Binocrit 30,000 UI/0.75 mL solution for injection in a pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

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

Binocrit 2,000 IU/1 ml solution for injection in pre-filled syringe

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

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

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

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

Binocrit 7,000 IU/0.7 ml solution for injection in pre-filled syringe

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

Binocrit 9,000 IU/0.9 ml solution for injection in pre-filled syringe

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

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

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

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

epoetin alfa

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Binocrit is and what it is used for

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

Binocrit is used to treat symptomatic anemia caused by kidney disease:

• In children on hemodialysis.

• In adults on hemodialysis or peritoneal dialysis.

• In adults with severe anemia who are not yet undergoing dialysis.

If you have kidney disease, you may have a low number of red blood cells because your kidney does not produce enough erythropoietin (which is 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 chemotherapy for the treatment of solid tumors, malignant lymphoma, or multiple myeloma (cancer of the bone marrow) who may require a blood transfusion. Binocrit may reduce the need for blood transfusions in these patients.

Binocrit is used in adults with moderate anemia who donate part of their blood before surgery, so that it can be reinfused during or after the procedure. Because Binocrit stimulates red blood cell production, doctors can collect 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 procedures), to reduce the potential need for blood transfusions.

Binocrit is used to treat anemia in adults with a bone marrow disorder causing a severe disturbance in blood cell formation (myelodysplastic syndromes). Binocrit may reduce the need for blood transfusion.

2. What you need to know before using Binocrit

Do not use Binocrit

• If you are allergic to epoetin alfa or to any of the other ingredients of this medicine (listed in section 6).

• If you have been diagnosed with pure red cell aplasia (the bone marrow cannot produce enough red blood cells) following previous treatment with any erythropoiesis-stimulating agent (including Binocrit). See section 4.

• If you have uncontrolled high blood pressure not properly managed 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 major elective orthopedic surgery (for example, hip or knee surgery) and you:

  • have severe heart disease,
  • have serious disorders of veins and arteries,
  • have recently had a heart attack or stroke,
  • cannot take medications to reduce blood thickness.

Binocrit may not be suitable for you. Speak with your doctor. Some people require medication to reduce the risk of blood clots during treatment with Binocrit. If you cannot take medications to prevent blood clot formation, you must not take Binocrit.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using Binocrit.

Binocrit and other erythropoiesis-stimulating agents may increase the risk of blood clots in all patients. This risk may be higher if you have other risk factors for blood clot formation (for example, if you have previously had a blood clot, are overweight, have diabetes, have 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 Binocrit is suitable for you.

It is important that you inform your doctor if any of the following apply to you. You may still be able to use Binocrit, but discuss this 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 Binocrit, your doctor will review your Binocrit dose, because repeatedly increasing the dose of Binocrit when not responding to treatment may increase the risk of heart or vascular problems and could increase the risk of myocardial infarction, stroke, and death.

If you are a cancer patient, you should know that erythropoiesis-stimulating agents (such as Binocrit) may act as growth factors and thus, in theory, may 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 Binocrit has been associated with reduced survival and higher mortality rates in patients with head and neck cancer and metastatic breast cancer who are receiving chemotherapy.

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

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

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

Take special care with other erythropoiesis-stimulating agents:

Binocrit is a medicine belonging to a group of erythropoiesis-stimulating agents, similar to erythropoietin, a human protein. Your healthcare provider will always record exactly which product you are using. If during your treatment you are given a different product from this group instead of Binocrit, consult your doctor or pharmacist before using it.

Other medicines and Binocrit

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

If you have hepatitis C and are receiving interferon and ribavirin

You should discuss this with your doctor, as the combination of epoetin alfa with interferon and ribavirin has rarely led to loss of response and the development of a condition called pure red cell aplasia (PRCA), a serious form of anemia. Binocrit is not approved for the treatment of anemia associated with hepatitis C.

If you are taking a medicine called ciclosporin (used, for example, after kidney transplantation), your doctor may order blood tests to monitor ciclosporin levels while you are receiving Binocrit.

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

If you visit a hospital, clinic, or general practitioner, inform them that you are receiving treatment with Binocrit, 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 Binocrit, but discuss this with your doctor first:

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

There are no data on the effects of Binocrit on fertility.

Binocrit contains sodium:

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

3. How to use Binocrit

Follow exactly the instructions for using 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 Binocrit.

Binocrit 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 Binocrit will be injected. Injections are usually performed by a doctor, nurse, or other healthcare professional. Later, and depending on the reason for treatment with Binocrit, some people may be trained to self-inject the medicine under the skin: see Instructions on how to self-inject Binocrit at the end of this leaflet.

Binocrit must not be used:

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

The dose of Binocrit you will receive is based on your body weight in kilograms. The cause of your anaemia 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 Binocrit.

Patients with kidney disease

• Your doctor will keep your haemoglobin levels between 10 and 12 g/dl, as high haemoglobin levels may increase the risk of blood clots and death. In children, haemoglobin levels should be maintained between 9.5 and 11 g/dl.

• The usual initial dose of Binocrit for adults and children is 50 international units (IU) per kilogram (kg) of body weight, administered three times per week. In patients undergoing peritoneal dialysis, Binocrit may be given twice per week.

• In both adults and children, Binocrit is administered by injection either into a vein (intravenously) or through a tube inserted into a vein. When venous access (via a vein or tube) is not easily available, your doctor may decide that Binocrit should be injected under the skin (subcutaneously). This includes patients on dialysis and those not yet on dial游戏副本.

• Your doctor will request periodic blood tests to monitor your response to treatment, generally no more frequently than every four weeks, and may adjust the dose. An increase in haemoglobin greater than 2 g/dl over a four-week period should be avoided.

• Once anaemia has been corrected, your doctor will continue to perform periodic blood tests. Your dose and frequency of Binocrit administration may be further adjusted to maintain your response to treatment. Your doctor will use the lowest effective dose to control the symptoms of anaemia.

• If you do not respond well to Binocrit, your doctor will review your dose and inform you if a dose adjustment is needed.

• If you receive Binocrit less frequently than once per week, you may not maintain adequate haemoglobin levels and may require an increase in either the dose or frequency of administration.

• You may be given iron supplements before and during treatment with Binocrit to enhance its effectiveness.

• If you are undergoing dialysis at the start of Binocrit therapy, your dialysis schedule may need to be adjusted. Your doctor will decide whether this is necessary.

Adults receiving chemotherapy

• Your doctor may start treatment with Binocrit if your haemoglobin level is 10 g/dl or lower.

  • Your doctor will maintain your haemoglobin levels between 10 and 12 g/dl, as high haemoglobin levels may increase the risk of blood clots and death.
  • The initial dose is 150 IU per kilogram of body weight three times per week, or 450 IU per kilogram of body weight once per week.

• Binocrit is administered by subcutaneous injection.

• Your doctor will request blood tests and may adjust the dose depending on how your anaemia responds to Binocrit treatment.

  • You may be given iron supplements before and during treatment with Binocrit to enhance its effectiveness.

• You will usually continue Binocrit treatment for one month after completion of chemotherapy.

Adults donating their own blood

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

Adults scheduled for major orthopaedic surgery

• The recommended dose is 600 IU per kilogram of body weight once per week.

• Binocrit is administered by subcutaneous injection once weekly for three weeks before surgery and on the day of surgery.

  • If there is a medical need to shorten the pre-surgery period, you will receive a daily dose of 300 IU/kg for up to ten days before surgery, on the day of surgery, and for four days immediately after.

• Treatment will be stopped if blood tests show that your haemoglobin level is too high before surgery.

• You may be given iron supplements before and during treatment with Binocrit to enhance its effectiveness.

Adults with myelodysplastic syndrome

• Your doctor may start treatment with Binocrit if your haemoglobin level is 10 g/dl or lower. The aim of treatment is to maintain your haemoglobin level between 10 and 12 g/dl, as higher haemoglobin levels may increase the risk of blood clots and death.
• Binocrit is administered by subcutaneous injection.
• The initial 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 anaemia responds to Binocrit treatment.

Instructions on how to self-inject Binocrit

When treatment is started, Binocrit is usually injected by medical or nursing staff. Later, your doctor may suggest that you or your caregiver learn to inject Binocrit 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 Binocrit given by your doctor or nurse.

• Ensure that you inject only the amount of liquid specified by your doctor or nurse.

• Only use Binocrit if it has been stored correctly; see section 5, Storage of Binocrit.

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

Withdraw only one dose of Binocrit from each syringe.

If Binocrit is injected under the skin (subcutaneously), the injected volume is usually no more than one millilitre (1 ml) per single injection.

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

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

At the end of this leaflet, you will find the Instructions on how to self-inject Binocrit.

If you use more Binocrit than you should

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

If you forget to use Binocrit

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

If you have any further questions about the use of this medicine, ask your doctor, nurse, or pharmacist.

4. Possible adverse effects

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

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

Severe skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been observed with administration of epoetins. These reactions may appear as red, target-like circular patches or blisters, often with central blisters on the trunk, skin peeling, and mouth, throat, nose, genital, and eye ulcers, and may be preceded by fever and flu-like symptoms. Stop using Binocrit if you experience these symptoms and contact your doctor or seek immediate medical attention. See also section 2.

Very common adverse effects

May affect more than 1 in 10 people.

• Diarrhea.
• Feeling nauseous.
• Vomiting.
• Fever.
• Respiratory congestion, such as stuffy nose and sore throat, which have been reported in patients with kidney disease who are not yet undergoing dialysis.

Common adverse effects

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 rise in blood pressure. This requires urgent treatment. Increased blood pressure may necessitate treatment with other medicines (or adjustment of any medication you are already taking for high blood pressure).
• Blood clots (including deep vein thrombosis and embolism), which may require urgent treatment. You may experience chest pain, difficulty breathing, and painful swelling and redness, usually in one leg, as symptoms.
• Cough.
• Skin rash, which may occur as a result of an allergic reaction.
• Bone or muscle pain.
• Flu-like symptoms, such as headache, joint pain, feeling weak, chills, fatigue, and dizziness. These may be more common at the beginning of treatment. If these symptoms occur during intravenous injection, a slower injection rate may help prevent them in the future.
• Redness, stinging, and pain at the injection site.
• Swelling of the ankles, feet, or fingers.

Uncommon adverse effects

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 adverse effect in patients undergoing hemodialysis).
• Seizures.
• Nasal or respiratory congestion.

Rare adverse effects

May affect up to 1 in 1,000 people.

• Symptoms of pure red cell aplasia (PRCA)

PRCA means that the bone marrow does not produce enough red blood cells. PRCA causes sudden and severe anemia. Symptoms include:

• Unusual tiredness.
• Feeling dizzy.
• Difficulty breathing.

PRCA has been reported in very rare cases, mainly in patients with kidney disease after months or years of treatment with epoetin alfa and other red blood cell-stimulating agents.

• An increase in the number of small blood cells (platelets), which normally help blood clotting, may occur, especially at the beginning of treatment. Your doctor will monitor this.

If you are undergoing hemodialysis:

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

• Blood clots may also form in your hemodialysis system. Your doctor may decide to increase 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 effects while receiving treatment with Binocrit.

If you think any of the adverse effects you experience are severe, or if you notice any adverse effect not listed in this leaflet, inform your doctor, nurse, or pharmacist.

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 detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Binocrit

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the label and on the carton after CAD/EXP. The expiry date refers to the last day of the month indicated.
• Store and transport refrigerated (between 2 °C and 8 °C).
• Binocrit may be removed from the refrigerator and kept 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.
• Keep in the original packaging to protect from light.

Do not use this medicine if you notice

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

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

6. Contents of the pack and other information

Composition of Binocrit

• The active substance is: epoetin alfa (for the amount, see the table below).
• The other components are: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, glycine, polysorbate 80, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

Appearance of the medicinal product and contents of the pack

Binocrit is presented as a clear, colourless injectable solution, for injection in a pre-filled syringe. The syringes are sealed in a blister.

Form	Corresponding presentations in quantity/volume for each dosage form	Amount of epoetin alfa
Pre-filled syringes*	2,000 IU/ml: 1,000 IU/0.5 ml 2,000 IU/1 ml 10,000 IU/ml: 3,000 IU/0.3 ml 4,000 IU/0.4 ml 5,000 IU/0.5 ml 6,000 IU/0.6 ml 7,000 IU/0.7 ml 8,000 IU/0.8 ml 9,000 IU/0.9 ml 10,000 IU/1 ml 40,000 IU/ml: 20,000 IU/0.5 ml 30,000 IU/0.75 ml 40,000 IU/1 ml	8.4 micrograms 16.8 micrograms 25.2 micrograms 33.6 micrograms 42.0 micrograms 50.4 micrograms 58.8 micrograms 67.2 micrograms 75.6 micrograms 84.0 micrograms 168.0 micrograms 252.0 micrograms 336.0 micrograms

*Package size of 1, 4 or 6 pre-filled syringe(s) with or without needle safety guard.

Only certain package sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sandoz GmbH

Biochemiestr. 10

6250 Kundl

Austria

More information on this medicine is available from the local representative of the Marketing Authorisation Holder:

Belgium/Belgium/Belgium Sandoz nv/sa Tel/Tel: +32 2 722 97 97	Lithuania Sandoz Pharmaceuticals d.d. branch Tel: +370 5 2636 037
	Luxembourg/Luxembourg Sandoz nv/sa Tél/Tel.: +32 2 722 97 97
Czech Republic Sandoz s.r.o. Tel: +420 225 775 111	Hungary Sandoz Hungária Kft. Tel.: +36 1 430 2890
Denmark/Norway/Iceland/Sweden Sandoz A/S Tlf: +45 63 95 10 00	Malta Sandoz Pharmaceuticals d.d. Tel: +356 9964 4126
Germany Hexal AG Tel: +49 8024 908 0	Netherlands Sandoz B.V. Tel: +31 36 52 41 600
Estonia Sandoz d.d. Estonian branch Tel: +372 665 2400	Austria Sandoz GmbH Tel: +43 5338 2000
Greece SANDOZ HELLAS MONOPROSOPIKI E.E. Tel: +30 216 600 5000	Poland Sandoz Polska Sp. z o.o. Tel.: +48 22 209 70 00
Spain Sandoz Farmacéutica, S.A. Tel: +34 900 456 856	Portugal Sandoz Farmacêutica Lda. Tel: +351 21 000 86 00
France Sandoz SAS Tél: +33 1 49 64 48 00	Romania Sandoz Pharmaceuticals SRL Tel: +40 21 407 51 60
Croatia Sandoz d.o.o. Tel: +385 1 23 53 111	Slovenia Sandoz farmacevtska družba d.d. Tel: +386 1 580 29 02
Ireland Rowex Ltd. Tel: +353 27 50077	Slovakia Sandoz d.d. - organisational unit Tel: +421 2 50 70 6111
Italy Sandoz S.p.A. Tel: +39 02 96541	Finland/Finland Sandoz A/S Puh/Tel: +358 10 6133 400
Cyprus Sandoz Pharmaceuticals d.d. Tel: +357 22 69 0690	United Kingdom (Northern Ireland) Sandoz GmbH Tel: +43 5338 2000
Latvia Sandoz d.d. Latvia branch Tel: +371 67 892 006

Date of the most recent revision of this leaflet: {MM/YYYY}.

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

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Self-injection instructions (for patients with symptomatic anaemia due to renal disease, adult patients receiving chemotherapy, adult patients scheduled only for traumatic surgical intervention, or adult patients with myelodysplastic syndromes)

This section contains information on how to self-administer an injection of Binocrit. It is important that you do not attempt to administer the injection yourself unless your doctor or nurse has first explained how to do so. Binocrit may or may not be supplied with a needle safety guard, which your doctor or nurse will show you how to use. If you are unsure whether you wish to administer the injection yourself or have any questions, consult your doctor or nurse.

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

1. Wash your hands.
2. Remove a syringe from its packaging and take off the needle cap. Syringes are marked with graduation rings to allow partial use if necessary. Each graduation ring corresponds to a volume of 0.1 ml. If partial use of the syringe is required, discard the unwanted solution before injection.
3. Clean the skin at the injection site with an alcohol-impregnated cotton pad.
4. Create a skin fold by pinching the skin between your thumb and index finger.
5. Insert the needle into the skin fold with a quick, firm motion. Inject the Binocrit solution as your doctor has instructed you. Consult your doctor or pharmacist if you have any doubts.

Prefilled syringe without needle safety guard While holding the skin pinched, press the plunger slowly and evenly. Once the liquid has been injected, withdraw the needle and release the skin. Apply pressure to the injection site with a dry, sterile gauze. Dispose of any unused medication and all materials that have come into contact with it. Use each syringe for only one injection.

Prefilled syringe with needle safety guard

While keeping the skin pinched, press the plunger slowly and evenly until the entire dose has been administered and the plunger can no longer move forward. Do not stop applying pressure on the plunger! Once the liquid has been injected, remove the needle while maintaining pressure on the plunger, then release the skin. Apply pressure to the injection site with a dry, sterile gauze. Release the plunger. The needle safety shield will quickly slide into place to cover the needle.

1. Dispose of any unused medication and all materials that have come into contact with it. Use each syringe only for one injection.