Silapo 3000 IU/0.9ml solution for injection in pre-filledsyringe

Silapo is a medicine that stimulates the bone marrow to produce more red blood cells.

Silapo is used

• in adults, children and adolescents on haemodialysis to treat symptomatic anaemia associated with chronic renal failure (kidney disease).
• in adult patients on peritoneal dialysis to treat symptomatic anaemia associated with chronic renal failure (kidney disease).
• in adult patients with renal insufficiency not yet on dialysis to treat severe anaemia associated with kidney disease accompanied by clinical symptoms.
• in adult patients receiving chemotherapy for solid tumours, malignant lymphoma (cancer of the lymphatic system) or multiple myeloma (bone marrow cancer) to treat anaemia and reduce the need for a blood transfusion, if the doctor decides there may be a high risk for needing for a blood transfusion.
• in moderately anaemic patients who are going to have surgery and prior to it, donate blood so that their own blood can be given to them during or after surgery (autologous pre-donation).

Do not use Silapo

• if you are allergic (hypersensitive) to erythropoietins or any of the other ingredients of Silapo
• if you have developed Pure Red Cell Aplasia (PRCA; reduced or stopped production of red blood cells) following treatment with any erythropoietin
• if you have high blood pressure, which is not properly controlled with blood pressure-lowering medicines
• if you cannot be given medicines to thin blood for the prevention of blood clots
• if you are donating your own blood before surgery, and:
• you had a heart attack or stroke in the month before your treatment
• you have unstable angina pectoris (new or increasing chest pain)
• you are at risk of blood clots in the veins (deep venous thrombosis)? for example, if you have had clots before.

Take special care with Silapo

Please tell your doctor if you know you are suffering, or have suffered, from any of the following:

• epileptic seizures
• liver disease
• cancer
• anaemia from other causes
• heart disease (such as angina)
• disorders of blood circulation resulting in pins and needles or cold hands or feet or muscle cramps in the legs
• blood clots/blood clotting disorders
• phenylketonuria (genetic enzyme deficiency that increases excretion of a chemical (phenylketone) in urine and may cause nervous system disorders)
• kidney disease.

Special warningsDuring treatment with Silapo
Your doctor will check that your haemoglobin does not exceed a certain level, as high haemoglobin concentrations could put you at risk of having a problem of the heart or the blood vessels and could increase risk of myocardial infarction, stroke and death.

Your doctor should try to keep your hemoglobin levels between 10 and 12 g/dL.
The haemoglobin values should not exceed a value of 12 g/dl.

Your doctor will monitor your blood pressure regularly while you are using Silapo. If you experience headaches, particularly sudden, stabbing migraine-like headaches or start to feel confused or have fits, tell your doctor or nursing staff immediately. These may be the warning signs of a sudden rise in blood pressure, which requires urgent treatment.

There may be a rise in the level of platelets (cells that help blood clotting) during treatment with this medicine. This should improve during the course of the treatment. It is recommended that the platelet count is regularly checked during the first 8 weeks of therapy.

Remember to tell your doctor that you are receiving Silapo if you have to visit the hospital or family doctor for any treatmentincluding a blood test, as Silapo may affect the results.

Take special care with other products that stimulate red blood cell production: Silapo is one of a group of products that stimulate the production of red blood cells like the human protein erythropoietin does. Your healthcare professional will always record the exact product you are using.

Kidney disease patients
Pure Red Cell Aplasia (PRCA) has been reported very rarely after months to years of subcutaneous treatment with other products containing erythropoietins and may not be ruled out with Silapo. PRCA means the inability to produce enough red blood cells in the bone marrow. If this occurs it can result in severe anaemia, the symptoms of which are unusual tiredness, feeling dizzy or breathlessness. PRCA may be caused by the production to antibodies against the erythropoietin product and, in the following, to your own erythropoietin.

You should discuss this information with your doctor. If PRCA, a very rare condition, occurs, the Silapo therapy will be stopped and your doctor will determine the best course of action to treat the anaemia. Although this complication is very rare, you should be aware that if you develop it, you would need to have regular blood transfusions, possibly lifelong, to treat your anaemia and the Silapo therapy would have to be discontinued. Tell your doctor immediately if you suddenly feel very tired or dizzy or suffer from shortness of breath. Your doctor can decide whether Silapo is not working properly for you and will end the treatment, if necessary.

Chronic renal failure patients on erythropoietin should have their haemoglobin (the part of a red blood cell that carries oxygen) levels measured on a regular basis until a stable level is achieved, and periodically thereafter to minimise the risk of an increase in blood pressure.

If you are a patient with chronic kidney disease, your doctor will check that your haemoglobin does not exceed a certain level as high haemoglobin could put you at risk of having a problem of the heart or the blood vessels and could increase risk of death.

Increases in blood potassium have happened in isolated cases. In chronic renal failure patients, correction for anaemia may lead to increased appetite, and potassium and protein intake. If you are receiving dialysis treatment when you begin treatment with Silapo, your dialysis regimen may need to be adjusted to maintain urea, creatinine and potassium levels in the desired range. Your doctor will decide this.

Serum electrolytes (substances in your blood) should be monitored in chronic renal failure patients. If an elevated (or rising) serum potassium level is detected, your doctor may consider to stop the treatment with Silapo until the level is back to normal.

An increase in the dose of a particular blood-thinning medicine (heparin) during haemodialysis is often needed during the course of therapy with Silapo to minimize the risk of blood clotting. Blockage of the dialysis system is possible if heparinisation is not optimum.

Cancer patients
Cancer patients are more likely to suffer from blood clots if receiving erythropoietin medicines, like Silapo (see section 4). Therefore, you should discuss the benefits of Silapo with your doctor, particularly if you are obese or have a history of blood clots/blood clotting disorders.

Cancer patients on erythropoietin should have haemoglobin (the part of a red blood cell that carries oxygen) levels measured on a regular basis until a stable level is achieved, and periodically thereafter.

If you are a cancer patient, you should be aware that Silapo may act as a blood cell growth factor and in some circumstances may have a negative impact on your cancer. Depending on your individual situation a blood transfusion may be preferable. Please discuss this with your doctor.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

In particular, if you are taking a medicine containing the active substance ciclosporin to suppress your immune system after a kidney transplant, your doctor may order special blood tests to measure ciclosporin levels while you are taking Silapo.

Iron supplements and other blood stimulants may increase the effectiveness of Silapo. Your doctor will decide if it is right for you to take them.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant or think you may be pregnant or are breast-feeding.

If you are pregnant or breast-feeding, Silapo should be used only if the potential benefit outweighs the potential risk to the foetus.

Ask your doctor for advice before taking any medicine.

Driving and using machines

Silapo has no or negligible effect on the ability to drive and use machines.

Important information about some of the ingredients of Silapo

This medicine contains phenylalanine and may be harmful for people with phenylketonuria. This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ?sodium-free?.

Silapo therapy is usually started under medical supervision. The injections can then be given by a doctor, trained nurse or other health care professional.

In case Silapo is injected under the skin (subcutaneously) you can also inject the solution yourself once you have been shown how. Always use Silapo exactly as your doctor has told you.

Dosage information

The dose you receive is based on your body weight in kilograms.

Your doctor will conduct investigations, for example blood tests, to help decide if it is necessary for you to have Silapo. He/she will work out the correct dose of Silapo for you to use, how long the treatment should continue and by what route the medicine will be given. These decisions will be influenced by what is causing your anaemia.

Use in kidney disease patients Silapo should be administered either under the skin (subcutaneously) or as an injection either into a vein or a tube that goes into a vein.

Use in adult patients receiving haemodialysis
Your doctor will maintain your haemoglobin concentration between 10 and 12 g/dl (6.2 - 7.5 mmol/l).

Silapo may be given during the dialysis session or after you have received a dialysis session.

The usual starting dose of Silapo is 50 IU/kg (International Units per kilogram). This is given 3 times a week. If the solution is given into a vein, it should be injected over 1-5 minutes.

Depending on how your anaemia responds to treatment, the dose may be adjusted approximately every 4 weeks until your condition is controlled. The dose you receive should not normally exceed 200 IU/kg 3 times a week.

Your doctor will order regular blood tests to ensure that your medicine is continuing to work properly. When your condition has been brought under control, you will receive regular doses of Silapo, 2 or 3 times a week. These doses may not be as high as those received initially.

Use in children and adolescents up to 18 years receiving haemodialysis
In children the doctor will maintain the haemoglobin concentration between 9.5 and 11 g/dl

Silapo should be given after the patient has received a dialysis session.

The dose for children and adolescentsis based on body weight in kilograms. The usual starting dose is 50 IU/kg. This is given three times a week, injected into a vein (over 1-5 minutes).

Depending on how the anaemia responds, the dose may be adjusted approximately every 4 weeks until the condition is controlled. Your doctor will order regular blood tests to see that this is being achieved.

Use in adult patients receiving peritoneal dialysis
Your doctor will maintain your haemoglobin concentration between 10 and 12 g/dl.

The usual starting dose is 50 IU/kg. This is given twice a week.

Depending on how your anaemia responds, the dose may be adjusted approximately every 4 weeks until your condition is controlled. The total weekly dose that you receive should not normally exceed 200 IU/kg.

Your doctor will order regular blood tests to ensure that your medicine is continuing to work properly.

Use in adult patients with kidney disease but not receiving dialysis

The usual starting dose is 50 IU/kg. This is given 3 times a week.

The starting dose may be adjusted by your doctor until your condition is controlled. After your condition has been brought under control, you will receive regular doses of Silapo, 3 times a week. The dosage should not normally exceed 200 IU/kg, 3 times a week.

Your doctor will order regular blood tests to ensure that your medicine is continuing to work properly.

Use in adult patients receiving chemotherapy
Your doctor may initiate treatment with Silapo if your haemoglobin level is 10 g/dl or less. After initiation of therapy, your doctor will maintain your haemoglobin level between 10 and 12 g/dl

The usual starting dose is 150 IU/kg. This is given 3 times a week by injection under the skin. Alternatively, your doctor may recommend a starting dose of 450 IU/kg once a week. The starting dose may be adjusted by your doctor depending on how your anaemia responds to treatment; you will usually receive Silapo until 1 month after the end of chemotherapy.

Use in adult patients in an autologous predonation programme
The usual starting dose is 600 IU/kg. This is given 2 times a week by injection into a vein. You will receive Silapo during the 3 weeks before your surgery. You will also take iron supplements before and during Silapo treatment to increase the effectiveness of Silapo.

Information on administration

The pre-filled syringe is ready for use. Each syringe should be used for a single injection only. Silapo must not be shaken or mixed with any other liquid.

If Silapo is injected under the skin the amount injected in any one place should not exceed 1 ml.

Always follow these instructions when using Silapo:

1. Take one sealed syringe blister and leave it to stand for a few minutes until it reaches room temperature prior to using it. This usually takes between 15 and 30 minutes.

2. Remove the syringe from the blister and check that the solution is clear, colourless and practically free from visible particles.

3. Remove the protective cap from the injection needle and expel air from the syringe and injection needle by holding the syringe vertically and gently pressing the plunger upwards.

4. Inject the solution as you have been shown by your doctor. You should check with your doctor or pharmacist if you are not sure.

Do not use Silapo if:

• the blister sealing is broken or the blister is damaged in any way
• the liquid is coloured or you can see particles floating in it
• any liquid has leaked out of the pre-filled syringe or condensation is visible within the sealed blister
• you know or think it may have been accidentally frozen

Changing from injecting into a vein to injecting under the skin (from intravenous into subcutaneous

injection) Once your condition is controlled you will receive regular doses of Silapo. Your doctor may decide that it is better for you to receive Silapo by injection under the skin (subcutaneous) rather than into a vein (intravenous).

The dose should remain the same while the change is being made. Afterwards, your doctor may order blood tests to see if any adjustment in dose is required.

Injecting Silapo under the skin yourself
At the start of your therapy, Silapo is injected by medical or nursing staff. However, your doctor may decide that it is right for you to learn how to inject Silapo under the skin (subcutaneously) yourself. You will receive appropriate training to enable you to do this. Under no circumstances should you attempt to inject yourself unless you have been trained to do so.

If you use more Silapo than you should

Silapo has a wide safety margin and side effects due to an overdose of using Silapo are unlikely. You should inform the doctor or nurse immediately if you think too much Silapo has been injected.

If you forget to use Silapo

Do not use a double dose to make up for a forgotten dose.

If you stop using Silapo

Do not to stop the treatment without consultation of your doctor.

If you have any further questions on the use of this product, ask your doctor.

Like all medicines, Silapo can cause side effects, although not everybody gets them.

If you experience headaches, particularly sudden, stabbing migraine-like headaches or feel confused or have fits, tell your doctor immediately. These may be the warning signs of a sudden rise in blood pressure which requires urgent treatment.

Tell your doctor or nurse immediately if you notice any of the effects in this list.

Very common side effects
These may affect more than 1 in every 10 people using Silapo.

• Flu-like symptoms, headache, joint pain, feeling of weakness, tiredness and dizziness.

Common side effects
These may affect 1 to 10 in every 100 people using Silapo.

• Increased blood pressure. Raised blood pressure may require treatment with drugs (or adjustment to any drugs you already take for high blood pressure). Your doctor may monitor your blood pressure regularly while you are using Silapo, particularly at the start of therapy.
• Chest pain, breathlessness, painful swelling in the leg which may be symptoms of blood clots (pulmonary embolism, deep vein thrombosis).
• Stroke (insufficient blood supply to the brain, which may lead to inability to move one or more limbs on one side of the body, inability to understand or formulate speech, or an inability to see one side of the visual field).
• Skin rash and swelling around the eyes (oedema), which may result from an allergic reaction.
• Blood clot in an artificial kidney.

Uncommon side effects
These may affect 1 to 10 in every 1,000 people using Silapo.

• Cerebral haemorrhages.

Rare side effects
These may affect 1 to 10 in every 10,000 people using Silapo.

• Hypersensitivity reactions.

Very rare side effects
These may affect less than 1 in 10,000 people using Silapo.

• Increased levels of small blood cells (called platelets), which are normally involved in the formation of a blood clot may occur. Your doctor will check on this.

Side effects with unknown frequency
The frequency of these side effects cannot be estimated from the available data.

• Swelling, mainly in the region of the eyelids and the lips (Quincke's oedema) and shock-like allergic reactions with symptoms of tingling, reddening, itching, hot flush and accelerated pulse.
• Vascular and thrombotic events (blood clotting) in blood vessels such as disturbance of blood perfusion in the brain, retinal thrombosis, disturbed blood perfusion of the heart, heart attack, arterial thrombosis, dilatation of the wall of a blood vessel (aneurysm).
• Pure red cell aplasia (PRCA). PRCA has been reported in patients after months to years of subcutaneous (injection under the skin) erythropoietin treatment. PRCA means the inability to produce enough red blood cells in the bone (see section ?Take special care with Silapo?).
• Itching (pruritus).

Other side effects:

Kidney patients

? raised blood pressure which may require treatment with medicinal products or adjustment of the dosage of medicinal products you already take for high blood pressure. Your doctor may monitor your blood pressure regularly while you are using Silapo, particularly at the start of therapy.

Occlusion in the connection between artery and vein shunt thrombosis may occur especially if you have low blood pressure or if your arteriovenous fistula has complications. Your doctor may check your shunt and prescribe a medicinal product to prevent thrombosis.

Cancer patients

? blood clotting (thrombotic vascular events) (see section ?Take special care with Silapo?). ? increase of blood pressure. Therefore your haemoglobin-levels and your blood pressure should be controlled.

If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Silapo after the expiry date which is stated on the label and the carton. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C - 8°C). Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

The syringe can be removed from the refrigerator and left at room temperature for a single period of maximum 3 days (but not above 25°C).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist about how to dispose of medicines that are no longer required. These measures will help to protect the environment.

What Silapo contains

The active substance is epoetin zeta produced by recombinant DNA technology in Chinese Hamster Ovary CHO cell line.

Silapo 1000 IU/0.3ml solution for injection in pre-filled syringe 1 pre-filled syringe with 0.3 ml solution for injection contains 1000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 3333 IU Epoetin zeta per ml.

Silapo 2000 IU/0.6ml solution for injection in pre-filled syringe 1 pre-filled syringe with 0.6 ml solution for injection contains 2000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 3333 IU Epoetin zeta per ml.

Silapo 3000 IU/0.9ml solution for injection in pre-filled syringe 1 pre-filled syringe with 0.9 ml solution for injection contains 3000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 3333 IU Epoetin zeta per ml.

Silapo 4000 IU/0.4ml solution for injection in pre-filled syringe

1 pre-filled syringe with 0.4 ml solution for injection contains 4000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 10000 IU Epoetin zeta per ml.

Silapo 5000 IU/0.5ml solution for injection in pre-filled syringe 1 pre-filled syringe with 0.5 ml solution for injection contains 5000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 10000 IU Epoetin zeta per ml.
Silapo 6000 IU/0.6ml solution for injection in pre-filled syringe 1 pre-filled syringe with 0.6 ml solution for injection contains 6000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 10000 IU Epoetin zeta per ml.

Silapo 8000 IU/0.8ml solution for injection in pre-filled syringe 1 pre-filled syringe with 0.8 ml solution for injection contains 8000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 10000 IU Epoetin zeta per ml.

Silapo 10000 IU/1.0ml solution for injection in pre-filled syringe 1 pre-filled syringe with 1.0 ml solution for injection contains 10000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 10000 IU Epoetin zeta per ml.

Silapo 20000 IU/0.5ml solution for injection in pre-filled syringe 1 pre-filled syringe with 0.5 ml solution for injection contains 20000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 40000 IU Epoetin zeta per ml.

Silapo 30000 IU/0.75ml solution for injection in pre-filled syringe 1 pre-filled syringe with 0.75 ml solution for injection contains 30000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 40000 IU Epoetin zeta per ml.

Silapo 40000 IU/1.0ml solution for injection in pre-filled syringe
1 pre-filled syringe with 1.0 ml solution for injection contains 40000 international units (IU) epoetin zeta (recombinant human erythropoietin). The solution contains 40000 IU Epoetin zeta per ml.

The other ingredients are disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride, calcium chloride dihydrate, polysorbate 20, glycine, leucine, isoleucine, threonine, glutamic acid, phenylalanine, water for injections, sodium hydroxide (pH adjuster), hydrochloric acid (pH adjuster).

What Silapo looks like and contents of the pack

Silapo is presented as a clear and colourless solution for injection in a pre-filled syringe with a fixed injection needle.

The pre-filled syringes contain between 0.3 and 1.0 ml solution, depending on the content of epoetin zeta (see ?What Silapo contains?).

One pack contains 1, 4 or 6 pre-filled syringes.

Marketing Authorisation Holder

STADA Arzneimittel AG

Stadastrasse 2-18
D-61118 Bad Vilbel
Germany

Manufacturer

STADA Arzneimittel AG
Stadastrasse 2-18
D-61118 Bad Vilbel
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

cell pharm GmbH
Theodor-Heuss-Str. 52
D-61118 Bad Vilbel
Tel: +49 (0) 6101 30 42 0
Fax: +49 (0) 6101 30 42 11

This leaflet was last approved in {MM/YYYY}.