Espogen Special Precautions

Espogen should not be administered to following patients: This product or other erythropoietin preparations should not be administered to patients with history of Pure Red Cell Aplasia (PRCA) after treatment of erythropoietin preparations; Patients with hypersensitivity to this product or other erythropoietin preparations; Patients with uncontrolled hypertension; Patients with hypersensitivity to mammalian cell-derived product or human albumin.
Espogen should be cautiously administered to following patients: Patients with hypertension (Rise in blood pressure caused by erythropoietin administration has been recognized and hypertensive encephalopathy may arise; Patients with history of hypersensitivity to drug; Patients with predisposition to allergy; Patients with myocardial infarction, pulmonary infarction, cerebral infarction and so on, or patients with a chance of thromboembolism by the history of these (It has been reported that the blood viscosity increases with erythropoietin and thromboembolism may be exacerbated or induced. Also since there is a chance of acceleration in blood coagulation, especially in case erythropoietin is administered in order to store autologous blood and after operation, sufficient monitoring is required); Premature with ventricular hemorrhage and intracerebral hemorrhage (Cerebral hemorrhage may be exacerbated by erythropoietin administration).
General Precautions: Administration of Espogen should be limited to patients with renal anemia and cancer who are causing inconvenience in daily lives by being accompanied during anemia. Moreover, Espogen should be intended for patients with less than 10g/dl of hemoglobin (30% as hematocrit) in case of renal anemia and with not less than 200mU/ml of erythropoietin in case of cancers.
Espogen should not be administered to the other anemias such as dehematizing anemia, panhematopenia, aluminum storage disease, etc.
Sufficient examination by asking should be made to estimate responses like shock, etc. Moreover, in case administration is initiated or the first dose after discontinuation is administered, it is desirable that total volume be administered after confirming that abnormal response would not occur, by injecting little amount into vein.
During therapy, hemoglobin and hematocrit should be regularly monitored (about once a week in the early phase of administration, once per every other week in the maintenance phase) with sufficient care to avoid exceeding target range of hematopoiesis (≥12g/dl as hemoglobin or ≥36% as hematocrit). If it is recognized hematopoiesis required is exceeded, appropriate treatments including discontinuance of administration should be exceeded, appropriate treatments including discontinuance of administration should be made.
Since rise in blood pressure and hypertensive encephalopathy may occur, blood pressure and hematocrit should be increased slowly. Also, hematocrit may increase even after administration is discontinued, and sufficient monitoring should be made. Therefore, blood pressure in patients treated with Espogen, particularly patients with cardiovascular disease or patients with chance of hypertension should be carefully monitored. As in case of patients with rapid increase in hematocrit (increases by more than 4% in a 2-week period), excessive rise in hematocrit may exacerbate hypertension, dose should be adjusted.
Among patients with chronic renal failure (CRF) involved in clinical trials of Espogen, seizures have been observed, Higher rate of seizures (about 2.5% of patients) appeared in patients on dialysis during the first 90 days of therapy than later time period. In double-blind, placebo-controlled trials involving cancer patients on chemotherapy, seizures were reported in 3.2% (N = 2/63) of patients treated with Espogen and 2.9% (N = 2/68) of patients related with placebo. Seizures occurred in 1.6% (N = 1/63) of patients treated with Espogen, associated with significant increase in blood pressure hematocrit. However, both patients treated with Espogen had underlying CNS disease which might have been related to seizures. Therefore, blood pressure and previously known neurologic symptoms should be closely monitored in patients with Espogen.
Since the thrombotic events such as myocardial infarction, pulmonary embolism, cerebrovascular accident, or transient ischemic attack were observed during Espogen therapy, the patients with vascular disease should be carefully monitored.
Since hyperkalemia may be caused by Espogen administration, proper dietary management should be carried out.
Because shunt occlusion and residual blood within the hemodialysis kits may occur, hemokinetic volume in shunt or hemodialysis kits should be sufficiently monitored. In such case, appropriate measures such as reestablishment of shunt or increase of anticoagulant and so on should be taken.
Since iron is important to Espogen therapy, in case of iron deficiency, iron should be supplemented.
Espogen is primarily a growth factor of erythropoiesis. However, the possibility that Espogen may act as a growth factor of tumor type, particularly such as myeloid malignancies cannot be excluded.
Incidence of Pure Red Cell Aplasia (PRCA) has been rarely reported among CRF patients with administration of erythropoietin preparation from months to years. Since most cases of PRCA were found after administration of erythropoietin preparation via s.c. injection, the i.v. route is recommended for the injection of this product. Anti-erythropoietin antibody was found in most cases of PRCA patients. In cases of unexpected diminish of effect, the patients should be checked for the typical causes of non-response to this preparation such as iron, folic acid, or vitamin B12 deficiency, aluminum storage disease, infection or inflammation, exsanguinations, and hematolysis. For the case of PRCA with unknown causes, inspection of marrow should be considered. Diagnosis of PRCA should be followed by checking the presence of anti-erythropoietin antibody and discontinue of administration of this preparation. Since antibodies against an erythropoietin preparation show cross-reactivity to other erythropoietin preparations, any erythropoietin preparations should not be used. Other causes of PRCA should be checked for adequate treatments.
Precautions on application: Espogen should not be injected in conjunction with other drugs.
In case of patients on hemodialysis, it is recommendable Espogen be injected after hemodialysis. And it is desirable Espogen be injected slowly over more than 5 minutes to the patients with flu-like symptoms.
Espogen should not be administered by intravenous infusion.
Use in Pregnancy: Since the safety of Espogen in pregnant patients has not been established, it is desirable not to administer Espogen to women who are pregnant or have possibility to be pregnant. However, Espogen may be administered only if benefit for the treatment exceeds potential risk.
Use in Children: The safety of Espogen in children has not been established.
Use in the Elderly: Since physiological function is generally lowered and cardiovascular complications such as hypertension increase in geriatric patients, dosage and frequency should be appropriate adjusted by measuring blood pressure, hemoglobin, or hematocrit and so on.