Eposis

Eposis

epoetin alfa

Manufacturer:

Daewoong Pharmaceutical

Distributor:

Leaderplus

Marketer:

Daewoong Pharmaceutical
Full Prescribing Info
Contents
Recombinant human erythropoietin alfa.
Description
Each 0.1 mL contains Recombinant human epoetin alfa 1,000 IU.
Indications/Uses
Eposis is indicated in symptomatic or transfusion requiring anaemia associated with chronic renal failure.
Dosage/Direction for Use
Route of administration: IV, SC.
Eposis is administered at an initial dose of 50 units/kg for 1-2 minutes three times a week. It can be given by either an intravenous or subcutaneous route. The dose increase is dependent upon the initial response. The dose increase is dependent upon the initial response. The dose can be increased, if necessary, by 25 units/kg in 4-week period. If hemoglobin is increased more than 2 g/dl at a dose of 50 units/kg, the frequency should be reduced to two times a week. To correct the anemia, the target concentration of hemoglobin is 10 g/ dl (30% as hematocrit). When the anemia is corrected, Eposis is given as a maintenance dose of 25 - 50 units/kg two or three times a week. The target range of hemoglobin is 10-12 g/dl. The patients with the treatment hemoglobin < 6 g/ dl need higher maintenance dose than the patients with pretreatment hemoglobin ≥ 8 g/ dl. And the dose may be adjusted according to the age of patients. The unit dose of Eposis should not be exceed of 200 units/kg, and the frequency should not be more than three 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 the patients are in aluminum intoxication or infected, delayed or diminished responses may be occurred. 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 per week have been shown to maintain 36 - 38% of hematocrit for more than six months.
Overdosage
The reaction for Eposis is different individuals according to the dose. When overdose, hypertension, erythrocytosis may occur. Venesection can be performed when erythrocytosis occur (Hemoglobin value is increased very excessively).
Contraindications
Eposis is contraindicated in patients with: Patients occurred pure red cell hypoplasia after treatment with epoetin products.
Known hypersensitivity to the drug or to other epoetin products.
Uncontrolled hypertension.
Known hypersensitivity to mammalian cell-derived products or Albumin (Human).
Special Precautions
Eposis should be administered with caution to the following patients: Patients with hypertension.
(Blood pressure may rise or hypertensive encephalopathy may occur during Eposis therapy.)
Patients with known history of a hypersensitivity to drugs.
Patients with known history of allergic reactions to drugs.
Patients with myocardial infarction, pulmonary infarction or cerebral embolus.
(It is reported that the density of the blood increased. Thromboembolism may be aggravated or occur. And hemocoagulation capacity can be increased when used autologous blood or after surgery, the enough observation is required.)
Patients with cerebral bleeding or premature infant with cerebral bleeding.
(Cerebral hemorrhage may be aggravated.)
Patients with ischemic vascular disease.
Patients with history of seizure.
Patients with epilepsy.
Patients with thrombocytosis.
Patients with chronic hepatic failure.
General Precautions: Eposis treatment should be limited in anemic patients with CRF less than 10g/dl of hemoglobin (30% as hematocrit) or cancer patients with serum epoetin less than 200mU/mL.
Eposis should not be used in patients with anemia from blood loss, hematocytopenia and aluminum intoxication. The deficiency of folic acid and vitamin B12 can decrease the effect of the Eposis.
Special monitoring of patient's history should be done to forecast shock or other responses. Low dosage should be allowed by intravenous route to determine a patient's responsiveness to the administration of Eposis before initiation the therapy or resumption after withholding.
During the Eposis 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 (more than 12g/ 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 Eposis, associated with a significant increase in hematocrit. Hematocrit increase may be occurred in case of discontinuation of the therapy. Blood pressure in patients treated with Eposis should be monitored carefully, particularly in patients with an underlying history of hypertension or cardiovascular disease. The dosage should be adjusted in patients with a fast rate of rise of hematocrit (greater than 4% in any two-week period) owing to the potential for an increased risk.
Seizures have occurred in patients with CRF participating in Eposis clinical trials. In patients on dialysis, there was a higher incidence of seizures during the first 90 days of therapy (occurring in approximately 2.5% of patients) as compared with later timepoints. Seizures also have occurred in cancer patients on chemotherapy. In double blind, placebo-controlled trials, 3.2% (N=2/63) of patients treated with Eposis and 2.9% (N=2/68) of placebo-treated patients had seizures. Seizures in 1.6% (N=1/63) of patients treated with Eposis occurred in the context of a significant increase in blood pressure and hematocrit from baseline values. However, both patients treated with Eposis also had underlying CNS pathology which may 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 eurologic symptoms should be monitored closely.
Since hyperkalemia may be occurred, the importance of compliance with dietary prescriptions should be reinforced.
It may be occurred shunt infarct or residual blood in dialysis kit, so, carefully monitored the blood circulation in shunt or dialysis kit.
In case of iron deficiency, adequate iron supplementation in order to support erythropoiesis should be done.
Eposis is a growth factor that primarily stimulates red blood cell production. However, the possibility that Eposis can act as a growth factor for any tumor type, particularly myeloid malignancies, cannot be excluded.
Rarely pure red cell aplasia (erythroblastopenic) was reported after treatment of this drug or epoetin drug for several months or years to the patients with chronic renal failure. These cases were normally related to the S.C, and Eposis may be administered to the patients with chronic renal failure by IV, if necessary. Most of the patients with pure red cell aplasia were observed the anti-body of epoetin. In case of the patients occurred the decrease of efficacy by sudden, the typical reasons (e.g. deficiency of Fe, Folic acid, or Vitamin B12, aluminum-poisoning, infection, or inflammation, hematozemia, and hemolyis) should be tested. If the cause didn't come out, marrow examination is considered. If pure red cell aplasia is diagnosed, then discontinue the drug immediately, and anti-epoetin test is considered. Anti-epoetin antibody is crossed with other epoetin agents, do not change to other drugs. Remove the cause of pure red cell aplasia, and perform the appropriate therapy.
Use in Children: The safety of the children is not established.
Use in the Elderly: Normally, the physiologic ability is decreased, and the cardiovascular diseases were combined in the elderly patients, so measure the blood pressure, concentration of the hemoglobin, or hetocridose for several times, and administration number should be controlled appropriately.
Use In Pregnancy & Lactation
In studies in female rats, there were decreases in body weight gain, delayed ossification, and increases of mortality when given in doses 20 times the 1week human dose.
Epoetin alfa has not shown any adverse effect at doses as high as 500 Unit/kg in pregnant rabbits (from day 6 to 18 of gestation).
Safety of the administration during pregnant is not established. So it is desirable not to administer in pregnant women or women of childbearing potential. But it should be given only if the benefits clearly outweigh any possible risk.
It is not known whether Eposis is excreted in human milk. Therefore, the administration should be avoided to nursing mother.
No adequate clinical experience in human pregnancy and lactation has been gained.
Adverse Reactions
Shock: Rarely shock may occur, so the observation should be taken. If the symptoms appear, the administration should be discontinued and an appropriate treatment should be taken.
Cardiovascular: Hypertension, thrombosis of blood vessel contact site such as fustula, sometimes palpitation may occur.
Hypertensive encephalopathy: As hypertensive encephalopathy (shows headache, conscious disorder, and seizures) and cerebral hemorrhage may occur, the drug should be administered cautiously with observation of the trends of blood pressure and hematocrit during the therapy.
Cerebral embolus: Cerebral embolus may occur, so full observation should be taken. If the symptoms appear, the administration should be discontinued and an appropriate treatment should be taken.
Skin: Sometimes, itching, skin rash, and decubitus may occur.
Liver: Elevation in AST, ALT, LDH, ALP, and total bilirubin may occur occasionally.
G.I: Occasionally, nausea vomiting, anorexia, diarrhea, and abdominal pain may occur.
Blood: Sometimes, leukocytosis, eosinophilia may occur. On occasion, granulocytopenia may occur in premature infant. Increased serum potassium, BUN, creatinine and uric acid have been reported occasionally. Rarely, thrombocytosis may occur. Rarely, pure red cell hypoplasia has been reported after treatment of epoetin products in chronic renal failure patients from several months to several years.
CNS: Sometimes headache, migraine, fatigue, chill, dizziness, fever, low fever, burning, general malaise may occur.
Others: Cerebral hemorrhage in the eyes, splenomegaly, nasal hemorrhage, edema, arthralgia, myalgia, bitter taste in mouth, tremor, and edema of eyelid may occur.
Eposis is generally well-tolerated. The adverse reactions reported are frequent sequela from patient's disease and are not necessarily attributable to Eposis therapy.
Chronic renal failure patients: In double-blind, placebo-controlled studies involving over 300 patients, the events reported in greater than 5% of patients treated with epoetin alfa were following. (See Table 1.)

Click on icon to see table/diagram/image

In the clinical studies in adult patients on dialysis (567 patients), the incidence of the most frequently reported adverse events were hypertension (0.75%), headache (0.40%), 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 events occurred at a rate of less than 0.10% events per patient per year. Events reported to have occurred within several hours of administration of epoetin alfa were rare, arthralgias and myalgias. In all studies analyzed to date, epoetin alfa administration was generally well-tolerated, irrespective of the route of administration.
Cancer patients: In double-blind, placebo-controlled studies of up to 3 months duration involving mild, and transient, and included injection site stinging in dialysis patients and flu-like symptoms such as 131 cancer patients, adverse events with an incidence>10% in either patients treated with epoetin alfa or placebo-treated patients were as indicated as follows. (See Table 2.)

Click on icon to see table/diagram/image

Although some statistically significant differences between patients being treated with epoetin alfa and placebo-treated patients were noted, the overall safety profile of epoetin alfa 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 927IU/kg, the adverse experience profile of epoetin alfa was consistent with the progression of advanced cancer. According to the basis for comparative data of survival rate, the rate of the patients with discontinuation of treatment by disease progress or adverse reactions (22% of test group, 13% of placebo group, p=0.25), the clinical result between test drug and placebo was similar. The useful data from animal tumor model, and the measurement result from clinical biopsy sample after administration showed that this drug does not promote the growth of the tumor. In spite of this, the possibility that this drug can promote the growth of the tumor such as myeloma cannot be excluded. To evaluate this fact, randomized, phase IV comparative clinical study is on-going. When compared with placebo group, the number of peripheral leukocyte was not changed by administration of the drug.
Drug Interactions
Cyclosporine is bonded with red blood cell, so when co-administered with this drug, monitor the blood concentration of cyclosporine, and dose adjustment of cyclosporine can be required according to the HCT increasing.
The efficacy can increase when it is co-administered with hematinic drug.
Caution For Usage
Caution for Application: Do not mix with other drugs when administration of this drug.
In case of the patients with hemodialysis, injection after hemodialysis is desirable.
Do not administer by IV infusion.
Storage
Store in a refrigerator (2-8 °C). Do not freeze.
Shelf-Life: 24 months from manufacturing date.
ATC Classification
B03XA01 - erythropoietin ; Belongs to the class of other antianemic preparations. Used in the treatment of anemia.
Presentation/Packing
Inj (pre-filled syringe) 3,000 IU/0.3 mL x 6's. 4,000 IU/0.4 mL x 6's. 5,000 IU/0.5 mL x 6's. 10,000 IU/mL x 6's.
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