EPIAO Epoetin Alfa 4000 IU/mL Solution for IV/SC Injection 1mL 1's

Epoetin Alfa (EPIAO) is indicated for the treatment of: Anemia due to chronic renal failure (CRF), including patients on hemodialysis (HD) or not on dialysis (ND).
Peri-operative patients in order to reduce the need for allogeneic RBC transfusions.
Anemia associated with chemotherapy in cancer patients with non-myeloid malignancies. Epoetin Alfa (EPIAO) is not indicated for the treatment of anemia caused by other factors such as iron or folate deficiencies, hemolysis or gastrointestinal bleeding.

Dosage: Anemia of renal failure: Epoetin Alfa (EPIAO) should be administered under direct medical supervision.
It can be administered intravenously or subcutaneously, dividing into 2-3 times weekly or once a week. The dose should be adjusted according to patient's haemoglobin concentration, age and other related factors. The following dose schedule is recommended: Initial dose: Weekly dividing dosing: The recommended initial dose is 100-150 IU/kg weekly for HD patients, and 75-100 IU/kg weekly for ND patients. If the increment of hematocrit (Hct) is less than 0.5 vol% per week after 4 weeks, the dose can be increased by 15-30 IU/kg weekly.
The maximum increase dose should not exceed 30 IU/kg/week. The target increase of Hct is at the range of 30-33 vol% but not exceeding 36 vol%.
Once a week dosing: The recommended dose is 10,000 IU/week for HD or PD adult patients.
Maintenance dose: Weekly dividing dosing: When the content of Hct reaches 30-33 vol% or hemoglobin (Hb) reaches 100-110 g/L, the dose should be adjusted to two-thirds of the initial dose. Hct should be monitored every 2-4 weeks to prevent excessive erythropoiesis and keep Hct and Hb at an adequate level.
Once a week dosing: When the content of Hct and haemoglobin (Hb) reach the above target, the dose frequency can be reduced (e.g., once every two weeks). The dose can be further adjusted according to the level of Hct and Hb.
Peri-operative patients: Elective surgery patients (except cardiac surgery) with Hb between 100-130 g/L can receive Epoetin Alfa (EPIAO) 150 IU/kg subcutaneously, 3 times weekly, starting 10 days prior to, and for 4 days after the surgery. Epoetin Alfa (EPIAO) can relieve Anemia during and after the surgery, reduce transfusion requirements, and correct anaemia after surgery. Oral iron supplement should be given at the same time in order to avoid iron deficiency.
Anemia in cancer patients on chemotherapy: Treatment with Epoetin Alfa (EPIAO) is not recommended for patients with endogenous baseline EPO level more than 200 mu/ml. It is demonstrated that patients with lower baseline serum EPO level respond more vigorously to Epoetin Alfa (EPIAO) than patients with higher baseline EPO level.
Weekly dividing dosing: The recommended initial dose is 150 IU/kg, 3 times a week by subcutaneous injection. If there is no significant increase of Hct or reduction of transfusion requirement after 8 weeks' treatment, the dose can be increased to 200 IU/kg, 3 times a week by subcutaneous injection. If the hematocrit exceeds 40%, the dose of Epoetin Alfa (EPIAO) should be withheld until the hematocrit falls to 36%. The dose of Epoetin Alfa (EPIAO) should be reduced by 25% when treatment is resumed and titrated to maintain the desired hematocrit. If the initial dose of Epoetin Alfa (EPIAO) results in a rapid hematocrit response (e.g., an increase of more than 4% in any 2-week period), the dose of Epoetin Alfa (EPIAO) should be reduced.
Once a week dosing: Weekly 36,000 IU of Epoetin Alfa (EPIAO) is recommended to be used subcutaneously if the blood Hb is <110 g/L in male or <100 g/L in female patients.
The treatment duration is 8 weeks. The administration should be discontinued if Hb rises to 120 g/L in less than 8 weeks and resumed if it decreases to <110 g/L in male and <100 g/L in female patients. The dose should be reduced appropriately if the absolute increase of haemoglobin exceeds 13 g/L within 2 weeks.
Instruction of administration: For single-use vials, use aseptic procedure, attach a sterile needle to a sterile syringe, and withdraw the required volume of Epoetin Alfa (EPIAO) solution into the syringe for intravenous or subcutaneous injection.
For prefilled syringes, open the outer package, take off the rubber capper on the front of syringe, then make intravenous or subcutaneous injection.

Epoetin Alfa (EPIAO) is contraindicated in patients with: Uncontrolled hypertension.
Allergic to the product and other mammalian cell derivatives, allergic to human serum albumin.
Uncontrolled combined infection.

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.

Common reactions: headache, fever and fatigue occur occasionally at the beginning of Epoetin Alfa (EPIAO) therapy. Myalgia and arthralgia have been observed rarely. Most of these symptoms can be corrected by expectant treatments and the therapy can be continued. If symptoms persist, the therapy should be discontinued.
Allergic reactions: There have been no reports of serious allergic reactions or anaphylaxis associated with erythropoietin administration during clinical trials. Skin rashes and urticaria have been observed rarely and when reported have generally been mild and transient in nature. A low dose administration prior to the full dose treatment is recommended for the patients starting or resuming the treatment of Epoetin Alfa (EPIAO). Any abnormality should be treated appropriately and the Epoetin Alfa (EPIAO) administration should be discontinued.
Cardio-cerebral vascular system: Increases in blood pressure, deterioration of hypertension, headache induced by hypertensive encephalopathy and seizures have been reported in clinical trials. Therefore, blood pressure should be monitored carefully and if necessary, the dose of Epoetin Alfa (EPIAO) should be adjusted/terminated and hypotensive agents may be used.
Blood system: With the increase of Hct due to administration of Epoetin Alfa (EPIAO), the blood viscosity can be increased; measures should be taken to prevent thrombosis.
Liver: Enhancement of GOT and GPT are rarely observed.
Gastrointestinal: Anorexia, nausea, vomiting and diarrhea occur rarely.

Haematopoietic Agents