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  • Eprex
    / Janssen


    Active Ingredient
    Recombinant-human Erythropoietin 1,000 U/0.5ml, 2,000 U/0.5ml, 3,000 U/0.3ml, 4,000 U/0.4ml, 5,000 U/0.5ml, 6,000 U/0.6ml, 8,000 U/0.8ml, 10,000 U/ml, 20,000 U/0.5ml, 30,000 U/0.75ml, 40,000 U/ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Pre-filled Syringe (solution for injection)

    6 x 1,000 U/0.5 ml

    partial basket chart 86977 5455

    Pre-filled Syringe (solution for injection)

    6 x 2,000 U/0.5 ml

    partial basket chart 86978 5456

    Pre-filled Syringe (solution for injection)

    6 x 3,000 U/0.3 ml

    partial basket chart 86979 5457

    Pre-filled Syringe (solution for injection)

    6 x 4,000 U/0.4 ml

    partial basket chart 86980 5458

    Pre-filled Syringe (solution for injection)

    6 x 5,000 U/0.5 ml

    partial basket chart 86982 5459

    Pre-filled Syringe (solution for injection)

    6 x 6,000 U/0.6 ml

    partial basket chart 86983 5460

    Pre-filled Syringe (solution for injection)

    6 x 8,000 U/0.8 ml

    partial basket chart 86984 5461

    Pre-filled Syringe (solution for injection)

    6 x 10,000 U/ml

    partial basket chart 86985 5462

    Pre-filled Syringe (solution for injection)

    1 x 20,000 U/0.5 ml

    partial basket chart 86952 5470

    Pre-filled Syringe (solution for injection)

    1 x 30,000 U/0.75 ml

    partial basket chart 86953

    Pre-filled Syringe (solution for injection)

    1 x 40,000 U/ml

    partial basket chart 86986 5463

    Related information


    Dosage

    Treatment of Severe Anemia associated with Chronic Renal Failure: Eprex is indicated in the treatment of severe anemia associated with chronic renal failure, including patients on dialysis (end-stage renal disease) and patients not on dialysis. Eprex is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or haemoglobin determination) and to decrease the need for transfusions in these patients. Prior to initiation of therapy, the patient’s iron stores, including transferrin saturation and serum ferritin, should be evaluated. Transferrin saturation should be at least 20% and ferritin at least 100 ng/ml. Blood pressure should be adequately controlled prior to initiation of Eprex therapy and must be closely monitored and controlled during therapy. Non-dialysis patients with symptomatic anemia considered for therapy should have hemoglobin less than 10g/dL. All patients on Eprex therapy should be monitored.
    For full details see prescribing information.


    recommended drugs

    Indications

    Treatment of severe anemia associated with chronic renal failure, treatment of anemia in Zidovudine-treated HIV-infected patients, treatment of anemia in cancer patients on chemotherapy, autologous blood donation, reduction of allogenic blood transfusion in surgery patients.


    Contra-Indications

    Uncontrolled hypertension, known hypersensitivity to mammalian cell-derived products, known hypersensitivity to Albumin (Human). Patients who develop antibody-mediated Pure Red Cell Aplasia (PRCA) following treatment with any erythropoietin should not receive Eprex or any other erythropoietin.


    Special Precautions

    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. 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 also be used with caution in the presence of 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 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 TVEs should be carefully weighed against the benefits to be derived from treatment with Epoetin alfa particularly in patients with pre-existing risk factors. 9 Chronic renal failure and cancer patients on epoetin alfa should have haemoglobin levels measured on a regular basis until a stable level is achieved, and periodically thereafter. In all patients, haemoglobin concentration should be closely monitored due to a potential increased risk of thromboembolic events and fatal outcomes when patients are treated at haemoglobin concentration above the 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 deficiency, haemolysis, blood loss, vitamin B12 or folate deficiencies, aluminium intoxication, infection or inflammation and bone marrow fibrosis of any origin) should be considered 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:
    Iron supplementation, e.g. 200-300 mg/day orally (100-200 mg/day for paediatric patients) is recommended for chronic renal failure patients whose serum ferritin levels are below 100 ng/ml. Oral iron substitution of 200-300 mg/day is recommended for all cancer patients whose transferrin saturation is below 20%. For patients in an autologous predonation programme, iron supplementation (elemental iron 200mg/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 200mg/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. All of these additive factors of anaemia should also be carefully considered when deciding to increase the dose of epoetin alfa in cancer patients. Very rarely, the initial presentation 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 the ESA all measures necessary and possible to ensure it should be taken (e.g. exact information on the product used should be documented in an appropriate way). Furthermore, patients should only be switched from one ESA to another under appropriate supervision. The safety and efficacy of Epoetinum alfa therapy have not been established in patients with underlying haematologic diseases (e.g. haemolytic anaemia, sickle cell anaemia, thalassemia).
    Pure Red Cell Aplasia: Antibody-mediated pure red cell aplasia (PRCA) has been reported after months to years of subcutaneous epoetin treatment mainly in chronic renal failure patients. Cases have also been reported in patients with hepatitis C treated with interferon and ribavirin, when ESAs are used concomitantly. EPREX is not approved in the management of anaemia 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 and 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 EPREX and perform anti-erythropoietin antibody testing. A bone marrow examination should also be considered for diagnosis of PRCA. No other ESA therapy should be commenced because of the risk of cross-reaction.
    Treatment of symptomatic anaemia in adult and chronic renal failure patients: 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 target a haemoglobin of greater than 11g/dl . 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. Chronic renal failure patients treated with EPREX by the subcutaneous route should be monitored regularly for loss of efficacy, defined as absent or decreased response to EPREX treatment in patients who previously responded to such therapy. This is characterised by a sustained decrease in haemoglobin despite an increase in EPREX dosage. 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. Patients with chronic renal failure and insufficient hemogloblin response to ESA therapy may be at even greater risk for cardiovascular events and mortality than other patients. 11 In some female chronic renal failure patients, menses have resumed following Epoetinum alfa therapy; the possibility of potential pregnancy should be discussed and the need for contraception evaluated.
    Treatment of patients with chemotherapy induced anaemia:
    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 controlled clinical studies, use of EPREX and other ESAs have shown: Decreased locoregional control in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin of greater than 14 g/dl (8.7 mmol/l), Shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/dl (7.5-8.7 mmol/l), Another ESA (darbepoietin alfa) increased risk of death when administered to target a haemoglobin of 12 g/dl (7.5 mmol/l) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for use in this patient population. In view of the above, 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. In cancer patients receiving chemotherapy, the 2-3 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. Thrombotic events can be a risk in this population and this possibility should be carefully weighed against the benefit 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). This medicinal product contains less than 1 mmol sodium (23 mg) per dose i.e essentially “sodium free”.
    HIV-Infected Patients If HIV-infected patients fail to respond or maintain a response to Epoetinum alfa, other etiologies including iron deficiency anaemia should be considered and evaluate.
    For full details see prescribing information.


    Side Effects

    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. 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 also be used with caution in the presence of 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 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 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 full details see prescribing information.


    Drug interactions

    No evidence exists that indicates that treatment with epoetin alfa alters the metabolism of other drugs. Drugs that decrease erythropoiesis may decrease the response to Epoetin alfa. However, since cyclosporin is bound by RBCs 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. The effect of Epoetinum alfa may be potentiated by the simultaneous therapeutic administration of a haematinic agent, such as ferrous sulphate, when a deficiency state exists. In patients with metastatic breast cancer, subcutaneous co-administration of 40,000 IU/mL Epoetinum alfa with trastuzumab (6 mg/kg) had no effect on the pharmacokinetics of trastuzumab.


    Pregnancy and Lactation

    There are no adequate and well-controlled studies in pregnant women. Studies in animals have shownreproduction toxicity. Consequently: Epoetin alfa should be used in pregnancy only if the potential benefit outweighs the potential risk to the foetus. In pregnant or lactating surgical patients participating in an autologous blood predonation programme, the use of epoetin alfa is not recommended.  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 breastfeeding to the child and the benefit of epoetin alfa therapy to the woman.


    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.


    Important notes

    Storage: Store in a refrigerator (2°C-8°C). This temperature range should be closely maintained until administration to the patient. Store in the original package in order to protect from light. Do not freeze or shake.
    For the purpose of ambulatory use, the patient may remove EPREX from the refrigerator and store it not above 25°C for one single period of up to 7 days.


    Manufacturer
    Cilag AG
    Licence holder
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