Epolitt 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.
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.
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. 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 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 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 anemia (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: 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 orthopedic 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. In order to improve 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 to another under appropriate supervision.
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. Epoetin alfa is not approved in the management of anemia associated with hepatitis C.
In 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 B deciency, aluminium intoxication, infection or inflammation, blood loss, haemolysis and bone marrow brosis of any origin) should be investigated.
A paradoxical decrease in haemoglobin and development of severe anemia 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. No other ESA therapy should be commenced because of the risk of cross-reaction.
Treatment of symptomatic anemia 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. As per published literature on another Epoetin alfa product, 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 anemia and to avoid blood transfusion.
Caution should be exercised with escalation of Epoetin alfa (Epolitt) 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. Chronic renal failure patients treated with epoetin alfa by the subcutaneous route should be monitored regularly for loss of efficacy, dened 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 hemodialysis patients, especially in those who have a tendency to hypotension or whose arteriovenous stulae 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.
Hyperkalemia 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 hyperkalemia, consideration should be given to ceasing epoetin alfa administration until the serum potassium level has been corrected. An increase in heparin dose during hemodialysis 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 anemia with epoetin alfa in adult patients with renal insuciency not yet undergoing dialysis does not accelerate the rate of progression of renal insuficiency.
Treatment of patients with chemotherapy-induced anemia: 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. In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anemia associated with cancer.
As per published literature on another Epoetin alfa product, in controlled clinical studies, use of epoetin alfa and other ESAs have shown: 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.
In view of the above, in some clinical situations blood transfusion should be the preferred treatment for the management of anemia in patients with cancer. The decision to administer recombinant erythropoietin treatment should be based on a benet-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 anemia; life-expectancy; the environment in which the patient is being treated; and patient preference.
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 orthopedic surgery: Good blood management practices should always be used in the perisurgical setting. Patients scheduled for major elective orthopedic 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 >13g/dl, 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.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been reported.