Label: information for the patient

Binocrit 1 000UI/0,5ml injectable solution in pre-filled syringe

Binocrit 2 000UI/1ml injectable solution in pre-filled syringe

Binocrit 3 000UI/0,3ml injectable solution in pre-filled syringe

Binocrit 4 000UI/0,4ml injectable solution in pre-filled syringe

Binocrit 5 000UI/0,5ml injectable solution in pre-filled syringe

Binocrit 6 000UI/0,6ml injectable solution in pre-filled syringe

Binocrit 7 000UI/0,7ml injectable solution in pre-filled syringe

Binocrit 8 000UI/0,8ml injectable solution in pre-filled syringe

Binocrit 9 000UI/0,9ml injectable solution in pre-filled syringe

Binocrit 10 000UI/1ml injectable solution in pre-filled syringe

Binocrit 20 000UI/0,5ml injectable solution in pre-filled syringe

Binocrit 30 000UI/0,75ml injectable solution in pre-filled syringe

Binocrit 40 000UI/1ml injectable solution in pre-filled syringe

epoetina alfa

Read this label carefully before starting to use this medication, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse,even if they do not appear in this label. See section4.

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

Binocritis used to treat symptomatic anemia caused by kidney disease:

• In children undergoing hemodialysis.

• In adults undergoing hemodialysis or peritoneal dialysis.

• In adults with severe anemia who have not yet undergone dialysis.

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

Binocrit is used to treat anemia in adults receiving chemotherapyfor the treatment of solid tumors, malignant lymphoma, or multiple myeloma (bone marrow cancer) that may require blood transfusions. Binocrit can reduce the need for blood transfusions in these patients.

Binocrit is used in adults with moderate anemia who donate part of their blood before a surgical intervention, so that it can be readministered during the intervention or afterwards. Since Binocrit stimulates red blood cell production, doctors can extract more blood from these individuals.

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

Binocrit is used to treat anemia in adults with a bone marrow disorder that causes a severe alteration of blood cell formation (myelodysplastic syndromes).Binocrit can reduce the need for a blood transfusion.

No use Binocrit

• If you are allergicto epoetina alfa or to any of the other components of this medication (including those listed in section6).

• If you have been diagnosed with pure red cell aplasia(your bone marrow cannot produce enough red blood cells) after previous treatment with any product that stimulates red blood cell production (including Binocrit).See section4.

• If you have high blood pressurethat is not correctly controlled with medication.
• To stimulate red blood cell production (so that your doctors can take more blood from you),if you cannot receive transfusions of your own bloodduring surgery or after it.

• If you are about to undergo an elective major orthopedic surgery(such as, for example, a hip or knee operation) and you:

• have a severe heart disease,
• have severe vein and artery disorders,
• have recently had a heart attack or stroke,
• cannot take medications to thin your blood.

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Binocrit.

Binocrit and other products that stimulate red blood cell production may increase the risk of blood clots in all patients. This risk may be higher if you have other risk factorsfor blood clots(for example, if you have had a blood clot in the past or have obesity, diabetes, have a heart disease or are bedridden for a long time due to surgery or illness). Inform your doctor about any of these things. Your doctor will help you decide if Binocrit is suitable for you.

It is important that you inform your doctorif you identify with any of the following situations.You may still be able to use Binocrit, but discuss it with your doctor first.

If you know that you haveor have had:

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

If you are a patient with chronic kidney disease,and especially if you do not respond well to Binocrit, your doctor will check your Binocrit dose, because repeatedly increasing the Binocrit dose if you do not respond to treatment may increase the risk of heart or vascular problems and may increase the risk of myocardial infarction, stroke, and death.

If you are a cancer patient,you should know that products that stimulate red blood cell production (such as Binocrit) may act as a growth factor and therefore, in theory, affect the progression of cancer.

Depending on your individual situation, it may be preferable to have a blood transfusion. Discuss this with your doctor.

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

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

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

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

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

Binocrit is a product belonging to a group of products that stimulate red blood cell production, just like erythropoietin, which is a human protein. Your doctor will always note exactly the product you are using. If, during your treatment, you are administered a product belonging to this group, different from Binocrit, consult your doctor or pharmacist before using it.

Other medications and Binocrit

Inform your doctor if you aretaking,havetakenrecently or may have to take any other medication.

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

You must discuss it with your doctor, as the combination of epoetina alfa with interferon and ribavirin has caused a loss of effect and the appearance of a severe disease called pure red cell aplasia (AEP), a severe form of anemia, in rare cases. Binocrit is not approved for the treatment of anemia associated with hepatitis C.

If you are taking a medication called ciclosporin(which is used, for example, after a kidney transplant), your doctor may request blood tests to check the ciclosporin concentration,while you are being treated with Binocrit.

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

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

Pregnancy, breastfeeding, and fertility

It is essential that you inform your doctorif you identify with any of the following situations.You may still be able to use Binocrit, but discuss it with your doctor first:

• if you are pregnant or breastfeeding,think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

There are no data on the effects of Binocrit on fertility

Binocrit contains sodium:

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

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

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

Binocritcan be administered by injection:

• Eitherinto a vein or through a tube inserted into a vein (intravenously).
• Orunder the skin (subcutaneously).

Your doctor will decide how Binocrit will be injected. The injections will usually be administered by a doctor, nurse, or other healthcare professional. Later, depending on the reason for the treatment with Binocrit, some people may learn to self-inject the medication under the skin: seeInstructions for injecting Binocritat the end of the leaflet.

Binocrit should not be used:

• after the expiration date on the label and the carton box;
• if you know or believe that it has been accidentally frozen, or
• if there has been a malfunction in the refrigerator.

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

Your doctor will monitor your blood pressureperiodically while you are on treatment with Binocrit.

People with kidney disease

• Your doctor will keep your hemoglobin levels between 10 and 12g/dl, as high hemoglobin levels can 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 initial doseof Binocrit for adults and children is 50units international (UI) per kilogram (kg) of body weight, administered three times a week. In patients on peritoneal dialysis, Binocrit can be administered twice a week.
• Binocrit is administered in the form of an injection, either into a vein (intravenously) or through a tube inserted into a vein. When it is not possible to easily access a vein or tube, your doctor may decide that Binocrit should be injectedunder the skin (subcutaneously). This includes patients on dialysis and those who are not yet on dialysis.
• Your doctor will ask for periodic blood tests to see how you are responding to the anemia, generally not more than every four weeks, and may adjust the dose. It should be avoided to increase hemoglobin levels above 2 g/dl over a period of four weeks.

• Once the anemia has been corrected, your doctor will continue to perform periodic blood tests. It is possible that you will need to adjust the dose and frequency of Binocrit administration to maintain your response to treatment. Your doctor will use the minimum effective dose to control the symptoms of anemia.
• If you do not respond well to Binocrit, your doctor will check your dose and inform you if you need to modify the dose of Binocrit.
• If you receive a wider dosing interval (more than once a week) of Binocrit, you may not maintain an adequate hemoglobin concentration and may require an increase in the dose of Binocrit or the frequency of its administration.
• You may be given iron supplements before starting treatment with Binocrit and during the treatment to increase its effectiveness.
• If at the time of starting Binocrit therapy you are on dialysis treatment, it may be necessary to adjust the dialysis schedule. Your doctor will decide if this is necessary.

Adults undergoing chemotherapy

• Your doctor may start treatment with Binocrit if your hemoglobin level is 10g/dl or lower.
• • Your doctor will keep your hemoglobin levels between 10 and 12g/dl, as high hemoglobin levels can increase the risk of blood clots and death.
  • The initial dose is 150UI per kilogram of body weight three times a week,or450UI per kilogram of body weight, once a week.

• Binocrit is administered by injection under the skin.
• Your doctor will ask for blood tests and may adjust the dose, depending on how you respond to the anemia treatment with Binocrit.
• • You may be given iron supplements before starting treatment with Binocrit and during the treatment to increase its effectiveness.
• Usually, you will continue treatment with Binocrit for a month after the end of chemotherapy.

Adults who donate their own blood

• The usual doseis 600UI per kilogram of body weight twice a week.
• Binocrit is administered by intravenous injection immediately after donating blood during the three weeks prior to the intervention.
• You may be given iron supplements before starting treatment with Binocrit and during the treatment to increase its effectiveness.

Adults scheduled for major orthopedic surgery

• The recommended doseis 600UI per kilogram of body weight once a week.
• Binocrit is administered by injection under the skin once a week for three weeks prior to the intervention and on the day of the intervention.
• • If there is a medical need to reduce the time prior to the intervention, you will be given a daily dose of 300UI/kg for a maximum of ten days before the intervention, on the day of the intervention, and for the four days immediately after.

• The treatment will be interrupted if blood tests show that your hemoglobin is too high before the intervention.
• You may be given iron supplements before starting treatment with Binocrit and during the treatment to increase its effectiveness.

Adults with myelodysplastic syndrome

• Your doctor may start treatment with Binocrit if your hemoglobin level is 10 g/dl or lower. The goal of treatment is to maintain your hemoglobin level between 10 and 12 g/dl, as high hemoglobin levels can increase the risk of blood clots and death.
• Binocrit is administered by injection under the skin.
• The initial dose is 450 UI per kilogram of body weight once a week.
• Your doctor will ask for blood tests and may adjust the dose, depending on how you respond to the anemia treatment with Binocrit.

Instructions for injecting Binocrit

When treatment begins, the medical or nursing staff usually injects Binocrit. Later, depending on the reason for the treatment with Binocrit, your doctor may suggest that you or your caregiver learn to inject Binocrit under the skin (subcutaneously) yourself.

• Do not attempt to self-inject unless your doctor or nurse has taught you how to do it.
• Follow exactly the administration instructions of Binocrit indicated by your doctor or nurse..
• Make sure to inject only the amount of liquid indicated by your doctor or nurse.
• Only useBinocritif it has been stored correctly; see section5,Storage of Binocrit.

• Before use, let the Binocrit syringe stand at room temperature until it reaches room temperature. This usually takes between 15 and 30minutes. Use the syringe within a maximum of 3days after removing it from the refrigerator.

Extract only one dose of Binocrit from each syringe.

If Binocrit is injected under the skin (subcutaneously), the usual amount injected is not more than one milliliter (1ml) in a single injection.

Binocrit is administered alone and not mixed with other injectable liquids.

Do not shake the Binocrit syringes.A prolonged and vigorous shaking can cause damage to the product. If the product has been shaken vigorously, do not use it.

You can find theInstructions for injecting Binocritat the end of this leaflet.

If you use more Binocrit than you should

Inform your doctor or nurse immediately if you think you have injected too much Binocrit. It is unlikely that you will experience adverse effects as a result of a Binocrit overdose.

If you forgot to use Binocrit

Take the next injection as soon as you remember. If there is less than a day to the next injection, skip the missed dose and continue with your regular program.Do not take a double dose to compensate for the missed doses.

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

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

Inform your doctor or nurse immediatelyif you notice any of the effects on this list.

Severe skin eruptions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been observed with the administration of epoetins. These reactions may appear as red, circular patches or macules 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 Binocrit if you experience these symptoms and contact your doctor or seek medical attention immediately. See also section2.

Very common side effects

May affect more than 1 in 10people.

Common side effects

May affect up to 1 in 10people.

• Increased blood pressure. Sudden, severe, and migraine-like headaches, confusion, and convulsions may be signs of a sudden increase in blood pressure. This requires urgent treatment. Increased blood pressure may require treatment with other medications (or adjustment of any medications already being taken for high blood pressure).
• Blood clots(including deep vein thrombosis and embolism) that may require urgent treatment. You may experiencechest pain, difficulty breathing, painful and swollen, and redness, usually of a legas symptoms.
• Cough.
• Skin rash, which may be caused by an allergic reaction.
• Musculoskeletal pain.
• Flu-like symptoms, such as headache, joint pain, feeling weak, chills, fatigue, and dizziness. These may be more frequent at the start of treatment. If these symptoms occur during intravenous injection, a slower injection rate may help prevent them in the future.
• Redness, itching, and pain at the injection site.
• Swelling of the ankles, feet, or fingers.

Uncommon side effects

May affect up to 1 in 100people.

• High levels of potassium in the bloodthat may cause an abnormal heart rhythm (this is a very common side effect in patients on hemodialysis).
• Convulsions.
• Nasal or respiratory tract congestion.

Rare side effects

May affect up to 1 in 1,000people.

• Symptoms of pure red cell aplasia (PRCA)

PRCA means that the bone marrow does not produce enough red blood cells. PRCA causes asevere and sudden anemia. The symptoms are:

• Unusual fatigue.
• Dizziness.
• Difficulty breathing.

PRCA has been reported in rare cases mainly in patients with kidney disease after months or years of treatment with epoetin alfa and other products that stimulate red blood cell production.

• Prolonged elevation of platelet counts, which normally intervene in the formation of blood clots, especially at the start of treatment. Your doctor will examine this.

If you are on hemodialysis:

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

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

Inform your doctor or nurse immediatelyif you notice any of these side effects, or if you notice any other side effect while receiving treatment with Binocrit.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this leaflet, inform your doctor, nurse, or pharmacist.

Reporting side effects

If you experience anytype of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this leaflet.You can also report them directly through the national notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the label and on the box after CAD/EXP. The expiration date is the last day of the month indicated.
• Store and transport refrigerated (between 2?°C and 8?°C).
• You may remove Binocrit from the refrigerator and keep it at room temperature (up to 25 °C) for a period not exceeding three 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.
• Store in the original packaging to protect it from light.

Do not use this medication if you observe

• that it may have been accidentally frozen or
• a refrigerator failure has occurred,
• the liquid is colored or you observe particles floating in it,
• the seal is broken.

Medicines should not be disposed of through the drains.Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Binocrit

• The active principle is: epoetina alfa (to know the amount, consult the table that appears below).
• The other components are: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, glycine, polisorbato 80, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment) and water for injectable solutions.

Aspect of the product and content of the packaging

Binocrit is presented as a transparent and colorless injectable solution, for injection in preloaded syringe. The syringes are sealed in a blister.

*Package size of 1, 4 or 6 preloaded syringe(s) with or without needle guard.

Only some package sizes may be marketed.

Marketing Authorization Holder

Sandoz GmbHBiochemiestr.10

6250 Kundl

Austria

Responsible for Manufacturing

Sandoz GmbH

Biochemiestr.10

6336 Langkampfen

Austria

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet: {MM/AAAA}.

For more detailed information about this medicinal product, please visit the website of the European Medicines Agency: http://www.ema.europa.eu.

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Self-injection instructions (for patients with symptomatic anemia caused by renal disease, for adult patients receiving chemotherapy, for adult patients scheduled for only surgical trauma intervention or for adult patients with myelodysplastic syndromes)

This section contains information on how to administer a Binocrit injection to yourself.It is essential that you do not attempt to administer the injection without first having your doctor or nurse explain how to do it.Binocrit may be administered with or without a needle guard, which your doctor or nurse will teach you to use. If you are unsure about self-administering the injection or have any questions, consult your doctor or nurse.

WARNING: Do not use if the syringe has fallen onto a hard surface or has been dropped after removing the needle cap. Do not use the preloaded Binocrit syringe if it is broken. Return the preloaded syringe and its packaging to the pharmacy.

1. Wash your hands.
2. Remove a syringe from the packaging and remove the needle cap. Syringes are engraved with graduation rings, allowing for partial use if necessary. Each graduation ring corresponds to a volume of 0.1ml. If partial use of the syringe is required, remove the unwanted solution before injection.
3. Clean the skin at the injection site with an alcohol-soaked cotton swab.
4. Form a fold in the skin, pinching the skin between your thumb and index finger.
5. Insert the needle into the skin fold quickly and firmly. Inject the Binocrit solution as instructed by your doctor. Consult your doctor or pharmacist if you are unsure.

Preloaded syringe without needle guard

1. Hold the skin pinched, push the plunger slowly and uniformly.
2. Once the liquid has been injected, remove the needle and release the skin. Apply pressure to the injection site with a dry, sterile gauze.
3. Dispose of any unused medication and materials that have come into contact with it. Use each syringe only once.

Preloaded syringe with needle guard

1. Hold the skin pinched, push the plunger slowly and uniformly until the entire dose has been administered and the plunger cannot move further. Do not release the pressure on the plunger!
2. Once the liquid has been injected, remove the needle while maintaining pressure on the plunger and release the skin. Apply pressure to the injection site with a dry, sterile gauze.
3. Release the plunger. The needle guard will quickly move to cover the needle.
4. Dispose of any unused medication and materials that have come into contact with it. Use each syringe only once.