Silapo

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Silapo 1 000 IU/0.3 ml solution for injection in pre-filled syringe
Silapo 2 000 IU/0.6 ml solution for injection in pre-filled syringe
Silapo 3 000 IU/0.9 ml solution for injection in pre-filled syringe
Silapo 4 000 IU/0.4 ml solution for injection in pre-filled syringe
Silapo 5 000 IU/0.5 ml solution for injection in pre-filled syringe
Silapo 6 000 IU/0.6 ml solution for injection in pre-filled syringe
Silapo 8 000 IU/0.8 ml solution for injection in pre-filled syringe
Silapo 10 000 IU/1 ml solution for injection in pre-filled syringe
Silapo 20 000 IU/0.5 ml solution for injection in pre-filled syringe
Silapo 30 000 IU/0.75 ml solution for injection in pre-filled syringe
Silapo 40 000 IU/1 ml solution for injection in pre-filled syringe

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Silapo 1 000 IU/0.3 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.3 ml solution for injection contains 1 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 3 333 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.15 mg phenylalanine.

Silapo 2 000 IU/0.6 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.6 ml solution for injection contains 2 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 3 333 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.30 mg phenylalanine.

Silapo 3 000 IU/0.9 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.9 ml solution for injection contains 3 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 3 333 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.45 mg phenylalanine.

Silapo 4 000 IU/0.4 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.4 ml solution for injection contains 4 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.20 mg phenylalanine.

Silapo 5 000 IU/0.5 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.5 ml solution for injection contains 5 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.25 mg phenylalanine.

Silapo 6 000 IU/0.6 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.6 ml solution for injection contains 6 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta per ml.



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Excipient with known effect
Each pre-filled syringe contains 0.30 mg phenylalanine.

Silapo 8 000 IU/0.8 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.8 ml solution for injection contains 8 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.40 mg phenylalanine.

Silapo 10 000 IU/1 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 1 ml solution for injection contains 10 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.50 mg phenylalanine.

Silapo 20 000 IU/0.5 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.5 ml solution for injection contains 20 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 40 000 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.25 mg phenylalanine.

Silapo 30 000 IU/0.75 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.75 ml solution for injection contains 30 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 40 000 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.38 mg phenylalanine.

Silapo 40 000 IU/1 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 1 ml solution for injection contains 40 000 international units (IU) epoetin 
zeta* (recombinant human erythropoietin). The solution contains 40 000 IU epoetin zeta per ml.

Excipient with known effect
Each pre-filled syringe contains 0.50 mg phenylalanine.

For the full list of excipients, see section 6.1.

*Produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell line.

3. PHARMACEUTICAL FORM

Solution for injection in pre-filled syringe.
Clear, colourless solution.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

 Treatment of symptomatic anaemia associated with chronic renal failure (CRF) in adult and 
paediatric patients:
o Treatment of anaemia associated with chronic renal failure in adult and paediatric patients 

on haemodialysis and adult patients on peritoneal dialysis (see section 4.4).



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o Treatment of severe anaemia of renal origin accompanied by clinical symptoms in adult 
patients with renal insufficiency not yet undergoing dialysis (see section 4.4).

 Treatment of anaemia and reduction of transfusion requirements in adult patients receiving 
chemotherapy for solid tumours, malignant lymphoma or multiple myeloma, and at risk of 
transfusion as assessed by the patient's general status (e.g. cardiovascular status, pre-existing 
anaemia at the start of chemotherapy).

 Silapo can be used to increase the yield of autologous blood from patients in a predonation 
programme. Its use in this indication must be balanced against the reported risk of 
thromboembolic events. Treatment should only be given to patients with moderate anaemia (no 
iron deficiency), if blood saving procedures are not available or insufficient when the scheduled 
major elective surgery requires a large volume of blood (4 or more units of blood for females or 
5 or more units for males).

 Silapo is indicated for non-iron deficient adults prior to major elective orthopaedic surgery 
having a high perceived risk for transfusion complications to reduce exposure to allogeneic 
blood transfusions. Use should be restricted to patients with moderate anaemia (e.g. 
haemoglobin concentration range between 10 to 13 g/dl) who do not have an autologous 
predonation programme available and with expected moderate blood loss (900 to 1 800 ml).

 Silapo can be used to increase haemoglobin concentration in symptomatic anaemia 
(haemoglobin concentration of ≤10 g/dl) in adults with low- or intermediate-1-risk primary 
myelodysplastic syndromes (MDS) who have low serum erythropoietin (<200 mU/ml).

4.2 Posology and method of administration

Treatment with Silapo has to be initiated under the supervision of physicians experienced in the 
management of patients with above indications.

Posology

 Treatment of symptomatic anaemia in adult and paediatric chronic renal failure patients

Silapo should be administered either subcutaneously or intravenously.

The haemoglobin concentration aimed for is between 10 and 12 g/dl (6.2-7.5 mmol/l), except in 
paediatric patients in whom the haemoglobin concentration should be between 9.5 and 11 g/dl (5.9-
6.8 mmol/l). The upper limit of the target haemoglobin concentration should not be exceeded.

Anaemia symptoms and sequelae may vary with age, gender and overall burden of disease; a 
physician´s evaluation of the individual patient´s clinical course and condition is necessary.

Silapo should be administered either subcutaneously or intravenously in order to increase haemoglobin 
to not greater than 12 g/dl (7.5 mmol/l). Due to intra-patient variability, occasional individual 
haemoglobin values for a patient above and below the desired haemoglobin level may be observed. 
Haemoglobin variability should be addressed through dose management, with consideration for the 
haemoglobin target range of 10 g/dl (6.2 mmol/l) to 12 g/dl (7.5 mmol/l).

A sustained haemoglobin level of greater than 12 g/dl should be avoided; guidance for appropriate 
dose adjustment for when haemoglobin values exceeding 12 g/dl (7.5 mmol/l) are observed are 
described below. A rise in haemoglobin of greater than 2 g/dl (1.25 mmol/l) over a four week period 
should be avoided. If it occurs, appropriate dose adjustment should be made as provided.

Patients should be monitored closely to ensure that the lowest approved effective dose of Silapo is 
used to provide adequate control of the symptoms of anaemia whilst maintaining a haemoglobin 
concentration below or at 12g/dl (7.5 mmol/l).

Caution should be exercised with escalation of Silapo doses in patients with chronic renal failure. In 
patients with a poor haemoglobin response to Silapo, alternative explanations for the poor response 
should be considered (see sections 4.4 and 5.1).



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In patients with chronic renal failure and clinically evident ischaemic heart disease or congestive heart 
failure, maintenance haemoglobin concentration should not exceed the upper limit of the target 
haemoglobin concentration.

Adult patients on haemodialysis

Silapo should be administered either subcutaneously or intravenously.

The treatment is divided into two stages:
1. Correction phase: 50 IU/kg 3 times per week. When a dose adjustment is necessary, this should 

be done in steps of at least four weeks. At each step, the increase or reduction 
in dose should be of 25 IU/kg 3 times per week.

2. Maintenance phase: Dose adjustment in order to maintain haemoglobin (Hb) values at the desired 
level: Hb between 10 and 12 g/dl (6.2-7.5 mmol/l). The recommended total 
weekly dose is between 75 and 300 IU/kg.

The clinical data available suggest that those patients whose initial haemoglobin is very low (< 6 g/dl 
or < 3.75 mmol/l) may require higher maintenance doses than those whose initial anaemia is less 
severe (Hb > 8 g/dl or > 5 mmol/l).

Paediatric patients on haemodialysis

The treatment is divided into two stages:
1. Correction phase 50 IU/kg, 3 times per week by the intravenous route. When a dose adjustment 

is necessary, this should be done in steps of 25 IU/kg, 3 times per week at 
intervals of at least 4 weeks until the desired goal is achieved.

2. Maintenance phase: Dose adjustment in order to maintain haemoglobin (Hb) values at the desired 
level: Hb between 9.5 and 11 g/dl (5.9-6.8 mmol/l).

Generally, children and adolescents under 30 kg body weight require higher maintenance doses than 
adults and children over 30 kg. The following maintenance doses were observed in clinical trials after 
6 months of treatment.

Dose (IU/kg given 3 times per week)

Weight (kg) Median Usual maintenance dose

< 10 100 75-150

10-30 75 60-150

> 30 33 30-100

The clinical data available suggest that those patients whose initial haemoglobin is very low 
(< 6.8 g/dl or < 4.25 mmol/l) may require higher maintenance doses than those whose initial 
haemoglobin is higher > 6.8 g/dl or> 4.25 mmol/l).

Adult patients on peritoneal dialysis

Silapo should be administered either subcutaneously or intravenously.

The treatment is divided into two stages:
1. Correction phase: Starting dose of 50 IU/kg 2 times per week.
2. Maintenance phase: Dose adjustment in order to maintain haemoglobin (Hb) values at the desired 

level: Hb between 10 and 12 g/dl (6.2-7.5 mmol/l). Maintenance dose between 
25 and 50 IU/kg 2 times per week into 2 equal doses.



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Adult patients with renal insufficiency not yet undergoing dialysis

Silapo should be administered either subcutaneously or intravenously.

The treatment is divided into two stages:
1. Correction phase: Starting dose of 50 IU/kg 3 times per week, followed if necessary by a dose 

increase with 25 IU/kg increments (3 times per week) until the desired goal is 
achieved (this should be done in steps of at least four weeks).

2. Maintenance phase: During the maintenance phase, Silapo can be administered either 3 times per 
week, and in the case of subcutaneous administration, once weekly or once 
every 2 weeks. Appropriate adjustment of dose and dose intervals should be 
made in order to maintain haemoglobin (Hb) values at the desired level: Hb 
between 10 and 12 g/dl (6.2-7.5 mmol/l). Extending dose intervals may 
require an increase in dose.

The maximum dosage should not exceed 150 IU/kg 3 times per week, 240 IU/kg (up to a maximum of 
20 000 IU) once weekly or 480 IU/kg (up to a maximum of 40 000 IU) once every 2 weeks.

 Treatment of patients with chemotherapy induced anaemia

Silapo should be administered by the subcutaneous route to patients with anaemia (e.g. haemoglobin 
concentration ≤ 10 g/dl (6.2 mmol/l). Anaemia symptoms and sequelae may vary with age, gender, 
and overall burden of disease; a physician´s evaluation of the individual patient´s clinical course and 
condition is necessary.

Due to intra-patient variability, occasional individual haemoglobin values for a patient above and 
below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed 
through dose management with consideration for the haemoglobin target range of 10 g/dl (6.2 mmol/l) 
to 12 g/dl (7.5 mmol/l). A sustained haemoglobin level of greater than 12 g/dl (7.5 mmol/l) should be 
avoided; guidance for appropriate dose adjustment for when haemoglobin values exceeding 12 g/dl 
(7.5 mmol/l) are observed are described below.

Patients should be monitored closely to ensure that the lowest approved dose of Silapo is used to 
provide adequate control of the symptoms of anaemia.

Silapo therapy should continue until one month after the end of chemotherapy.

The initial dose is 150 IU/kg given subcutaneously 3 times per week. Alternatively, Silapo can be 
administered at an initial dose of 450 IU/kg subcutaneously once weekly.

If the haemoglobin has increased by at least 1 g/dl (0.62 mmol/l) or the reticulocyte count has 
increased ≥ 40 000 cells/µl above baseline after 4 weeks of treatment, the dose should remain at 
150 IU/kg 3 times per week or 450 IU/kg once weekly. If the haemoglobin increase is < 1 g/dl 
(< 0.62 mmol/l) and the reticulocyte count has increased < 40 000 cells/µl above baseline, increase the 
dose to 300 IU/kg 3 times per week. If after an additional 4 weeks of therapy at 300 IU/kg 3 times per 
week, the haemoglobin has increased ≥ 1 g/dl (0.62 mmol/l) or the reticulocyte count has increased 
≥ 40 000 cells/µl the dose should remain at 300 IU/kg 3 times per week. However, if the haemoglobin 
has increased < 1 g/dl (< 0.62 mmol/l) and the reticulocyte count has increased < 40 000 cells/µl above 
baseline, response is unlikely and treatment should be discontinued.

The recommended dosing regimen is described in the following diagram:



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Once the therapeutic objective for an individual patient has been achieved, the dose should be reduced 
by 25 to 50% in order to maintain haemoglobin at that level. Appropriate dose titration should be
considered.

Dose adjustment
At a rate of rise in haemoglobin of > 2 g/dl (> 1.25 mmol/l) per month the Silapo dose should be 
reduced by about 25-50%. If haemoglobin level exceeds 12 g/dl (7.5 mmol/l), discontinue therapy 
until it falls to 12 g/dl (7.5 mmol/l) or lower and then reinstitute Silapo therapy at a dose 25% below 
the previous dose.

 Adult surgery patients in an autologous predonation programme.

Silapo should be given by the intravenous route.

At the time of donating blood, Silapo should be administered after the completion of the blood 
donation procedure.

Mildly anaemic patients (haematocrit of 33-39%) requiring predeposit of ≥ 4 units of blood should be 
treated with Silapo at a dose of 600 IU/kg body weight 2 times weekly for 3 weeks prior to surgery.

Reticulocyte count increase ≥ 40 000/μl
or Hb increase ≥ 1 g/dl

150 IU/kg 3x/week
or 450 IU/kg once weekly

for 4 weeks

Reticulocyte count increase < 40 000/μl
and Hb increase < 1 g/dl

Target Hb
(10 - 12 g/dl)

300 IU/kg
3x/week

for 4 weeks

Reticulocyte count increase ≥ 40 000/μl
or Hb increase ≥ 1 g/dl

Reticulocyte count increase < 40 000/μl
and Hb increase < 1 g/dl

Discontinue therapy



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All patients being treated with Silapo should receive adequate iron supplementation (e.g. 200 mg oral 
elemental iron daily) throughout the course of treatment. Iron supplementation should be started as 
soon as possible, even several weeks prior to initiating the autologous predeposit, in order to achieve 
high iron stores prior to starting Silapo therapy.

 Treatment of adult patients scheduled for major elective orthopaedic surgery

Silapo should be administered subcutaneously.

The recommended dose is 600 IU/kg administered subcutaneously weekly for three weeks (days -21, -
14 and -7) prior to surgery and on the day of surgery.

In cases where there is a medical need to shorten the lead time before surgery to less than three weeks, 
300 IU/kg should be administered subcutaneously daily for 10 consecutive days prior to surgery, on 
the day of surgery and for four days immediately thereafter.

If the haemoglobin level reaches 15 g/dl, or higher, during the preoperative period, administration of 
Silapo should be stopped and further dosages should not be administered.

The safety and efficacy of epoetin zeta in paediatrics have not been established. No data are available.

 Treatment of adult patients with low- or intermediate-1-risk MDS

Silapo should be administered subcutaneously.

Silapo should be administered to patients with symptomatic anaemia (e.g. haemoglobin concentration 
≤10 g/dl (6.2 mmol/l)).

The recommended starting dose of Silapo is 450 IU/kg (maximum total dose is 40 000 IU). This is 
given subcutaneously once every week, with not less than 5 days between doses.

Appropriate dose adjustments should be made to maintain haemoglobin concentrations within the 
target range of 10 g/dl to 12 g/dl (6.2 to 7.5 mmol/l). It is recommended that initial erythroid response 
be assessed 8 to 12 weeks following initiation of treatment. Dose increases and decreases should be 
done one dosing step at a time (see diagram below). A haemoglobin concentration of greater than 
12 g/dl (7.5 mmol/l) should be avoided.

Dose increase
Dose should not be increased over the maximum of 1 050 IU/kg (total dose 80 000 IU) per week. If 
the patient loses response or haemoglobin concentration drops by ≥1 g/dl upon dose reduction the dose 
should be increased by one dosing step. A minimum of 4 weeks should elapse between dose increases.

Dose hold and decrease
Silapo should be withheld when the haemoglobin concentration exceeds 12 g/dl (7.5 mmol/l). Once 
the haemoglobin level is <11 g/dl the dose can be restarted on the same dosing step or one dosing step 
down based on physician judgement. Decreasing the dose by one dosing step should be considered if 
there is a rapid increase in haemoglobin (>2 g/dl over 4 weeks).

337.5 IU/kg

450 IU/kg

787.5 IU/kg

1050 IU/kg

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Anaemia symptoms and sequelae may vary with age, gender, and co-morbid medical conditions; a 
physician's evaluation of the individual patient's clinical course and condition is necessary.

Method of administration

Intravenous injection
The dose should be administered over at least 1-5 minutes, depending on the total dose. In 
haemodialysed patients, a bolus injection may be given during the dialysis session through a suitable 
venous port in the dialysis line. Alternatively, the injection can be given at the end of the dialysis 
session via the fistula needle tubing, followed by 10 ml of sodium chloride 9 mg/ml (0.9%) solution 
for injection to rinse the tubing and ensure satisfactory injection of the medicinal product into the 
circulation.

A slower injection is preferable in patients who react to the treatment with “flu-like” symptoms.

Silapo must not be administered by intravenous infusion.
Silapo must not be mixed with other medicinal products (see section 6.2).

Subcutaneous injection
A maximum volume of 1 ml at one injection site should generally not be exceeded. In case of larger 
volumes, more than one site should be chosen for the injection.

The injections are given in the limbs or the anterior abdominal wall.

For instructions on handling of the medicinal product before administration, see section 6.6.

4.3 Contraindications

 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
 Patients who develop Pure Red Cell Aplasia (PRCA) following treatment with any

erythropoietin must not receive Silapo or any other erythropoietin (see section 4.4).
 Uncontrolled hypertension.
 In the indication "increasing the yield of autologous blood": myocardial infarction or stroke in 

the month preceding treatment, unstable angina pectoris, increased risk of deep venous 
thrombosis such as history of venous thromboembolic disease.

 The use of Silapo in patients scheduled for major elective orthopaedic surgery and not 
participating in an autologous blood predonation programme is contraindicated in patients with 
severe coronary, peripheral arterial, carotid or cerebral vascular disease, including patients with 
recent myocardial infarction or cerebral vascular accident.

 Patients who for any reason cannot receive adequate antithrombotic prophylaxis.

4.4 Special warnings and precautions for use

General

Like in all patients receiving erythropoietin, blood pressure may rise during treatment with Silapo. 
Blood pressure should be closely monitored and adequately controlled in all epoetin treatment naïve as 
well as pre-treated patients before, at initiation of, and during treatment with Silapo. It may be 
necessary to add or increase anti-hypertensive treatment. If blood pressure cannot be well controlled, 
Silapo treatment should be discontinued.

Silapo should also be used with caution in the presence of epilepsy and chronic liver failure.

There may be a moderate dose-dependent rise in the platelet count within the normal range during 
treatment with erythropoietin. This regresses during the course of continued therapy. It is 
recommended that the platelet count is regularly monitored during the first 8 weeks of therapy.



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All other causes of anaemia (iron deficiency, haemolysis, blood loss, vitamin B12- or folate 
deficiencies) should be considered and treated prior to initiating and during therapy with Silapo. In 
most cases, the ferritin values in the serum fall simultaneously with the rise in packed cell volume. In 
order to ensure optimum response to erythropoietin, adequate iron stores should be assured:
 iron supplementation, e.g. 200-300 mg/day orally (100-200 mg/day for paediatric patients) is 

recommended for chronic renal failure patients whose serum ferritin levels are below 100 ng/ml
 oral iron substitution of 200-300 mg/day is recommended for all cancer patients whose 

transferrin saturation is below 20%.
 For patients scheduled for major elective orthopaedic surgery, iron supplementation (elemental 

iron 200 mg/day orally) should be administered throughout the course of epoetin zeta therapy. If 
possible, iron supplementation should be initiated prior to starting epoetin zeta therapy to 
achieve adequate iron stores.

All of these additive factors of anaemia should also be carefully considered when deciding to increase 
the dose of erythropoietin in cancer patients.

A paradoxical decrease in haemoglobin and development of severe anaemia associated with low 
reticulocyte counts should prompt to discontinue treatment with epoetin and perform anti-
erythropoietin antibody testing. Cases have been reported in patients with hepatitis C treated with 
interferon and ribavirin, when epoetins are used concomitantly. Epoetins are not approved in the 
management of anaemia associated with hepatitis C.

In order to improve the traceability of erythropoiesis-stimulating agents (ESAs), the name of the 
prescribed ESA should be clearly recorded (or: stated) in the patient file.

Patients scheduled for major elective orthopaedic surgery

Good blood management practices should always be used in the perisurgical setting.

Patients scheduled for major elective orthopaedic surgery should receive adequate antithrombotic 
prophylaxis, as thrombotic and vascular events may occur in surgical patients, especially in those with 
underlying cardiovascular disease. In addition, special precaution should be taken in patients with 
predisposition for development of DVTs. Moreover, in patients with a baseline haemoglobin of 
> 13 g/dl, the possibility that epoetin zeta treatment may be associated with an increased risk of 
postoperative thrombotic/vascular events cannot be excluded. Therefore, epoetin zeta should not be 
used in patients with baseline haemoglobin > 13 g/dl.

Chronic renal failure patients

Haemoglobin concentration
In patients with chronic renal failure, maintenance haemoglobin concentration should not exceed the 
upper limit of the target haemoglobin concentration recommended in section 4.2. In clinical trials, an 
increased risk of death, serious cardiovascular events or cerebrovascular events including stroke were 
observed when ESAs were administered to target a haemoglobin of greater than 12 g/dl (7.5 mmol/l).

Controlled clinical trials have not shown significant benefits attributable to the administration of 
epoetins when haemoglobin concentration is increased beyond the level necessary to control 
symptoms of anaemia and to avoid blood transfusion.

Haemoglobin levels should be measured on a regular basis until a stable level is achieved and 
periodically thereafter. The rate of increase in haemoglobin should be approximately 1 g/dl 
(0.62 mmol/l) per month and should not exceed 2 g/dl (1.25 mmol/l) per month to minimise the risk of 
developing or worsening of hypertension.

Chronic renal failure patients treated with Silapo by the subcutaneous route should be monitored 
regularly for loss of efficacy, defined as absent or decreased response to Silapo treatment in patients 



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who previously responded to such therapy. This is characterised by a sustained decrease in 
haemoglobin despite an increase in Silapo dosage.

Some patients with more extended dosing intervals (greater than once weekly) of epoetin may not 
maintain adequate haemoglobin levels (see section 5.1) and may require an increase in epoetin dose. 
Haemoglobin levels should be monitored regularly.

Caution should be exercised with escalation of Silapo doses in patients with chronic renal failure, 
since high cumulative epoetin doses may be associated with an increased risk of mortality, serious 
cardiovascular and cerebrovascular events. In patients with a poor haemoglobin response to epoetins,
alternative explanations for the poor response should be considered (see sections 4.2 and 5.1).

Non response to erythropoietin therapy should prompt a search for causative factors. These include: 
iron, folate, or Vitamin B12 deficiency; aluminium intoxication; intercurrent infections; inflammatory 
or traumatic episodes; occult blood loss; haemolysis, and bone marrow fibrosis of any origin.

Cases of antibody-mediated PRCA have been very rarely reported in chronic renal failure patients 
with erythropoietin administered by the subcutaneous route. In patients developing sudden lack of 
efficacy, defined by a decrease in haemoglobin (1-2 g/dl per month) with increased need for 
transfusions, a reticulocyte count should be obtained and typical causes of non-response (e.g. iron, 
folate, or Vitamin B12-deficiency, aluminium intoxication, infection or inflammation, blood loss, and 
haemolysis) should be investigated. If no cause is identified, a bone marrow examination should be 
considered for diagnosis of PRCA.

If PRCA is diagnosed, therapy with Silapo must be immediately discontinued and testing for 
erythropoietin antibodies should be considered. Patients should not be switched to another medicinal 
product as anti-erythropoietin antibodies cross-react with other erythropoietins. Other causes of PRCA 
should be excluded, and appropriate therapy initiated.

Monitoring of reticulocyte count on a regular basis is recommended to detect possible occurrence of 
lack of efficacy in chronic renal failure patients.

Hyperkalaemia has been observed in isolated cases. In chronic renal failure patients, correction for 
anaemia may lead to increased appetite, and potassium and protein intake. Dialysis prescriptions may 
have to be adjusted periodically to maintain urea, creatinine and potassium in the desired range. Serum 
electrolytes should be monitored in chronic renal failure patients. If an elevated (or rising) serum 
potassium level is detected then consideration should be given to ceasing erythropoietin administration 
until hyperkalaemia has been corrected.

An increase in heparin dose during haemodialysis is frequently required during the course of therapy 
with erythropoietin as a result of the increased packed cell volume. Occlusion of the dialysis system is 
possible if heparinisation is not optimum.

Based on information available to date, correction of anaemia with erythropoietin in adult patients 
with renal insufficiency not yet undergoing dialysis does not accelerate the rate of progression of renal 
insufficiency.

Adult cancer patients with symptomatic anaemia receiving chemotherapy

In cancer patients receiving chemotherapy, the 2-3 week delay between erythropoietin administration 
and the appearance of erythropoietin-induced red cells should be taken into account when assessing if 
Silapo therapy is appropriate (patient at risk of being transfused).

Haemoglobin levels should be closely monitored until a stable level is achieved and periodically 
thereafter. If the rate of increase in haemoglobin exceeds 2 g/dl (1.25 mmol/l) per month or the 
haemoglobin level exceeds 12 g/dl (7.5 mmol/l), the dose adjustment detailed in section 4.2 should be 
thoroughly performed to minimise the risk of thrombotic events (see section 4.2).



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As an increased incidence of thrombotic vascular events (TVEs) has been observed in cancer patients 
receiving erythropoietic agents (see section 4.8), this risk should be carefully weighed against the 
benefit to be derived from treatment (with Silapo) particularly in cancer patients with an increased risk 
of thrombotic vascular events, such as obesity and patients with a prior history of TVEs (e.g. deep 
venous thrombosis or pulmonary embolism).

Adult surgery patients in an autologous predonation programme

All special warnings and precautions associated with autologous predonation programmes, especially 
routine volume replacement, should be respected.

Tumour growth potential

Epoetins are growth factors that primarily stimulate red blood cell production. Erythropoietin 
receptors may be expressed on the surface of a variety of tumour cells. As with all growth factors, 
there is a concern that epoetins could stimulate the growth of any type of malignancy. In several 
controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of 
tumour progression in patients with anaemia associated with cancer.

Several controlled clinical studies in which epoetins were administered to patients with a variety of 
common tumours including squamous head and neck cancer, lung cancer, and breast cancer, have 
shown an unexplained excess mortality.

In controlled clinical studies, use of epoetin alfa and other ESAs have shown:
 shortened time to tumour progression in patients with advanced head and neck cancer receiving 

radiation therapy when administered to target a haemoglobin of greater than 14 g/dl
(8.7 mmol/l),

 shortened overall survival and increased deaths attributed to disease progression at 4 months in 
patients with metastatic breast cancer receiving chemotherapy when administered to target a 
haemoglobin of 12-14 g/dl (7.5 -8.7 mmol/l),

 increased risk of death when administered to target a haemoglobin of 12 g/dl (7.5 mmol/l) in 
patients with active malignant disease receiving neither chemotherapy nor radiation therapy. 
ESAs are not indicated for use in this patient population.

In view of the above, in some clinical situations blood transfusion should be the preferred treatment 
for the management of anaemia in patients with cancer. The decision to administer recombinant 
erythropoietins should be based on a benefit-risk assessment with the participation of the individual 
patient, which should take into account the specific clinical context. Factors that should be considered 
in this assessment should include the type of tumour and its stage; the degree of anaemia; life-
expectancy; the environment in which the patient is being treated; and patient preference (see section 
5.1).

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic 
epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association 
with epoetin treatment. More severe cases have been observed with long-acting epoetins.

At the time of prescription patients should be advised of the signs and symptoms and monitored 
closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Silapo should 
be withdrawn immediately and an alternative treatment considered.
If the patient has developed a severe cutaneous skin reaction such as SJS or TEN due to the use of 
Silapo, treatment with Silapo must not be restarted in this patient at any time.



13

This medicinal product contains up to 0.5 mg phenylalanine in each dosage unit. Phenylalanine may 
be harmful for patients with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine 
builds up because the body cannot remove it properly.

This medicinal product contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say
essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

There is no evidence to indicate that treatment with erythropoietin alters the metabolism of other 
medicinal products.

However, since ciclosporin is bound by red blood cells there is potential for interactions with other 
medicinal products. If erythropoietin is given concomitantly with ciclosporin, blood levels of 
ciclosporin should be monitored and the dose of ciclosporin adjusted as the haematocrit rises.

No evidence exists that indicates an interaction between epoetin alfa and G-CSF or GM-CSF with 
regard to haematological differentiation or proliferation of tumour biopsy specimens in vitro.

4.6 Fertility, pregnancy and lactation

There are no adequate and well-controlled studies in pregnant women. Studies in animals have shown 
reproduction toxicity (see section 5.3). It is not known whether exogenous epoetin zeta is excreted in 
human milk. Consequently, erythropoietin should generally be used during pregnancy and lactation 
only if the potential benefit outweighs the potential risk to the foetus.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

Summary of the safety profile
Data from clinical studies with Silapo are in line with the safety profile of other authorised 
erythropoietins. Based on the results from clinical trials with other authorised erythropoietins 
approximately 8% of patients treated with erythropoietin are expected to experience adverse reactions. 
Adverse reactions during treatment with erythropoietin are observed predominantly in patients with 
chronic renal failure or underlying malignancies. These adverse reactions are most commonly 
headache and a dose dependent increase in blood pressure. Hypertensive crisis with encephalopathy-
like symptoms can occur. Attention should be paid to sudden stabbing migraine-like headaches as a 
possible warning signal.

Respiratory tract congestion, which includes events of upper respiratory tract congestion, nasal 
congestion and nasopharyngitis, have been reported in studies with extended interval dosing in adult 
patients with renal insufficiency not yet undergoing dialysis.

Thrombotic/vascular events, such as myocardial ischaemia, myocardial infarction, cerebrovascular 
accidents (cerebral haemorrhage and cerebral infarction), transient ischaemic attacks, deep vein 
thrombosis, arterial thrombosis, pulmonary emboli, aneurysms, retinal thrombosis, and clotting of an 
artificial kidney have been reported in patients receiving erythropoietic agents.
Antibody-mediated erythroblastopenia (PRCA) has been reported after months to years of treatment 
with epoetin alfa. In most of these patients, antibodies to erythropoietins have been observed (see 
sections 4.3 and 4.4).

Tabulated list of adverse reactions
Of a total 3 417 subjects in 25 randomised, double-blinded, placebo or standard of care controlled 
studies, the overall safety profile of epoetin alfa was evaluated in 2 094 anaemic subjects. Included 



14

were 228 epoetin alfa-treated CRF subjects in 4 chronic renal failure studies (2 studies in predialysis 
[N = 131 exposed CRF subjects] and 2 in dialysis [N = 97 exposed CRF subjects]); 1 404 exposed 
cancer subjects in 16 studies of anaemia due to chemotherapy; 147 exposed subjects in 2 studies for 
autologous blood donation; 213 exposed subjects in 1 study in the perisurgical period, and 
102 exposed subjects in 2 MDS studies. Adverse drug reactions reported by ≥1% of subjects treated 
with epoetin alfa in these trials are shown in the table below.

Frequency estimate: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to 
<1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000), not known (frequency cannot be 
estimated from the available data).

MedDRA System Organ 
Classification (SOC)

Adverse Reaction (Preferred Term 
Level)

Frequency

Blood and lymphatic system 
disorders

Pure red cell aplasia3, 
Thrombocythemia

Rare

Metabolism and nutrition disorders Hyperkalaemia1 Uncommon

Immune system disorders Hypersensitivity3 Uncommon

Anaphylactic reaction3 Rare

Nervous system disorders Headache Common

Convulsion Uncommon

Vascular disorders Hypertension, Venous and arterial 
thromboses2

Common

Hypertensive crisis3 Not known

Respiratory, thoracic and 
mediastinal disorders

Cough Common

Respiratory tract congestion Uncommon

Gastrointestinal disorders Diarrhoea, Nausea, Vomiting Very common

Skin and subcutaneous tissue 
disorders

Rash Common

Urticaria3 Uncommon

Angioneurotic oedema3 Not known

Musculoskeletal and connective 
tissue disorders

Arthralgia, Bone pain, Myalgia, Pain 
in extremity

Common

Congenital, familial and genetic 
disorders

Porphyria acute3 Rare

General disorders and 
administration site conditions

Pyrexia Very common

Chills, Influenza like illness, Injection 
site reaction, Oedema peripheral

Common

Drug ineffective3 Not known

Investigations Anti-erythropoeitin antibody positive Rare
1

Common in dialysis
2

Includes arterial and venous, fatal and non fatal events, such as deep venous thrombosis, pulmonary emboli, 
retinal thrombosis, arterial thrombosis (including myocardial infarction), cerebrovascular accidents 
(including cerebral infarction and cerebral haemorrhage) transient ischaemic attacks, and shunt thrombosis 
(including dialysis equipment) and thrombosis within arteriovenous shunt aneurisms

3
Addressed in the subsection below and/or in section 4.4

Description of selected adverse reactions

Adult and paediatric haemodialysis patients, adult peritoneal dialysis patients and adult patients with 
renal insufficiency not yet undergoing dialysis

The most frequent adverse reaction during treatment with epoetin alfa is a dose-dependent increase in 
blood pressure or aggravation of existing hypertension. These increases in blood pressure can be 



15

treated with medicinal products. Moreover, monitoring of the blood pressure is recommended 
particularly at the start of therapy. The following reactions have also occurred in isolated patients with 
normal or low blood pressure: hypertensive crisis with encephalopathy-like symptoms (e.g. headaches 
and confused state) and generalised tonoclonal seizures, requiring the immediate attention of a 
physician and intensive medical care. Particular attention should be paid to sudden stabbing migraine 
like headaches as a possible warning signal.
Shunt thromboses may occur, especially in patients who have a tendency to hypotension or whose 
arteriovenous fistulae exhibit complications (e.g. stenoses, aneurysms, etc.). Early shunt revision and 
thrombosis prophylaxis by administration of acetylsalicylic acid, for example, is recommended in 
these patients.

Adult cancer patients with symptomatic anaemia receiving chemotherapy

Hypertension may occur in epoetin alfa treated patients. Consequently, haemoglobin and blood 
pressure should be closely monitored.
An increased incidence of thrombotic vascular events (see section 4.4 and section 4.8 - General) has 
been observed in patients receiving erythropoietic agents.

Surgery patients

Independent of erythropoietin treatment, thrombotic and vascular events may occur in surgical patients 
with underlying cardiovascular disease following repeated phlebotomy. Therefore, routine volume 
replacement should be performed in such patients.

In patients with a baseline haemoglobin of > 13 g/dl, the possibility that Silapo treatment may be 
associated with an increased risk of postoperative thrombotic/vascular events cannot be excluded.

Adult patients with low- or intermediate-1-risk MDS

In the randomised, double-blind, placebo-controlled, multicentre study 4 (4.7%) subjects experienced 
TVEs (sudden death, ischaemic stroke, embolism, and phlebitis). All TVEs occurred in the epoetin 
alfa group and in the first 24 weeks of the study. Three were confirmed TVE and in the remaining case 
(sudden death), the thromboembolic event was not confirmed. Two subjects had significant risk 
factors (atrial fibrillation, heart failure and thrombophlebitis).

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic 
epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association 
with epoetin treatment (see section 4.4).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

The therapeutic margin of erythropoietin is very wide. Overdose of erythropoietin may produce effects 
that are extensions of the pharmacological effects of the hormone. Phlebotomy may be performed if 
excessively high haemoglobin levels occur. Additional supportive care should be provided as 
necessary.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


16

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other antianaemic preparations, erythropoietin
ATC code: B03XA01

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

Pharmacodynamic effects
Erythropoietin is a glycoprotein that stimulates, as a mitosis-stimulating factor and differentiating 
hormone, the formation of erythrocytes from precursors of the stem cell compartment.

The apparent molecular weight of erythropoietin is 32 000-40 000 Dalton. The protein moiety of the 
molecule contributes about 58% of total molecular weight and consists of 165 amino acids. The four 
carbohydrate chains are attached via three N-glycosidic bonds and one O-glycosidic bond to the 
protein. Epoetin zeta is identical in its amino acid sequence and similar in carbohydrate composition to 
endogenous human erythropoietin that has been isolated from the urine of anaemic patients.

The biological efficacy of erythropoietin has been demonstrated in various animal models in vivo
(normal and anaemic rats, polycythaemic mice). After administration of erythropoietin, the number of 
erythrocytes, the Hb values and reticulocyte counts increase as well as the 59Fe-incorporation rate.

An increased 3H-thymidine incorporation in the erythroid nucleated spleen cells has been found 
in vitro (mouse spleen cell culture) after incubation with erythropoietin. It could be shown with the aid 
of cell cultures of human bone marrow cells that erythropoietin stimulates erythropoiesis specifically 
and does not affect leukopoiesis. Cytotoxic actions of erythropoietin on bone marrow cells could not 
be detected.

As with other haematopoietic growth factors, erythropoietin has shown in vitro stimulating properties 
on human endothelial cells.

Adult patients with renal insufficiency not yet undergoing dialysis

In 2 studies with extended interval dosing of erythropoietin (3 times per week, once weekly, once 
every 2 weeks and once every 4 weeks) some patients with longer dosing intervals did not maintain 
adequate haemoglobin levels and reached protocol-defined haemoglobin withdrawal criteria (0% in 
once weekly, 3.7% in once-every-2-weeks and 3.3% in the once-every-4-weeks groups).

Treatment of adult patients scheduled for major elective orthopaedic surgery
In patients scheduled for major elective orthopaedic surgery with a pretreatment haemoglobin of > 10 
to ≤ 13 g/dl, epoetin alfa has been shown to decrease the risk of receiving allogeneic transfusions and 
hasten erythroid recovery (increased haemoglobin levels, haematocrit levels, and reticulocyte counts).

Clinical efficacy and safety
721 cancer patients receiving non-platinum chemotherapy were included in three placebo-controlled 
studies, 389 patients with haematological malignancies (221 multiple myeloma, 144 non-Hodgkin's 
lymphoma, and 24 other haematological malignancies) and 332 with solid tumours (172 breast, 
64 gynaecological, 23 lung, 22 prostate, 21 gastrointestinal, and 30 other tumour types). In two large, 
open-label studies, 2 697 cancer patients receiving non-platinum chemotherapy were included, 
1 895 with solid tumours (683 breast, 260 lung, 174 gynaecological, 300 gastrointestinal, and 
478 other tumour types) and 802 with haematological malignancies.

In a prospective, randomised, double-blind, placebo-controlled trial conducted in 375 anaemic patients 
with various non-myeloid malignancies receiving non-platinum chemotherapy, there was a significant 
reduction of anaemia-related sequelae (e.g. fatigue, decreased energy, and activity reduction), as 

http://www.ema.europa.eu/


17

measured by the following instruments and scales: Functional Assessment of Cancer Therapy-
Anaemia (FACT-An) general scale, FACT-An fatigue scale, and Cancer Linear Analogue Scale 
(CLAS). Two other smaller, randomised, placebo-controlled trials failed to show a significant 
improvement in quality of life parameters on the EORTC-QLQ-C30 scale or CLAS, respectively.
Erythropoietin is a growth factor that primarily stimulates red cell production. Erythropoietin receptors 
may be expressed on the surface of a variety of tumour cells.

Survival and tumour progression have been examined in five large controlled studies involving a total 
of 2 833 patients, of which four were double-blind placebo-controlled studies and one was an open-
label study. The studies either recruited patients who were being treated with chemotherapy (two 
studies) or used patient populations in which erythropoiesis stimulating agents are not indicated: 
anaemia in patients with cancer not receiving chemotherapy, and head and neck cancer patients 
receiving radiotherapy. The target haemoglobin concentration in two studies was > 13 g/dl; in the 
remaining three studies it was 12-14 g/dl. In the open-label study there was no difference in overall 
survival between patients treated with recombinant human erythropoietin and controls. In the four 
placebo-controlled studies the hazard ratios for overall survival ranged between 1.25 and 2.47 in 
favour of controls. These studies have shown a consistent unexplained statistically significant excess 
mortality in patients who have anaemia associated with various common cancers who received 
recombinant human erythropoietin compared to controls. Overall survival outcome in the trials could 
not be satisfactorily explained by differences in the incidence of thrombosis and related complications 
between those given recombinant human erythropoietin and those in the control group.

A systematic review has also been performed involving more than 9 000 cancer patients participating 
in 57 clinical trials. Meta-analysis of overall survival data produced a hazard ratio point estimate of 
1.08 in favour of controls (95% CI: 0.99, 1.18; 42 trials and 8 167 patients). An increased relative risk 
of thromboembolic events (RR 1.67, 95% CI: 1.35, 2.06, 35 trials and 6 769 patients) was observed in 
patients treated with recombinant human erythropoietin. There is an increased risk for 
thromboembolic events in patients with cancer treated with recombinant human erythropoietin and a 
negative impact on overall survival cannot be excluded. The extent to which these outcomes might 
apply to the administration of recombinant human erythropoietin to patients with cancer, treated with 
chemotherapy to achieve haemoglobin concentrations less than 13 g/dl, is unclear because few patients 
with these characteristics were included in the data reviewed.

A patient-level data analysis has also been performed on more than 13 900 cancer patients (chemo-, 
radio-, chemoradio-, or no therapy) participating in 53 controlled clinical trials involving several 
epoetins. Meta-analysis of overall survival data produced a hazard ratio point estimate of 1.06 in 
favour of controls (95% CI: 1.00, 1.12; 53 trials and 13 933 patients) and for the cancer patients 
receiving chemotherapy, the overall survival hazard ratio was 1.04 (95% CI: 0.97, 1.11; 38 trials and 
10 441 patients). Meta-analyses also indicate consistently a significantly increased relative risk of 
thromboembolic events in cancer patients receiving recombinant human erythropoietin (see section 
4.4).

In a randomised, double-blind, placebo-controlled study of 4 038 CRF patients not on dialysis with 
type 2 diabetes and haemoglobin levels ≤ 11 g/dl, patients received either treatment with darbepoetin 
alfa to target haemoglobin levels of 13 g/dl or placebo (see section 4.4). The study did not meet either 
primary objective of demonstrating a reduction in risk for all-cause mortality, cardiovascular 
morbidity, or end stage renal disease (ESRD). Analysis of the individual components of the composite
endpoints showed the following HR (95% CI): death 1.05 (0.92, 1.21), stroke 1.92 (1.38, 2.68), 
congestive heart failure (CHF) 0.89 (0.74, 1.08), myocardial infarction (MI) 0.96 (0.75, 1.23), 
hospitalisation for myocardial ischaemia 0.84 (0.55, 1.27), ESRD 1.02 (0.87, 1.18).

Pooled post-hoc analyses of clinical studies of ESAs have been performed in CRF patients (on 
dialysis, not on dialysis, in diabetic and non-diabetic patients). A tendency towards increased risk 
estimates for all-cause mortality, cardiovascular and cerebrovascular events associated with higher 
cumulative ESA doses independent of the diabetes or dialysis status was observed (see sections 4.2
and 4.4).



18

Major elective orthopaedic surgery
The effect of epoetin alfa (300 IU/kg or 100 IU/kg) on the exposure to allogeneic blood transfusion 
has been evaluated in a placebo-controlled, double-blind clinical trial in non-iron deficient adult 
patients scheduled for major elective orthopaedic hip or knee surgery. Epoetin alfa was administered 
subcutaneously for 10 days prior to surgery, on the day of surgery, and for four days after surgery. 
Patients were stratified according to their baseline haemoglobin (≤ 10 g/dl, > 10 to ≤ 13 g/dl and 
> 13 g/dl).

Epoetin alfa 300 IU/kg significantly reduced the risk of allogeneic transfusion in patients with a 
pretreatment haemoglobin of > 10 to ≤ 13 g/dl. Sixteen percent of epoetin alfa 300 IU/kg, 23% of 
epoetin alfa 100 IU/kg and 45% of placebo-treated patients required transfusion.

An open-label, parallel-group trial in non-iron deficient adult subjects with a pretreatment 
haemoglobin of ≥ 10 to ≤ 13 g/dl who were scheduled for major orthopaedic hip or knee surgery 
compared epoetin alfa 300 IU/kg subcutaneously daily for 10 days prior to surgery, on the day of 
surgery and for four days after surgery to epoetin alfa 600 IU/kg subcutaneously once weekly for 
3 weeks prior to surgery and on the day of surgery.

From pretreatment to presurgery, the mean increase in haemoglobin in the 600 IU/kg weekly group 
(1.44 g/dl) was twice than that observed in the 300 IU/kg daily group (0.73 g/dl). Mean haemoglobin 
levels were similar for the two treatment groups throughout the postsurgical period.

The erythropoietic response observed in both treatment groups resulted in similar transfusion rates 
(16% in the 600 IU/kg weekly group and 20% in the 300 IU/kg daily group).

Treatment of adult patients with low- or intermediate-1-risk MDS

A randomised, double-blind, placebo-controlled, multicentre study evaluated the efficacy and safety of 
epoetin alfa in adult anaemic subjects with low- or intermediate-1-risk MDS.

Subjects were stratified by serum erythropoetin (sEPO) level and prior transfusion status at screening. 
Key baseline characteristics for the <200 mU/ml stratum are shown in the table below.

Baseline Characteristics for Subjects with sEPO<200 mU/ml at Screening
Randomised

Epoetin alfa Placebo
Total (N)b 85a 45
Screening sEPO <200 mU/ml (N) 71 39
Haemoglobin (g/l)
N 71 39
Mean 92.1 (8.57) 92.1 (8.51)
Median 94.0 96.0
Range (71, 109) (69, 105)
95% CI for Mean (90.1, 94.1) (89.3, 94.9)
Prior Transfusions
N 71 39
Yes 31 (43.7%) 17 (43.6%)
≤2 RBC Units 16 (51.6%) 9 (52.9%)
˃2 and ≤4 RBC Units 14 (45.2%) 8 (47.1%)
˃4 RBC Units 1 (3.2%) 0
No 40 (56.3%) 22 (56.4%)
a one subject did not have sEPO data
b in the ≥200 mU/ml stratum there were 13 subjects in the epoetin alfa group and 6 subjects in the placebo 

group

Erythroid response was defined according to International Working Group (IWG) 2006 criteria as a 
haemoglobin increase ≥1.5 g/dl from baseline or a reduction of RBC units transfused by an absolute 



19

number of at least 4 units every 8 weeks compared to the 8 weeks prior to baseline, and a response 
duration of at least 8 weeks.

Erythroid response during the first 24 weeks of the study was demonstrated by 27/85 (31.8%) of the 
subjects in the epoetin alfa group compared to 2/45 (4.4%) of the subjects in the placebo group 
(p<0.001). All of the responding subjects were in the stratum with sEPO <200 mU/ml during 
screening. In that stratum, 20/40 (50%) subjects without prior transfusions demonstrated erythroid 
response during the first 24 weeks, compared with 7/31 (22.6%) subjects with prior transfusions (two 
subjects with prior transfusion reached primary endpoint based on reduction of RBC units transfused 
by an absolute number of at least 4 units every 8 weeks compared to the 8 weeks prior to baseline).

Median time from baseline to first transfusion was statistically significantly longer in the epoetin alfa 
group compared to placebo (49 vs. 37 days; p=0.046). After 4 weeks of treatment the time to first 
transfusion was further increased in the epoetin alfa group (142 vs. 50 days, p=0.007). The percentage 
of subjects who were transfused in the epoetin alfa group decreased from 51.8% in the 8 weeks prior 
to baseline to 24.7% between weeks 16 and 24, compared to the placebo group which had an increase 
in transfusion rate from 48.9% to 54.1% over the same time periods.

5.2 Pharmacokinetic properties

Intravenous route
Measurement of erythropoietin following multiple dose intravenous administration revealed a half-life 
of approximately 4 hours in healthy volunteers and a somewhat more prolonged half-life of 
approximately 5 hours in renal failure patients. A half-life of approximately 6 hours has been reported 
in children.

Subcutaneous route
Following subcutaneous injection, serum levels of erythropoietin are much lower than the levels 
achieved following intravenous injection, the levels increase slowly and reach a peak between 12 and 
18 hours postdose. The peak is always well below the peak achieved using the intravenous route 
(approximately 1/20th of the value).

There is no accumulation: the levels remain the same, whether they are determined 24 hours after the
first injection or 24 hours after the last injection.

The half-life is difficult to evaluate for the subcutaneous route and is estimated to be about 24 hours. 
The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the 
intravenous medicinal product and is approximately 20%.

5.3 Preclinical safety data

In some pre-clinical toxicological studies in dogs and rats, but not in monkeys, erythropoietin therapy 
was associated with subclinical bone marrow fibrosis (bone marrow fibrosis is a known complication 
of chronic renal failure in humans and may be related to secondary hyperparathyroidism or unknown 
factors. The incidence of bone marrow fibrosis was not increased in a study of haemodialysis patients 
who were treated with erythropoietin for 3 years compared to a matched control group of dialysis 
patients who had not been treated with erythropoietin).

In animal studies, erythropoietin has been shown to decrease foetal body weight, delay ossification 
and increase foetal mortality when given in weekly doses of approximately 20 times the recommended 
human weekly dose. These changes are interpreted as being secondary to decreased maternal body 
weight gain.

Erythropoietin did not show any changes in bacterial and mammalian cell culture mutagenicity tests 
and an in vivo micronucleus test in mice. Long-term carcinogenicity studies have not been carried out. 
There are conflicting reports in the literature regarding whether erythropoietin may play a major role 



20

as tumour proliferator. These reports are based on in vitro findings from human tumour samples, but 
are of uncertain significance in the clinical situation.

6. PHARMACEUTICAL PARTICULARS

6.1 List of Excipients

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)

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.

6.3 Shelf life

30 months

6.4 Special precautions for storage

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.

For the purpose of ambulatory use, the patient may remove the product from the refrigerator and store 
it at room temperature (not above 25°C) for one single period of up to 3 days.

6.5 Nature and contents of container

Silapo 1 000 IU/0.3 ml solution for injection in pre-filled syringe
0.3 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1 or 6 pre-filled syringes.

Silapo 2 000 IU/0.6 ml solution for injection in pre-filled syringe
0.6 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1 or 6 pre-filled syringes.

Silapo 3 000 IU/0.9 ml solution for injection in pre-filled syringe
0.9 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1 or 6 pre-filled syringes.



21

Silapo 4 000 IU/0.4 ml solution for injection in pre-filled syringe
0.4 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1 or 6 pre-filled syringes.

Silapo 5 000 IU/0.5 ml solution for injection in pre-filled syringe
0.5 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1 or 6 pre-filled syringes.

Silapo 6 000 IU/0.6 ml solution for injection in pre-filled syringe
0.6 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1 or 6 pre-filled syringes.

Silapo 8 000 IU/0.8 ml solution for injection in pre-filled syringe
0.8 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1 or 6 pre-filled syringes.

Silapo 10 000 IU/1 ml solution for injection in pre-filled syringe
1 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1 or 6 pre-filled syringes.

Silapo 20 000 IU/0.5 ml solution for injection in pre-filled syringe
0.5 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1, 4 or 6 pre-filled syringes.

Silapo 30 000 IU/0.75 ml solution for injection in pre-filled syringe
0.75 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1, 4 or 6 pre-filled syringes.

Silapo 40 000 IU/1 ml solution for injection in pre-filled syringe
1 ml solution for injection in pre-filled syringe Type I glass with a fixed steel injection needle and a 
plunger stopper with PTFE coating with or without a needle guard device.
Each pack contains 1, 4 or 6 pre-filled syringes.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Handling instructions for Silapo:
1. After removing one syringe from the blister pack the solution should be checked to ensure that 

it is clear, colourless and practically free from visible particles.
2. The protective cap is removed from the injection needle and air is expelled from the syringe and 

needle by holding the syringe vertically and gently pressing the plunger upwards.
3. The syringe is now ready for use.

Silapo must not be used 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.
 It may have been accidentally frozen.



22

This medicinal product is for single use only.

Do not shake.

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

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

8. MARKETING AUTHORISATION NUMBER(S)

Silapo 1 000 IU/0.3 ml solution for injection in pre-filled syringe
EU/1/07/432/001 [1 pre-filled syringe]
EU/1/07/432/002 [6 pre-filled syringes]
EU/1/07/432/023 [1 pre-filled syringe with needle guard]
EU/1/07/432/024 [6 pre-filled syringes with needle guard]

Silapo 2 000 IU/0.6 ml solution for injection in pre-filled syringe
EU/1/07/432/003 [1 pre-filled syringe]
EU/1/07/432/004 [6 pre-filled syringes]
EU/1/07/432/025 [1 pre-filled syringe with needle guard]
EU/1/07/432/026 [6 pre-filled syringes with needle guard]

Silapo 3 000 IU/0.9 ml solution for injection in pre-filled syringe
EU/1/07/432/005 [1 pre-filled syringe]
EU/1/07/432/006 [6 pre-filled syringes]
EU/1/07/432/027 [1 pre-filled syringe with needle guard]
EU/1/07/432/028 [6 pre-filled syringes with needle guard]

Silapo 4 000 IU/0.4 ml solution for injection in pre-filled syringe
EU/1/07/432/007 [1 pre-filled syringe]
EU/1/07/432/008 [6 pre-filled syringes]
EU/1/07/432/029 [1 pre-filled syringe with needle guard]
EU/1/07/432/030 [6 pre-filled syringes with needle guard]

Silapo 5 000 IU/0.5 ml solution for injection in pre-filled syringe
EU/1/07/432/009 [1 pre-filled syringe]
EU/1/07/432/010 [6 pre-filled syringes]
EU/1/07/432/031 [1 pre-filled syringe with needle guard]
EU/1/07/432/032 [6 pre-filled syringes with needle guard]

Silapo 6 000 IU/0.6 ml solution for injection in pre-filled syringe
EU/1/07/432/011 [1 pre-filled syringe]
EU/1/07/432/012 [6 pre-filled syringes]
EU/1/07/432/033 [1 pre-filled syringe with needle guard]
EU/1/07/432/034 [6 pre-filled syringes with needle guard]



23

Silapo 8 000 IU/0.8 ml solution for injection in pre-filled syringe
EU/1/07/432/013 [1 pre-filled syringe]
EU/1/07/432/014 [6 pre-filled syringes]
EU/1/07/432/035 [1 pre-filled syringe with needle guard]
EU/1/07/432/036 [6 pre-filled syringes with needle guard]

Silapo 10 000 IU/1 ml solution for injection in pre-filled syringe
EU/1/07/432/015 [1 pre-filled syringe]
EU/1/07/432/016 [6 pre-filled syringes]
EU/1/07/432/037 [1 pre-filled syringe with needle guard]
EU/1/07/432/038 [6 pre-filled syringes with needle guard]

Silapo 20 000 IU/0.5 ml solution for injection in pre-filled syringe
EU/1/07/432/017 [1 pre-filled syringe]
EU/1/07/432/020 [4 pre-filled syringes]
EU/1/07/432/039 [1 pre-filled syringe with needle guard]
EU/1/07/432/040 [4 pre-filled syringes with needle guard]
EU/1/07/432/045 [6 pre-filled syringes with needle guard]

Silapo 30 000 IU/0.75 ml solution for injection in pre-filled syringe
EU/1/07/432/018 [1 pre-filled syringe]
EU/1/07/432/021 [4 pre-filled syringes]
EU/1/07/432/041 [1 pre-filled syringe with needle guard]
EU/1/07/432/042 [4 pre-filled syringes with needle guard]
EU/1/07/432/046 [6 pre-filled syringes with needle guard]

Silapo 40 000 IU/1 ml solution for injection in pre-filled syringe
EU/1/07/432/019 [1 pre-filled syringe]
EU/1/07/432/022 [4 pre-filled syringes]
EU/1/07/432/043 [1 pre-filled syringe with needle guard]
EU/1/07/432/044 [4 pre-filled syringes with needle guard]
EU/1/07/432/047 [6 pre-filled syringes with needle guard]

9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION

Date of first authorisation: 18 December 2007
Date of latest renewal: 20 December 2012

10. DATE OF REVISION OF THE TEXT

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

http://www.ema.europa.eu/


24

ANNEX II

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT



25

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers of the biological active substance

Norbitec GmbH
Pinnauallee 4
D-25436 Uetersen
Germany

Name and address of the manufacturer responsible for batch release

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

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2).

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



26

ANNEX III

LABELLING AND PACKAGE LEAFLET



27

A. LABELLING



28

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 1 000 IU/0.3 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 1 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.3 ml solution for injection
6 pre-filled syringes without needle guard containing 0.3 ml solution for injection
1 pre-filled syringe with needle guard containing 0.3 ml solution for injection
6 pre-filled syringes with needle guard containing 0.3 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



29

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/001 [1 pre-filled syringe]
EU/1/07/432/002 [6 pre-filled syringes]
EU/1/07/432/023 [1 pre-filled syringe with needle guard]
EU/1/07/432/024 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 1 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



30

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 1 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

1 000 IU/0.3 ml 

6. OTHER



31

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 2 000 IU/0.6 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 2 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.6 ml solution for injection
6 pre-filled syringes without needle guard containing 0.6 ml solution for injection
1 pre-filled syringe with needle guard containing 0.6 ml solution for injection
6 pre-filled syringes with needle guard containing 0.6 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



32

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/003 [1 pre-filled syringe]
EU/1/07/432/004 [6 pre-filled syringes]
EU/1/07/432/025 [1 pre-filled syringe with needle guard]
EU/1/07/432/026 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 2 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



33

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 2 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

2 000 IU/0.6 ml 

6. OTHER



34

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 3 000 IU/0.9 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 3 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.9 ml solution for injection
6 pre-filled syringes without needle guard containing 0.9 ml solution for injection
1 pre-filled syringe with needle guard containing 0.9 ml solution for injection
6 pre-filled syringes with needle guard containing 0.9 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



35

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/005 [1 pre-filled syringe]
EU/1/07/432/006 [6 pre-filled syringes]
EU/1/07/432/027 [1 pre-filled syringe with needle guard]
EU/1/07/432/028 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 3 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



36

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 3 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

3 000 IU/0.9 ml 

6. OTHER



37

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 4 000 IU/0.4 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 4 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.4 ml solution for injection
6 pre-filled syringes without needle guard containing 0.4 ml solution for injection
1 pre-filled syringe with needle guard containing 0.4 ml solution for injection
6 pre-filled syringes with needle guard containing 0.4 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



38

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/007 [1 pre-filled syringe]
EU/1/07/432/008 [6 pre-filled syringes]
EU/1/07/432/029 [1 pre-filled syringe with needle guard]
EU/1/07/432/030 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 4 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



39

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 4 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

4 000 IU/0.4 ml 

6. OTHER



40

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 5 000 IU/0.5 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 5 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.5 ml solution for injection
6 pre-filled syringes without needle guard containing 0.5 ml solution for injection
1 pre-filled syringe with needle guard containing 0.5 ml solution for injection
6 pre-filled syringes with needle guard containing 0.5 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



41

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/009 [1 pre-filled syringe]
EU/1/07/432/010 [6 pre-filled syringes]
EU/1/07/432/031 [1 pre-filled syringe with needle guard]
EU/1/07/432/032 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 5 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



42

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 5 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

5 000 IU/0.5 ml 

6. OTHER



43

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 6 000 IU/0.6 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 6 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.6 ml solution for injection
6 pre-filled syringes without needle guard containing 0.6 ml solution for injection
1 pre-filled syringe with needle guard containing 0.6 ml solution for injection
6 pre-filled syringes with needle guard containing 0.6 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



44

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/011 [1 pre-filled syringe]
EU/1/07/432/012 [6 pre-filled syringes]
EU/1/07/432/033 [1 pre-filled syringe with needle guard]
EU/1/07/432/034 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 6 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



45

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 6 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6 000 IU/0.6 ml 

6. OTHER



46

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 8 000 IU/0.8 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 8 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.8 ml solution for injection
6 pre-filled syringes without needle guard containing 0.8 ml solution for injection
1 pre-filled syringe with needle guard containing 0.8 ml solution for injection
6 pre-filled syringes with needle guard containing 0.8 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



47

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/013 [1 pre-filled syringe]
EU/1/07/432/014 [6 pre-filled syringes]
EU/1/07/432/035 [1 pre-filled syringe with needle guard]
EU/1/07/432/036 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 8 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



48

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 8 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

8 000 IU/0.8 ml 

6. OTHER



49

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 10 000 IU/1 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 10 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 1 ml solution for injection
6 pre-filled syringes without needle guard containing 1 ml solution for injection
1 pre-filled syringe with needle guard containing 1 ml solution for injection
6 pre-filled syringes with needle guard containing 1 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



50

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/015 [1 pre-filled syringe]
EU/1/07/432/016 [6 pre-filled syringes]
EU/1/07/432/037 [1 pre-filled syringe with needle guard]
EU/1/07/432/038 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 10 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



51

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 10 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

10 000 IU/1 ml 

6. OTHER



52

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 20 000 IU/0.5 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 20 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.5 ml solution for injection
4 pre-filled syringes without needle guard containing 0.5 ml solution for injection
1 pre-filled syringe with needle guard containing 0.5 ml solution for injection
4 pre-filled syringes with needle guard containing 0.5 ml solution for injection
6 pre-filled syringes with needle guard containing 0.5 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



53

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/017 [1 pre-filled syringe]
EU/1/07/432/020 [4 pre-filled syringes]
EU/1/07/432/039 [1 pre-filled syringe with needle guard]
EU/1/07/432/040 [4 pre-filled syringes with needle guard]
EU/1/07/432/045 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 20 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



54

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 20 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

20 000 IU/0.5 ml 

6. OTHER



55

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 30 000 IU/0.75 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 30 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 0.75 ml solution for injection
4 pre-filled syringes without needle guard containing 0.75 ml solution for injection
1 pre-filled syringe with needle guard containing 0.75 ml solution for injection
4 pre-filled syringes with needle guard containing 0.75 ml solution for injection
6 pre-filled syringes with needle guard containing 0.75 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



56

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/018 [1 pre-filled syringe]
EU/1/07/432/021 [4 pre-filled syringes]
EU/1/07/432/041 [1 pre-filled syringe with needle guard]
EU/1/07/432/042 [4 pre-filled syringes with needle guard]
EU/1/07/432/046 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 30 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



57

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 30 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

30 000 IU/0.75 ml 

6. OTHER



58

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Silapo 40 000 IU/1 ml solution for injection in pre-filled syringe
epoetin zeta

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 pre-filled syringe contains 40 000 IU epoetin zeta

3. LIST OF EXCIPIENTS

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).

Contains phenylalanine, see leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection in pre-filled syringe.

1 pre-filled syringe without needle guard containing 1 ml solution for injection
4 pre-filled syringes without needle guard containing 1 ml solution for injection
1 pre-filled syringe with needle guard containing 1 ml solution for injection
4 pre-filled syringes with needle guard containing 1 ml solution for injection
6 pre-filled syringes with needle guard containing 1 ml solution for injection

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous or subcutaneous use.
Read the package leaflet before use.
Do not shake.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 
OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



59

9. SPECIAL STORAGE CONDITIONS

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.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

STADA Arzneimittel AG 
Stadastrasse 2-18
61118 Bad Vilbel 
Germany

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/07/432/019 [1 pre-filled syringe]
EU/1/07/432/022 [4 pre-filled syringes]
EU/1/07/432/043 [1 pre-filled syringe with needle guard]
EU/1/07/432/044 [4 pre-filled syringes with needle guard]
EU/1/07/432/047 [6 pre-filled syringes with needle guard]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Silapo 40 000 IU

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



60

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABELS

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Silapo 40 000 IU Injection
epoetin zeta
iv/sc use

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

40 000 IU/1 ml 

6. OTHER



61

B. PACKAGE LEAFLET



62

Package leaflet: Information for the user

Silapo 1 000 IU/0.3 ml solution for injection in pre-filled syringe
Silapo 2 000 IU/0.6 ml solution for injection in pre-filled syringe
Silapo 3 000 IU/0.9 ml solution for injection in pre-filled syringe
Silapo 4 000 IU/0.4 ml solution for injection in pre-filled syringe
Silapo 5 000 IU/0.5 ml solution for injection in pre-filled syringe
Silapo 6 000 IU/0.6 ml solution for injection in pre-filled syringe
Silapo 8 000 IU/0.8 ml solution for injection in pre-filled syringe
Silapo 10 000 IU/1 ml solution for injection in pre-filled syringe
Silapo 20 000 IU/0.5 ml solution for injection in pre-filled syringe
Silapo 30 000 IU/0.75 ml solution for injection in pre-filled syringe
Silapo 40 000 IU/1 ml solution for injection in pre-filled syringe

epoetin zeta

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor or pharmacist.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

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

1. What Silapo is and what it is used for

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

Silapo is used
 in adults, children and adolescents on haemodialysis to treat symptomatic anaemia (low red 

blood cell counts) 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).

 in moderately anaemic adults about to have major orthopaedic surgery (for example hip or knee 
replacement operations), to reduce the potential need for blood transfusions.



63

 in anaemic adult patients with myelodysplastic syndrome to reduce the need for a blood 
transfusion.

2. What you need to know before you use Silapo

Do not use Silapo

 if you are allergic to erythropoietins or any of the other ingredients of this medicine (listed in 
section 6)

 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.
 if you are due to have major elective orthopaedic surgery (such as hip or knee surgery), and you:

 have severe heart disease
 have severe disorders of the veins and arteries
 have recently had a heart attack or stroke
 can’t take medicines to thin the blood

Warnings and precautions

Talk to your doctor before using Silapo 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
 kidney disease.

Special warnings

During 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 haemoglobin 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.



64

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 treatment including a blood test, as Silapo may affect the results.

Serious skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis 
(TEN) have been reported in association with epoetin treatment. SJS/TEN can appear initially as 
reddish target-like spots or circular patches often with central blisters on the trunk. Also, ulcers of 
mouth, throat, nose, genitals and eyes (red and swollen eyes) can occur. These serious skin rashes are 
often preceded by fever and/or flu-like symptoms. The rashes may progress to widespread peeling of 
the skin and life-threatening complications. If you develop a serious rash or another of these skin 
symptoms, stop taking Silapo and contact your doctor or seek medical attention immediately.

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 of 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 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 renal failure, and particularly if you do not respond properly to 
Silapo, your doctor will check your dose of Silapo because repeatedly increasing your dose of Silapo 
if you are not responding to treatment may increase the risk of having a problem of the heart or the 
blood vessels and could increase risk of myocardial infarction, stroke and 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.



65

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 minimise 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.

Other medicines and Silapo

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

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

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

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.

Silapo contains phenylalanine

This medicine contains up to 0.5 mg phenylalanine in each dosage unit. Phenylalanine may be harmful 
if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because 
the body cannot remove it properly.

Silapo contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially 
‘sodium-free’.



66

3. How to use Silapo

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 this medicine exactly as your doctor has told you. Check 
with your doctor if you are not sure.

Dose 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. Your doctor will use the lowest effective dose to control 
the symptoms of your anaemia. If you do not respond adequately to Silapo, your doctor will check 
your dose and will inform you if you need to change doses of Silapo.

You may be given iron supplements before and during Silapo treatment to make it more effective.

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 recommended 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.

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 adolescents is based on body weight in kilograms. The recommended 
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 recommended starting dose is 50 IU/kg. This is given twice a week.



67

Depending on how your anaemia responds, the dose may be adjusted approximately every 4 weeks 
until your condition is controlled.

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 recommended 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, or, 
if you have your injections under the skin, it may also be given once weekly or once every 2 weeks). 
The maximum dosage should not exceed 150 IU/kg, 3 times per week, 240 IU/kg (up to a maximum 
of 20 000 IU) once weekly or 480 IU/kg (up to a maximum of 40 000 IU) once every 2 weeks.

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

If you are on a more extended dosing interval (greater than once weekly) of Silapo, you may not 
maintain adequate haemoglobin levels and you may require an increase in Silapo dose or frequency of 
administration.

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 recommended 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 recommended 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.

Use in adults scheduled for major orthopaedic surgery
 The recommended dose is 600 IU per kilogram bodyweight once a week.
 Silapo is given by injection under the skin each week for three weeks before surgery and on the day 

of surgery.
 If there is a medical need to reduce the time before your operation, you will be given a daily dose 

of 300 IU/kg for up to ten days before surgery, on the day of surgery and for four days immediately 
afterwards.

 If blood tests show your haemoglobin is too high before the operation, the treatment will be 
stopped.

 You may be given iron supplements before and during Silapo treatment to make it more effective.

Use in adult patients with myelodysplastic syndrome

Your doctor may initiate treatment with Silapo if your haemoglobin is 10 g/dl or less. The aim of 
treatment is to maintain your haemoglobin level between 10 and 12 g/dl as a higher haemoglobin level 
may increase the risk of blood clots and death.

Silapo is given by injection under the skin.

The starting dose is 450 IU per kilogram bodyweight once a week.

Your doctor will order blood tests, and may adjust the dose, depending on how your anaemia responds 
to Silapo treatment.



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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. Good 
injection sites are the top of the thigh and around the tummy (abdomen) but away from the navel. Vary 
the site from day to day.

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
When treatment starts, Silapo is usually injected by medical or nursing staff. Later, your doctor may 
suggest that you or your caregiver learn how to inject it under the skin (subcutaneously) yourself. 

 Do not attempt to inject yourself unless you have been trained to do so by your doctor or nurse.
 Always use Silapo exactly as instructed by your doctor or nurse.
 Only use this medicine if it has been stored correctly (see section 5).
 Before use, leave the syringe to stand until it reaches room temperature. This usually takes 

between 15 and 30 minutes.

Only use one dose of Silapo from each syringe.

If this medicine is injected under the skin (subcutaneously), the amount injected is not normally more 
than 1 ml in a single injection.

Silapo is given alone and not mixed with other liquids for injection.

Do not shake the syringes. Prolonged vigorous shaking may damage the product. If the product has 
been shaken vigorously, don’t use it.



69

How to inject yourself using a pre-filled syringe:
 Take a syringe out of the refrigerator. The liquid needs to come to room temperature. Do not 

remove the syringe’s needle cover while allowing it to reach room temperature.
 Check the syringe, to make sure it is the right dose, has not passed its expiry date, is not 

damaged, and the liquid is clear and not frozen.
 Choose an injection site. Good sites are the top of the thigh and around the tummy (abdomen) 

but away from the navel. Vary the site from day to day.
 Wash your hands. Use an antiseptic swab on the injection site, to disinfect it.
 Hold the pre-filled syringe by the body of the syringe with the covered needle pointing upward.
 Do not hold by the plunger head, plunger or needle cover.
 Do not pull back on the plunger at any time.
 Do not remove the needle cover from the pre-filled syringe until you are ready to inject Silapo.
 Take the needle cover off the syringe by holding the barrel and pulling the needle cover off 

carefully without twisting it. Don’t push the plunger, touch the needle or shake the syringe.
 Pinch a fold of skin between your thumb and index finger. Don’t squeeze it.
 Push the needle in fully. Your doctor or nurse may have shown you how to do this.
 Push the plunger with your thumb as far as it will go to inject the entire amount of liquid. Push 

it slowly and evenly, keeping the skin fold pinched.
 When the plunger is pushed as far as it will go, take out the needle and let go of the skin.
 When the needle is pulled out of your skin, there may be a little bleeding at the injection site. 

This is normal. You can press an antiseptic swab over the injection site for a few seconds after 
the injection.

 Dispose of your used syringe in a sharps container. Do not try to replace the needle cover.
 Never put used syringes into your normal household waste bin.

How to inject yourself using a pre-filled syringe:
Your pre-filled syringe has a passive needle guard device attached to it in order to protect you from 
needle stick injury.
 Take a syringe out of the refrigerator. The liquid needs to come to room temperature. Do not 

remove the syringe’s needle cover while allowing it to reach room temperature.
 Check the syringe, to make sure it is the right dose, has not passed its expiry date, is not 

damaged, and the liquid is clear and not frozen.
 Choose an injection site. Good sites are the top of the thigh and around the tummy (abdomen) 

but away from the navel. Vary the site from day to day.
 Wash your hands. Use an antiseptic swab on the injection site, to disinfect it.
 Hold the pre-filled syringe by the body of the syringe with the covered needle pointing upward.
 Do not hold by the plunger head, plunger or needle cover.
 Do not pull back on the plunger at any time.
 Do not remove the needle cover from the pre-filled syringe until you are ready to inject Silapo.
 Take the needle cover off the syringe by holding the barrel and pulling the needle cover off 

carefully without twisting it. Don’t push the plunger, touch the needle or shake the syringe.
 Pinch a fold of skin between your thumb and index finger. Don’t squeeze it.
 Push the needle in fully. Your doctor or nurse may have shown you how to do this.
 Depress the plunger while grasping the finger flange until the entire dose has been given. The 

needle guard will NOT activate unless the ENTIRE dose has been given.



70

 When the plunger is pushed as far as it will go, take out the needle and let go of the skin.
 Let go of the plunger and allow the syringe to move up until the entire needle is guarded and 

locks into place.

 When the needle is pulled out of your skin, there may be a little bleeding at the injection site. 
This is normal. You can press an antiseptic swab over the injection site for a few seconds after 
the injection.

 Dispose of your used syringe in a sharps container. Do not try to replace the needle cover.
 Never put used syringes into your normal household waste bin.

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 medicine, ask your doctor.

4. Possible side effects

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

Serious side effects:

Serious skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis have been 
reported in association with epoetin treatment. These can appear as reddish target-like macules or 
circular patches often with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, 
genitals and eyes and can be preceded by fever and flu-like symptoms.
Stop using Silapo if you develop these symptoms and contact your doctor or seek medical attention 
immediately. See also section 2.

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.



71

Other side effects:

Very common: may affect more than 1 in 10 people
 Diarrhoea
 Feeling sick in your stomach
 Vomiting
 Fever
 Respiratory tract congestion, such as stuffy nose and sore throat, has been reported in patients 

with kidney disease not yet on dialysis.

Common: may affect up to 1 in 10 people
 Increased blood pressure. Raised blood pressure may require treatment with medicines (or 

adjustment to any medicines 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.

 Blood clots (including deep vein thrombosis and embolism) that may require urgent treatment. 
You may have chest pain, breathlessness, and painful swelling and redness, usually in the leg as 
symptoms.

 Cough
 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 rashes and swelling around the eyes (oedema), which may result from an allergic reaction.
 Blood clot in an artificial kidney.
 Bone or muscle pain
 Flu-like symptoms, such as headache, aches and pains in the joints, feeling of weakness, chills, 

tiredness and dizziness. These may be more common at the start of treatment. If you have these 
symptoms during injection into the vein, a slower delivery of the injection may help to avoid 
them in the future.

 Redness, burning and pain at the site of injection
 Swelling of the ankles, feet or fingers
 Arm or leg pain

Uncommon: may affect up to 1 in 100 people
 Cerebral haemorrhages.
 High levels of blood potassium which can cause abnormal heart rhythm (this is a very common 

side effect in patients on dialysis).
 Fits
 Nose or airway congestion
 Allergic reaction
 Hives

Rare: may affect up to 1 in 1 000 people
 Symptoms of pure red cell aplasia (PRCA)

PRCA means the bone marrow does not make enough red blood cells. PRCA causes sudden and 
severe anaemia. The symptoms are:
o unusual tiredness,
o feeling dizzy,
o breathlessness.

PRCA has been very rarely reported mostly in patients with kidney disease after months to 
years of treatment with Silapo and other products that stimulate red blood cell production.



72

 An increase in levels of small blood cells (called platelets), which are normally involved in the 
formation of a blood clot may occur, particularly when starting treatment. Your doctor will 
check on this.

 Severe allergic reaction that may include:
o a swollen face, lips, mouth, tongue or throat
o difficulty swallowing or breathing
o itchy rash (hives)

 Problem with the blood that may cause pain, dark coloured urine or increased sensitivity of the 
skin to sunlight (porphyria)

If you are receiving haemodialysis:
 Blood clots (thrombosis) may form in your dialysis shunt. This is more likely if you have low 

blood pressure or if your fistula has complications.
 Blood clots may also form in your haemodialysis system. Your doctor may decide to increase 

your heparin dose during dialysis.

Tell your doctor or nurse immediately if you are aware of any of these effects, or if you notice any 
other effects while you are receiving treatment with Silapo.

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 including adult patients with myelodysplastic syndrome
– blood clotting (thrombotic vascular events) (see section “Warnings and precautions”).
– increase of blood pressure. Therefore your haemoglobin-levels and your blood pressure should 

be controlled.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Silapo

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 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.

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73

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).

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Silapo contains

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

Silapo 1 000 IU/0.3 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.3 ml solution for injection contains 1 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 3 333 IU epoetin zeta 
per ml.

Silapo 2 000 IU/0.6 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.6 ml solution for injection contains 2 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 3 333 IU epoetin zeta 
per ml.

Silapo 3 000 IU/0.9 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.9 ml solution for injection contains 3 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 3 333 IU epoetin zeta 
per ml.

Silapo 4 000 IU/0.4 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.4 ml solution for injection contains 4 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta 
per ml.

Silapo 5 000 IU/0.5 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.5 ml solution for injection contains 5 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta 
per ml.

Silapo 6 000 IU/0.6 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.6 ml solution for injection contains 6 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta 
per ml.

Silapo 8 000 IU/0.8 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.8 ml solution for injection contains 8 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta 
per ml.

Silapo 10 000 IU/1 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 1 ml solution for injection contains 10 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 10 000 IU epoetin zeta 
per ml.



74

Silapo 20 000 IU/0.5 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.5 ml solution for injection contains 20 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 40 000 IU epoetin zeta 
per ml.

Silapo 30 000 IU/0.75 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 0.75 ml solution for injection contains 30 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 40 000 IU epoetin zeta 
per ml.

Silapo 40 000 IU/1 ml solution for injection in pre-filled syringe
1 pre-filled syringe with 1 ml solution for injection contains 40 000 international units (IU) 
epoetin zeta (recombinant human erythropoietin). The solution contains 40 000 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 ml solution, depending on the content of epoetin 
zeta (see “What Silapo contains”).

One pack contains 1, 4 or 6 pre-filled syringes with or without a needle guard device.

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:

STADAPHARM GmbH
Stadastraße 2-18
D-61118 Bad Vilbel
Tel: +49 (0) 6101 603-0
Fax: +49 (0) 6101 603-3888

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

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


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET