and carefully pulling off the needle cap without twisting it. Discard the needle cap. Do not recap the needle. Do not push the plunger, touch the needle, or shake the syringe.

• Pinch a skin fold between your thumb and index finger. Do not compress it.
• With your other hand, hold the pre-filled syringe like a pencil. Use a quick “dart-like” motion to insert the needle at an approximate 45-degree angle into the skin.

• Insert the needle completely. Your doctor or nurse has shown you how to do this.
• Press the plunger while holding the collar with your fingers until the full dose has been administered. The needle safety device will not activate unless the dose has been administered in its ENTIRETY.

• When the plunger reaches the end, remove the needle and release the skin.
• Release the plunger and allow the syringe to move upwards until the entire needle is retracted and securely locked in place.

• When the needle is withdrawn from the skin, there may be slight bleeding at the injection site.

This is normal. You may press an antiseptic swab against the injection site for a few seconds after the injection.

• Do not attempt to recap the needle. Dispose of the used syringe in a sharps container (puncture-resistant).
• Never place used syringes in the regular household waste bin.

How to self-inject subcutaneously using a pre-filled syringe with a needle-capture safety device (needle trap)

Your syringe has an attached needle-capture safety device (needle trap), specifically designed to help prevent accidental injuries after correct administration of injectable medication. It consists of a plastic device that blocks the needle, firmly attached to the syringe label. Together, these two components perform the function of a needle trap (safety).

The plastic blocking shield attached to the syringe label requires specific actions by the user to "activate" it, rendering the needle harmless after injection administration:

• Remove the pre-filled syringe package from the refrigerator.
• Remove the blister with the pre-filled syringe from the package. When the package contains multiple pre-filled syringes in blisters, cut off one blister along the perforated line, return the remaining blisters with pre-filled syringes to the package, and return the package to the refrigerator.
• Open the blister with the pre-filled syringe with needle trap by removing the cover after taking it out of the refrigerator.
• Hold the syringe body to remove the pre-filled syringe from the blister.

• Do not remove the needle cap from the pre-filled syringe until you are ready to inject your medicine.
• Allow the liquid to reach room temperature. Do not remove the needle cap from the syringe while letting the pre-filled syringe reach room temperature.
• Check the syringe to ensure it is the correct dose, has not passed its expiry date, is not damaged, and the liquid is clear and unfrozen.
• Do not use the pre-filled syringe if:
  • The package is open or damaged.
  • The medicine is cloudy or has changed colour, or the liquid contains particles floating in it.
  • Any part of the pre-filled syringe appears cracked or broken, or liquid has leaked from the syringe.
  • The pre-filled syringe has been dropped. The pre-filled syringe may be broken even if you cannot see the break.
  • The needle cap is missing or not properly in place.
  • The expiry date printed on the label has passed.

In all of the above cases, discard the pre-filled syringe and use a new pre-filled syringe.

• Choose an injection site. Suitable sites are the upper thigh and around the abdomen (belly), but away from the navel. Vary the site from day to day.
• Wash your hands. Use an antiseptic swab at the injection site to disinfect it.
• Hold the pre-filled syringe by the syringe body with the covered needle pointing upwards.
  • Do not hold it by the plunger head, plunger, or needle cap.
  • Do not pull the plunger at any time.
  • Grasp the plastic needle tip and pull it away from the needle cap.

• Do not remove the needle cap from the pre-filled syringe until you are ready to inject your medicine.

• Remove the needle cap from the syringe by holding the syringe body and carefully pulling off the needle cap without twisting it. Discard the needle cap. Do not recap the needle. Do not push the plunger, touch the needle, or shake the syringe.

• Pinch a skin fold between your thumb and index finger. Do not compress it.
• With your other hand, hold the pre-filled syringe like a pencil. Use a quick “dart-like” motion to insert the needle at an approximate 45-degree angle into the skin.

• Insert the needle completely. Your doctor or nurse has shown you how to do this.
• Push the plunger with your thumb as far as possible and inject all the liquid. Push gently and evenly, keeping the skin fold pinched.
• When the plunger will go no further, remove the needle and withdraw it from the skin.
• Place the needle trap device on a hard, stable surface and, with one hand, twist the syringe barrel upwards against the needle, forcing the needle into the trap, where it will lock (an audible click will be heard when the needle is locked in the trap). Continue bending the syringe needle until it exceeds a 45-degree angle with the flat surface to ensure it is permanently disabled.

• When the needle is withdrawn from the skin, there may be slight bleeding at the injection site. This is normal. You may press an antiseptic swab against the injection site for a few seconds after the injection.
• Do not attempt to recap the needle. Dispose of the used syringe in a sharps container (puncture-resistant).
• Never place used syringes in the regular household waste bin.

If you use more Retacrit than you should

Inform your doctor or nurse immediately if you think you have been given too much Retacrit. Adverse effects due to an overdose of Retacrit are unlikely.

If you forget to use Retacrit

Take the next injection as soon as you remember. If less than one day remains 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 discuss this with your doctor, as in rare cases, the combination of epoetin zeta with interferon and ribavirin has led to loss of effect and the development of a condition called pure red cell aplasia (PRCA), a severe form of anaemia. Retacrit is not approved for the treatment of anaemia 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 experience any of the effects listed below.

Severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been observed with the administration of epoetins. These reactions may appear as macules or circular red spots, 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 Retacrit if you develop these symptoms and contact your doctor or seek immediate medical attention. See also section 2.

Very common: may affect more than 1 in 10 people.

• Diarrhea

• Stomach discomfort

• Vomiting

• Fever

• In patients with renal insufficiency who have not yet started dialysis, respiratory tract congestion, such as nasal congestion and sore throat, has been reported.

Common: may affect up to 1 in 10 people.

• Increased blood pressure. Headaches, especially sudden, sharp, migraine-type headaches, confusion or seizures may be signs of a sudden increase in blood pressure. This requires urgent treatment. This increase may require medication (or adjustment of the dosage of medicines you are already taking for high blood pressure).
• Blood clots (including deep vein thrombosis and embolism) that may require urgent treatment. You may experience chest pain, difficulty breathing, and painful swelling and redness, usually in one leg.
• Cough
• Itching of the skin, which may result from an allergic reaction.
• Bone or muscle pain
• Flu-like symptoms, such as headache, joint pricks and pains, feeling weak, chills, fatigue, and dizziness. These may be more common at the beginning of treatment. If you experience these symptoms during intravenous injection, a slower administration of the injection may help prevent them from recurring.
• Redness, burning, and pain at the injection site
• Swelling of the ankles, feet, or fingers
• Pain in arm or leg

Uncommon: may affect up to 1 in 100 people.

• 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).
• Tremors
• Nasal or airway congestion
• Allergic reaction
• Skin rash (hives)

Rare: 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 cause a sudden and severe anemia. Symptoms are:

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

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

• An increase in the number of small blood cells (called platelets), which normally play a role in blood clotting, may occur, especially when treatment is initiated. Your doctor will monitor this.

• Severe allergic reactions, which 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. 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 Retacrit, tell 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 through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Retacrit Storage

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

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

Store in a refrigerator (2°C–8°C). Retacrit may be removed from the refrigerator and kept at room temperature (up to 25°C) for a maximum period of 3 days. Once a syringe has been removed from the refrigerator and has reached room temperature (up to 25°C), it must be used within three days or discarded.

Do not freeze or shake.

Keep in the outer packaging to protect from light.

Do not use this medicine if the seal is broken or if the liquid shows discoloration or visible floating particles. If you observe any of these conditions, discard the medicine.

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

6. Contents of the pack and other information

Composition of Retacrit

The active substance is epoetin zeta (produced by recombinant DNA technology in Chinese hamster ovary cell lines).

Retacrit 1 000 IU/0.3 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 0.3 ml of solution for injection contains 1 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 3 333 IU of epoetin zeta per ml.

Retacrit 2 000 IU/0.6 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 0.6 ml of solution for injection contains 2 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 3 333 IU of epoetin zeta per ml.

Retacrit 3 000 IU/0.9 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 0.9 ml of solution for injection contains 3 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 3 333 IU of epoetin zeta per ml.

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

1 pre-filled syringe containing 0.4 ml of solution for injection contains 4 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU of epoetin zeta per ml.

Retacrit 5 000 IU/0.5 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 0.5 ml of solution for injection contains 5 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU of epoetin zeta per ml.

Retacrit 6 000 IU/0.6 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 0.6 ml of solution for injection contains 6 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU of epoetin zeta per ml.

Retacrit 8 000 IU/0.8 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 0.8 ml of solution for injection contains 8 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU of epoetin zeta per ml.

Retacrit 10000 IU/1 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 1 ml of solution for injection contains 10 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU of epoetin zeta per ml.

Retacrit 20000 IU/0.5 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 0.5 ml of solution for injection contains 20 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 40 000 IU of epoetin zeta per ml.

Retacrit 30000 IU/0.75 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 0.75 ml of solution for injection contains 30 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 40 000 IU of epoetin zeta per ml.

Retacrit 40000 IU/1 ml solution for injection in pre-filled syringe

1 pre-filled syringe containing 1 ml of solution for injection contains 40 000 international units (IU) of epoetin zeta (recombinant human erythropoietin). The solution contains 40 000 IU of epoetin zeta per ml.

The other components are sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride (see section 2 “Retacrit contains sodium”), calcium chloride dihydrate, polysorbate 20 (E432) (see section 2 “Retacrit contains polysorbate 20”), glycine, leucine, isoleucine, threonine, glutamic acid, phenylalanine (see section 2 “Retacrit contains phenylalanine”), water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment).

Appearance of the product and contents of the pack

Retacrit is a clear, colourless solution for injection supplied in transparent glass syringes with a fixed injection needle.

The pre-filled syringes contain between 0.3 and 1 ml of solution, depending on the epoetin zeta content (see "Composition of Retacrit").

Each pack contains 1, 4 or 6 pre-filled syringes, with or without a safety needle cover or with a plastic needle lock attached to the syringe label.

Multi-pack cartons contain 4 (4 packs of 1) or 6 (6 packs of 1) pre-filled syringes.

Marketing Authorisation Holder

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturers

STADA Arzneimittel AG
Stadastrasse 2-18
D-61118 Bad Vilbel
Germany

Hospira Zagreb d.o.o.
Prudnicka cesta 60
10291 Prigorje Brdovecko
Croatia

For more information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgium/Belgium/Belgium Luxembourg/Luxembourg Pfizer NV/SA Tel/Tel: +32 (0)2 554 62 11	Latvia Pfizer Luxembourg SARL branch office Latvia Tel: + 371 670 35 775
	Lithuania Pfizer Luxembourg SARL branch in Lithuania Tel: +370 5 251 4000
Czech Republic Pfizer, spol. s r.o. Tel: +420-283-004-111	Hungary Pfizer Ltd. Tel.: + 36 1 488 37 00
Denmark Pfizer ApS Tlf.: + 45 44 20 11 00	Malta Drugsales Ltd Tel: +356 21419070/1/2
Germany PFIZER PHARMA GmbH Tel: +49 (0)30 550055-51000	Netherlands Pfizer bv Tel: +31 (0)800 63 34 636
Estonia Pfizer Luxembourg SARL Estonia branch Tel: +372 666 7500	Norway Pfizer AS Tlf: +47 67 52 61 00
Greece Pfizer Hellas S.A. Tel: + 30 210 6785800	Austria Pfizer Corporation Austria Ges.m.b.H. Tel: +43 (0)1 521 15-0
Spain Pfizer, S.L. Tel: +34 91 490 99 00	Poland Pfizer Polska Sp. z o.o. Tel.: +48 22 335 61 00
France Pfizer Tél: + 33 (0)1 58 07 34 40	Portugal Laboratórios Pfizer, Lda. Tel: +351 21 423 5500
Croatia Pfizer Croatia d.o.o. Tel: +385 1 3908 777	Romania Pfizer Romania S.R.L. Tel: +40 (0)21 207 28 00
Ireland Pfizer Healthcare Ireland Unlimited Company Tel: 1800 633 363 (toll free) Tel: +44 (0)1304 616161	Slovenia Pfizer Luxembourg SARL Pfizer, branch office for pharmaceutical consulting, Ljubljana Tel: +386 (0)1 52 11 400
Iceland Icepharma hf. Tel: +354 540 8000	Slovakia Pfizer Luxembourg SARL, organizational unit Tel: + 421 2 3355 5500
Italy Pfizer S.r.l. Tel: +39 06 33 18 21	Finland Pfizer Oy Tel: +358 (0)9 430 040
Cyprus Pfizer Hellas S.A. (Cyprus Branch) Tel: +357 22 817690	Sweden Pfizer AB Tel: +46 (0)8 550 520 00

Date of the most recent review of this leaflet:

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