Retacrit

Patient Information Leaflet

Retacrit 1,000 IU/0.3 mL solution for injection in pre-filled syringe, 2,000 IU/0.6 mL solution for injection in pre-filled syringe, 3,000 IU/0.9 mL solution for injection in pre-filled syringe, 4,000 IU/0.4 mL solution for injection in pre-filled syringe, 5,000 IU/0.5 mL solution for injection in pre-filled syringe, 6,000 IU/0.6 mL solution for injection in pre-filled syringe, 8,000 IU/0.8 mL solution for injection in pre-filled syringe, 10,000 IU/1 mL solution for injection in pre-filled syringe, 20,000 IU/0.5 mL solution for injection in pre-filled syringe, 30,000 IU/0.75 mL solution for injection in pre-filled syringe, 40,000 IU/1 mL solution for injection in pre-filled syringe

epoetin zeta
Please read all of this 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 give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of 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 in the blood, which carry haemoglobin (a substance that binds oxygen). Epoetin zeta is a copy of the human protein erythropoietin and works in the same way.

• Retacrit is used to treat symptomatic anaemia caused by kidney disease:
• in children undergoing haemodialysis;
• in adults undergoing haemodialysis or peritoneal dialysis;
• in severely anaemic adults not yet undergoing dialysis.

If you have kidney disease, you may have low levels 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 used to treat anaemia in adults undergoing chemotherapy for solid tumours, malignant lymphoma, or multiple myeloma (a tumour of the bone marrow), who might otherwise require a blood transfusion. Retacrit can reduce the need for blood transfusions in these patients;
• Retacrit is used in adults with moderate anaemia who are donating their own blood prior to surgery, so that it can be re-transfused back to them during or after the operation. Because Retacrit stimulates red blood cell production, doctors can collect more blood from these individuals;
• Retacrit is used in moderately anaemic adults about to undergo major orthopaedic surgery (e.g. hip or knee surgery) to reduce the potential need for blood transfusions;
• Retacrit is used to treat anaemia in adults with a bone marrow disorder causing a severe imbalance in blood cell production (myelodysplastic syndromes). Retacrit can 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 a disease called "pure red cell aplasia" (the bone marrow fails to produce enough red blood cells), following previous treatment with any product that stimulates red blood cell production (including Retacrit). See section 4.
• If you have high blood pressure that cannot be adequately controlled with medication.
• For stimulating red blood cell production (so that doctors can collect a larger amount of your blood), if you cannot receive transfusions of your own blood during or after surgery.
• If you are about to undergo elective major orthopaedic surgery (such as hip or knee surgery), and you:
  • have severe heart problems
  • have severe blood vessel disorders
  • have recently had a heart attack or stroke
  • cannot take blood-thinning medications.

Retacrit may not be suitable for you. Consult your doctor. During treatment with Retacrit,
some people require medication to reduce the risk of blood clots forming. If you cannot take
medications that prevent blood clot formation, you must not take Retacrit.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Retacrit.

Special precautions with Retacrit
In all patients, Retacrit and other products that stimulate red blood cell production may increase
the risk of blood clots. This risk may be higher if other risk factors for blood clot formation are
present (e.g., if you have previously had a blood clot, are overweight, have diabetes, have heart*
**disease, or must remain immobile for prolonged periods due to surgery or illness)*. Inform your
doctor about any of these conditions. Your doctor will help determine whether Retacrit is
suitable for you.

Tell 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 or have previously had:
  • high blood pressure;
  • epileptic seizures or convulsions;
  • liver disease;
  • anaemia due to other causes;
  • porphyria (a rare blood disorder);
• If you have chronic kidney failure, and particularly if you do not respond adequately to Retacrit, your doctor will monitor your Retacrit dose carefully, because if you do not respond to treatment, repeatedly increasing the dose of Retacrit may increase the risk of heart or blood vessel problems, and may increase the risk of heart attack, stroke, and death.
• If you have a tumour, you should know that medicines that stimulate red blood cell production (such as Retacrit) may act as growth factors and could theoretically affect tumour progression. Depending on your individual situation, a blood transfusion may be preferable. Consult your doctor.
• If you have a tumour, you should know that in patients with head and neck cancer or metastatic breast cancer receiving chemotherapy, the use of Retacrit has been associated with shorter survival and a higher mortality rate.
• Severe skin reactions have been reported in association with epoetin treatment, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Stevens-Johnson syndrome and toxic epidermal necrolysis may initially appear on the trunk as reddish, target-like spots or circular patches, often with central blisters. Mouth ulcers, throat, nasal, genital, and eye lesions (red, swollen eyes) may also occur. These serious skin rashes are often preceded by fever and/or flu-like symptoms. The rashes may progress to widespread skin peeling and life-threatening complications.
If you develop a severe skin rash or any of these skin symptoms, stop taking Retacrit and contact your doctor immediately.

Pay special attention to other products that stimulate red blood cell production:
Retacrit belongs to a group of products that stimulate red blood cell production, such as the human protein erythropoietin. Your healthcare provider will always record the exact name of the product you are using.
If during treatment you are given a medicine 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 take any other medicines.
If you are taking a medicine called ciclosporin (used, for example, after kidney transplants), your doctor may prescribe blood tests to monitor ciclosporin levels during Retacrit therapy.
Taking iron supplements and other substances that stimulate red blood cell production may enhance the effectiveness of Retacrit. Your doctor will decide whether you should continue taking these substances.
If you visit a hospital, clinic, or your general practitioner, inform them that you are being treated with Retacrit. This may affect other treatments or test results.

Pregnancy, breastfeeding, and fertility
It is important that you inform your doctor if any of the following conditions apply. You may still be able to continue taking Retacrit, but discuss it with your doctor first.

• If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
• If you are breastfeeding.

No data are available on the effects of epoetin zeta on fertility.

Driving and using machines
Retacrit has no or negligible effect on the ability to drive or use machines.

Retacrit contains phenylalanine
This medicine contains 0.5 mg of phenylalanine per mL.
Phenylalanine may be harmful if you have phenylketonuria, a rare genetic disorder that causes phenylalanine to accumulate because the body cannot eliminate it properly.

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

3. How to use Retacrit

Use this medicine exactly as your doctor has instructed you. If you have any doubts, consult
your doctor.
Based on your blood tests, your doctor has determined that you need to take Retacrit.
Retacrit can be administered by injection:

• Directly into a vein or via a catheter inserted into a vein (intravenous route)
• Or under the skin (subcutaneous route).

Your doctor will decide how Retacrit will be administered. Injections are usually given by a
doctor, nurse, or other healthcare professional. Some people, depending on the reason for
treatment with Retacrit, may later be trained to self-administer subcutaneous injections: see Instructions for self-injecting 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;
• If there has been a refrigerator malfunction.

The dose of Retacrit is based on your body weight in kilograms. The cause of your anemia is also a factor your doctor considers when determining the correct dose.
While using Retacrit, your doctor will regularly monitor your blood pressure.

Patients with kidney disease

• Your doctor will maintain your haemoglobin level between 10 and 12 g/dL, as a higher haemoglobin level may increase the risk of blood clots and death. In children, the haemoglobin level should be maintained between 9.5 and 11 g/dL.
• The usual starting dose of Retacrit for adults and children is 50 International Units (IU) per kilogram (/kg) of body weight, administered three times a week.
• For patients on peritoneal dialysis, Retacrit may be given twice a week.
• In adults and children, Retacrit is administered by injection into a vein (intravenous) or via a venous catheter. If these venous access routes are not readily available, your doctor may decide to administer Retacrit under the skin (subcutaneous route). This applies to both dialysed and non-dialysed patients.
• Your doctor will prescribe periodic blood tests to monitor how your anaemia is responding and may adjust the dose as needed, usually at intervals of no less than four weeks. An increase in haemoglobin greater than 2 g/dL within four weeks should be avoided.
• Once your anaemia is corrected, your doctor will continue to prescribe periodic blood tests. The dose and frequency of Retacrit may still be adjusted to ensure the medicine continues to have the desired effect. Your doctor will use the lowest effective dose to control anaemia symptoms.
• If you do not respond adequately to Retacrit, your doctor will review your dose and inform you if any changes are needed.
• If you are receiving Retacrit with extended dosing intervals (less than once a week), you may not maintain adequate haemoglobin levels and may require an increase in the dose or frequency of Retacrit administration.
• Before and during treatment with Retacrit, you may also be given iron supplements to make the treatment more effective.
• If you are undergoing dialysis when starting Retacrit treatment, adjustments to your dialysis parameters may be necessary. Your doctor will decide on this.

Adults undergoing chemotherapy

• Your doctor may start Retacrit therapy if your haemoglobin level is ≤10 g/dL.
• Your doctor will maintain haemoglobin levels between 10 and 12 g/dL, as higher levels may increase the risk of blood clots and death.
• The starting dose is 150 IU per kilogram of body weight three times a week or 450 IU per kilogram of body weight once a week.
• Retacrit is administered by subcutaneous injection.
• Your doctor will prescribe blood tests and may adjust the dose based on how your anaemia responds to Retacrit.
• Before and during treatment with Retacrit, you may also be given iron supplements to enhance treatment effectiveness.
• You will usually continue Retacrit treatment for an additional month after completing chemotherapy.

Adults donating their own blood

• The usual dose is 600 IU per kilogram of body weight twice a week.
• Retacrit is administered by intravenous injection immediately after blood donation, during the 3 weeks before surgery.
• Before and during treatment with Retacrit, you may also be given iron supplements to enhance treatment effectiveness.

Adults undergoing major elective orthopaedic surgery

• The recommended dose is 600 IU per kilogram of body weight once a week.
• Retacrit is administered by subcutaneous injection once a week for three weeks before surgery and on the day of surgery.
• If, for medical reasons, the time before surgery is shortened, you will receive a daily dose of 300 IU/kg for ten days before surgery, on the day of surgery, and for four days after.
• If blood tests before surgery show haemoglobin levels that are too high, treatment will be stopped.
• Before and during treatment with Retacrit, you may also be given iron supplements to enhance treatment effectiveness.

Adults with myelodysplastic syndrome

• Your doctor may start Retacrit treatment if your haemoglobin level is ≤10 g/dL. The goal of treatment is to maintain haemoglobin levels between 10 and 12 g/dL, as higher 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 a week.
• Your doctor will prescribe blood tests and may adjust the dose based on how your anaemia responds to Retacrit.

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

• Do not attempt to self-inject unless your doctor or nurse has shown you how to do so.
• Always use Retacrit exactly as instructed by your doctor or nurse.
• Only use Retacrit if it has been properly stored – see section 5, How to store Retacrit.
• Before use, remove the Retacrit syringe from the refrigerator and allow it to reach room temperature. This usually takes 15–30 minutes.

Draw up a single dose of Retacrit from each syringe.
When Retacrit is administered subcutaneously, the injected volume is normally no more than one millilitre (1 mL) per injection. If a larger volume is required, multiple injection sites should be used.
Retacrit must be administered alone and must not be mixed with other injectable liquids.
Do not shake Retacrit syringes. Prolonged or vigorous shaking may damage the medicine. Do not use the medicine if it has been vigorously shaken.

How to self-inject using a pre-filled syringe

• Remove the box containing the pre-filled syringe from the refrigerator.
• Remove the blister pack containing the pre-filled syringe from the box. If the box contains multiple syringes, tear along the perforated section to separate one blister containing a single syringe, return the remaining blister to the box, and place the box back in the refrigerator.
• Open the blister containing the pre-filled syringe after removing it from the refrigerator. Allow the liquid to reach room temperature. Do not remove the needle cap while the syringe is warming to room temperature.

• Check the syringe to ensure it is the correct dose, has not expired, is undamaged, and the liquid is clear and not frozen.
• Do not use the pre-filled syringe if:
  • The box is open or damaged.
  • The medicine is cloudy, discoloured, or contains floating particles.
  • Any part of the pre-filled syringe appears cracked or broken, or if any liquid has leaked out.
  • The pre-filled syringe has been dropped (it may be broken even if not visibly damaged).
  • The needle cap is missing or not securely attached.
  • The expiry date printed on the label has passed.
    In any of these cases, discard the syringe and use a new one.
• Choose the injection site. Suitable sites are the upper thigh and abdomen (excluding the area around the navel). Change the injection site each time.
• Wash your hands. Use an antiseptic swab to clean the injection site.
• Hold the pre-filled syringe by the barrel with the needle cap pointing upwards.
  • Do not hold the syringe by the plunger tip, plunger, or needle cap.
  • Do not pull back on the plunger.
  • Do not remove the needle cap until you are ready to inject the medicine.
• Remove the needle cap by holding the barrel and pulling the cap straight off, without twisting, away from your body. Discard the 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 squeeze too hard.
• With the other hand, hold the pre-filled syringe like a pencil. With a quick motion, as if throwing a dart, insert the needle under the skin at an angle of about 45°.

• Push the needle fully in. Your doctor or nurse will have shown you how to do this.
• Push the plunger slowly and steadily with your thumb until all the liquid is injected, keeping the skin pinched.
• When the plunger is fully depressed, remove the needle and release the skin.
• A small amount of blood may appear at the injection site after needle removal. This is normal. You may press the antiseptic swab on the site for a few seconds after injection.
• Do not attempt to recap the needle. Dispose of the used syringe in a sharps disposal container (puncture-resistant).
• Never dispose of used syringes in household waste.

How to self-inject using a pre-filled syringe with a passive needle safety device
The pre-filled syringe may include a passive needle safety device to protect against accidental needle sticks.

• Remove the box containing the pre-filled syringe with the passive needle safety device from the refrigerator.
• Remove the blister pack containing the syringe from the box. If the box contains multiple syringes, tear along the perforated section to separate one blister, return the rest to the box, and place the box back in the refrigerator.
• Open the blister by removing the lid.
• Remove the pre-filled syringe from the blister by holding the body.
  • Do not grip the grey needle cap or plunger rod.

• Check the syringe and ensure the safety shield covers the needle. Do not push the safety shield over the cap before injection, as this may activate or block the device. If the safety shield covers the needle, it has been activated.
• Allow the liquid to reach room temperature. Do not remove the needle cap while the syringe is warming.

1 Safety shield
2 Needle cap
3 Medicine
4 Plunger rod

• Check the syringe to ensure it is the correct dose, has not expired, is undamaged, and the liquid is clear and not frozen.

• Do not use the pre-filled syringe if:

  • The box is open or damaged.
  • The safety shield is missing, detached, or has been activated.
  • The medicine is cloudy, discoloured, or contains floating particles. Do not inspect the product through the plastic safety shield.
  • Any part of the syringe appears cracked or broken, or if liquid has leaked.
  • The syringe has been dropped (may be damaged even if not visible).
  • The needle cap is missing or not securely attached.
  • The expiry date has passed.
    In any of these cases, discard the syringe and use a new one.

• Choose the injection site. Suitable sites are the upper thigh and abdomen (excluding the navel area). Change the site each time.

• Wash your hands. Use an antiseptic swab to clean the injection site.

• Hold the pre-filled syringe by the safety shield body with the needle cap pointing upwards.

  • Do not hold the syringe by the plunger tip, plunger, or needle cap.
  • Do not pull back on the plunger.
  • Do not remove the needle cap until you are ready to inject.

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

• Pinch a skin fold between thumb and index finger. Do not squeeze.
• With the other hand, hold the syringe like a pencil. With a quick motion, insert the needle under the skin at about 45°.

• Insert the needle fully. Your doctor or nurse will have shown you how.
• While holding the syringe with fingers on the support rim, press the plunger steadily until the full dose is injected. The safety shield will not activate unless the entire dose is administered.

• When the plunger is fully depressed, remove the needle and release the skin.
• Release the plunger; the syringe will move forward until the safety shield covers and locks the needle in place.

• A small amount of blood may appear at the injection site. This is normal. Press the antiseptic swab on the site for a few seconds.
• Do not attempt to recap the needle. Dispose of the used syringe in a sharps disposal container.
• Never dispose of used syringes in household waste.

How to self-inject using a pre-filled syringe with Needle-Trap needle protection
Your syringe may have a Needle-Trap safety feature designed to prevent accidental needle sticks after injection. It consists of a plastic “catch” securely attached to the syringe label. Together, these form the Needle-Trap safety system.
The Needle-Trap requires specific actions by the user to “activate” it, rendering the needle harmless after injection.

• Remove the box containing the pre-filled syringe from the refrigerator.
• Remove the blister pack from the box. If the box contains multiple syringes, tear along the perforated section to separate one blister, return the rest to the box, and place the box back in the refrigerator.
• After removing from the refrigerator, open the blister containing the Needle-Trap syringe by removing the cover.
• Grasp the syringe body to remove it from the blister.

• Do not remove the needle cap until you are ready to inject.

• Allow the liquid to reach room temperature. Do not remove the needle cap during warming.

• Check the syringe for correct dose, expiry, damage, and clear, unfrozen liquid.

• Do not use the pre-filled syringe if:

  • The box is open or damaged.
  • The medicine is cloudy, discoloured, or contains particles.
  • Any part of the syringe is cracked, broken, or leaking.
  • The syringe has been dropped (may be damaged even if not visible).
  • The needle cap is missing or loose.
  • The expiry date has passed.
    In any of these cases, discard the syringe and use a new one.

• Choose the injection site. Suitable sites: upper thigh and abdomen (avoid navel area). Change site each time.

• Wash hands. Clean the site with an antiseptic swab.

• Hold the pre-filled syringe by the barrel with needle cap pointing up.

  • Do not hold by plunger tip, plunger, or needle cap.
  • Do not pull back on the plunger.
  • Grip the plastic catch tip and bend it away from the needle cap.

• Do not remove the needle cap until ready to inject.

• Remove the needle cap by holding the barrel and pulling straight off, without twisting, away from your body. Discard the cap. Do not recap. Do not push plunger, touch needle, or shake.

• Pinch a skin fold. Do not squeeze.
• With the other hand, hold the syringe like a pencil. With a quick motion, insert the needle under the skin at about 45°.

• Insert needle fully.
• Push the plunger with your thumb until all liquid is injected. Push slowly and steadily while holding the skin fold.
• When the plunger is fully depressed, remove the needle and release the skin.
• Place the plastic catch on a hard, stable surface. With one hand, push the syringe body upward, towards the needle, forcing the needle into the plastic catch until you hear a “click” (indicating the needle is locked). Continue bending until the syringe forms an angle greater than 45° to render it unusable.

• A small amount of blood may appear at the injection site. This is normal. Press the antiseptic swab for a few seconds.
• Do not attempt to recap the needle. Dispose of the used syringe in a sharps disposal container.
• Never dispose of used syringes in household waste.

If you use more Retacrit than you should
Inform your doctor or nurse immediately if you think you have injected too much Retacrit.
Overdose-related side effects are unlikely.

If you forget to use Retacrit
Inject the next dose as soon as you remember. If less than one day remains until the next scheduled dose, skip the missed dose and continue with your regular schedule. Do not double the dose to make up for a missed injection.

If you have hepatitis C and are taking interferon and ribavirin
Discuss this with your doctor, as in rare cases, the combination of epoetin zeta with interferon and ribavirin has led to loss of response and development of Pure Red Cell Aplasia (PRCA), a serious form of anaemia. Retacrit is not approved for managing anaemia associated with hepatitis C.

If you have any questions about using this medicine, consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Tell your doctor or nurse if you notice any of the effects listed below.

Serious skin reactions have been reported with epoetin treatment, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These may appear as red, target-like spots or circular patches, often with central blisters on the trunk, skin peeling, mouth ulcers, and sores in the throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms. If you develop any of these symptoms, stop treatment with Retacrit immediately and contact your doctor without delay. See also section 2.

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

• Diarrhoea
• Feeling unwell in the stomach
• Vomiting
• Fever
• In patients with kidney disease not yet on dialysis, respiratory tract congestion, such as stuffy nose and sore throat, has been reported.

Common: may affect up to 1 in 10 people.

• Increased blood pressure. Headache, particularly if sudden and severe, resembling migraine, or confusion or seizures, may be signs of a sudden rise in blood pressure requiring urgent treatment. Increased blood pressure may require treatment with medicines (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 rashes, which may be due to an allergic reaction.
• Bone or muscle pain
• Flu-like symptoms, such as headache, joint aches and pains, weakness, chills, fatigue, and dizziness. These reactions are more common at the beginning of treatment. If you experience these symptoms during intravenous injection, 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: 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).
• Seizures
• Nasal or airway congestion
• Allergic reaction
• Skin rash

Rare: may affect up to 1 in 1,000 people.

• 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 anaemia, whose symptoms are:
  o unusual tiredness,
  o dizziness,
  o shortness of breath.

PRCA has been very rarely observed, particularly in patients with kidney disease, after months or years of treatment with Retacrit and other substances stimulating red blood cell production.

• Especially at the beginning of treatment, an increase in the level of small blood cells (called platelets), normally involved in blood clotting, may occur. 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).
• A problem with the blood compartment that may cause pain, dark-coloured urine, or increased skin sensitivity to sunlight (porphyria).

If you are on haemodialysis:

• 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 haemodialysis 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 effects, or if you experience any other side effects during treatment with Retacrit.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, nurse, or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Retacrit

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 after "Exp."/"EXP". The expiry date refers to the last day of that month.
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 no more than 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 3 days or 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 solution does not appear colourless, or if visible particles are present. If you observe any of these abnormalities, discard the medicine.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Retacrit contains

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

Retacrit 1,000 UI/0.3 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 UI/0.6 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 UI/0.9 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 UI/0.4 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 UI/0.5 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 UI/0.6 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 UI/0.8 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 10,000 UI/1 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 1.0 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 20,000 UI/0.5 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 30,000 UI/0.75 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 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 40,000 UI/1 mL solution for injection in pre-filled syringe
1 pre-filled syringe with 1.0 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 excipients are disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride (see section 2 “Retacrit contains sodium”), calcium chloride dihydrate, polysorbate 20, glycine, leucine, isoleucine, threonine, glutamic acid, phenylalanine (see section 2 “Retacrit contains phenylalanine”), and water for injections, sodium hydroxide (to adjust pH), hydrochloric acid (to adjust pH).

Description of the appearance of Retacrit and contents of the pack

Retacrit is a clear, colourless solution for injection, contained in pre-filled syringes with fixed needle.
The pre-filled syringes contain between 0.3 mL and 1 mL of solution, depending on the epoetin zeta content (see section “What Retacrit contains”).
A pack contains 1, 4 or 6 pre-filled syringes, with or without needle protection device or with Needle Trap needle.
Multiple packs contain 4 (4x1) or 6 (6x1) 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.
Prudnička cesta 60
10291 Prigorje Brdovečko
Croatia

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

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg Pfizer Luxembourg SARL filialas Lietuvoje
Pfizer NV/SA Tel: +370 5 251 4000
Tél/Tel: +32 (0)2 554 62 11

България Magyarország
Пфайзер Люксембург САРЛ, Клон България Pfizer Kft.
Тел.: +359 2 970 4333 Tel.: + 36 1 488 37 00

Česká republika Malta
Pfizer, spol. s r.o. Drugsales Ltd
Tel: +420-283-004-111 Tel: +356 21419 070/1/2

Danmark Nederland
Pfizer ApS Pfizer bv
Tlf: + 45 44 20 11 00 Tel: +31 (0)800 63 34 636

Deutschland Norge
PFIZER PHARMA GmbH Pfizer AS
Tel: + 49 (0)30 550055-51000 Tlf: +47 67 52 61 00

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
Pfizer Ελλάς A.E. Pfizer Polska Sp. z o.o.
Τηλ: + 30 210 6785800 Tel.: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Tel: +34 91 490 99 00 Tel: +351 21 423 5500

France România
Pfizer Pfizer Romania S.R.L.
Tél: + 33 (0)1 58 07 34 40 Tel: +40 (0)21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL
Tel: +385 1 3908 777 Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ireland Slovenská republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: 1800 633 363 (toll free) Tel: + 421 2 3355 5500
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Sími: +354 540 8000 Puh/Tel: +358 (0)9 430 040

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00

Κύπρος United Kingdom
Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch) Hospira UK Limited
Τηλ: +357 22 817690 Tel: + 44 (0) 1628 515500

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: + 371 670 35 775

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.