Epoetin Alfa Hexal

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 1,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 2,000 IU/1 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 3,000 IU/0.3 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 4,000 IU/0.4 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 5,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 6,000 IU/0.6 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 7,000 IU/0.7 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 8,000 IU/0.8 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 9,000 IU/0.9 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 10,000 IU/1 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 20,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 30,000 IU/0.75 mL solution for injection in a pre-filled syringe 
Epoetin alfa HEXAL 40,000 IU/1 mL solution for injection in a pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Epoetin alfa HEXAL 1,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 2,000 IU of epoetin alfa* corresponding to 16.8 micrograms per mL 
A pre-filled syringe of 0.5 mL contains 1,000 international units (IU) corresponding to 8.4 micrograms 
epoetin alfa. * 
 
Epoetin alfa HEXAL 2,000 IU/1 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 2,000 IU of epoetin alfa* corresponding to 16.8 micrograms per mL 
A pre-filled syringe of 1 mL contains 2,000 international units (IU) corresponding to 16.8 micrograms 
epoetin alfa. * 
 
Epoetin alfa HEXAL 3,000 IU/0.3 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 10,000 IU of epoetin alfa* corresponding to 84.0 micrograms per mL 
A pre-filled syringe of 0.3 mL contains 3,000 international units (IU) corresponding 
to 25.2 micrograms epoetin alfa. * 
 
Epoetin alfa HEXAL 4,000 IU/0.4 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 10,000 IU of epoetin alfa* corresponding to 84.0 micrograms per mL 
A pre-filled syringe of 0.4 mL contains 4,000 international units (IU) corresponding 
to 33.6 micrograms epoetin alfa. * 
 
Epoetin alfa HEXAL 5,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 10,000 IU of epoetin alfa* corresponding to 84.0 micrograms per mL 
A pre-filled syringe of 0.5 mL contains 5,000 international units (IU) corresponding 
to 42.0 micrograms epoetin alfa. *  
 
Epoetin alfa HEXAL 6,000 IU/0.6 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 10,000 IU of epoetin alfa* corresponding to 84.0 micrograms per mL 
A pre-filled syringe of 0.6 mL contains 6,000 international units (IU) corresponding 
to 50.4 micrograms epoetin alfa. * 
 
Epoetin alfa HEXAL 7,000 IU/0.7 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 10,000 IU of epoetin alfa* corresponding to 84.0 micrograms per mL 
A pre-filled syringe of 0.7 mL contains 7,000 international units (IU) corresponding 
to 58.8 micrograms epoetin alfa. * 
 



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Epoetin alfa HEXAL 8,000 IU/0.8 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 10,000 IU of epoetin alfa* corresponding to 84.0 micrograms per mL 
A pre-filled syringe of 0.8 mL contains 8,000 international units (IU) corresponding 
to 67.2 micrograms epoetin alfa. * 
 
Epoetin alfa HEXAL 9,000 IU/0.9 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 10,000 IU of epoetin alfa* corresponding to 84.0 micrograms per mL 
A pre-filled syringe of 0.9 mL contains 9,000 international units (IU) corresponding 
to 75.6 micrograms epoetin alfa. * 
 
Epoetin alfa HEXAL 10,000 IU/1 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 10,000 IU of epoetin alfa* corresponding to 84.0 micrograms per mL 
A pre-filled syringe of 1 mL contains 10,000 international units (IU) corresponding 
to 84.0 micrograms epoetin alfa. * 
 
Epoetin alfa HEXAL 20,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 40,000 IU of epoetin alfa* corresponding to 336.0 micrograms per mL 
A pre-filled syringe of 0.5 mL contains 20,000 international units (IU) corresponding 
to 168.0 micrograms epoetin alfa. * 
 
Epoetin alfa HEXAL 30,000 IU/0.75 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 40,000 IU of epoetin alfa* corresponding to 336.0 micrograms per mL 
A pre-filled syringe of 0.75 mL contains 30,000 international units (IU) corresponding 
to 252.0 micrograms epoetin alfa. * 
 
Epoetin alfa HEXAL 40,000 IU/1 mL solution for injection in a pre-filled syringe 
Each mL of solution contains 40,000 IU of epoetin alfa* corresponding to 336.0 micrograms per mL 
A pre-filled syringe of 1 mL contains 40,000 international units (IU) corresponding 
to 336.0 micrograms epoetin alfa. * 
 
* Produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology  
For the full list of excipients, see section 6.1. 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium 
free”. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection in a pre-filled syringe (injection) 
Clear, colourless solution 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Epoetin alfa HEXAL is indicated for the treatment of symptomatic anaemia associated with chronic 
renal failure (CRF): 
 
- in adults and children aged 1 to 18 years on haemodialysis and adult patients on peritoneal 

dialysis (see section 4.4). 
- in adults with renal insufficiency not yet undergoing dialysis for the treatment of severe 

anaemia of renal origin accompanied by clinical symptoms in patients (see section 4.4).  
 



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Epoetin alfa HEXAL is indicated in adults 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) for the treatment of 
anaemia and reduction of transfusion requirements.  
 
Epoetin alfa HEXAL is indicated in adults in a predonation programme to increase the yield of 
autologous blood. Treatment should only be given to patients with moderate anaemia (haemoglobin 
[Hb] concentration range between 10 to 13 g/dL [6.2 to 8.1 mmol/L], 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). 
 
Epoetin alfa HEXAL 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 or 6.2 to 8.1 mmol/L) who do not have an autologous 
predonation programme available and with expected moderate blood loss (900 to 1,800 mL).  
 
Epoetin alfa HEXAL is indicated for the treatment of 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 Epoetin alfa HEXAL has to be initiated under the supervision of physicians 
experienced in the management of patients with the above indications. 
 
Posology 
 
All other causes of anaemia (iron, folate or vitamin B12 deficiency, aluminium intoxication, infection 
or inflammation, blood loss, haemolysis and bone marrow fibrosis of any origin) should be evaluated 
and treated prior to initiating therapy with epoetin alfa, and when deciding to increase the dose. In 
order to ensure optimum response to epoetin alfa, adequate iron stores should be assured and iron 
supplementation should be administered if necessary (see section 4.4). 
 
Treatment of symptomatic anaemia in adult chronic renal failure patients 
 
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. 
 
The recommended desired haemoglobin concentration range is between 10 g/dL to 12 g/dL 
(6.2 to 7.5 mmol/L). Epoetin alfa HEXAL should be administered in order to increase haemoglobin to 
not greater than 12 g/dL (7.5 mmol/L). 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. 
 
Due to intra-patient variability, occasional individual haemoglobin values for a patient above and 
below the desired haemoglobin concentration range may be observed. Haemoglobin variability should 
be addressed through dose management, with consideration for the haemoglobin concentration 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. If the 
haemoglobin is rising by more than 2 g/dL (1.25 mmol/L) per month, or if the sustained haemoglobin 
exceeds 12 g/dL (7.5 mmol/L) reduce the Epoetin alfa HEXAL dose by 25%. If the haemoglobin 
exceeds 13 g/dL (8.1 mmol/L), discontinue therapy until it falls below 12 g/dL (7.5 mmol/L) and then 
reinstitute Epoetin alfa HEXAL therapy at a dose 25% below the previous dose. 
 



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Patients should be monitored closely to ensure that the lowest approved effective dose of Epoetin alfa 
HEXAL is used to provide adequate control of anaemia and of the symptoms of anaemia whilst 
maintaining a haemoglobin concentration below or at 12 g/dL (7.5 mmol/L). 
 
Caution should be exercised with escalation of Epoetin alfa HEXAL doses in patients with chronic 
renal failure. In patients with a poor haemoglobin response to Epoetin alfa HEXAL, alternative 
explanations for the poor response should be considered (see section 4.4 and 5.1). 
 
Treatment with Epoetin alfa HEXAL is divided into two stages – correction and maintenance phase. 
 
Adult haemodialysis patients  
 
In patients on haemodialysis where intravenous access is readily available, administration by the 
intravenous route is preferable. 
 
Correction phase 
The starting dose is 50 IU/kg, 3 times per week.  
 
If necessary, increase or decrease the dose by 25 IU/kg (3 times per week) until the desired 
haemoglobin concentration range between 10 g/dL to 12 g/dL (6.2 to 7.5 mmol/L) is achieved (this 
should be done in steps of at least four weeks).  
 
Maintenance phase  
The recommended total weekly dose is between 75 IU/kg and 300 IU/kg. 
 
Appropriate adjustment of the dose should be made in order to maintain haemoglobin values within 
the desired concentration range between 10 g/dL to 12 g/dL (6.2 to 7.5 mmol/L). 
 
Patients with very low initial haemoglobin (< 6 g/dL or < 3.75 mmol/L) may require higher 
maintenance doses than patients whose initial anaemia is less severe (> 8 g/dL or > 5 mmol/L). 
 
Adult patients with renal insufficiency not yet undergoing dialysis 
 
Where intravenous access is not readily available Epoetin alfa HEXAL may be administered 
subcutaneously. 
 
Correction phase 
Starting dose of 50 IU/kg, 3 times per week, followed if necessary by a dosage 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).  
 
Maintenance phase 
During the maintenance phase, Epoetin alfa HEXAL 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 
values at the desired level: haemoglobin between 10 g/dL and 12 g/dL (6.2 to 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. 
 
Adult peritoneal dialysis patients 
 
Where intravenous access is not readily available Epoetin alfa HEXAL may be administered 
subcutaneously. 
 



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Correction phase 
The starting dose is 50 IU/kg, 2 times per week.  
 
Maintenance phase 
The recommended maintenance dose is between 25 IU/kg and 50 IU/kg, 2 times per week in 2 equal 
injections. 
Appropriate adjustment of the dose should be made in order to maintain haemoglobin values at the 
desired level between 10 g/dL to 12 g/dL (6.2 to 7.5 mmol/L).  
 
Treatment of adult patients with chemotherapy-induced anaemia 
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. 
 
Epoetin alfa HEXAL should be administered to patients with anaemia (e.g. haemoglobin concentration 
≤ 10 g/dL (6.2 mmol/L)).  
 
The initial dose is 150 IU/kg subcutaneously, 3 times per week. 
 
Alternatively, Epoetin alfa HEXAL can be administered at an initial dose of 450 IU/kg subcutaneously 
once weekly. 
 
Appropriate adjustment of the dose should be made in order to maintain haemoglobin concentrations 
within the desired concentration range between 10 g/dL to 12 g/dL (6.2 to 7.5 mmol/L). 
 
Due to intra-patient variability, occasional individual haemoglobin concentrations for a patient above 
and below the desired haemoglobin concentration range may be observed. Haemoglobin variability 
should be addressed through dose management, with consideration for the desired haemoglobin 
concentration range between 10 g/dL (6.2 mmol/L) to 12 g/dL (7.5 mmol/L). A sustained 
haemoglobin concentration of greater than 12 g/dL (7.5 mmol/L) should be avoided; guidance for 
appropriate dose adjustment for when haemoglobin concentrations exceed 12 g/dL (7.5 mmol/L) is 
described below. 
- If the haemoglobin concentration 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 concentration 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 concentration 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.  

- If the haemoglobin concentration 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. 

 
Dose adjustment to maintain haemoglobin concentrations between 10 g/dL to 12 g/dL 
(6.2 to 7.5 mmol/L) 
 
If the haemoglobin concentration is increasing by more than 2 g/dL (1.25 mmol/L) per month, or if the 
haemoglobin concentration level exceeds 12 g/dL (7.5 mmol/L), reduce the Epoetin alfa HEXAL dose 
by about 25 to 50%.  
 
If the haemoglobin concentration level exceeds 13 g/dL (8.1 mmol/L), discontinue therapy until it falls 
below 12 g/dL (7.5 mmol/L) and then reinitiate Epoetin alfa HEXAL therapy at a dose 25% below the 
previous dose. 
 



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The recommended dosing regimen is described in the following diagram:  
 

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

     
for 4 weeks 

     
     
     
     

 Reticulocyte count increase ≥ 40,000/µL Reticulocyte count increase 
< 40,000/µL 

 or Hb increase ≥ 1 g/dL and Hb increase < 1 g/dL 
     
     
     
  Target Hb 300 IU/kg 
  (≤ 12 g/dL) 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 
 
Patients should be monitored closely to ensure that the lowest approved dose of 
erythropoiesis-stimulating agent (ESA) is used to provide adequate control of the symptoms of 
anaemia. 
 
Epoetin alfa therapy should continue until one month after the end of chemotherapy. 
 
Treatment of adult surgery patients in an autologous predonation programme 
Mildly anaemic patients (haematocrit of 33 to 39%) requiring predeposit of ≥ 4 units of blood should 
be treated with Epoetin alfa HEXAL 600 IU/kg intravenously, 2 times per week for 3 weeks prior to 
surgery. Epoetin alfa HEXAL should be administered after the completion of the blood donation 
procedure. 
 
Treatment of adult patients scheduled for major elective orthopaedic surgery 
 
The recommended dose is Epoetin alfa HEXAL 600 IU/kg, administered subcutaneously weekly for 
three weeks (days -21, -14 and -7) prior to surgery and on the day of surgery (day 0).  
 
In cases where there is a medical need to shorten the lead time before surgery to less than three weeks, 
Epoetin alfa HEXAL 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.  
 



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If the haemoglobin level reaches 15 g/dL (9.38 mmol/L), or higher, during the preoperative period, 
administration of Epoetin alfa HEXAL should be stopped and further dosages should not be 
administered. 
 
Treatment of adult patients with low- or intermediate-1-risk MDS 
 
Epoetin alfa HEXAL should be administered to patients with symptomatic anaemia (e.g. haemoglobin 
concentration ≤ 10 g/dL (6.2 mmol/L)). 
 
The recommended starting dose is Epoetin alfa HEXAL 450 IU/kg (maximum total dose is 40,000 IU) 
administered 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 1050 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: Epoetin alfa 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). 

 
 
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. 
 
Paediatric population 
 
Treatment of symptomatic anaemia in chronic renal failure patients on haemodialysis 
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. 
 
In paediatric patients the recommended haemoglobin concentration range is between 9.5 g/dL 
to 11 g/dL (5.9 to 6.8 mmol/L). Epoetin alfa HEXAL should be administered in order to increase 
haemoglobin to not greater than 11 g/dL (6.8 mmol/L). 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. 



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Patients should be monitored closely to ensure that the lowest approved dose of Epoetin alfa HEXAL 
is used to provide adequate control of anaemia and of the symptoms of anaemia. 
 
Treatment with Epoetin alfa HEXAL is divided into two stages – correction and maintenance phase. 
 
In paediatric patients on haemodialysis where intravenous access is readily available, administration 
by the intravenous route is preferable. 
 
Correction phase 
The starting dose is 50 IU/kg intravenously, 3 times per week. 
 
If necessary, increase or decrease the dose by 25 IU/kg (3 times per week) until the desired 
haemoglobin concentration range of between 9.5 g/dL to 11 g/dL (5.9 to 6.8 mmol/L) is achieved (this 
should be done in steps of at least four weeks). 
 
Maintenance phase 
Appropriate adjustment of the dose should be made in order to maintain haemoglobin levels within the 
desired concentration range between 9.5 g/dL to 11 g/dL (5.9 to 6.8 mmol/L). 
 
Generally, children under 30 kg require higher maintenance doses than children over 30 kg and adults. 
Paediatric patients with very low initial haemoglobin (< 6.8 g/dL or < 4.25 mmol/L) may require 
higher maintenance doses than patients whose initial haemoglobin is higher (> 6.8 g/dL or 
> 4.25 mmol/L). 
 
Anaemia in chronic renal failure patients before initiation of dialysis or on peritoneal dialysis 
The safety and efficacy of epoetin alfa in chronic renal failure patients with anaemia before initiation 
of dialysis or on peritoneal dialysis have not been established. Currently available data for 
subcutaneous use of epoetin alfa in these populations are described in section 5.1 but no 
recommendation on posology can be made. 
 
Treatment of paediatric patients with chemotherapy-induced anaemia 
The safety and efficacy of epoetin alfa in paediatric patients receiving chemotherapy have not been 
established (see section 5.1). 
 
Treatment of paediatric surgery patients in an autologous predonation programme 
The safety and efficacy of epoetin alfa in paediatrics have not been established. No data are available. 
 
Treatment of paediatric patients scheduled for major elective orthopaedic surgery 
The safety and efficacy of epoetin alfa in paediatrics have not been established. No data are available. 
 
Method of administration  
 
Precautions to be taken before handling or administering the medicinal product. 
 
Before use, leave the Epoetin alfa HEXAL syringe to stand until it reaches room temperature. This 
usually takes between 15 and 30 minutes. 
As with any other injectable product, check that there are no particles in the solution or change in 
colour. Epoetin alfa HEXAL is a sterile but unpreserved product and is for single use only. Administer 
the amount required. 
 
Treatment of symptomatic anaemia in adult chronic renal failure patients 
 
In patients with chronic renal failure where intravenous access is routinely available (haemodialysis 
patients) administration of Epoetin alfa HEXAL by the intravenous route is preferable. 
 



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Where intravenous access is not readily available (patients not yet undergoing dialysis and peritoneal 
dialysis patients) Epoetin alfa HEXAL may be administered as a subcutaneous injection. 
 
Treatment of adult patients with chemotherapy-induced anaemia 
Epoetin alfa HEXAL should be administered as a subcutaneous injection. 
 
Treatment of adult surgery patients in an autologous predonation programme 
Epoetin alfa HEXAL should be administered by the intravenous route. 
 
Treatment of adult patients scheduled for major elective orthopaedic surgery 
Epoetin alfa HEXAL should be administered as a subcutaneous injection. 
 
Treatment of adult patients with low- or intermediate-1-risk MDS 
Epoetin alfa HEXAL should be administered as a subcutaneous injection. 
 
Treatment of symptomatic anaemia in paediatric chronic renal failure patients on haemodialysis 
 
In paediatric patients with chronic renal failure where intravenous access is routinely available 
(haemodialysis patients) administration of Epoetin alfa HEXAL by the intravenous route is preferable.  
 
Intravenous administration 
Administer over at least one to five 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 isotonic saline to rinse the tubing and ensure satisfactory injection of the 
product into the circulation (see Posology, “Adult haemodialysis patients”). 
 
A slower administration is preferable in patients who react to the treatment with “flu-like” symptoms 
(see section 4.8). 
 
Do not administer Epoetin alfa HEXAL by intravenous infusion or in conjunction with other 
medicinal product solutions (please refer to section 6.6 for further information). 
 
Subcutaneous administration  
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 should be given in the limbs or the anterior abdominal wall. 
 
In those situations in which the physician determines that a patient or caregiver can safely and 
effectively administer Epoetin alfa HEXAL subcutaneously themselves, instruction as to the proper 
dosage and administration should be provided. 
 
Graduation rings 
The syringe contains graduation rings to provide for the administration of a part of the dose (see 
section 6.6). However the product is for single use only. Only one dose of Epoetin alfa HEXAL from 
each syringe should be taken. 
 
“Instructions on how to inject Epoetin alfa HEXAL yourself” can be found at the end of the package 
leaflet. 
 
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 

should not receive Epoetin alfa HEXAL or any other erythropoietin (see section 4.4). 



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- Uncontrolled hypertension. 
 
- All contraindications associated with autologous blood predonation programmes should be 

respected in patients being supplemented with Epoetin alfa HEXAL. 
 
The use of Epoetin alfa HEXAL 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.  
 
- Surgery patients who for any reason cannot receive adequate antithrombotic prophylaxis. 
 
4.4 Special warnings and precautions for use 
 
General 
 
In all patients receiving epoetin alfa, blood pressure should be closely monitored and controlled as 
necessary. Epoetin alfa should be used with caution in the presence of untreated, inadequately treated 
or poorly controllable hypertension. It may be necessary to add or increase anti-hypertensive 
treatment. If blood pressure cannot be controlled, epoetin alfa treatment should be discontinued.  
 
Hypertensive crisis with encephalopathy and seizures, requiring the immediate attention of a physician 
and intensive medical care, have occurred also during epoetin alfa treatment in patients with 
previously normal or low blood pressure. Particular attention should be paid to sudden stabbing 
migraine-like headaches as a possible warning signal (see section 4.8). 
 
Epoetin alfa should be used with caution in patients with epilepsy, history of seizures, or medical 
conditions associated with a predisposition to seizure activity such as CNS infections and brain 
metastases. 
 
Epoetin alfa should be used with caution in patients with chronic liver failure. The safety of epoetin 
alfa has not been established in patients with hepatic dysfunction. 
 
An increased incidence of thrombotic vascular events (TVEs) has been observed in patients receiving 
ESAs (see section 4.8). These include venous and arterial thromboses and embolism (including some 
with fatal outcomes), such as deep venous thrombosis, pulmonary emboli, retinal thrombosis, and 
myocardial infarction. Additionally, cerebrovascular accidents (including cerebral infarction, cerebral 
haemorrhage and transient ischaemic attacks) have been reported. 
 
The reported risk of these TVEs should be carefully weighed against the benefits to be derived from 
treatment with epoetin alfa particularly in patients with pre-existing risk factors for TVE, including 
obesity and prior history of TVEs (e.g. deep venous thrombosis, pulmonary embolism, and cerebral 
vascular accident). 
 
In all patients, haemoglobin levels should be closely monitored due to a potential increased risk of 
thromboembolic events and fatal outcomes when patients are treated at haemoglobin levels above the 
concentration range for the indication of use. 
 
There may be a moderate dose-dependent rise in the platelet count within the normal range during 
treatment with epoetin alfa. This regresses during the course of continued therapy. In addition, 
thrombocythaemia above the normal range has been reported. It is recommended that the platelet 
count is regularly monitored during the first 8 weeks of therapy.  
 
All other causes of anaemia (iron, folate or vitamin B12 deficiency, aluminium intoxication, infection 
or inflammation, blood loss, haemolysis and bone marrow fibrosis of any origin) should be evaluated 
and treated prior to initiating therapy with epoetin alfa, and when deciding to increase the dose. In 



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most cases, the ferritin values in the serum fall simultaneously with the rise in packed cell volume. In 
order to ensure optimum response to epoetin alfa, adequate iron stores should be assured and iron 
supplementation should be administered if necessary (see section 4.2):  
 
- For chronic renal failure patients, iron supplementation (elemental iron 200 to 300 mg/day 

orally for adults and 100 to 200 mg/day orally for paediatrics) is recommended if serum ferritin 
levels are below 100 ng/mL. 

 
- For cancer patients, iron supplementation (elemental iron 200 to 300 mg/day orally) is 

recommended if transferrin saturation is below 20%.  
 
- For patients in an autologous predonation programme, iron supplementation (elemental 

iron 200 mg/day orally) should be administered several weeks prior to initiating the autologous 
predeposit in order to achieve high iron stores prior to starting epoetin alfa therapy, and 
throughout the course of epoetin alfa therapy. 

 
- For patients scheduled for major elective orthopaedic surgery, iron supplementation (elemental 

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

 
Very rarely, development of or exacerbation of porphyria has been observed in epoetin alfa-treated 
patients. Epoetin alfa should be used with caution in patients with porphyria. 
 
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, Epoetin alfa 
HEXAL 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 
Epoetin alfa HEXAL, treatment with Epoetin alfa HEXAL must not be restarted in this patient at any 
time. 
 
In order to improve the traceability of erythropoiesis-stimulating agents (ESAs), the trade name and 
the batch number of the administered ESA should be clearly recorded (or stated) in the patient file. 
Patients should only be switched from one ESA to another under appropriate supervision. 
 
Pure Red Cell Aplasia (PRCA) 
 
Antibody-mediated PRCA has been reported after months to years of epoetin alfa treatment. Cases 
have also been reported in patients with hepatitis C treated with interferon and ribavirin, when ESAs 
are used concomitantly. Epoetin alfa is not approved in the management of anaemia associated with 
hepatitis C. 
 
In patients developing sudden lack of efficacy defined by a decrease in haemoglobin (1 to 2 g/dL 
or 0.62 to 1.25 mmol/L 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, haemolysis and bone marrow fibrosis of any 
origin) should be investigated. 
 
A paradoxical decrease in haemoglobin and development of severe anaemia associated with low 
reticulocyte counts should prompt to discontinue treatment with epoetin alfa and perform 
anti-erythropoietin antibody testing. A bone marrow examination should also be considered for 
diagnosis of PRCA. 



13 

 
No other ESA therapy should be commenced because of the risk of cross-reaction. 
 
Treatment of symptomatic anaemia in adult and paediatric chronic renal failure patients 
 
Chronic renal failure patients being treated with epoetin alfa should have haemoglobin levels 
measured on a regular basis until a stable level is achieved, and periodically thereafter. 
 
In chronic renal failure patients 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 risks of 
an increase in hypertension. 
In patients with chronic renal failure, maintenance haemoglobin concentration should not exceed the 
upper limit of the haemoglobin concentration range as recommended in section 4.2. In clinical trials, 
an increased risk of death and serious cardiovascular events was observed when ESAs were 
administered to achieve a haemoglobin concentration level 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. 
 
Caution should be exercised with escalation of Epoetin alfa HEXAL 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 
section 4.2 and 5.1). 
 
Chronic renal failure patients treated with epoetin alfa by the subcutaneous route should be monitored 
regularly for loss of efficacy, defined as absent or decreased response to epoetin alfa treatment in 
patients who previously responded to such therapy. This is characterised by a sustained decrease in 
haemoglobin despite an increase in epoetin alfa dosage (see section 4.8). 
 
Some patients with more extended dosing intervals (greater than once weekly) of epoetin alfa may not 
maintain adequate haemoglobin levels (see section 5.1) and may require an increase in epoetin alfa 
dose. Haemoglobin levels should be monitored regularly.  
 
Shunt thromboses have occurred in haemodialysis patients, especially in those 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.  
 
Hyperkalaemia has been observed in isolated cases though causality has not been established. Serum 
electrolytes should be monitored in chronic renal failure patients. If an elevated or rising serum 
potassium level is detected, then in addition to appropriate treatment of the hyperkalaemia, 
consideration should be given to ceasing epoetin alfa administration until the serum potassium level 
has been corrected.  
 
An increase in heparin dose during haemodialysis is frequently required during the course of therapy 
with epoetin alfa 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 epoetin alfa in adult patients with 
renal insufficiency not yet undergoing dialysis does not accelerate the rate of progression of renal 
insufficiency. 



14 

 
 
 
Treatment of patients with chemotherapy-induced anaemia 
 
Cancer patients being treated with epoetin alfa should have haemoglobin levels measured on a regular 
basis until a stable level is achieved, and periodically thereafter.  
 
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 tumours. The role of ESAs on tumour 
progression or reduced progression-free survival cannot be excluded. In controlled clinical studies, use 
of epoetin alfa and other ESAs have been associated with decreased locoregional tumour control or 
decreased overall survival:  
 
- decreased locoregional control in patients with advanced head and neck cancer receiving 

radiation therapy when administered to achieve a haemoglobin concentration level 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 achieve a 
haemoglobin concentration range of 12 to 14 g/dL (7.5 to 8.7 mmol/L), 

 
- increased risk of death when administered to achieve a haemoglobin concentration level 

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, 

 
- an observed 9% increase in risk for progress of disease (PD) or death in the epoetin alfa plus 

SOC group from a primary analysis and a 15% increased risk that cannot be statistically ruled 
out in patients with metastatic breast cancer receiving chemotherapy when administered to 
achieve a haemoglobin concentration range of 10 to 12 g/dL (6.2 to 7.5 mmol/L). 

 
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 
erythropoietin treatment 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). 
 
In cancer patients receiving chemotherapy, the 2 to 3 week delay between ESA administration and the 
appearance of erythropoietin-induced red cells should be taken into account when assessing if epoetin 
alfa therapy is appropriate (patient at risk of being transfused). 
 
Surgery patients in autologous predonation programmes 
 
All special warnings and special precautions associated with autologous predonation programmes, 
especially routine volume replacement, should be respected. 
 
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 



15 

> 13 g/dL (> 8.1 mmol/L), the possibility that epoetin alfa treatment may be associated with an 
increased risk of postoperative thrombotic/vascular events cannot be excluded. Therefore, epoetin alfa 
should not be used in patients with baseline haemoglobin > 13 g/dL (> 8.1 mmol/L). 
 
Excipients 
 
This medicine contains less than 1 mmol sodium (23 mg) per pre-filled syringe, that is to say 
essentially “sodium-free”. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No evidence exists that indicates that treatment with epoetin alfa alters the metabolism of other 
medicinal products.  
Medicinal products that decrease erythropoiesis may decrease the response to epoetin alfa. 
 
Since cyclosporin is bound by red blood cells (RBCs) there is potential for a medicinal product 
interaction. If epoetin alfa is given concomitantly with cyclosporin, blood levels of cyclosporin should 
be monitored and the dose of cyclosporin adjusted as the haematocrit rises.  
 
No evidence exists that indicates an interaction between epoetin alfa and granulocyte 
colony-stimulating factor (G-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) 
with regard to haematological differentiation or proliferation of tumour biopsy specimens in vitro.  
 
In female adult patients with metastatic breast cancer, subcutaneous co-administration 
of 40,000 IU/mL epoetin alfa with trastuzumab 6 mg/kg had no effect on the pharmacokinetics of 
trastuzumab. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of epoetin alfa in pregnant women. Studies in 
animals have shown reproductive toxicity (see section 5.3). Consequently, epoetin alfa should be used 
in pregnancy only if the potential benefit outweighs the potential risk to the foetus. The use of epoetin 
alfa is not recommended in pregnant surgical patients participating in an autologous blood predonation 
programme. 
 
Breast-feeding 
 
It is unknown whether exogenous epoetin alfa is excreted in human milk. Epoetin alfa should be used 
with caution in nursing women. A decision must be made whether to discontinue breast-feeding or to 
discontinue/abstain from therapy with epoetin alfa taking into account the benefit of breast-feeding for 
the child and the benefit of epoetin alfa therapy for the woman. 
 
The use of epoetin alfa is not recommended in lactating surgical patients participating in an autologous 
blood predonation programme. 
 
Fertility 
 
There are no studies assessing the potential effect of epoetin alfa on male or female fertility.  
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Epoetin alfa 
HEXAL has no or negligible influence on the ability to drive and use machines. 
 



16 

4.8 Undesirable effects 
 
Summary of the safety profile 
The most frequent adverse drug reaction during treatment with epoetin alfa is a dose-dependent 
increase in blood pressure or aggravation of existing hypertension. Monitoring of the blood pressure 
should be performed, particularly at the start of therapy (see section 4.4).  
 
The most frequently occurring adverse drug reactions observed in clinical trials of epoetin alfa are 
diarrhoea, nausea, vomiting, pyrexia and headache. Influenza-like illness may occur especially at the 
start of treatment.  
 
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.  
 
An increased incidence of thrombotic vascular events (TVEs) has been observed in patients receiving 
ESAs (see section 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 
were 228 epoetin alfa-treated CRF subjects in 4 chronic renal failure studies (2 studies in pre-dialysis 
[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 (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, 
Thrombocythaemia Rare 

Metabolism and nutrition 
disorders Hyperkalaemia

1 Uncommon 

Immune system disorders Hypersensitivity
3 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 acute

3 Rare 

General disorders and Pyrexia Very common 



17 

MedDRA System Organ 
Classification (SOC) 

Adverse Reaction (Preferred 
Term Level) 

Frequency 

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

Common 

Medicinal product ineffective3 Not known 

Investigations Anti-erythropoietin 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 
 
Hypersensitivity reactions, including cases of rash (including urticaria), anaphylactic reactions, and 
angioneurotic oedema have been reported (see section 4.4). 
 
Hypertensive crisis with encephalopathy and seizures, requiring the immediate attention of a physician 
and intensive medical care, have occurred also during epoetin alfa treatment in patients with 
previously normal or low blood pressure. Particular attention should be paid to sudden stabbing 
migraine-like headaches as a possible warning signal (see section 4.4).  
 
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). 
 
Antibody-mediated pure red cell aplasia has been very rarely reported in < 1/10,000 cases per patient 
year after months to years of treatment with epoetin alfa (see section 4.4). More cases have been 
reported with subcutaneous (SC) route of administration, compared with the IV route. 
 
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). 
 
Paediatric population with chronic renal failure on haemodialysis 
The exposure of paediatric patients with chronic renal failure on haemodialysis in clinical trials and 
post-marketing experience is limited. No paediatric-specific adverse reactions not mentioned 
previously in the table above, or any that were not consistent with the underlying disease were 
reported in this population. 
 
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. 
 



18 

4.9 Overdose 
 
The therapeutic margin of epoetin alfa is very wide. Overdosage of epoetin alfa 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.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: other antianaemic preparations, erythropoietin, ATC code: B03XA01. 
 
Epoetin alfa HEXAL is a biosimilar medicinal product. Detailed information is available on the 
website of the European Medicines Agency http://www.ema.europa.eu. 
 
Mechanism of action 
 
Erythropoietin (EPO) is a glycoprotein hormone produced primarily by the kidney in response to 
hypoxia and is the key regulator of red blood cell (RBC) production. EPO is involved in all phases of 
erythroid development, and has its principal effect at the level of erythroid precursors. After EPO 
binds to its cell surface receptor, it activates signal transduction pathways that interfere with apoptosis 
and stimulates erythroid cell proliferation.  
Recombinant human EPO (epoetin alfa), expressed in Chinese hamster ovary cells, has a 165 amino 
acid sequence identical to that of human urinary EPO; the 2 are indistinguishable on the basis of 
functional assays. The apparent molecular weight of erythropoietin is 32,000 to 40,000 dalton.  
 
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. 
 
Pharmacodynamic effects 
 
Healthy volunteers 
After single doses (20,000 to 160,000 IU subcutaneously) of epoetin alfa, a dose-dependent response 
was observed for the pharmacodynamic markers investigated including: reticulocytes, RBCs, and 
haemoglobin. A defined concentration-time profile with peak and return to baseline was observed for 
changes in percent reticulocytes. A less defined profile was observed for RBCs and haemoglobin. In 
general, all pharmacodynamic markers increased in a linear manner with dose reaching a maximum 
response at the highest dose levels. 
 
Further pharmacodynamic studies explored 40,000 IU once weekly versus 150 IU/kg 3 times per 
week. Despite differences in concentration-time profiles the pharmacodynamic response (as measured 
by changes in percent reticulocytes, haemoglobin, and total RBCs) was similar between these 
regimens. Additional studies compared the 40,000 IU once-weekly regimen of epoetin alfa with 
biweekly doses ranging from 80,000 to 120,000 IU subcutaneously. Overall, based on the results of 
these pharmacodynamic studies in healthy subjects, the 40,000 IU once-weekly dosing regimen seems 
to be more efficient in producing RBCs than the biweekly regimens despite an observed similarity in 
reticulocyte production in the once-weekly and biweekly regimens. 
 
Chronic renal failure 
Epoetin alfa has been shown to stimulate erythropoiesis in anaemic patients with CRF, including 
dialysis and pre-dialysis patients. The first evidence of a response to epoetin alfa is an increase in the 
reticulocyte count within 10 days, followed by increases in the red cell count, haemoglobin and 
haematocrit, usually within 2 to 6 weeks. The haemoglobin response varies between patients and may 
be impacted by iron stores and the presence of concurrent medical problems. 
 



19 

Chemotherapy-induced anaemia 
Epoetin alfa administered 3 times per week or once weekly has been shown to increase haemoglobin 
and decrease transfusion requirements after the first month of therapy in anaemic cancer patients 
receiving chemotherapy. 
 
In a study comparing the 150 IU/kg, 3 times per week and 40,000 IU, once-weekly dosing regimens in 
healthy subjects and in anaemic cancer subjects the time profiles of changes in percent reticulocytes, 
haemoglobin, and total red blood cells were similar between the two dosing regimens in both healthy 
and anaemic cancer subjects. The AUCs of the respective pharmacodynamic parameters were similar 
between the 150 IU/kg, 3 times per week and 40,000 IU, once-weekly dosing regimens in healthy 
subjects and also in anaemic cancer subjects. 
 
Adult surgery patients in an autologous predonation programme 
Epoetin alfa has been shown to stimulate red blood cell production in order to augment autologous 
blood collection, and to limit the decline in haemoglobin in adult patients scheduled for major elective 
surgery who are not expected to predeposit their complete perioperative blood needs. The greatest 
effects are observed in patients with low haemoglobin (≤ 13 g/dL). 
 
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 
 
Chronic renal failure 
Epoetin alfa has been studied in clinical trials in adult anaemic CRF patients, including haemodialysis 
and pre-dialysis patients, to treat anaemia and maintain haematocrit within a target concentration range 
of 30 to 36%. 
 
In clinical trials at starting doses of 50 to 150 IU/kg, three times per week, approximately 95% of all 
patients responded with a clinically significant increase in haematocrit. After approximately two 
months of therapy, virtually all patients were transfusion-independent. Once the target haematocrit 
was achieved, the maintenance dose was individualised for each patient. 
 
In the three largest clinical trials conducted in adult patients on dialysis, the median maintenance dose 
necessary to maintain the haematocrit between 30 to 36% was approximately 75 IU/kg given 3 times 
per week. 
 
In a double-blind, placebo-controlled, multicentre, quality of life study in CRF patients on 
haemodialysis, clinically and statistically significant improvement was shown in the patients treated 
with epoetin alfa compared to the placebo group when measuring fatigue, physical symptoms, 
relationships and depression (Kidney Disease Questionnaire) after six months of therapy. Patients 
from the group treated with epoetin alfa were also enrolled in an open-label extension study which 
demonstrated improvements in their quality of life that were maintained for an additional 12 months. 
 
Adult patients with renal insufficiency not yet undergoing dialysis 
In clinical trials conducted in patients with CRF not on dialysis treated with epoetin alfa, the average 
duration of therapy was nearly five months. These patients responded to epoetin alfa therapy in a 
manner similar to that observed in patients on dialysis. Patients with CRF not on dialysis demonstrated 
a dose-dependent and sustained increase in haematocrit when epoetin alfa was administered by either 
an intravenous or subcutaneous route. Similar rates of rise of haematocrit were noted when epoetin 
alfa was administered by either route. Moreover, epoetin alfa doses of 75 to 150 IU/kg per week have 
been shown to maintain haematocrits of 36 to 38% for up to six months. 
 



20 

In 2 studies with extended interval dosing of epoetin alfa (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). 
 
A randomised prospective trial evaluated 1,432 anaemic chronic renal failure patients who were not 
undergoing dialysis. Patients were assigned to epoetin alfa treatment targeting a maintenance 
haemoglobin level of 13.5 g/dL (higher than the recommended haemoglobin concentration level) 
or 11.3 g/dL. A major cardiovascular event (death, myocardial infarction, stroke or hospitalisation for 
congestive heart failure) occurred among 125 (18%) of the 715 patients in the higher haemoglobin 
group compared to 97 (14%) among the 717 patients in the lower haemoglobin group (hazard ratio 
[HR] 1.3, 95% CI: 1.0, 1.7, p = 0.03). 
 
Pooled post-hoc analyses of clinical studies of ESAs have been performed in chronic renal failure 
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 
section 4.2 and section 4.4). 
 
Treatment of patients with chemotherapy-induced anaemia 
Epoetin alfa has been studied in clinical trials in adult anaemic cancer patients with lymphoid and 
solid tumors, and patients on various chemotherapy regimens, including platinum and 
non-platinum-containing regimens. In these trials, epoetin alfa administered 3 times per week and 
once weekly has been shown to increase haemoglobin and decrease transfusion requirements after the 
first month of therapy in anaemic cancer patients. In some studies, the double-blind phase was 
followed by an open-label phase during which all patients received epoetin alfa and a maintenance of 
effect was observed. 
 
Available evidence suggests patients with haematological malignancies and solid tumours respond 
equivalently to epoetin alfa therapy, and that patients with or without tumour infiltration of the bone 
marrow respond equivalently to epoetin alfa therapy. Comparable intensity of chemotherapy in the 
epoetin alfa and placebo groups in the chemotherapy trials was demonstrated by a similar area under 
the neutrophil time curve in patients treated with epoetin alfa and placebo-treated patients, as well as 
by a similar proportion of patients in groups treated with epoetin alfa and placebo-treated groups 
whose absolute neutrophil counts fell below 1,000 and 500 cells/µL. 
 
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 
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.  
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 ESAs are not indicated: anaemia in patients with cancer 
not receiving chemotherapy, and head and neck cancer patients receiving radiotherapy. The desired 
haemoglobin concentration level in two studies was > 13 g/dL (8.1 mmol/L); in the remaining three 
studies it was 12 to 14 g/dL (7.5 to 8.7 mmol/L). 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. 



21 

 
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). 
 
A randomised, open-label, multicentre study was conducted in 2,098 anaemic women with metastatic 
breast cancer, who received first line or second line chemotherapy. This was a non inferiority study 
designed to rule out a 15% risk increase in tumour progression or death of epoetin alfa plus standard of 
care (SOC) as compared with SOC alone. At the time of clinical data cutoff, the median progression 
free survival (PFS) per investigator assessment of disease progression was 7.4 months in each arm 
(HR 1.09, 95% CI: 0.99, 1.20), indicating the study objective was not met. Significantly fewer patients 
received RBC transfusions in the epoetin alfa plus SOC arm (5.8% versus 11.4%); however, 
significantly more patients had thrombotic vascular events in the epoetin alfa plus SOC arm (2.8% 
versus 1.4%). At the final analysis, 1653 deaths were reported. Median overall survival in the epoetin 
alfa plus SOC group was 17.8 months compared with 18.0 months in the SOC alone group (HR 1.07, 
95% CI: 0.97, 1.18). The median time to progression (TTP) based on investigator-determined 
progressive disease (PD) was 7.5 months in the epoetin alfa plus SOC group and 7.5 months in the 
SOC group (HR 1.099, 95% CI: 0.998, 1.210). The median TTP based on IRC-determined PD was 8.0 
months in the epoetin alfa plus SOC group and 8.3 months in the SOC group (HR 1.033, 95% CI: 
0.924, 1.156). 
 
Autologous predonation programme 
The effect of epoetin alfa in facilitating autologous blood donation in patients with low haematocrits 
(≤ 39% and no underlying anaemia due to iron deficiency) scheduled for major orthopaedic surgery 
was evaluated in a double-blind, placebo-controlled study conducted in 204 patients, and a 
single-blind placebo controlled study in 55 patients.  
 
In the double-blind study, patients were treated with epoetin alfa 600 IU/kg or placebo intravenously 
once daily every 3 to 4 days over 3 weeks (total 6 doses). On average, patients treated with epoetin 
alfa were able to predeposit significantly more units of blood (4.5 units) than placebo-treated patients 
(3.0 units). 
 
In the single-blind study, patients were treated with epoetin alfa 300 IU/kg or 600 IU/kg or placebo 
intravenously once daily every 3 to 4 days over 3 weeks (total 6 doses). Patients treated with epoetin 
alfa were also able to predeposit significantly more units of blood (epoetin alfa 300 IU/kg = 4.4 units; 
epoetin alfa 600 IU/kg = 4.7 units) than placebo-treated patients (2.9 units). 
 
Epoetin alfa therapy reduced the risk of exposure to allogeneic blood by 50% compared to patients not 
receiving epoetin alfa. 
 
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. 
 



22 

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 
Total (N)b Epoetin alfa 

85a 
Placebo 

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 
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). 
 



23 

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. 
 
Paediatric population 
 
Chronic renal failure 
Epoetin alfa was evaluated in an open-label, non-randomised, open dose-range, 52-week clinical study 
in paediatric CRF patients undergoing haemodialysis. The median age of patients enrolled in the study 
was 11.6 years (range 0.5 to 20.1 years). 
 
Epoetin alfa was administered at 75 IU/kg/week intravenously in 2 or 3 divided doses post-dialysis, 
titrated by 75 IU/kg/week at intervals of 4 weeks (up to a maximum of 300 IU/kg/week), to achieve 
a 1 g/dL/month increase in haemoglobin. The desired haemoglobin concentration range 
was 9.6 to 11.2 g/dL. Eighty-one percent of patients achieved the haemoglobin concentration level. 
The median time to target was 11 weeks and the median dose at target was 150 IU/kg/week. Of the 
patients who achieved the target, 90% did so on a 3 times-per-week dosing regimen. 
 
After 52 weeks, 57% of patients remained in the study, receiving a median dose of 200 IU/kg/week. 
 
Clinical data with subcutaneous administration in children are limited. In 5 small, open label, 
uncontrolled studies (number of patients ranged from 9-22, total N = 72), Epoetin alfa has been 
administered subcutaneously in children at starting doses of 100 IU/kg/week to 150 IU/kg/week with 
the possibility to increase up to 300 IU/kg/week. In these studies, most were predialysis patients 
(N = 44), 27 patients were on peritoneal dialysis and 2 were on haemodialysis with age ranging 
from 4 months to 17 years. Overall, these studies have methodological limitations but treatment was 
associated with positive trends towards higher haemoglobin levels. No unexpected adverse events 
were reported (see section 4.2). 
 
Chemotherapy-induced anaemia 
 
Epoetin alfa 600 IU/kg (administered intravenously or subcutaneously once weekly) has been 
evaluated in a randomised, double-blind, placebo-controlled, 16-week study and in a randomised, 
controlled, open-label, 20-week study in anaemic paediatric patients receiving myelosuppressive 
chemotherapy for the treatment of various childhood non-myeloid malignancies. 
 
In the 16-week study (n = 222), in the epoetin alfa-treated patients there was no statistically significant 
effect on patient-reported or parent-reported Paediatric Quality of Life Inventory or Cancer Module 
scores compared with placebo (primary efficacy endpoint). In addition, there was no statistical 
difference between the proportion of patients requiring pRBC transfusions between the Epoetin alfa 
group and placebo. 
 
In the 20-week study (n = 225), no significant difference was observed in the primary efficacy 
endpoint, i.e. the proportion of patients who required a RBC transfusion after Day 28 (62% of epoetin 
alfa patients versus 69% of standard therapy patients). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Following subcutaneous injection, serum levels of epoetin alfa reach a peak between 12 and 18 hours 
post-dose. There was no accumulation after multiple dose administration of 600 IU/kg administered 
subcutaneously weekly. 
 



24 

The absolute bioavailability of subcutaneous injectable epoetin alfa is approximately 20% in healthy 
subjects. 
 
Distribution 
The mean volume of distribution was 49.3 mL/kg after intravenous doses of 50 and 100 IU/kg in 
healthy subjects. Following intravenous administration of epoetin alfa in subjects with chronic renal 
failure, the volume of distribution ranged from 57-107 mL/kg after single dosing (12 IU/kg) to 42–
64 mL/kg after multiple dosing (48–192 IU/kg), respectively. Thus, the volume of distribution is 
slightly greater than the plasma space. 
 
Elimination 
The half-life of epoetin alfa following multiple dose intravenous administration is 
approximately 4 hours in healthy subjects.  
The half-life for the subcutaneous route is estimated to be approximately 24 hours in healthy subjects.  
 
The mean CL/F for the 150 IU/kg 3 times-per-week and 40,000 IU once-weekly regimens in healthy 
subjects were 31.2 and 12.6 mL/h/kg, respectively. The mean CL/F for 
the 150 IU/kg, 3 times-per-week and 40,000 IU, once-weekly regimens in the anaemic cancer subjects 
were 45.8 and 11.3 mL/h/kg, respectively. In most anaemic subjects with cancer receiving cyclic 
chemotherapy, CL/F was lower after subcutaneous doses of 40,000 IU once weekly 
and 150 IU/kg, 3 times-per-week compared with the values for healthy subjects. 
 
Linearity/Non-linearity 
In healthy subjects, a dose-proportional increase in serum epoetin alfa concentrations was observed 
after intravenous administration of 150 and 300 IU/kg, 3 times per week. Administration of single 
doses of 300 to 2,400 IU/kg subcutaneous epoetin alfa resulted in a linear relationship between mean 
Cmax and dose and between mean AUC and dose. An inverse relationship between apparent clearance 
and dose was noted in healthy subjects. 
 
In studies to explore extending the dosing interval (40,000 IU once weekly and 80,000, 100,000, 
and 120,000 IU biweekly), a linear but non-dose-proportional relationship was observed between 
mean Cmax and dose, and between mean AUC and dose at steady state. 
 
Pharmacokinetic/pharmacodynamic relationships 
Epoetin alfa exhibits a dose-related effect on haematological parameters which is independent of route 
of administration. 
 
Paediatric population 
A half-life of approximately 6.2 to 8.7 hours has been reported in paediatric subjects with chronic 
renal failure following multiple dose intravenous administration of epoetin alfa. The pharmacokinetic 
profile of epoetin alfa in children and adolescents appears to be similar to that of adults. 
 
Pharmacokinetic data in neonates is limited. 
 
A study of 7 preterm very low birth weight neonates and 10 healthy adults given i.v. erythropoietin 
suggested that distribution volume was approximately 1.5 to 2 times higher in the preterm neonates 
than in the healthy adults, and clearance was approximately 3 times higher in the preterm neonates 
than in healthy adults. 
 
Renal impairment 
In chronic renal failure patients, the half-life of intravenously administered epoetin alfa is slightly 
prolonged, approximately 5 hours, compared to healthy subjects. 
 
5.3 Preclinical safety data 
 
In repeated dose toxicological studies in dogs and rats, but not in monkeys, epoetin alfa therapy was 
associated with subclinical bone marrow fibrosis. Bone marrow fibrosis is a known complication of 



25 

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 epoetin alfa for 3 years compared to a matched control group of dialysis 
patients who had not been treated with epoetin alfa. 
 
Epoetin alfa does not induce bacterial gene mutation (Ames Test), chromosomal aberrations in 
mammalian cells, micronuclei in mice, or gene mutation at the HGPRT locus.  
 
Long-term carcinogenicity studies have not been carried out. Conflicting reports in the literature, 
based on in vitro findings from human tumour samples, suggest erythropoietins may play a role as 
tumour proliferators. This is of uncertain significance in the clinical situation. 
 
In cell cultures of human bone marrow cells, epoetin alfa stimulates erythropoiesis specifically and 
does not affect leucopoiesis. Cytotoxic actions of epoetin alfa on bone marrow cells could not be 
detected. 
 
In animal studies, epoetin alfa 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, and the significance to humans is unknown given therapeutic dose levels.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium dihydrogen phosphate dihydrate 
Disodium phosphate dihydrate 
Sodium chloride 
Glycine 
Polysorbate 80 
Water for injections 
Hydrochloric acid (for pH-adjustment) 
Sodium hydroxide (for pH-adjustment) 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Store and transport refrigerated (2°C to 8°C). This temperature range should be closely maintained 
until administration to the patient. 
For the purpose of ambulatory use, the medicinal product may be taken out of the refrigerator, without 
being replaced, for a maximum period of 3 days at a temperature not above 25°C. If the medicinal 
product has not been used at the end of this period, it should be disposed of. 
 
Do not freeze or shake. 
Store in the original package in order to protect from light. 
 



26 

6.5 Nature and contents of container 
 
Pre-filled syringes (glass type I), with or without a needle safety guard, with plunger stopper 
(Teflon-faced rubber) sealed in a blister. 
 
Epoetin alfa HEXAL 1,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.5 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 2,000 IU/1 mL solution for injection in a pre-filled syringe 
Each syringe contains 1 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 3,000 IU/0.3 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.3 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 4,000 IU/0.4 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.4 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 5,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.5 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 6,000 IU/0.6 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.6 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 7,000 IU/0.7 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.7 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 8,000 IU/0.8 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.8 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 9,000 IU/0.9 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.9 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 10,000 IU/1 mL solution for injection in a pre-filled syringe 
Each syringe contains 1 mL of solution for injection. 
Pack of 1 or 6 syringes.  
 
Epoetin alfa HEXAL 20,000 IU/0.5 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.5 mL of solution for injection. 
Pack of 1, 4 or 6 syringes.  
 
Epoetin alfa HEXAL 30,000 IU/0.75 mL solution for injection in a pre-filled syringe 
Each syringe contains 0.75 mL of solution for injection. 
Pack of 1, 4 or 6 syringes.  
 
Epoetin alfa HEXAL 40,000 IU/1 mL solution for injection in a pre-filled syringe 
Each syringe contains 1 mL of solution for injection. 
Pack of 1, 4 or 6 syringes.  
 



27 

Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Epoetin alfa HEXAL should not be used and discarded 
- if the liquid is coloured or you can see particles floating in it, 
- if the seal is broken, 
- if you know, or think that it may have been accidentally frozen, or 
- if there has been a refrigerator failure. 
 
The pre-filled syringes are ready to use (see section 4.2). The pre-filled syringe should not be shaken. 
Syringes are embossed with graduation rings in order to enable partial use if required. Each graduation 
ring corresponds to a volume of 0.1 mL. The product is for single use only. Only take one dose of 
Epoetin alfa HEXAL from each syringe discarding unwanted solution before injection. 
 
Using the pre-filled syringe with a needle safety guard 
 
The needle safety guard covers the needle after injection to prevent needle stick injury. This does not 
affect normal operation of the syringe. Depress the plunger slowly and evenly until the entire dose has 
been given and the plunger cannot be depressed any further. While maintaining pressure on the 
plunger, remove the syringe from the patient. The needle safety guard will cover the needle when 
releasing the plunger.  
 
Using the pre-filled syringe without a needle safety guard 
 
Administer the dose as per standard protocol. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Hexal AG 
Industriestr. 25 
D-83607 Holzkirchen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Epoetin alfa HEXAL 1,000 IU/0.5 mL solution for injection in a pre-filled syringe 
EU/1/07/411/001 
EU/1/07/411/002 
EU/1/07/411/027 
EU/1/07/411/028 
 
Epoetin alfa HEXAL 2,000 IU/1 mL solution for injection in a pre-filled syringe 
EU/1/07/411/003 
EU/1/07/411/004 
EU/1/07/411/029 
EU/1/07/411/030 
 



28 

 
Epoetin alfa HEXAL 3,000 IU/0.3 mL solution for injection in a pre-filled syringe 
EU/1/07/411/005 
EU/1/07/411/006 
EU/1/07/411/031 
EU/1/07/411/032 
 
Epoetin alfa HEXAL 4,000 IU/0.4 mL solution for injection in a pre-filled syringe 
EU/1/07/411/007 
EU/1/07/411/008 
EU/1/07/411/033 
EU/1/07/411/034 
 
Epoetin alfa HEXAL 5,000 IU/0.5 mL solution for injection in a pre-filled syringe 
EU/1/07/411/009 
EU/1/07/411/010 
EU/1/07/411/035 
EU/1/07/411/036 
 
Epoetin alfa HEXAL 6,000 IU/0.6 mL solution for injection in a pre-filled syringe 
EU/1/07/411/011 
EU/1/07/411/012 
EU/1/07/411/037 
EU/1/07/411/038 
 
Epoetin alfa HEXAL 7,000 IU/0.7 mL solution for injection in a pre-filled syringe 
EU/1/07/411/017 
EU/1/07/411/018 
EU/1/07/411/039 
EU/1/07/411/040 
 
Epoetin alfa HEXAL 8,000 IU/0.8 mL solution for injection in a pre-filled syringe 
EU/1/07/411/013 
EU/1/07/411/014 
EU/1/07/411/041 
EU/1/07/411/042 
 
Epoetin alfa HEXAL 9,000 IU/0.9 mL solution for injection in a pre-filled syringe 
EU/1/07/411/019 
EU/1/07/411/020 
EU/1/07/411/043 
EU/1/07/411/044 
 
Epoetin alfa HEXAL 10,000 IU/1 mL solution for injection in a pre-filled syringe 
EU/1/07/411/015 
EU/1/07/411/016 
EU/1/07/411/045 
EU/1/07/411/046 
 
Epoetin alfa HEXAL 20,000 IU/0.5 mL solution for injection in a pre-filled syringe 
EU/1/07/411/021 
EU/1/07/411/022 
EU/1/07/411/047 
EU/1/07/411/053 
EU/1/07/411/048 
 



29 

Epoetin alfa HEXAL 30,000 IU/0.75 mL solution for injection in a pre-filled syringe 
EU/1/07/411/023 
EU/1/07/411/024 
EU/1/07/411/049 
EU/1/07/411/054 
EU/1/07/411/050 
 
Epoetin alfa HEXAL 40,000 IU/1 mL solution for injection in a pre-filled syringe 
EU/1/07/411/025 
EU/1/07/411/026 
EU/1/07/411/051 
EU/1/07/411/055 
EU/1/07/411/052 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 August 2007  
Date of latest renewal: 18 June 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. 



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS 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 



31 

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

 
Name and address of the manufacturer of the biological active substance 
 
Lek Pharmaceuticals d.d. 
Kolodvorska 27 
SI-1234 Menges 
Slovenia 
 
Name and address of the manufacturer responsible for batch release 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6336 Langkampfen 
Austria 
 
 
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 
 
The requirements for submission of periodic safety update reports 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 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. 



32 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



33 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 1,000 IU/0.5 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.5 mL contains 1,000 international units (IU) corresponding to 8.4 micrograms 
epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.5 mL 
6 pre-filled syringes of 0.5 mL 
1 pre-filled syringe of 0.5 mL with a needle safety guard 
6 pre-filled syringes of 0.5 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/001 
EU/1/07/411/002 
EU/1/07/411/027 
EU/1/07/411/028 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 1,000 IU/0.5 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 1,000 IU/0.5 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 2,000 IU/1 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 1 mL contains 2,000 international units (IU) corresponding to 16.8 micrograms 
epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 1 mL 
6 pre-filled syringes of 1 mL 
1 pre-filled syringe of 1 mL with a needle safety guard 
6 pre-filled syringes of 1 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/003 
EU/1/07/411/004 
EU/1/07/411/029 
EU/1/07/411/030 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 2,000 IU/1 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 2,000 IU/1 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 3,000 IU/0.3 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.3 mL contains 3,000 international units (IU) corresponding 
to 25.2 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.3 mL 
6 pre-filled syringes of 0.3 mL 
1 pre-filled syringe of 0.3 mL with a needle safety guard 
6 pre-filled syringes of 0.3 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/005 
EU/1/07/411/006 
EU/1/07/411/031 
EU/1/07/411/032 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 3,000 IU/0.3 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 3,000 IU/0.3 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



43 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 4,000 IU/0.4 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.4 mL contains 4,000 international units (IU) corresponding 
to 33.6 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.4 mL 
6 pre-filled syringes of 0.4 mL 
1 pre-filled syringe of 0.4 mL with a needle safety guard 
6 pre-filled syringes of 0.4 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/007 
EU/1/07/411/008 
EU/1/07/411/033 
EU/1/07/411/034 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 4,000 IU/0.4 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 4,000 IU/0.4 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



46 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 5,000 IU/0.5 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.5 mL contains 5,000 international units (IU) corresponding 
to 42.0 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.5 mL 
6 pre-filled syringes of 0.5 mL 
1 pre-filled syringe of 0.5 mL with a needle safety guard 
6 pre-filled syringes of 0.5 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/009 
EU/1/07/411/010 
EU/1/07/411/035 
EU/1/07/411/036 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 5,000 IU/0.5 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 5,000 IU/0.5 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



49 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 6,000 IU/0.6 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.6 mL contains 6,000 international units (IU) corresponding 
to 50.4 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.6 mL 
6 pre-filled syringes of 0.6 mL 
1 pre-filled syringe of 0.6 mL with a needle safety guard 
6 pre-filled syringes of 0.6 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/011 
EU/1/07/411/012 
EU/1/07/411/037 
EU/1/07/411/038 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 6,000 IU/0.6 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 6,000 IU/0.6 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



52 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 7,000 IU/0.7 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.7 mL contains 7,000 international units (IU) corresponding 
to 58.8 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.7 mL 
6 pre-filled syringes of 0.7 mL 
1 pre-filled syringe of 0.7 mL with a needle safety guard 
6 pre-filled syringes of 0.7 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/017 
EU/1/07/411/018 
EU/1/07/411/039 
EU/1/07/411/040 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 7,000 IU/0.7 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 7,000 IU/0.7 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



55 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 8,000 IU/0.8 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.8 mL contains 8,000 international units (IU) corresponding 
to 67.2 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.8 mL 
6 pre-filled syringes of 0.8 mL 
1 pre-filled syringe of 0.8 mL with a needle safety guard 
6 pre-filled syringes of 0.8 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/013 
EU/1/07/411/014 
EU/1/07/411/041 
EU/1/07/411/042 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 8,000 IU/0.8 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 8,000 IU/0.8 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



58 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 9,000 IU/0.9 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.9 mL contains 9,000 international units (IU) corresponding 
to 75.6 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.9 mL 
6 pre-filled syringes of 0.9 mL 
1 pre-filled syringe of 0.9 mL with a needle safety guard 
6 pre-filled syringes of 0.9 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/019 
EU/1/07/411/020 
EU/1/07/411/043 
EU/1/07/411/044 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 9,000 IU/0.9 mL 
 
 
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 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 9,000 IU/0.9 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



61 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 10,000 IU/1 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 1 mL contains 10,000 international units (IU) corresponding to 84.0 micrograms 
epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 1 mL 
6 pre-filled syringes of 1 mL 
1 pre-filled syringe of 1 mL with a needle safety guard 
6 pre-filled syringes of 1 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 
 



62 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/015 
EU/1/07/411/016 
EU/1/07/411/045 
EU/1/07/411/046 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 10,000 IU/1 mL 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



63 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 10,000 IU/1 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



64 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 20,000 IU/0.5 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.5 mL contains 20,000 international units (IU) corresponding 
to 168.0 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.5 mL 
6 pre-filled syringes of 0.5 mL 
1 pre-filled syringe of 0.5 mL with a needle safety guard 
4 pre-filled syringes of 0.5 mL with a needle safety guard 
6 pre-filled syringes of 0.5 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 
 
 



65 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/021 
EU/1/07/411/022 
EU/1/07/411/047 
EU/1/07/411/053 
EU/1/07/411/048 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 20,000 IU/0.5 mL 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



66 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



67 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 20,000 IU/0.5 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



68 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 30,000 IU/0.75 mL solution for injection in a pre-filled syringe 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 0.75 mL contains 30,000 international units (IU) corresponding 
to 252.0 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 0.75 mL 
6 pre-filled syringes of 0.75 mL 
1 pre-filled syringe of 0.75 mL with a needle safety guard 
4 pre-filled syringes of 0.75 mL with a needle safety guard 
6 pre-filled syringes of 0.75 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 
 



69 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/023 
EU/1/07/411/024 
EU/1/07/411/049 
EU/1/07/411/054 
EU/1/07/411/050 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 30,000 IU/0.75 mL 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



70 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 30,000 IU/0.75 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



71 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Epoetin alfa HEXAL 40,000 IU/1 mL solution for injection in a pre-filled syringe 
 
Epoetin alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe of 1 mL contains 40,000 international units (IU) corresponding 
to 336.0 micrograms epoetin alfa. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, 
glycine, polysorbate 80, hydrochloric acid (for pH-adjustment), sodium hydroxide (for 
pH-adjustment), and water for injections. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a pre-filled syringe. 
1 pre-filled syringe of 1 mL 
6 pre-filled syringes of 1 mL 
1 pre-filled syringe of 1 mL with a needle safety guard 
4 pre-filled syringes of 1 mL with a needle safety guard 
6 pre-filled syringes of 1 mL with a needle safety guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For subcutaneous and intravenous 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 
 
 



72 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store and transport refrigerated (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 
 
Hexal AG, Industriestr. 25, D-83607 Holzkirchen, Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/411/025 
EU/1/07/411/026 
EU/1/07/411/051 
EU/1/07/411/055 
EU/1/07/411/052 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Epoetin alfa HEXAL 40,000 IU/1 mL 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



73 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



74 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL/SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Epoetin alfa HEXAL 40,000 IU/1 mL injection 
 
Epoetin alfa 
IV/SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



75 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



76 

 
Package leaflet: Information for the patient 

 
Epoetin alfa HEXAL 1,000 IU/0.5 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 2,000 IU/1 mL solution for injection in a pre-filled syringe  

 
Epoetin alfa HEXAL 3,000 IU/0.3 mL solution for injection in a pre-filled syringe  

 
Epoetin alfa HEXAL 4,000 IU/0.4 mL solution for injection in a pre-filled syringe  

 
Epoetin alfa HEXAL 5,000 IU/0.5 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 6,000 IU/0.6 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 7,000 IU/0.7 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 8,000 IU/0.8 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 9,000 IU/0.9 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 10,000 IU/1 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 20,000 IU/0.5 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 30,000 IU/0.75 mL solution for injection in a pre-filled syringe 

 
Epoetin alfa HEXAL 40,000 IU/1 mL solution for injection in a pre-filled syringe 

Epoetin alfa 
 
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, pharmacist or nurse. 
- 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 Epoetin alfa HEXAL is and what it is used for 
2. What you need to know before you use Epoetin alfa HEXAL 
3. How to use Epoetin alfa HEXAL 
4. Possible side effects 
5. How to store Epoetin alfa HEXAL 
6. Contents of the pack and other information 
 
 
1. What Epoetin alfa HEXAL is and what it is used for 
 
Epoetin alfa HEXAL contains the active substance epoetin alfa, a protein that stimulates the bone 
marrow to produce more red blood cells which carry haemoglobin (a substance that transports 
oxygen). Epoetin alfa is a copy of the human protein erythropoietin (ee-rith-roe-po-eh-tin) and acts in 
the same way. 
 
Epoetin alfa HEXAL is used to treat symptomatic anaemia caused by kidney disease: 
• in children on haemodialysis 



77 

• in adults on haemodialysis or peritoneal dialysis 
• in severely anaemic adults not yet undergoing dialysis  
 
If you have kidney disease, you may be short of red blood cells if your kidney does not produce 
enough erythropoietin (necessary for red cell production). Epoetin alfa HEXAL is prescribed to 
stimulate your bone marrow to produce more red blood cells. 
 
Epoetin alfa HEXAL is used to treat anaemia in adults receiving chemotherapy for solid 
tumours, malignant lymphoma or multiple myeloma (bone marrow cancer) who may have a need for 
a blood transfusion. Epoetin alfa HEXAL can reduce the need for a blood transfusion in these patients. 
 
Epoetin alfa HEXAL is used in moderately anaemic adults who donate some of their blood 
before surgery, so that it can be given back to them during or after the operation. Because Epoetin 
alfa HEXAL stimulates the production of red blood cells, doctors can take more blood from these 
people. 
 
Epoetin alfa HEXAL is used 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. 
 
Epoetin alfa HEXAL is used to treat anaemia in adults with a bone marrow disorder that causes 
a severe disruption in the creation of blood cells (myelodysplastic syndromes). Epoetin alfa 
HEXAL can reduce the need for a blood transfusion. 
 
 
2. What you need to know before you use Epoetin alfa HEXAL  
 
Do not use Epoetin alfa HEXAL: 
 
• if you are allergic to epoetin alfa or any of the other ingredients of this medicine (listed in 

section 6). 
• if you have been diagnosed with Pure Red Cell Aplasia (the bone marrow cannot produce 

enough red blood cells) after previous treatment with any product that stimulates red blood cell 
production (including Epoetin alfa HEXAL). See section 4. 

• if you have high blood pressure not properly controlled with medicines. 
• to stimulate the production of your red blood cells (so that doctors can take more blood from 

you) if you cannot have transfusions with your own blood during or after surgery. 
• 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 
Epoetin alfa HEXAL may not be suitable for you. Please discuss with your doctor. While on 
Epoetin alfa HEXAL, some people need medicines to reduce the risk of blood clots. If you 
can’t take medicines that prevent blood clotting, you must not have Epoetin alfa HEXAL. 

 
Warnings and precautions: 
 
Talk to your doctor, pharmacist or nurse before using Epoetin alfa HEXAL.  
 
Epoetin alfa HEXAL and other products that stimulate red cell production may increase the 
risk of developing blood clots in all patients. This risk may be higher if you have other risk 
factors for developing blood clots (for example, if you have had a blood clot in the past or are 
overweight, have diabetes, have heart disease or you are off your feet for a long time because of 



78 

surgery or illness). Please tell your doctor about any of these things. Your doctor will help you to 
decide if Epoetin alfa HEXAL is suitable for you.  
 
It is important to tell your doctor if any of the following apply to you. You may still be able to use 
Epoetin alfa HEXAL, but discuss it with your doctor first. 
 
If you know you suffer, or have suffered, from: 
• high blood pressure; 
• epileptic seizures or fits; 
• liver disease; 
• anaemia from other causes; 
• porphyria (a rare blood disorder). 
 
If you are a cancer patient be aware that products that stimulate red blood cell production (like 
Epoetin alfa HEXAL) may act as a growth factor and therefore in theory may affect the progression of 
your cancer. 
 
Depending on your individual situation a blood transfusion may be preferable. Please discuss 
this with your doctor. 
 
If you are a patient with hepatitis C and you receive interferon and ribavirin, you should discuss 
this with your doctor because a combination of epoetin alfa with interferon and ribavirin has led to a 
loss of effect and development of a condition called pure red cell aplasia (PRCA), a severe form of 
anaemia, in rare cases. Epoetin alfa HEXAL is not approved in the management of anaemia associated 
with hepatitis C. 
 
If you are a patient with chronic renal failure, and particularly if you do not respond properly to 
Epoetin alfa HEXAL, your doctor will check your dose of Epoetin alfa HEXAL because repeatedly 
increasing your dose of Epoetin alfa HEXAL 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. 
 
If you are a cancer patient, be aware that use of Epoetin alfa HEXAL may be associated with shorter 
survival and a higher death rate in head and neck, and metastatic breast cancer patients who are 
receiving chemotherapy.  
 
Take special care with other products that stimulate red blood cell production: 
 
Epoetin alfa HEXAL 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. If you are given a product in this group other than Epoetin alfa HEXAL during 
your treatment, speak to your doctor or pharmacist before using it. 
 
Take special care with Epoetin alfa HEXAL: 
 
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 Epoetin alfa HEXAL and 
contact your doctor or seek medical attention immediately. 



79 

 
Other medicines and Epoetin alfa HEXAL 
 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
If you are taking a medicine called cyclosporin (used e.g. after kidney transplants), your doctor may 
order blood tests to check the level of cyclosporin while you are taking Epoetin alfa HEXAL. 
 
Iron supplements and other blood stimulants may increase the effectiveness of Epoetin alfa 
HEXAL. Your doctor will decide if it is right for you to take them. 
 
If you visit a hospital, clinic or family doctor, tell them you are having Epoetin alfa HEXAL 
treatment. It may affect other treatments or test results. 
 
Pregnancy and breast-feeding  
 
It is important to tell your doctor if any of the following apply to you. You may still be able to use 
Epoetin alfa HEXAL, but discuss it with your doctor first: 
• if you are pregnant, or think you may be pregnant. 
• if you are breast-feeding. 
 
Epoetin alfa HEXAL contains sodium 
 
Epoetin alfa HEXAL contains less than 1 mmol sodium (23 mg) per dose that is to say essentially 
“sodium free”. 
 
 
3. How to use Epoetin alfa HEXAL  
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are 
not sure.  
 
Your doctor has carried out blood tests and decided you need Epoetin alfa HEXAL.  
 
Epoetin alfa HEXAL may be given by injection: 
• Either into a vein or a tube that goes into a vein (intravenously) 
• Or under the skin (subcutaneously). 
 
Your doctor will decide how Epoetin alfa HEXAL will be injected. Usually the injections will be 
given to you by a doctor, nurse or other health care professional. Some people, depending on why they 
need Epoetin alfa HEXAL treatment, may later learn how to inject themselves under the skin: see 
Instructions on how to inject Epoetin alfa HEXAL yourself at the end of the leaflet. 
 
Epoetin alfa HEXAL should not be used: 
• after the expiry date on the label and outer carton 
• if you know, or think that it may have been accidentally frozen, or  
• if there has been a refrigerator failure. 
 
The dose of Epoetin alfa HEXAL you receive is based on your body weight in kilograms. The cause 
of your anaemia is also a factor in your doctor deciding the correct dose. 
 
Your doctor will monitor your blood pressure regularly while you are using Epoetin alfa HEXAL. 
 
People with kidney disease 
 



80 

• Your doctor will maintain your haemoglobin level between 10 and 12 g/dL as a high 
haemoglobin level may increase the risk of blood clots and death. In children the haemoglobin 
level should be maintained between 9.5 and 11 g/dL. 

• The usual starting dose of Epoetin alfa HEXAL for adults and children is 50 International 
Units (IU) per kilogram (/kg) of body weight given three times a week. For patients on 
peritoneal dialysis Epoetin alfa HEXAL may be given twice a week. 

• For adults and children Epoetin alfa HEXAL is given as an injection either into a vein 
(intravenously) or a tube that goes into a vein. When this access (via a vein or tube) is not 
readily available, your doctor may decide that Epoetin alfa HEXAL should be injected under the 
skin (subcutaneously). This includes patients on dialysis and patients not yet on dialysis. 

• Your doctor will order regular blood tests to see how your anaemia is responding and may 
adjust the dose, usually no more frequently than every four weeks. A rise in haemoglobin of 
greater than 2 g/dL over a four week period should be avoided.  

• Once your anaemia has been corrected, your doctor will continue to check your blood regularly. 
Your Epoetin alfa HEXAL dose and frequency of administration may be further adjusted to 
maintain your response to treatment. Your doctor will use the lowest effective dose to control 
the symptoms of your anaemia. 

• If you do not respond adequately to Epoetin alfa HEXAL, your doctor will check your dose and 
will inform you if you need to change doses of Epoetin alfa HEXAL. 

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

• You may be given iron supplements before and during Epoetin alfa HEXAL treatment to make 
it more effective. 

• If you are having dialysis treatment when you begin treatment with Epoetin alfa HEXAL, your 
dialysis regime may need to be adjusted. Your doctor will decide this. 

 
Adults on chemotherapy 
 
• Your doctor may initiate treatment with Epoetin alfa HEXAL if your haemoglobin is 10 g/dL or 

less. 
• Your doctor will maintain your haemoglobin level between 10 and 12 g/dL as a high 

haemoglobin level may increase the risk of blood clots and death. 
• The starting dose is either 150 IU per kilogram body weight three times a week or 450 IU per 

kilogram body weight once a week. 
• Epoetin alfa HEXAL is given by injection under the skin.  
• Your doctor will order blood tests, and may adjust the dose, depending on how your anaemia 

responds to Epoetin alfa HEXAL treatment.  
• You may be given iron supplements before and during Epoetin alfa HEXAL treatment to make 

it more effective. 
• You will usually continue Epoetin alfa HEXAL treatment for one month after the end of 

chemotherapy. 
 
Adults donating their own blood 
 
• The usual dose is 600 IU per kilogram body weight twice a week. 
• Epoetin alfa HEXAL is given by injection into a vein immediately after you have donated blood 

for 3 weeks before your surgery.  
• You may be given iron supplements before and during Epoetin alfa HEXAL treatment to make 

it more effective. 
 
Adults scheduled for major orthopaedic surgery 
 
• The recommended dose is 600 IU per kilogram body weight once a week. 
• Epoetin alfa HEXAL is given by injection under the skin each week for three weeks before 

surgery and on the day of surgery. 



81 

• 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 Epoetin alfa HEXAL treatment to make 
it more effective. 

 
Adults with myelodysplastic syndrome 
 
• Your doctor may initiate treatment with Epoetin alfa HEXAL 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. 

• Epoetin alfa HEXAL 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 Epoetin alfa HEXAL treatment. 
 
Instructions on how to inject Epoetin alfa HEXAL yourself  
 
When treatment starts, Epoetin alfa HEXAL is usually injected by a medical professional or a nurse. 
Later, your doctor may suggest that you or your caregiver learn how to inject Epoetin alfa HEXAL 
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 Epoetin alfa HEXAL exactly as instructed by your doctor or nurse. 
• Ensure that you only inject the amount of liquid as instructed by your doctor or nurse. 
• Only use Epoetin alfa HEXAL if it has been stored correctly – see section 5, How to store 

Epoetin alfa HEXAL. 
• Before use, leave the Epoetin alfa HEXAL syringe to stand until it reaches room 

temperature. This usually takes between 15 and 30 minutes. Use the syringe within 3 days 
of taking it out of the refrigerator.  

 
Only take one dose of Epoetin alfa HEXAL from each syringe. 
 
If Epoetin alfa HEXAL is injected under the skin (subcutaneously), the amount injected is not 
normally more than one millilitre (1 mL) in a single injection. 
 
Epoetin alfa HEXAL is given alone and not mixed with other liquids for injection. 
 
Do not shake Epoetin alfa HEXAL syringes. Prolonged vigorous shaking may damage the product. 
If the product has been shaken vigorously, don’t use it. 
 
Instructions on how to inject yourself with Epoetin alfa HEXAL can be found at the end of this leaflet. 
 
If you use more Epoetin alfa HEXAL than you should 
 
Tell your doctor or nurse immediately if you think too much Epoetin alfa HEXAL has been injected. 
Side effects from an overdose of Epoetin alfa HEXAL are unlikely. 
 
If you forget to use Epoetin alfa HEXAL 
 
Make the next injection as soon as you remember. If you are within a day of your next injection, forget 
the missed one and carry on with your normal schedule. Do not double up the injections to make up 
for a forgotten dose. 



82 

 
If you have any further questions on the use of this product, ask your doctor, nurse or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor or nurse immediately if you notice any of the effects in this list. 
 
Very common side effects 
These may affect more than 1 in 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 side effects 
These may affect up to 1 in 10 people. 
 
• Increased blood pressure. Headaches, particularly sudden, stabbing migraine-like headaches, 

feeling confused or having fits may be signs of a sudden increase in blood pressure. This 
requires urgent treatment. Raised blood pressure may require treatment with medicines (or 
adjustment to any medicines you already take for high blood pressure). 

• 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. 
• Skin rashes, which may result from an allergic reaction. 
• 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 side effects  
These may affect up to 1 in 100 people.  
 
• 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 side effects 
These may affect up to 1 in 1,000 people. 
 
• Symptoms of pure red cell aplasia (PRCA) 
 



83 

PRCA means the bone marrow does not make enough red blood cells. PRCA causes sudden and 
severe anaemia. The symptoms are: 
• unusual tiredness, 
• feeling dizzy, 
• breathlessness. 
 
PRCA has been very rarely reported mostly in patients with kidney disease after months to years of 
treatment with epoetin alfa and other products that stimulate red blood cell production. 
 
• 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: 

• a swollen face, lips, mouth, tongue or throat, 
• difficulty swallowing or breathing, 
• 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. 
 
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 Epoetin alfa 
HEXAL if you develop these symptoms and contact your doctor or seek medical attention 
immediately. See also section 2. 
 
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 Epoetin alfa HEXAL.  
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor, nurse or pharmacist. 
 
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 Epoetin alfa HEXAL  
 
• 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 carton after EXP. 
• Store and transport refrigerated (2°C-8°C). 



84 

• You may take Epoetin alfa HEXAL out of the refrigerator and keep it at room temperature (up 
to 25°C) for no longer than 3 days. Once a syringe has been removed from the refrigerator and 
has reached room temperature (up to 25°C) it must either be used within 3 days or disposed of. 

• Do not freeze or shake.  
• Store in the original package in order to protect from light. 
 
Do not use this medicine if you notice that 
• it may have been accidentally frozen, or 
• if there has been a refrigerator failure, 
• the liquid is coloured or you can see particles floating in it, 
• the seal is broken. 
 
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 Epoetin alfa HEXAL contains 
 
- The active substance is: epoetin alfa (for quantity see the table below).  
- The other ingredients are: sodium dihydrogen phosphate dihydrate, disodium phosphate 

dihydrate, sodium chloride, glycine, polysorbate 80, hydrochloric acid (for 
pH-adjustment), sodium hydroxide (for pH-adjustment), and water for injections. 

 
What Epoetin alfa HEXAL looks like and contents of the pack 
 
Epoetin alfa HEXAL is presented as a clear, colourless solution for injection in a pre-filled syringe. 
The syringes are sealed in a blister.  
 
Presentation Corresponding Presentations in 

Quantity/Volume for each Strength 
Amount of  
epoetin alfa 

Pre-filled syringes* 2,000 IU/mL: 
1,000 IU/0.5 mL 
2,000 IU/1 mL 
 
10,000 IU/mL: 
3,000 IU/0.3 mL 
4,000 IU/0.4 mL 
5,000 IU/0.5 mL 
6,000 IU/0.6 mL 
7,000 IU/0.7 mL 
8,000 IU/0.8 mL 
9,000 IU/0.9 mL 
10,000 IU/1 mL 
 
40,000 IU/mL: 
20,000 IU/0.5 mL 
30,000 IU/0.75 mL 
40,000 IU/1 mL 

 
8.4 micrograms 
16.8 micrograms 
 
 
25.2 micrograms 
33.6 micrograms 
42.0 micrograms 
50.4 micrograms 
58.8 micrograms 
67.2 micrograms 
75.6 micrograms 
84.0 micrograms 
 
 
168.0 micrograms 
252.0 micrograms 
336.0 micrograms 

 
*Pack size of 1, 4 or 6 pre-filled syringe(s) with or without a needle safety guard. 
Not all pack sizes may be marketed.  
 
 
 
 



85 

Marketing Authorisation Holder 
 
Hexal AG 
Industriestr. 25 
D-83607 Holzkirchen 
Germany 
 
Manufacturer 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6336 Langkampfen 
Austria 
 
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. 
 
------------------------------------------------------------------------------------------------------------------ 
 
Instructions on how to inject yourself (for patients with symptomatic anaemia caused by kidney 
disease, for adult patients receiving chemotherapy, adult patients scheduled for orthopaedic 
surgery, or adult patients with myelodysplastic syndromes only) 
 
This section contains information on how to give yourself an injection of Epoetin alfa HEXAL. It is 
important that you do not try to give yourself the injection unless you have received special 
training from your doctor or nurse. Epoetin alfa HEXAL is provided with or without a needle 
safety guard and you will be shown how to use this by your doctor or nurse. If you are not sure about 
giving the injection or you have any questions, please ask your doctor or nurse for help. 
 
1. Wash your hands. 
2. Remove one syringe from the pack and remove the protective cap from the injection needle. 

Syringes are embossed with graduation rings in order to enable partial use if required. Each 
graduation ring corresponds to a volume of 0.1 mL. If partial use of a syringe is required, 
remove unwanted solution before injection. 

3. Clean the skin at the injection site using an alcohol wipe.  
4. Form a skin fold by pinching the skin between thumb and forefinger. 
5. Insert the needle into the skin fold with a quick, firm action. Inject the Epoetin alfa HEXAL 

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

 
Pre-filled syringe without needle safety guard 
 
6. Always keeping your skin pinched, depress the plunger slowly and evenly. 
7. After injecting the liquid, remove the needle and let go of your skin. Apply 

pressure over the injection site with a dry, sterile pad. 
8. Discard any unused product or waste material. Only use each syringe for 

one injection. 
 
Pre-filled syringe with needle safety guard 
 
6. Always keeping your skin pinched, depress the plunger slowly and evenly 

until the entire dose has been given and the plunger cannot be depressed 
any further. Do not release the pressure on the plunger! 



86 

7. After injecting the liquid, remove the needle while maintaining pressure on the plunger and then 
let go of your skin. Apply pressure over the injection site with a dry, sterile pad.  

8. Let go of the plunger. The needle safety guard will rapidly move to cover the needle. 
9. Discard any unused product or waste material. Only use each syringe for one injection. 


	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