Binocrit

Patient Information Leaflet

Binocrit 1,000 IU/0.5 mL solution for injection in pre-filled syringe, 2,000 IU/1 mL solution for injection in pre-filled syringe, 3,000 IU/0.3 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, 7,000 IU/0.7 mL solution for injection in pre-filled syringe, 8,000 IU/0.8 mL solution for injection in pre-filled syringe, 9,000 IU/0.9 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 alfa
Please read all of this leaflet carefully before you start using this medicine, as 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this 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 carrying haemoglobin (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 anaemia caused by kidney disease:

• in children undergoing haemodialysis
• in adults undergoing haemodialysis or peritoneal dialysis
• in adults with severe anaemia who are not yet on dialysis

In kidney disease, a shortage of red blood cells may occur if the kidneys do 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 anaemia in adults undergoing chemotherapy for solid tumours, malignant lymphoma or multiple myeloma (a tumour of the bone marrow) who might otherwise require blood transfusions. Binocrit may reduce the need for blood transfusions in these patients.
Binocrit is used in moderately anaemic adults who donate part of their own blood before surgery, so that the collected blood can be given back to them during or after the surgical procedure. Because Binocrit stimulates red blood cell production, doctors can collect more blood from these individuals.
Binocrit is used in moderately anaemic adults who are about to undergo major orthopaedic surgery (e.g. hip or knee replacement surgery) to reduce the potential need for blood transfusions.
Binocrit is used to treat anaemia in adults with a bone marrow disorder causing severe disruption in blood cell production (myelodysplastic syndromes). Binocrit may reduce the need for blood transfusions.

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 fails to produce enough red blood cells) following treatment with any medicine that stimulates red blood cell production (including Binocrit). See section 4.
• if you have uncontrolled high blood pressure , not adequately controlled with medication.
• to stimulate red blood cell production (so that doctors can collect more of your blood) if you cannot receive transfusions with your own blood during or after surgery.
• if you are about to undergo elective major orthopedic surgery (such as hip or knee surgery) and:
• you have severe heart disease
• you have serious disorders of veins or arteries
• you have recently had a heart attack or stroke
• you cannot take medicines to make your blood less likely to clot. Binocrit may not be suitable for you. Discuss this with your doctor. During treatment with Binocrit, some people need medication to reduce the risk of blood clots. If you cannot take medicines that prevent blood clots, you must not take Binocrit .

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using 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 factors for developing blood clots
(e.g., if you have previously had a blood clot, or if you are overweight, have diabetes, have heart
disease, or need to remain lying down for a prolonged period due to surgery or illness). Inform your
doctor of any such 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 situations apply to you.
You may still be able to use Binocrit, but you should discuss it with your doctor first.
If you know you have or have previously had:

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

If you are a patient with chronic kidney failure , and particularly if you do not respond adequately
to Binocrit, your doctor will monitor the dose of Binocrit you receive, because repeatedly increasing
the dose of Binocrit when you do not respond to treatment may increase the risk of heart or blood
vessel problems, as well as the risk of myocardial infarction, stroke, and death.
If you are a cancer patient , be aware that medicines that stimulate red blood cell production (such as Binocrit) may act as growth factors and could theoretically affect tumor progression.
Depending on your individual situation, a blood transfusion might be preferable. Discuss this with your doctor.
If you are a cancer patient , be aware that Binocrit has been associated with shorter survival and a higher mortality rate in patients with head and neck cancer and metastatic breast cancer undergoing chemotherapy.
Severe skin reactions , including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported during treatment with epoetin.
SJS and TEN may initially appear as red target-like spots or circular patches, often with central blisters on the trunk. Mouth, throat, nose, genital, and eye ulcers (red, swollen eyes) may also occur. These severe skin rashes are often preceded by fever and/or flu-like symptoms. The skin rashes may progress to widespread skin peeling and life-threatening complications.
If you develop a severe skin rash or any of these other skin symptoms, stop taking Binocrit and contact your doctor immediately.
Exercise particular caution with other products that stimulate red blood cell production:
Binocrit belongs to a group of products that, like the human protein erythropoietin, stimulate red blood cell production. Your healthcare provider will always record the specific product you are using. If you are given a different medicine from this group during your treatment, talk to your doctor or pharmacist before using it.
Other medicines and Binocrit
Inform 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
You should discuss this with your doctor, because combining epoetin alfa with interferon and ribavirin has rarely led to loss of effect and development of a condition called pure red cell aplasia (PRCA), a serious form of anemia. Binocrit is not approved for the management of anemia associated with hepatitis C.
If you are taking a medicine called cyclosporine (used, for example, after kidney transplants), your doctor may perform blood tests to monitor cyclosporine levels during treatment with Binocrit.
Iron supplements and other blood stimulants may enhance the effectiveness of Binocrit. Your doctor will decide whether it is appropriate for you to take them.
If you go to hospital, a clinic, or visit your general practitioner , inform them that you are being treated with Binocrit. This may affect other treatments or test results.
Pregnancy, breastfeeding, and fertility
It is important to inform your doctor if any of the following situations apply to you.
You may still be able to use Binocrit, but you must discuss it with your doctor first:

• if you are pregnant , suspect you may be pregnant, plan to become pregnant, or are breastfeeding
  with breast milk , ask your doctor or pharmacist for advice before taking this medicine.

There are no data available on the effects of Binocrit on fertility.
Binocrit contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Binocrit

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.
Your doctor has performed blood tests and decided that you need Binocrit.
Binocrit can be administered by injection:

• into a vein or into a tube leading to a vein (intravenous route)
• or under the skin (subcutaneous route).

Your doctor will decide how Binocrit will be administered. Usually, injections are given by a doctor, nurse, or other healthcare professional. Some patients, depending on the reason for treatment with Binocrit, may later be trained to self-inject under the skin: see Instructions for self-injection of Binocrit at the end of this leaflet.

Binocrit must not be used:

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

The dose of Binocrit you will be given depends on your body weight in kilograms. The cause of the anemia is also important for the doctor to determine the correct dose.
Your doctor will regularly monitor your blood pressure during treatment with Binocrit.

Patients with kidney disease

• Your doctor will maintain your hemoglobin level between 10 and 12 g/dL, as a higher hemoglobin level may increase the risk of blood clots and death. In children, the hemoglobin level should be maintained between 9.5 and 11 g/dL.
• The usual initial dose of Binocrit in adults and children is 50 International Units (IU) per kilogram (/kg) of body weight, administered three times a week. In patients undergoing peritoneal dialysis, Binocrit may be given twice a week.
• In adults and children, Binocrit is administered as an injection into a vein (intravenous route) or into tubing leading to a vein. When this access (via a vein or tubing) is not readily available, your doctor may decide to inject Binocrit under the skin (subcutaneous route). This applies to patients on dialysis and those not yet on dialysis.
• Your doctor will regularly order blood tests to assess how the anemia responds to treatment and may adjust the dose, usually no more frequently than every four weeks. An increase in hemoglobin greater than 2 g/dL over four weeks should be avoided.
• Once the anemia has been corrected, your doctor will continue to monitor your blood regularly. The dose and frequency of Binocrit administration may be further adjusted to maintain the treatment response. Your doctor will use the lowest effective dose to control the symptoms of anemia.
• If you do not respond adequately to Binocrit, your doctor will review the dose you are receiving and inform you if adjustments to your Binocrit doses are needed.
• If you are using a longer interval (more than once weekly) between Binocrit doses, you may not be able to maintain adequate hemoglobin levels and may require an increase in dose or frequency of administration.
• Before and during treatment with Binocrit, you may also receive iron supplementation to enhance treatment effectiveness.
• If you are on dialysis when starting treatment with Binocrit, your dialysis schedule may need to be adjusted. Your doctor will make this decision.

Adults undergoing chemotherapy

• Your doctor may start treatment with Binocrit if your hemoglobin level is ≤10 g/dL.
• Your doctor will maintain your hemoglobin level between 10 and 12 g/dL, as higher hemoglobin levels may increase the risk of blood clots and death.
• The usual initial dose is 150 IU per kilogram of body weight three times a week or 450 IU per kilogram of body weight once a week.
• Binocrit is administered by subcutaneous injection.
• Your doctor will prescribe regular blood tests and may adjust the dose depending on how your anemia responds to treatment.
• Before and during treatment with Binocrit, you may also receive iron supplementation to enhance treatment effectiveness.
• Treatment with Binocrit usually continues for one month after completion of chemotherapy.

Adults donating their own blood

• The usual dose is 600 IU per kilogram of body weight, twice a week.
• Binocrit is administered by intravenous injection immediately after blood donation, for 3 weeks prior to surgery.
• Before and during treatment with Binocrit, you may also receive iron supplementation to enhance treatment effectiveness.

Adults awaiting major orthopedic surgery

• The recommended dose is 600 IU per kilogram of body weight once a week.
• Binocrit is administered by subcutaneous injection once weekly for three weeks before surgery and on the day of surgery.
• If there is a need to shorten the time before surgery, a daily dose of 300 IU/kg may be given for up to ten days before surgery, on the day of surgery, and for four days afterward.
• If blood tests show excessively high hemoglobin levels before surgery, treatment will be discontinued.
• Before and during treatment with Binocrit, you may receive iron supplementation to enhance treatment effectiveness.

Adults with myelodysplastic syndromes

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

Instructions for self-injection of Binocrit
At the beginning of treatment, Binocrit is usually injected by medical or paramedical staff.
Later, your doctor may suggest that you, or someone assisting you, learn to self-administer Binocrit under the skin (subcutaneously).

• Do not attempt to self-inject the medicine unless a doctor or nurse has shown you how to do so.
• Always use Binocrit exactly as instructed by your doctor or nurse.
• Ensure you inject only the amount of liquid specified by your doctor or nurse.
• Use Binocrit only if it has been stored correctly – see section 5, How to store Binocrit.
• Before use, allow the Binocrit syringe to sit until it reaches room temperature. This usually takes 15–30 minutes. Use the syringe within 3 days after removing it from the refrigerator.

Use a single dose of Binocrit from each syringe.
If Binocrit is injected under the skin (subcutaneously), the injected volume generally does not exceed one milliliter (1 mL) per injection.
Binocrit must be administered alone and must not be mixed with other injectable liquids.
Do not shake Binocrit syringes. Prolonged vigorous shaking may damage the product. If the product has been shaken vigorously, do not use it.
Instructions for self-injection of Binocrit are provided at the end of this leaflet.

If you use more Binocrit than you should
Inform your doctor or nurse immediately if you think too much Binocrit has been injected. Adverse effects due to overdose with Binocrit are unlikely.

If you forget to use Binocrit
Administer the missed 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 use a double dose to make up for a forgotten dose.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Immediately inform your doctor or nurse if you notice any of the side effects listed below.
Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in association with treatment with epoetin. These may appear as target-like red patches or circular patches, often with central blisters on the trunk, skin peeling, mouth, throat, nose, genital, or eye ulcers, and may be preceded by fever and flu-like symptoms. Stop using Binocrit and contact your doctor immediately if you develop any of these symptoms. See also section 2.

Very common side effects
May affect more than 1 in 10 people.

• Diarrhoea
• Nausea
• Vomiting
• Fever
• Respiratory congestion, such as nasal congestion and sore throat, has 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. The following signs may indicate a sudden rise in blood pressure: headache, particularly if sudden in onset and sharp, like a migraine, confusion or seizures. These signs require urgent treatment. Increased blood pressure may require treatment with medicines (or adjustment of the dose of medicines you are already taking for high blood pressure).
• Blood clots (including deep vein thrombosis and embolism), which may require urgent intervention. Symptoms may include chest pain, shortness of breath, and swelling with pain and redness, usually in the legs.
• Cough.
• Skin rashes, which may be due to an allergic reaction.
• Bone or muscle pain.
• Flu-like symptoms such as headache, joint pain and stiffness, feeling weak, chills, fatigue, and dizziness. These symptoms may be more common at the beginning of treatment. If you experience these symptoms during intravenous injection, a slower injection may help prevent them in the future.
• Redness, burning, and pain at the injection site.
• Swelling of the ankles, feet, or fingers.
• Pain in the arm or leg.

Uncommon side effects
May affect up to 1 in 100 people.

• High levels of potassium in the blood, which may cause irregular heart rhythms (this is a very common side effect in patients on dialysis).
• Seizures.
• Nasal or airway congestion.
• Allergic reaction.
• Hives (urticaria).

Rare side effects
May affect up to 1 in 1,000 people.

• Symptoms of pure red cell aplasia (PRCA)

Pure red cell aplasia (PRCA) means that the bone marrow does not produce enough red blood cells. PRCA causes sudden and severe anaemia. Symptoms are:

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

PRCA has been reported very rarely, particularly in patients with kidney disease, after months or years of treatment with epoetin alfa and other medicines that stimulate red blood cell production.

• An increase in the number of certain small blood cells (called platelets), which normally play a role in clotting, may occur, particularly at the beginning of treatment. Your doctor will perform appropriate monitoring.
• Severe allergic reaction which may include:
• swelling of the face, lips, mouth, tongue, or throat,
• difficulty swallowing or breathing,
• skin rash with itching (urticaria).
• A blood disorder 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 fistula. This is more likely to occur if you have low blood pressure or complications affecting the fistula.
• Clots may also form in the haemodialysis system. Your doctor may decide to increase the dose of heparin during dialysis.

Immediately inform your doctor or nurse if you notice any of these effects or any other side effects during treatment with Binocrit.
If any of the side effects worsen, or if you notice a side effect not listed in this leaflet, inform your doctor, nurse, or pharmacist.
Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store 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 after “EXP” and on the carton after “Scad.”. The expiry date refers to the last day of that month.
• Store and transport in a refrigerator (2 °C - 8 °C).
• You may remove Binocrit from the refrigerator and store it at room temperature (up to 25 °C) for a maximum of 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.
• Store in the original packaging to protect the medicine from light.

Do not use this medicine if you notice

• that it has been accidentally frozen, or
• that there has been a refrigerator malfunction,
• that the liquid is discoloured or if you see particles floating in it,
• that the seal is broken.

Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines
you no longer use. This will help protect the environment.

6. Package contents and other information

What Binocrit contains

• The active substance is epoetin alfa (for the amount, see the following table).
• The other components are monosodium phosphate monohydrate, disodium phosphate dihydrate, sodium chloride, glycine, polysorbate 80, hydrochloric acid (to adjust pH), sodium hydroxide (to adjust pH), water for injections.

Description of the appearance of Binocrit and package contents
Binocrit is a clear, colourless injectable solution in a pre-filled syringe. The syringes are sealed in blisters.

Packages containing 1, 4 or 6 pre-filled syringes, with or without needle safety device.
Not all pack sizes may be marketed.
Marketing Authorization Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria
Manufacturer
Sandoz GmbH
Biochemiestr. 10
6336 Langkampfen
Austria
For further information about this medicinal product, please contact the local representative of the marketing authorization holder:
België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037
България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97
Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890
Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf: +45 63 95 10 00 Tel: +35699644126
Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600
Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000
Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00
España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00
France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 21 407 51 60
Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02
Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: + 353 27 50077 Tel: +421 2 50 70 6111
Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400
Κύπρος United Kingdom (Northern Ireland)
Sandoz Pharmaceuticals d.d. Sandoz GmbH
Τηλ: +357 22 69 0690 Tel: +43 5338 2000
Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

Instructions for self-injection (for patients with symptomatic anaemia due to renal disease, adult patients undergoing chemotherapy, adult patients awaiting orthopaedic surgery, or adult patients with myelodysplastic syndromes)
This section contains information on how to self-administer Binocrit. It is important that you do not
attempt to self-inject the medicine before you have been specifically trained by your doctor or nurse. Binocrit is supplied with or without a needle safety device: your doctor or nurse will show you how to use it. If you have any doubts or questions about self-injection, please consult your doctor or nurse.
WARNING: Do not use the syringe if it has been dropped on a hard surface or if it has been dropped after removing the needle cap. Do not use the pre-filled syringe of Binocrit if it is broken. Return the pre-filled syringe and its original packaging to the pharmacy.

1. Wash your hands.
2. Remove a syringe from its packaging and remove the protective cap from the needle. The syringes are marked with raised graduations; this allows partial use if necessary. Each graduation corresponds to a volume of 0.1 mL. If partial use of the syringe is required, discard the unused solution before administering the injection.
3. Disinfect the skin at the injection site using an alcohol swab.
4. Pinch a fold of skin between your thumb and index finger.
5. With a quick, firm motion, insert the needle into the skin fold. Inject the Binocrit solution as shown to you by your doctor. If in doubt, consult your doctor or pharmacist.

Pre-filled syringe without needle safety device

6. While maintaining the skin fold between your fingers, slowly and steadily push the plunger.
7. After injecting the liquid, withdraw the needle and release the skin. Apply pressure to the injection site with a dry sterile gauze.
8. Dispose of any unused medicine and waste material derived from this medicine. Use each syringe only for a single injection.

Pre-filled syringe with needle safety device

6. While maintaining the skin fold between your fingers, slowly and steadily

push the plunger uniformly until the full dose has been delivered and the plunger cannot be pushed further. Do not release pressure on the plunger!

7. After injecting the liquid, withdraw the needle while maintaining pressure on the plunger, then release the skin. Apply pressure to the injection site with a dry sterile gauze.
8. Release the plunger. The safety device will automatically cover the needle immediately.
9. Dispose of any unused medicine and waste material derived from this medicine. Use each syringe only for a single injection.