BINOCRIT 10,000 IU/1 ml INJECTABLE SOLUTION IN A PRE-FILLED SYRINGE

2. What you need to know before you use Binocrit

Do not use Binocrit

• If you are allergicto epoetin alfa or 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 the production of red blood cells (including Binocrit). See section 4.

• If you have uncontrolled high blood pressure.
• To stimulate the production of red blood cells (so that your doctors can take more blood from you), if you cannot receive transfusions of your own bloodduring or after surgery.

• If you are about to undergo elective major orthopaedic surgery(e.g. hip or knee replacement) and you:

• have severe heart disease,
• have severe disorders of the veins and arteries,
• have recently had a heart attack or stroke,
• cannot take medicines to prevent blood clots.

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

Warnings and precautions

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

Binocrit and other products that stimulate the production of red blood cells may increase the risk of blood clots in all patients.This risk may be higher if you have other risk factors for blood clots (e.g. if you have had a blood clot in the past or have excess weight, diabetes, heart disease, or are bedridden for a long time due to surgery or illness). Inform your doctor about any of these. 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;
• seizures or convulsions;
• liver disease;
• anaemia from 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 dose of Binocrit if you do not respond to treatment may increase the risk of heart or blood vessel problems and may increase the risk of heart attack, stroke, and death.

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

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 may be associated with lower 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 the administration of epoetins.

SJS/TEN may initially appear as red, circular patches, often with central blisters on the trunk. Ulcers on the mouth, throat, nose, genitals, and eyes (irritation and swollen eyes) may also appear. These severe skin reactions often precede 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 contact your doctor or seek medical attention immediately.

Be careful with other products that stimulate the production of red blood cells:

Binocrit is a product belonging to a group of products that stimulate the production of red blood cells, like erythropoietin, which is a human protein. Your healthcare professional will always record the exact product you are using. If, during your treatment, you are given a product from this group that is different from Binocrit, talk to your doctor or pharmacist before using it.

Other medicines and Binocrit

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

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

Talk to your doctor, as the combination of epoetin alfa with interferon and ribavirin has led to a loss of effect and the occurrence of a disease called pure red cell aplasia (PRCA), a serious form of anaemia, in rare cases. Binocrit is not approved for the treatment of anaemia associated with hepatitis C.

If you are taking a medicine called ciclosporin(which is used, for example, after a kidney transplant), your doctor may request blood tests to check the concentration of ciclosporin 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, tell them that you are being treated with Binocrit, as it may affect other treatments or test results.

Pregnancy, breast-feeding, and fertility

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:

• , think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

There is 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; this is, essentially, “sodium-free”.

3. How to use Binocrit

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.

Binocrit can be administered by injection:

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

Your doctor will decide how Binocrit will be injected. The injections will usually be performed by a doctor, nurse, or other healthcare professional. Later on, and depending on the reason why you need treatment with Binocrit, some people may learn to self-inject the medication under the skin: see Instructions on how to inject Binocritat the end of the prospectus.

Binocrit should not be used:

• after the expiration date on the label and carton;
• if you know or believe it may have been accidentally frozen, or
• if there has been a refrigerator failure.

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

Your doctor will periodically check your blood pressurewhile you are being treated with Binocrit.

People with kidney disease

• Your doctor will keep your hemoglobin levels between 10 and 12 g/dl, as high hemoglobin levels can increase the risk of blood clots and death. In children, the hemoglobin level should be kept between 9.5 and 11 g/dl.
• The usual initial doseof Binocrit for adults and children is 50 international units (IU) per kilogram (kg) of body weight, administered three times a week. In patients on peritoneal dialysis, Binocrit can be administered twice a week.
• Both in adults and children, Binocrit is administered by injection, either in a vein (intravenously) or through a tube that is inserted into a vein. When it is not possible to easily access a vein or tube, your doctor may decide that Binocrit should be injected under the skin (subcutaneously). This includes patients on dialysis and those who are not yet on dialysis.
• Your doctor will request periodic blood tests to see how your anemia is responding, usually no more than every four weeks, and may adjust the dose. An increase in hemoglobin of more than 2 g/dl during a four-week period should be avoided.

• Once the anemia has been corrected, your doctor will continue to perform periodic blood tests. They may adjust the dose and frequency of administration of Binocrit 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 administration.
• You may be given iron supplements before and during treatment with Binocrit to increase its effectiveness.
• If you are on dialysis at the start of therapy with Binocrit, it may be necessary to adjust your 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 10 g/dl or lower.
• • Your doctor will keep your hemoglobin levels between 10 and 12 g/dl, as high hemoglobin levels can increase the risk of blood clots and death.
  • The initial dose is 150 IU per kilogram of body weight three times a week, or450 IU per kilogram of body weight once a week.

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

Adults who donate their own blood

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

Adults scheduled for major orthopedic surgery

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

• Treatment will be stopped if blood tests show that your hemoglobin is too high before surgery.
• You may be given iron supplements before and during treatment with Binocrit 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 keep your hemoglobin level between 10 and 12 g/dl, as higher hemoglobin levels can increase the risk of blood clots and death.
• Binocrit is administered by injection under the skin.
• The initial dose is 450 IU per kilogram of body weight once a week.
• Your doctor will request blood tests and may adjust the dose, depending on how your anemia responds to treatment with Binocrit.

Instructions on how to inject Binocrit

When starting treatment, medical or nursing staff usually inject Binocrit. Later on, your doctor may suggest that you or your caregiver learn to inject Binocrit under the skin (subcutaneously) by 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 as 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 sit at room temperature until it reaches room temperature. This usually takes between 15 and 30minutes. Use the syringe within 3days of removing it from the refrigerator.

Only withdraw one dose of Binocrit from each syringe.

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

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

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

At the end of this prospectus, you can find the Instructions on how to 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. It is unlikely that adverse effects will occur as a result of an overdose of Binocrit.

If you forget to use Binocrit

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

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

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

Severe skin rashes, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been observed with the administration of epoetins. These reactions can appear as red, circular patches, 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 Binocrit if you experience these symptoms and contact your doctor or seek medical attention immediately. See also section 2.

Very common side effects

May affect more than 1 in 10 people.

• Diarrhea.
• Feeling of nausea.
• Vomiting.
• Fever.
• Congestion of the respiratory tract, such as a stuffy nose and sore throat, which have been reported in patients with kidney disease who are not yet on dialysis.

Common side effects

May affect up to 1 in 10 people.

• Increased blood pressure. Headaches, especially sudden, severe, and migraine-like, feeling of confusion or seizures, can 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 medication 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 of one leg, as symptoms.
• Cough.
• Skin rash, which can occur as a result of an allergic reaction.
• Bone or muscle pain.
• Flu-like symptoms, such as headache, joint pain, feeling of weakness, chills, fatigue, and dizziness. These may be more frequent at the start of treatment. If these symptoms occur during injection into a vein, slower administration of the injection may help avoid 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 100 people.

• High levels of potassium in the bloodthat can cause an abnormal heart rhythm (this is a very common side effect in patients on hemodialysis).
• Seizures.
• Congestion of the nose or respiratory tract.

Rare side 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. The symptoms are:

• Unusual fatigue.
• Feeling of dizziness.
• 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 products that stimulate red blood cell production.

• There may be an increase in the number of small blood cells (platelets) that normally participate in the formation of blood clots, especially at the start of treatment. Your doctor will check this.

If you are on hemodialysis:

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

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

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

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

Reporting of side effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Binocrit

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date on the label and carton after EXP. The expiration date is the last day of the month indicated.
• Store and transport refrigerated (between 2 °C and 8 °C).
• You can remove Binocrit from the refrigerator and store 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 notice

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

Medicines should not be disposed of via wastewater.Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Container contents and additional information

Composition of Binocrit

• The active substance is: epoetin alfa (to know the quantity, 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 injectable solutions.

Appearance of the product and container contents

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

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

Only some pack sizes may be marketed.

Marketing authorization holder

Sandoz GmbH

Biochemiestr. 10

6250 Kundl

Austria

Manufacturer

Sandoz GmbH

Biochemiestr. 10

6336 Langkampfen

Austria

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of last revision ofthis leaflet: {MM/YYYY}.

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

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Self-injection instructions (for patients withsymptomatic anemia caused by a kidney disease, for adult patients receiving chemotherapy, adult patients scheduled for major orthopedic surgery or adult patients with myelodysplastic syndromes)

This section contains information on how to administer a Binocrit injection yourself. It is important that you do not attempt to administer the injection without your doctor or nurse having explained how to do it.Binocrit may be supplied with or without a needle safety protector, which your doctor or nurse will show you how 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 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 the packaging and remove the needle cap. The syringes are graduated with markings to allow for partial use if necessary. Each marking corresponds to a volume of 0.1 ml. If partial use of the syringe is required, discard the unused solution before injection.
3. Clean the skin at the injection site with an alcohol swab.
4. Form a fold in the skin by pinching the skin between your thumb and index finger.
5. Insert the needle into the skin fold with a quick and firm action. Inject the Binocrit solution as your doctor has shown you. Consult your doctor or pharmacist if you have any doubts.

Pre-filled syringe without needle safety protector

1. While keeping the skin pinched, press the plunger slowly and evenly.
2. Once the liquid has been injected, remove the needle and release the skin. Apply pressure to the injection site with a dry and sterile gauze.
3. Discard unused medication and all materials that have come into contact with it. Use each syringe only for one injection.

Pre-filled syringe with needle safety protector

1. While keeping the skin pinched, press the plunger slowly and evenly until the entire dose has been administered and the plunger cannot be pushed further. Do not release 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 and sterile gauze.
3. Release the plunger. The needle safety protector will quickly move to cover the needle.
4. Discard unused medication and all materials that have come into contact with it. Use each syringe only for one injection.