Epokine

Epokine

epoetin alfa

Manufacturer:

CJ Corp

Distributor:

Macropharma Corp
Full Prescribing Info
Contents
Epoetin-α.
Description
Epokine also contains human serum albumin 2.5 mg/mL as stabilizer.
Action
Epoetin-α is a recombinant human erythropoietin, type a. It is a glycoprotein hormone which stimulates the division and differentiation of committed erythroid progenitors in the bone marrow. Epoetin-α frees the same biological and immunological effects as endogenous erythropoietin and contains the identical amino acid sequence of isolated neutral erythropoietin.
Indications/Uses
Treatment of Anemia in Chronic Renal Failure: Treatment of anemia associated with chronic renal failure, including patients on dialysis and not on dialysis. To elevate or maintain red blood cell level and to decrease the need for transfusions.
Treatment of Anemia in Cancer Patients on Chemotherapy: To elevate the red blood cell level to donate autologous blood. To prevent from reducing of hemoglobin for patients scheduled for major surgery and who are not able to participate in an autologous blood donation program eg, low hemoglobin concentration, patients scheduled for major surgery, females who need >4 units of blood and males who need >5 units of blood, in case of immediate need for autologous blood donation before surgery.
Dosage/Direction for Use
Chronic Renal Failure (CRF) Patients: Initial Dose: 60 units/kg for 1-2 min 3 times a week, IV or SC for patients with CRF who are not on dialysis. The dose increase is dependent upon the initial response. The dose can be increased if necessary by 25 units/kg in a 4-week period. If hemoglobin is increased >2 g/dL at a dose of 50 units/kg, the frequency should be reduced to twice a week. To correct the anemia, the target concentration of hemoglobin is 10 g/dL (30% as hematocrit). When anemia is corrected, epoetin-α is given at a maintenance dose of 25-50 units/kg 2 or 3 times a week. The target range of hemoglobin <6 g/dL needs higher maintenance dose than those patients with pre-treatment hemoglobin >8 g/dL. And the dose may be adjusted according to the age of the patient. The unit dose of epoetin-α should not exceed 200 units/kg, and the frequency should not be more than 3 times a week. Prior to initiation of therapy or during the therapy, the patient's iron stores should be evaluated; if necessary, iron should be supplied. If patients are in aluminum intoxication or infected, delayed or diminished responses may occur. In patients with CRF not on dialysis, the maintenance dose must also be individualized according to the severity of anemia or age, however, the dose of 70-150 units/kg/week have been shown to maintain 36-38% of hematocrit for >6 months.
Cancer Patients on Chemotherapy: Recommended Initial Dose: 150 units/kg SC 3 times a week. If the response is unsatisfactory after 8 weeks of therapy, the dose can be increased up to 300 units/kg 3 times a week. If patients have not responded satisfactorily to an epoetin-α dose of 300 units/kg 3 times a week, it is unlikely that they will respond to higher doses of epoetin-α. If the hematocrit is >40%, the dose of epoetin-α should be withheld until it falls to 36%. The dose should be reduced by 25% when treatment is resumed or the dose is titrated to maintain the desired hematocrit. If the initial dose includes a very rapid hematocrit response (eg, an increase of >4% points in any 2-week period), the dose should be reduced. In general, patients with lower baseline serum epoetin levels responded more vigorously to Epokine than patients with higher epoetin levels. Although no specific serum epoetin level can be stipulated which patients would be unlikely to respond to Epokine therapy of patients with grossly elevated serum epoetin levels >200 mU/mL, is not recommended. The hematocrit should be monitored on a weekly basis in patients receiving Epokine therapy until hematocrit becomes stable.
Program: Prior to major surgery, it is recommended to take autologous blood twice a week for 3 weeks. Based on previous studies, epoetin-α 150-300 units/kg IV can be given twice a week for 3 weeks to elevate the red blood levels. The recommended maximum dose to promote erythropoiesis is 600 units/kg IV, twice a week for 3 weeks. The concentration of hemoglobin should be controlled weekly for patients who are expected to require >4 units of blood with pre-treatment of hemoglobin >11 g/dL (<6.8 mmol/L), or the patients to undergo surgery within 1-3 weeks.
Iron Supply: All surgery patients being treated with Epokine should receive adequate iron supply (eg, 200 mg of iron preparations per day orally) throughout the course of therapy in order to support erythropoiesis and avoid depletion of iron stores. Iron supply should be initiated as soon as possible, several weeks before blood transfusion.
Overdosage
The dose response of Epokine depends upon the conditions of the patient. In case of overdosage, hypertension may occur. If polycythemia is of concern, phlebotomy may indicate the decrease of hematocrit.
Contraindications
Known hypersensitivity to Epokine or to other erythropoietin products. Uncontrolled hypertension, known hypersensitivity to mammalian cell-derived products or albumin (human).
Warnings
Epoetin-α treatment should be limited in anemic patients with CRF <10 g/dL of hemoglobin (30% as hematocrit) or cancer patients with serum <200 mU/mL.
Epoetin-α should not be used in patients with anemia from blood loss, hematocytopenia and aluminum intoxication.
Special monitoring of patient's history should be done to forecast shock or other responses. Low dosage should be allowed by IV route to determine a patient's responsiveness to the administration of epoetin-α before the initiation of therapy or resumption after withholding.
During the epoetin-α therapy, hemoglobin concentration or hematocrit should be observed periodically (once a week at initial therapy, biweekly at maintenance therapy). Special caution should be taken not to result in excessive erythropoiesis (>12 g/dL of hemoglobin or 36% of hematocrit). In case of excessive erythropoiesis, withholding of the drug or appropriate treatment should be taken.
Hypertension and hypertensive encephalopathy have been reported in patients treated with epoetin-α, associated with a significant increase in hematocrit. Hematocrit increase may occur in case of discontinuation of the therapy. Blood pressure in patients treated with epoetin-α should be monitored carefully, particularly in patients with a fast rise of hematocrit (>4% in any 2-week period) owing to the potential for an increased risk.
Seizures have occurred in patients with CRF participating in Epokine clinical trials. In patients on dialysis, there was a high incidence of seizures during the first 90 days of therapy (occurring in approximately 2.5% of patients) as compared with later time points. Seizures have also occurred in cancer patients on chemotherapy. In double-blind, placebo-controlled trials, 3.2% (N=2/63) of patients treated with Epokine and 2.9% (N=2/68) of placebo-treated patients had seizures. Seizures in 1.6% (N=1/63) of patients treated with Epokine occurred in the context of a significant increase in blood pressure and hematocrit from baseline values. However, both patients treated with Epokine also had underlying CNS pathology which have been related to seizure activity. Given the potential for an increased risk of seizures during the therapy, blood pressure and the presence of premonitory neurologic symptoms should be monitored closely.
Thrombotic events may occur eg, myocardial infarction, pulmonary embolism, cerebrovascular accident or ischemic attack. The patients with vascular disease should be monitored cautiously.
Since hyperkalemia may occur, the importance of compliance with dietary prescriptions should be reinforced.
Shunt infarct or residual blood in dialysis kit may occur, so careful monitoring of blood circulation in shunt or dialysis kit is a must.
In case of iron deficiency, adequate iron supplementation is very important in order to support erythropoiesis.
Epoetin-α is a growth factor that primarily stimulates red blood cell production. However, the possibility that epoetin-α can act as a growth factor for any tumor type, particularly myeloid malignancies, cannot be excluded.
Use in pregnancy: The safety of Epokine in pregnant women has not been established. It should be used in pregnancy only if potential benefit justifies the risk.
Use in children: Safety of Epokine in children has not been established.
Use in the elderly: When Epokine is administered to geriatric patients, dosage and frequency should be controlled on the basis of the observed blood pressure, hemoglobin concentration or hematocrit.
Special Precautions
Epoetin-α should be administered with caution to the following patients: Patients with hypertension (blood pressure may rise or hypertensive encephalopathy may occur during epoetin-α therapy), known hypersensitivity to drugs or history of allergic reactions to drugs, myocardial infarction, pulmonary infarction or cerebral embolus and cerebral bleeding or premature infant with cerebral bleeding.
Adverse Reactions
Shock: As shock has been reported, full observation should be taken. If the symptoms appear, the administration should be discontinued and an appropriate treatment should be taken.
Cardiovascular: Hypertension, thrombosis of lacrimal duct or A-V shunt and tachycardia have been reported rarely.
Hypertensive Encephalopathy: As hypertensive encephalopathy (shows headache, conscious disorder and seizures) and cerebral hemorrhage have been reported occasionally, the drug should be administered cautiously with observation of the trends of blood pressure and hematocrit during therapy.
Cerebral Embolus: As cerebral embolus has been reported, full observation should be taken.
Skin: Itching, skin rash and decubitus have been reported.
Liver: Elevation in AST, ALT, LDH, AL-P and total bilirubin may occur occasionally.
Blood: Leukocytosis, eosinophilia have been reported and granulocytopenia may occur in premature infants. Increased serum kalium, BUN, creatinine and uric acid have been reported.
GI: Nausea, vomiting, anorexia, diarrhea and abdominal pain may occur.
Others: Cerebral hemorrhage in the eyes, splenomegaly, nasal hemorrhage, edema, headache, dizziness, fever, fatigue, arthralgia, myalgia, bitter taste in the mouth, tremor and edema of eyelid may occasionally be associated with epoetin-α therapy.
Studies analyzed to date indicate that epoetin-α is generally well tolerated. The adverse reactions reported are frequent sequelae from patient's disease, and are not necessarily attributable to epoetin-α therapy.
Chronic Renal Failure Patients: In double-blind, placebo-controlled studies involving >300 patients with CRF, the reactions reported in >5% of patients treated with Epokine during the blinded phase were: (See Table 1.)

Click on icon to see table/diagram/image

In the epoetin-α studies in patients on dialysis (N=567), the incidence of the most frequently reported adverse reactions were: Hypertension (0.75%), headache (0.4%), tachycardia (0.31%), nausea/vomiting (0.26%), clotted vascular access (0.25%), shortness of breath (0.14%), hyperkalemia (0.11%) and diarrhea (0.11%). Other reported reactions occurred at a rate of <0.1% of reactions per patient per year. Reactions reported to have occurred within several hours after administration of Epokine were rare, mild and transient, and included flu-like symptoms eg, arthralgias and myalgias. In all studies analyzed to date, Epokine administration was generally tolerated, irrespective of the route of administration.
Cancer Patients on Chemotherapy: In double-blind, placebo-controlled studies of up to 3-month duration involving 131 cancer patients, adverse reactions with incidence >10% in either patients treated with Epokine or placebo-treated patients are shown in Table 2: (See Table 2.)

Click on icon to see table/diagram/image

Although some statistically significant differences between patients treated with Epokine and placebo-treated patients were noted, the overall safety profile of Epokine appeared to be consistent with the disease process of advanced cancer. During double-blind and subsequent open-label therapy in which patients (N=72) were treated for up to 32 weeks with doses as high as 927 units/kg, the adverse reaction profile of Epokine was consistent with the progression of advanced cancer. Based on comparable survival data and on the percentage of patients treated with Epokine and placebo-treated patients who discontinued therapy due to death, disease progression or adverse reactions (22% and 13%, respectively; p=0.25), the clinical outcome in patients treated with Epokine and placebo-treated patients appeared to be similar. Available data from animal tumor models and measurement of proliferation of solid tumor cells from clinical biopsy specimens in response to epoetin-α suggest that Epokine does not potentiate tumor growth. Nevertheless, as a growth factor, the possibility that Epokine may potentiate growth of some tumors, particularly myeloid tumors, can not be excluded. A randomized phase IV study is currently ongoing to further evaluate this issue. The mean peripheral white blood cell count was unchanged following Epokine therapy compared to the corresponding value in the placebo-treated group.
Drug Interactions
Epokine is potentiated by hematinic agents.
Caution For Usage
Do not dilute or administer in conjunction with other drug solutions.
Administer Epokine after dialysis in patients on dialysis and slowly inject for up to 5 min longer in patients with flu-like symptoms.
Epokine should not be administered by IV infusion.
Storage
Store at 2-8°C. Protect from light.
Shelf-Life: 24 months.
ATC Classification
B03XA01 - erythropoietin ; Belongs to the class of other antianemic preparations. Used in the treatment of anemia.
Presentation/Packing
Inj (pre-filled syringe, sterile, colorless solution) 2000 IU/0.5 mL x 1's. 4000 IU/0.4 mL x 1's. 10,000 IU/mL x 1's.
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