Epiao Special Precautions

As reported from clinical trial with chronic renal failure patients, the patients experienced greater risks for death, serious cardiovascular events and stroke when administered erythropoiesis-stimulating agents (ESAs) to target haemoglobin levels of 13g/dL and above.
Individualize dosing to achieve and maintain haemoglobin levels within the range of 10 to 12 g/dL.
Patients with chronic renal failure experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target haemoglobin levels of 13 g/dL and above in clinical studies. Patients with chronic renal failure and an insufficient haemoglobin response to ESA therapy may be at even greater risk for cardiovascular events and mortality than other patients. ESAs increased the risks for death and serious cardiovascular events in controlled clinical trials of patients with cancer. These events included myocardial infarction, stroke, congestive heart failure, and hemodialysis vascular access thrombosis. A rate of haemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks.
As reported from clinical trial with cancer patients, ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.
Use ESAs only for treatment of anaemia due to concomitant myelosuppressive chemotherapy.
ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure. Discontinue following the completion of a chemotherapy course.
As reported from clinical trial with peri-operative patients, recombinant human erythropoietin increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.
Cases of pure red cell aplasia (PRCA) and of severe anaemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported. This has been reported predominantly in patients with CRF receiving ESAs by subcutaneous administration. PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin. Any patient who develops a sudden loss of response to Epoetin Alfa (EPIAO), accompanied by severe anaemia and low reticulocyte count, should be evaluated for the etiology of loss of effect, including the presence of neutralizing antibodies to erythropoietin. If anti-erythropoietin antibody-associated anaemia is suspected, withhold ESAs.
Recombinant human erythropoietin should be permanently discontinued in patients with antibody-mediated anaemia. Patients should not be switched to other ESAs as antibodies may cross-react.
General precautions: The parenteral administration of any biologic product should be attended by appropriate precautions in case allergic or other untoward reactions occur.
Hematocrit should be monitored regularly (once a week in initial treatment phase and twice a week in maintenance phase) to avoid excessive erythropoiesis. Hematocrit should be no more than 36vol%. Epoetin Alfa (EPIAO) should be discontinued if excessive erythropoiesis occurs.
Haemoglobin should also be monitored regularly (once every 1-2 weeks) when 36000 IU/mL is used, and Epoetin Alfa (EPIAO) should be discontinued if the haemoglobin is more than 120 g/L.
Exacerbation of porphyria has been observed rarely in patients with CRF treated. Recombinant human erythropoietin should be used with caution in patients with known porphyria.
During therapy, absolute or functional iron deficiency may develop. Functional iron deficiency, with normal ferritin levels but low transferrin saturation, is presumably due to the inability to mobilize iron stores rapidly enough to support increased erythropoiesis.
Transferrin saturation should be at least 20% and ferritin should be at least 100 ng/mL. Prior to and during therapy, the patient's iron status, including transferrin saturation (serum iron divided by iron binding capacity) and serum ferritin, should be evaluated.
Virtually all patients will eventually require supplemental iron to increase or maintain transferrin saturation to levels which will adequately support erythropoiesis stimulated by Epoetin Alfa (EPIAO). All surgery patients being treated with Epoetin Alfa (EPIAO) should receive adequate iron supplementation throughout the course of therapy in order to support erythropoiesis and avoid depletion of iron stores.
Blood pressure should be controlled adequately before initiation of therapy, blood pressure may rise during therapy. During the early phase of treatment when the hematocrit is increasing, approximately 25% of patients on dialysis may require initiation of, or increases in, antihypertensive therapy. Special care should be taken to closely monitor and aggressively control blood pressure in patients treated with Epoetin Alfa (EPIAO). Patients should be advised as to the importance of compliance with antihypertensive therapy and dietary restrictions. If blood pressure is difficult to control by initiation of appropriate measures, the haemoglobin may be reduced by decreasing or withholding the dose of Epoetin Alfa (EPIAO).
It is recommended that the dose of Epoetin Alfa (EPIAO) should be decreased if the haemoglobin increase exceeds 1 g/dL in any 2-week period, because of the possible association of excessive rate of rise of haemoglobin with an exacerbation of hypertension. In CRF patients on hemodialysis with clinically evident ischemic heart disease or congestive heart failure, the dose of EPIAO should be carefully adjusted to achieve and maintain haemoglobin levels between 10-12 g/dL.
The safety and efficacy of therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anaemia, myelodysplastic syndromes, or hypercoagulable disorders). Given the potential for an increased risk of seizures during the first 90 days of therapy, blood pressure and the presence of premonitory neurologic symptoms should be monitored closely. Patients should be cautioned to avoid potentially hazardous activities such as driving or operating heavy machinery during this period.
During hemodialysis, patients treated may require increased anticoagulation with heparin to prevent clotting of the artificial kidney. The risk of thrombotic events, including vascular access thrombosis, was significantly increased in adult patients with ischemic heart disease or congestive heart failure receiving therapy with the goal of reaching a normal hematocrit (42%) as compared to a target hematocrit of 30%. Patients with pre-existing cardiovascular disease should be monitored closely.
Attention should be paid to patients with symptoms such as cardiac infarction, pulmonary infarction, cerebral infarction or those with allergic history of drugs and manifestation of allergy.
Deficiency of folic acid or vitamin B 12 may diminish the efficacy of Epoetin Alfa (EPIAO), as well as aluminum intoxication.
Use in Children: The safety and effectiveness of EPO have not been established in premature infants, new-borns and infants. The prescribing physician should fully weigh the benefits and risks of using EPO in paediatric patients.
Use in the Elderly: For the elders, blood pressure and hematocrit should be monitored frequently and the dose and frequency of administration should be adjusted accordingly.