Epodion

Recombinant human erythropoietin alfa.

EPODION is a sterile, clear and colorless solution for intravenous or subcutaneous injection.
Each prefilled syringe (0.5 mL) contains: Recombinant human erythropoietin alfa 2,000 IU.
Each prefilled syringe (0.3 mL) contains: Recombinant human erythropoietin alfa 3,000 IU.
Each prefilled syringe (0.4 mL) contains: Recombinant human erythropoietin alfa 4,000 IU.
Each prefilled syringe (1.0 mL) contains: Recombinant human erythropoietin alfa 10,000 IU.

Pharmacology: EPODION has recombinant human erythropoietin alfa (INN; Epoetin alfa) as an active ingredient, that is a single chain glycoprotein composed of 165 amino acids, and its molecular weight is 26-30 kDa with glycosylation. Epoetin alfa obtained by gene technology is identical in its amino acid sequence to erythropoietin that has been isolated from the urine of anaemic patients. Generally, human erythropoietin is produced in fibroblastoid interstitial cells in the kidneys and liver and then travels to the bone marrow to stimulate red blood cell production. Due to this nature of human erythropoietin, indication of Epoetin alfa is hormone-replacement therapy in the anemia.

Treatment of anemia associated with chronic renal failure in adult patients on haemodialysis and peritoneal dialysis. Treatment of severe anemia of renal origin accompanied by clinical symptoms in adult patients with renal insufficiency not yet undergoing dialysis. Treatment of anemia and reduction of transfusion requirements in adult patients receiving chemotherapy. EPODION can be used to facilitate autologous blood collection within a predeposit programme and decrease the risk of receiving allogenic blood transfusion in patients with moderate anemia (hematocrits of 33-39%, haemoglobin of 10-13 g/dL, [6.2-8.1 mmol/L], no iron deficiency), who are scheduled for major elective surgery and are expected to require more blood than that which can be obtained through autologous blood collection techniques in the absence of Epoetin alfa. EPODION can be used to augment erythropoiesis in the perisurgical period in order to reduce allogeneic blood transfusions and correct postoperative anemia in adult non-iron deficient patients undergoing major elective orthopaedic surgery. Treatment of anemia in symptomatic HIV-infected patients being treated with AZT (Zidovudine) and who are transfusion-dependent.

Method of administration: EPODION may be administered by intravenous or subcutaneous injection. As for any parenterally administrated drug, the injection solution should be inspected for particles and discolouration prior to administration. Do not shake, shaking may denature the glycoprotein, rendering it inactive. Epoetin alfa in single use syringes contains no preservatives. Do not re-use syringe. Discard unused portion.
Chronic renal failure patients: In patients with chronic renal failure, where intravenous access is routinely available (haemodialysis patients) administration of EPODION by the intravenous route is preferable. Where intravenous access is not readily available (patients not yet on dialysis and peritoneal dialysis patients) EPODION may be administered subcutaneously. The recommended desired haemoglobin concentration range is between 10 g/dL to 12 g/dL (6.2-7.5 mmol/L) in adults. In patients with chronic renal failure and clinically evident ischaemic heart disease or congestive heart failure, maintenance haemoglobin concentration should not exceed the upper limit of the target haemoglobin concentration. Iron status should be evaluated prior to and during treatment and iron supplementation should be administered if necessary. Other causes of anaemia (folate or Vitamin B12 deficiency) should be excluded before starting therapy with EPODION. Non-response to EPODION therapy should prompt a search for causative factors. These include: iron, folate or Vitamin B12 deficiency, aluminium intoxication, intercurrent infections; inflammatory or traumatic episodes, blood loss, haemolysis and bone marrow fibrosis of any origin.
Adult haemodialysis patients: In patients on haemodialysis where intravenous access is readily available, administration by intravenous route is preferable.
The treatment is divided into two stages: 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 (6.2-7.5 mmol/L) is achieved (this should be done in steps of at least four weeks).
Maintenance phase: The maintenance dose should be individualized for each chronic renal failure patient. 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 (6.2-7.5 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 peritoneal dialysis patients: Where intravenous access is not readily available, EPODION may be administered subcutaneously.
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 (6.2-7.5 mmol/L) is achieved (this should be done in steps of at least four weeks).
Maintenance phase: The usual dose to maintain the target haemoglobin is between 17 and 33 IU/kg three times per week. The maximum dosage should not exceed 200 IU/kg three times per week. 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 (6.2-7.5 mmol/L).
Adult patients with renal insufficiency not yet undergoing dialysis: Where intravenous access is not readily available, EPODION 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, EPODION can be administered either 3 times per week or 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 (6.2-7.5 mmol/L). The recommended dosage adjustment is between 17 and 33 IU/kg three times per week. The maximum dosage should not exceed 200 IU/kg three times per week.
Treatment of adult patients with chemotherapy-induced anaemia: EPODION should be administered to patients with anaemia (e.g. haemoglobin concentration ≤10.5 g/dL (6.5 mmol/L)). The subcutaneous route of administration should be used. The target haemoglobin concentration should be up to 12 g/dL (7.5 mmol/L) in men and women and it should not be exceeded. EPODION therapy should continue until one month after the end of chemotherapy. However, the need to continue EPODION therapy should be re-evaluated periodically.
The initial dose is 150 IU/kg subcutaneously, 3 times per week. 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. If the haemoglobin concentration has not increased by ≥1 g/dL (≥0.62 mmol/L) and the reticulocyte count has not increased by ≥40,000 cells/µL above baseline after 4 weeks of treatment, at the initial dose should be increased 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 after an additional 4 weeks of therapy at 300 IU/kg 3 times per week, haemoglobin concentration has increased <1 g/dL (<0.62 mmol/L) and the reticulocyte count has increased <40,000 cells/µL above baseline after an additional 4 weeks of therapy, response is unlikely and treatment should be discontinued.
[The recommended dosing regimen is described in the following diagram: (See figure)].


Click on icon to see table/diagram/image


A rate of rise in haemoglobin of greater than 2 g/dL (1.25 mmol/L) per month should be avoided.
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 EPODION 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 EPODION therapy at a dose 25% below the previous dose.
Treatment of adult surgery patients in an autologous predonation programme: The intravenous route of administration should be used. EPODION should be administered after the completion of the blood donation procedure. 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. Mildly anaemic patients (haematocrit of 33 to 39% and/or haemoglobin 10 to 13 g/dL) requiring predeposit of ≥4 units of blood should be treated with EPODION 600 IU/kg intravenously, 2 times per week for 3 weeks prior to surgery.
Perisurgery patients without autologous blood donation: The subcutaneous route of administration should be used. Patient should receive adequate iron supplementation (at least 200 mg/daily orally) which should be initiated no later than the beginning of treatment with EPODION and should continue throughout the course of therapy. Recommended dosage regimen is 600 IU/kg of EPODION given weekly for three weeks, days -21, -14 and -7 prior to surgery and on the day of surgery.
Treatment of adult patients scheduled for major elective orthopaedic surgery: The subcutaneous route of administration should be used. The recommended dose is EPODION 600 IU/kg administered subcutaneously weekly for three weeks (days -21, -14 and -7) prior to surgery and on the day of surgery. 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. In cases where there is a medical need to shorten the lead time before surgery to less than three weeks, EPODION 300 IU/kg should be administered subcutaneously daily for 10 consecutive days prior to surgery, on the day of surgery and for four days immediately thereafter. If the haemoglobin level reaches 15 g/dL, or higher, during the preoperative period, administration of EPODION should be stopped and further dosages should not be administered. Care should be taken to ensure that at the outset of the treatment patients are not iron deficient.
HIV-infected patients being treated with AZT (Zidovudine): Prior to beginning EPODION therapy, it is recommended that the endogenous serum erythropoietin level be determined (prior to transfusion). Available evidence suggests that patients receiving zidovudine with levels >500 mU/mL are unlikely to respond to therapy with EPODION unless the dose of zidovudine is reduced or temporarily stopped.
Starting Dose: For patients with serum erythropoietin levels ≤500 mU/mL, the recommended starting dose of EPODION is 100 IU/kg as an intravenous or subcutaneous injection three times weekly for eight weeks.
Increase Dose: During the dose adjustment phase of therapy, the haemoglobin should be monitored weekly. If the response is not satisfactory in terms of reducing transfusion requirements or increasing haemoglobin after eight weeks of therapy, the dose of EPODION can be increased by 50-100 IU/kg three times per week. Response should be evaluated every 4-8 weeks thereafter and the dose adjusted accordingly by 50-100 IU/kg increments three times per week. If patients have not responded satisfactorily to an EPODION dose of 300 IU/kg three times per week up to month 12 of therapy, further continuation of treatment is not warranted as it is unlikely that they will respond to higher doses of EPODION.
Maintenance Dose: After attainment of the desired response (i.e., reduced transfusion requirements or increased haemoglobin), the dose of EPODION should be titrated to maintain the response based on factors such as variations in zidovudine dose and the presence of intercurrent infectious or inflammatory episodes. If the haemoglobin exceeds 12 g/dL, the dose should be temporarily withheld until the haemoglobin falls below 12 g/dL. Resume dosing at 25% less than the previous dose and titrate the dose to maintain the desired haemoglobin.
Haemoglobin Range: Maximum benefit from EPODION therapy appears to occur when the haemoglobin is maintained in the range of 12-13 g/dL; however, the haemoglobin for zidovudine-treated/HIV-infected patients should not exceed 12 g/dL.

Overdosage of Epoetin alfa may produce effects that are extensions of the pharmacological effects of the hormone (critical increase of haemoglobin or haematocrit levels). Phlebotomy may be performed if excessively high haemoglobin or haemotocrit levels occur.

EPODION is contraindicated in patients with: Hypersensitivity to the active substance or to any of the excipients.
Patients who develop pure red cell aplasia (PRCA) following treatment with any erythropoietin should not receive EPODION or any other erythropoietin.
Uncontrolled hypertension.
All contraindications associated with autologous blood predonation programmes should be respected in patients being supplemented with EPODION.
The use of EPODION 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.
The use of Epoetin alpha in the indication "to facilitate autologous blood collection" is contraindicated in patients with: Myocardial infarction or stroke in the month preceding treatment; Unstable angina pectoris; Increased risk of deep venous thrombosis such as history of venous thromboembolic disease.

General: Blood pressure should be adequately controlled prior to initiation of Epoetin alfa therapy. 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 initiate or increase anti-hypertensive treatment during Epoetin alfa therapy. 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. 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. The safety and efficacy of Epoetin alfa therapy have not been established in patients with underlying haematological diseases (e.g. haemolytic anaemia, sickle cell anaemia, thalassemia, porphyria). 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. Due to decreased metabolism, patients with hepatic dysfunction may have increased erythropoiesis with Epoetin alfa. An increased incidence of thrombotic vascular events (TVEs) has been observed in patients receiving erythropoiesis-stimulating agents ESAs. 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 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. 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. In order to improve the traceability of erythropoiesis-stimulating agents (ESAs), the trade name of the administered ESA should be clearly recorded (or stated) in the patient file. Patients should only be switched from one ESA (such as EPODION) to another ESA under appropriate supervision of physician.
Pure Red Cell Aplasia: Antibody-mediated pure red cell aplasia (PRCA) has been rarely reported after months to years of subcutaneous Epoetin treatment mainly in chronic renal failure patients. Cases also have been reported in patients with hepatitis C treated with interferon and ribavirin, when ESAs are used concomitantly. ESAs are not approved in the management of anemia associated with hepatitis C. In chronic renal failure patients developing sudden lack of efficacy defined by a decrease in haemoglobin (1 to 2 g/dL per month) with increased need for transfusions, a reticulocyte count should be obtained and typical causes of non-response (e.g. iron, folate or Vitamin B12 deficiency, aluminium intoxication, infection or inflammation, blood loss, haemolysis should be investigated. If the reticulocyte count corrected for anemia (i.e. the reticulocyte "index") is low (<20,000/mm³ or <20,000/µL or <0.5%), platelet and white blood cell counts are normal, and if no other cause of loss of effect has been found, anti-erythropoietin antibodies should be determined and bone marrow examination should be considered for diagnosis of PRCA. If anti-erythropoietin, antibody-mediated PRCA is suspected, therapy with Epoetin alfa should be discontinued immediately. No other ESA therapy should be commenced because of the risk cross-reaction. Appropriate therapy, such as blood transfusions, may be given to patients when indicated.
Treatment of symptomatic anaemia in adult 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 (1.2 mmol/L) per month to minimise risks of an increase in hypertension. Dose should be reduced when haemoglobin approaches 12 g/dL. In patients with chronic renal failure, maintenance haemoglobin concentration should not exceed the upper limit of the haemoglobin concentration range as recommended under Dosage & Administration. Haemoglobin levels greater than 12 g/dL may be associated with a higher risk of cardiovascular events, including death. 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. Some patients with more extended dosing intervals (greater than once weekly) of Epoetin alfa may not maintain adequate haemoglobin levels 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. Based on information available to date, the use of Epoetin alfa in predialysis (end stage renal insufficiency) patients does not accelerate the rate of progression of renal insufficiency. 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 optimal. In some female chronic renal failure patients, menses have resumed following Epoetin alfa therapy; the possibility of potential pregnancy should be discussed and the need for contraception evaluated. Rarely, exacerbation of porphyria has been observed in Epoetin alfa-treated patients with chronic renal failure. Epoetin alfa should be used with caution in patients with known porphyria.
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. The target haemoglobin should be up to 12 g/dL [7.5 mmol/L] in men and women and it should not be exceeded. In cancer patients receiving chemotherapy, should the rate of increase in haemoglobin exceed 1 g/dL per two week or 2 g/dL per month or the haemoglobin concentration is approaching 12 g/dL or the haemoglobin concentration exceeds 12 g/dL, the dose adjustment detailed in Dosage & Administration-Cancer patients should be followed to minimize potential risk factors of thrombotic events. An increased incidence of thrombotic vascular events (TVEs) has been observed in patients receiving erythropoiesis-stimulating agents ESAs. 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). 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. In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anaemia associated with cancer. In order to ensure optimum response to Epoetin alfa, adequate iron stores should be assured, and folic acid and vitamin B12 deficiencies should be excluded prior to initiating therapy. In most cases, the ferritin values in the serum fall simultaneously with the rise in packed cell volume. Therefore, iron supplementation, eg, 200-300 mg/day orally is recommended for all cancer patients whose transferrin saturation is below 20%. 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 whether or not Epoetin alfa therapy is appropriate (in particular for patient at risk of being transfusion).
HIV-Infected patients: If HIV-infected patients fail to respond or maintain a response to Epoetin alfa, other etiologies including iron deficiency anaemia should be considered and evaluated.
Surgery patients in autologous predonation programmes: All special warnings and special precautions associated with autologous predonation programmes, especially routine volume replacement, should be respected in patients being supplemented with Epoetin alfa.
Adult perisurgery patients (without autologous blood donation): In patients scheduled for major elective orthopaedic surgery the cause of anaemia should be established and treated, if possible, before the start of Epoetin alfa treatment. In patients scheduled for major elective orthopaedic surgery, thrombotic events can be a risk and this possibility should be carefully weighed against the benefit if to be derived from the treatment in this patient group. Patients scheduled for major elective orthopaedic surgery should receive adequate antithrombotic prophylaxis, as thrombotic and vascular events may occur in surgical patients, especially in those with underlying cardiovascular disease. In addition, special precaution should be taken in patients with predisposition for development of DVTs. Moreover, in patients with a baseline haemoglobin of >13 g/dL (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, it should not be used in patients with baseline haemoglobin >13 g/dL (8.1 mmol/L).
Effects on ability to drive and use machines: Due to increased risk of hypertension during the initial phase of Epoetin alfa treatment, patients with chronic renal failure should use caution when performing potentially hazardous activities, such as driving or operating machinery until the optimal maintenance dose of Epoetin alfa has been established.
Use in Children: The safety of the children is not established.
Use in the Elderly: Since the physiological ability in elderly patients is normally decreased and the risk of cardiovascular diseases is high, some parameters (such as blood pressure, haemoglobin, and dosing frequency) should be monitored carefully.

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Epoetin alfa should be used in pregnancy only if the potential benefit outweighs the potential risk to the fetus. The use of Epoetin alfa is not recommended in pregnant surgical patients participating in an autologous blood predonation programme.
Lactation: It is not known whether exogenous Epoetin alfa is excreted in human milk. Epoetin alfa should be used with caution in nursing women. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Epoetin alfa should be made taking into account the benefit of breast-feeding to the child and the benefit of Epoetin alfa therapy to the woman. The use of Epoetin alfa is not recommended in lactating surgical patients participating in an autologous blood predonation programme.

For safety with respect to transmissible agents, see Precautions.
Clinial Trial Data: 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. Other common adverse drug reactions observed in clinical trials of Epoetin alfa are diarrhoea, nausea, headache, influenza-like illness, pyrexia, rash, vomiting, deep vein thrombosis, pulmonary embolism, seizures. Influenza-like illness including headache, joint pains, myalgia, and dizziness and tiredness, may occur especially at the start of treatment. Frequencies may vary depending on the indication see table as follows.
The overall safety profile of Epoetin alfa was evaluated in 142 subjects with chronic renal failure and in 765 subjects with cancer who participated in placebo-controlled, double-blind clinical registration trials. Adverse drug reactions reported by ≥0.2% of Epoetin alfa-treated subjects in these trials, additional clinical trials and from post­-marketing experience are listed as follows by SOC and frequency. Frequencies are defined as: 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).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness: (See table).


Click on icon to see table/diagram/image

No evidence exists that indicates that treatment with Epoetin alfa alters the metabolism of other drugs.
Drugs that can affect erythropoiesis may affect the therapeutic response of Epoetin alfa.
Since cyclosporin is bound by red blood cells there is potential for a drug 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 G-CSF or GM-CSF with regard to haematological differentiation or proliferation of tumour biopsy specimens in vitro.

Caution for application: Do not mix with other drugs when administration of this drug.
In case of the patients with hemodialysis, injection after hemodialysis is desirable.
Do not administer by IV infusion.

Store at 2-8°C. Do not freeze. Protect from light.
Shelf Life: 36 months from manufacturing date.

Haematopoietic Agents

B03XA01 - erythropoietin ; Belongs to the class of other antianemic preparations. Used in the treatment of anemia.

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