EPORATIO Solution for injection Ref.[8883] Active ingredients: Epoetin theta

Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: ratiopharm GmbH, Graf-Arco-Straße 3, 89079 Ulm, Germany

Therapeutic indications

Treatment of symptomatic anaemia associated with chronic renal failure in adult patients.
Treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.

Posology and method of administration

Epoetin theta treatment should be initiated by physicians experienced in the above-mentioned indications.

Posology

Symptomatic anaemia associated with chronic renal failure

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 theta should be administered either subcutaneously or intravenously in order to increase haemoglobin level to not greater than 12 g/dl (7.45 mmol/l).

Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dl (6.21 mmol/l) to 12 g/dl (7.45 mmol/l). A sustained haemoglobin level of greater than 12 g/dl (7.45 mmol/l) should be avoided; guidance for appropriate dose adjustment if haemoglobin values exceeding 12 g/dl (7.45 mmol/l) are observed are described below.

A rise in haemoglobin of greater than 2 g/dl (1.24 mmol/l) over a four week period should be avoided. If the rise in haemoglobin is greater than 2 g/dl (1.24 mmol/l) in 4 weeks or the haemoglobin value exceeds 12 g/dl (7.45 mmol/l), the dose should be reduced by 25 to 50%. It is recommended that haemoglobin be monitored every two weeks until levels have stabilised and periodically thereafter. If the haemoglobin level continues to increase, therapy should be interrupted until the haemoglobin level begins to decrease, at which point therapy should be restarted at a dose approximately 25% below the previously administered dose.

In the presence of hypertension or existing cardiovascular, cerebrovascular or peripheral vascular diseases, the increase in haemoglobin and the target haemoglobin value should be determined individually taking into account the clinical picture.

Treatment with epoetin theta is divided into two stages.

Correction phase

Subcutaneous administration: The initial posology is 20 IU/kg body weight 3 times per week. The dose may be increased after 4 weeks to 40 IU/kg, 3 times per week, if the increase in haemoglobin is not adequate (<1 g/dl [0.62 mmol/l] within 4 weeks). Further increases of 25% of the previous dose may be made at monthly intervals until the individual target haemoglobin level is obtained.

Intravenous administration: The initial posology is 40 IU/kg body weight 3 times per week. The dose may be increased after 4 weeks to 80 IU/kg, 3 times per week, and by further increases of 25% of the previous dose at monthly intervals, if needed.

For both routes of administration, the maximum dose should not exceed 700 IU/kg body weight per week.

Maintenance phase

The dose should be adjusted as necessary to maintain the individual target haemoglobin level between 10 g/dl (6.21 mmol/l) to 12 g/dl (7.45 mmol/l), whereby a haemoglobin level of 12 g/dl (7.45 mmol/l) should not be exceeded. If a dose adjustment is required to maintain the desired haemoglobin level, it is recommended that the dose be adjusted by approximately 25%.

Subcutaneous administration: The weekly dose can be given as one injection per week or three times per week.

Intravenous administration: Patients who are stable on a three times weekly dosing regimen may be switched to twice-weekly administration.

If the frequency of administration is changed, haemoglobin level should be monitored closely and dose adjustments may be necessary.

The maximum dose should not exceed 700 IU/kg body weight per week.

If epoetin theta is substituted for another epoetin, haemoglobin level should be monitored closely and the same route of administration should be used.

Patients should be monitored closely to ensure that the lowest approved effective dose of epoetin theta is used to provide adequate control of the symptoms of anaemia whilst maintaining a haemoglobin concentration below or at 12 g/dl (7.45 mmol/l).

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

Symptomatic anaemia in cancer patients with non-myeloid malignancies receiving chemotherapy

Epoetin theta should be administered by the subcutaneous route to patients with anaemia (e.g. haemoglobin concentration ≤10 g/dl [6.21 mmol/l]). Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary.

The recommended initial dose is 20,000 IU, independent of bodyweight, given once-weekly. If, after 4 weeks of therapy, the haemoglobin value has increased by at least 1 g/dl (0.62 mmol/l), the current dose should be continued. If the haemoglobin value has not increased by at least 1 g/dl (0.62 mmol/l) a doubling of the weekly dose to 40,000 IU should be considered. If, after an additional 4 weeks of therapy, the haemoglobin increase is still insufficient an increase of the weekly dose to 60,000 IU should be considered.

The maximum dose should not exceed 60,000 IU per week.

If, after 12 weeks of therapy, the haemoglobin value has not increased by at least 1 g/dl (0.62 mmol/l), response is unlikely and treatment should be discontinued.

If the rise in haemoglobin is greater than 2 g/dl (1.24 mmol/l) in 4 weeks or the haemoglobin level exceeds 12 g/dl (7.45 mmol/l), the dose should be reduced by 25 to 50%. Treatment with epoetin theta should be temporarily discontinued if haemoglobin levels exceed 13 g/dl (8.07 mmol/l). Therapy should be reinitiated at approximately 25% lower than the previous dose after haemoglobin levels fall to 12 g/dl (7.45 mmol/l) or below.

Therapy should be continued up to 4 weeks after the end of chemotherapy.

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

Special populations

Paediatric population

The safety and efficacy of Eporatio in children and adolescents aged up to 17 years have not yet been established. No data are available.

Method of administration

The solution can be administered subcutaneously or intravenously. Subcutaneous use is preferable in patients who are not undergoing haemodialysis, in order to avoid puncturing peripheral veins. If epoetin theta is substituted for another epoetin, the same route of administration should be used. In cancer patients with non-myeloid malignancies receiving chemotherapy epoetin theta should be administered by the subcutaneous route only.

Subcutaneous injections should be given into the abdomen, arm or thigh.

The injection sites should be rotated and the injection performed slowly to avoid discomfort at the site of injection.

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

Overdose

The therapeutic margin of epoetin theta is very wide. In the case of overdose, polycythaemia can occur. In the event of polycythaemia, epoetin theta should be temporarily withheld.

If severe polycythaemia occurs, conventional methods (phlebotomy) may be indicated to reduce the haemoglobin level

Shelf life

Eporatio 1,000 IU/0.5 ml solution for injection in pre-filled syringe: 2 years.

Eporatio 2,000 IU/0.5 ml solution for injection in pre-filled syringe: 2 years.

Eporatio 3,000 IU/0.5 ml solution for injection in pre-filled syringe: 2 years.

Eporatio 4,000 IU/0.5 ml solution for injection in pre-filled syringe: 2 years.

Eporatio 5,000 IU/0.5 ml solution for injection in pre-filled syringe: 30 months.

Eporatio 10,000 IU/1 ml solution for injection in pre-filled syringe: 30 months.

Eporatio 20,000 IU/1 ml solution for injection in pre-filled syringe: 30 months.

Eporatio 30,000 IU/1 ml solution for injection in pre-filled syringe: 30 months.

For the purpose of ambulatory use, the patient may remove the product from the refrigerator and store it at a temperature not above 25°C for a single period of up to 7 days without exceeding the expiry date. Once removed from the refrigerator, the medicinal product must be used within this period or disposed of.

Special precautions for storage

Store in a refrigerator (2°C-8°C).

Do not freeze.

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

Nature and contents of container

Eporatio 1,000 IU/0.5 ml solution for injection in pre-filled syringe:

0.5 ml solution in a pre-filled syringe (type I glass) with a tip cap (bromobutyl rubber), a plunger stopper (teflonised chlorobutyl rubber) and an injection needle (stainless steel) or an injection needle (stainless steel) with a safety shield (safety needle) or an injection needle (stainless steel) with a safety device.

Pack sizes of 6 pre-filled syringes; 6 pre-filled syringes with safety needle or 6 pre-filled syringes with safety device.