Erypoietin® (Epoetin alfa of Amoun) is a 165 amino acid glycoprotein manufactured by recombinant DNA technology.
Epoetin is the internationally accepted, non-proprietary name of recombinant human erythropoietin (rHu-EPO)
It is produced by mammalian cells into which the human erythropoietin gene has been introduced. It contains the identical amino acid sequence of isolated natural erythropoietin.
Erypoietin® has a molecular weight of 30, 400 daltons and has the same biological effects as endogenous erythropoietin.
Erypoietin® is formulated as a sterile colorless, preservative-free liquid for intravenous or subcutaneous administration. Erypoietin® single dose vial contains:
- Epoetin alfa: 2000 or 4000 units
- Albumin (human): 2.5 mg
- Sodium citrate: 2.5 mg
- Sodium chloride: 5.8 mg
- Citric acid in sterile Water for injection: 0.06 mg
Erypoietin® (epoetin alfa) stimulates erythropoiesis in anemic patients whose anemia is caused –completely or partly-by defect in erythropoiesis.
By IV administration, epoetin alfa is eliminated at a rate consistent with first order kinetics with a half-life 4-13 hours. Within the therapeutic dose range, detectable levels of plasma erythropoietin are maintained for 24 hours.
By SC administration, epoetin alfa peak serum levels are achieved within 5-24 hours after administration, and decline slowly thereafter. There is no difference in half-life between CRF patients not on dialysis (with a serum creatinine levels higher than 3) and patients on dialysis.
Anemia of chronic renal failure (CRF) patients
Erypoietin® (epoetin alfa) is indicated for the treatment of anemia in CRF patients whether being not on dialysis or in those who require regular dialysis (end-stage-renal disease)
Erypoietin® is indicated to elevate or maintain the red blood cell mass measured by the hematocrit (Hct) or the hemoglobin (Hb) and to decrease the need for blood transfusions in these patients.
In non-dialysis patients with symptomatic anemia, Erypoietin® is considered when hematocrit level is less than 30%
Anemia of cancer patients
Erypoietin® (epoetin alfa) is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy.
Reduction of perioperative allogeneic blood transfusions
Erypoietin® is indicated for the anemic patients (hg> 10 to 13g/dl) undergoing an elective non-cardiac, non-vascular surgery to reduce the need for allogeneic blood transfusion.
Zidovudine-induced anemia in AIDS patients
Anemia of chronic disease(e.g., rheumatoid arthritis), where the inappropriately low level of endogenous erythropoietin is a contributing factor.
Epoetin alfa is contraindicated in patients with:
- Uncontrolled hypertension
- Known hypersensitivity to mammalian cell-derived products
- Known hypersensitivity to albumin (human).
Dosage and Administration
Dosage in anemia of chronic renal failure
Erypoietin® may be given as an IV or SC injection.
In patients on hemodialysis, Erypoietin® is usually administered as an IV bolus three times weekly using the venous line at the end of the dialysis procedure to avoid the need for additional venous access.
Prior to and during Erypoietin® therapy, the patient’s iron stores (transferring saturation and serum ferritin) should be evaluated.
Transferrin saturation should be at least 20% and ferritin should be at least 100ng/ml. Virtually all patients will eventually require supplemental iron.
The starting dose of Erypoietin® in the range of 50-100 units / Kg 3 times weekly is safe and effective.
The dosage must be individualized to maintain the hematocrit within the suggested target range (30-36%) which may be expanded – at the physician’s decision- to achieve maximal benefit.
A period of 2-6 weeks is required to elicit a clinically significant change in hematocrit following any dose adjustment.
Dose adjustment should not be more frequently than once a month (unless clinically indicated)
Following any dose adjustment, the hematocrit should be determined twice weekly for at least 2-6 weeks.
The dose is increased when:
- Hct does not increase by 5 to 6% points after 8 weeks of therapy.
- Hct is below suggested target range.
The dose is reduced when Hct approaches 36% or Hct increase by more than 4% points in any 2-week period.
The doses are temporarily withheld when the reduced dose does not stop the rise in hematocrit which exceeds 36%. This is until the hematocrit begins to decrease, then therapy should be reinitiated at a lower dose.
The maintenance dose of Erypoietin® should be individually titrated for both patients on dialysis and patients not on dialysis.
If the hematocrit remains below or falls below the suggested target range, iron stores should be re-evaluated:
If transferring saturation is less than 20% supplemental iron should be administered.
If transferring saturation is greater than 20% the dose of Erypoietin® may be increased.
Most patients respond to epoetin alfa with clinically significant increase in hematocrit and virtually become transfusion-independent within approximately 2 months of initiation of therapy with epoetin alfa.
If a patient fails to respond or to maintain a response, other causes can be considered and investigated.
Dosage in Anemia of cancer patients
The starting dose of Erypoietin® is 150 units/kg SC three times weekly.
The dose of Erypoietin® is increased up to 300 units/kg three times weekly, if the response is not satisfactory in increasing hematocrit after 8 weeks of therapy.
If there is no satisfactory response to this dose, it is unlikely to have a response to higher doses of epoetin.
The dose of Erypoietin® is reduced when the initial dose induces a very rapid increase in hematocrit i.e. of more than 4% points in any 2-week period.
The dose of Erypoietin® is withheld if the hematocrit exceeds 40% until the hematocrit falls to 36%. Then Erypoietin® is resumed at a dose reduced by 25%.
General: Headache, dizziness, fever, hot flushes, malaise, flu-like syndrome (arthralgia, myalgia), bitter taste and hyperkalemia may occur occasionally.
Allergic reactions: There have been no reports of serious allergic reactions or anaphylaxis associated with epoetin administration. There has been no evidence for development of antibodies to epoetin in patients tested to date. Nevertheless, if an anaphylactoid reaction occurs, Erypoietin® should be immediately discontinued and appropriate therapy initiated. Skin rashes and uriticaria may be rarely observed and when reported they are mild and transient.
In chronic renal failure patients: Erypoietin® is generally well tolerated. The adverse events that may occur be frequent sequelae of CRF and not necessarily attributable to Erypoietin® therapy:
Hypertension: Increases in blood pressure can occur often during the first 90 days of therapy. The hypertensive adverse event seems to occur more frequently in patients on dialysis with a faster rate of rise of hematocrit.
Seizures: Seizures may occur during the first 90 days of therapy.
Thrombotic events: Clotting of the vascular access (A-V shunt) can occur in dialysis patients on epoetin, especially in patients who had clinically evident ischemic heart disease or congestive heart failure.
Other thrombotic events can occur as myocardial infarction, cerebral vascular accident, transient ischemic attack and pulmonary embolism. These vascular ischemic events were increased in patients targeted to a Hct of 42%.
Erypoietin®, as any parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Any vial exhibiting particulate matter or discoloration should not be used.
General: The parenteral administration of any biologic product should be attended by appropriate precautions in case allergic or other adverse reactions occur.
Erypoietin® and pregnancy : Erypoietin® should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.
Erypoietin® and nursing mothers : It is not known whether epoetin is excreted in human milk. Therefore, caution should be exercised when Erypoietin® is administered to a nursing mother.
Despite exacerbation of porphyria has been observed rarely in CRF patients treated with epoetin, Erypoietin® should be used with caution in patients with known porphyria.
In CRF patients, hematocrit should be measured twice a week and once a week in other indications until being stabilized, then to be measured periodically.
Prior to and during Erypoietin® therapy, the patient’s iron status including transferring saturation and serum ferritin should be evaluated. Virtually all patients will eventually require adequate iron supplementation throughout the course of therapy in order to support erythropoiesis.
If the patient fails to respond or maintain a response to doses within the recommended dosing range, the following etiologies should be considered and evaluated:
- Iron deficiency
- Occult blood loss
- Underlying infectious, inflammatory or malignant processes
- Underlying hematologic diseases (thalassemia, refractory anemia, or other myelodysplastic disorders)
- Vitamin deficiencies: folic acid or vitamin B12
- Aluminium intoxication
- Osteitis fibrosa cystica
Carcinogenic potential of epoetin has not been evaluated. Epoetin does not induce bacterial gene mutation, chromosomal aberrations in mammalian cells, micronuclei in mice.
Erypoietin® in chronic renal failure not on dialysis
Blood pressure and hematocrit should be monitored frequently.
Renal function and fluid and electrolyte balance should be closely monitored as an improved sense of well-being may obscure the need to initiate dialysis in some patients.
Sufficient time (2-6 weeks) should be allowed to determine a patient’s responsiveness to a dosage of Erypoietin® before adjusting the dose.
The guidelines for dose and frequency of dose adjustments (see dosage) should be properly followed to avoid reaching the target hematocrit (30-36%) too rapidly. Moreover, a rapid increase in hematocrit (more than 4% points in any 2 week period) can be associated with exacerbation of hypertension.
Erypoietin® with dialysis
The resulting increase in hematocrit with epoetin therapy did not appear to adversely affect dialysis function or the efficiency of high flux hemodialysis.
During hemodialysis, patients treated with Erypoietin® may require increased anticoagulation with heparin to prevent clotting of the artificial kidney.
Erypoietin® with cancer patients
Although hypertension associated with a significant increase in hematocrit is rarely noted in patients treated with epoetin, blood pressure should be monitored carefully particularly in patients with an underlying history of hypertension or cardiovascular disease.
Erypoietin® is a growth factor that mainly stimulates red cell production. However, the possibility that Erypoietin® can act as a growth factor for any tumor type, particularly myeloid malignancies, can not be excluded.
There is no evidence of interaction of epoetin alfa with other drugs.
Preparation and administration of Erypoietin®
Erypoietin® is a preservative-free, single dose vial of 1 ml. Therefore, use one dose per vial and do not re-enter the vial.
Erypoietin® is available as preservative-free, single-dose vial containing 1 ml of epoetin alfa.
- Each 1ml contains 2000 or 4000 I U
- Erypoietin® vial is available in pack of 1 vial.
Storage: Erypoietin® should be stored at 2-8 ºC, it should not be frozen or shaken.
Keep all medicaments out of reach of children
Product of: AMOUN PHARMACEUTICAL CO. El-Obour City, Cairo, Egypt. ATC Code: B03XA01 .