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.