Hemactiv Warnings

Cardiovascular and thrombotic events/increased mortality: An increase in thrombotic vascular events in patients receiving erythropoiesis stimulating agents such as Epo alpha has been observed. These include venous and arterial thrombosis and embolism (including some with fatal outcome), such as deep vein thrombosis, pulmonary embolism, retinal thrombosis and myocardial infarction. Additionally, strokes (including cerebral infarction, cerebral hemorrhage and transient ischemic attacks) have been reported.
An adequate weighing of benefit from treatment with erythropoietin on reported risks of thrombotic events, particularly in patients with previous risk factors, is suggested.
The hemoglobin concentration should also be monitored closely due to the potential risk of thromboembolic events when patients are treated and have Hb concentrations above the range of use.
Use in patients with cancer diagnosis: Erythropoietin is a growth factor that primarily stimulates red cell production. As with all growth factors, there is a concern about the possibility that they stimulate tumor growth. Controlled clinical studies have demonstrated the following: The use of erythropoiesis stimulating agents shortened the overall survival and increased deaths attributed to disease progression at 4 months in patients with advanced breast cancer, when administered to achieve a hemoglobin level between 12 mg/dL and 14 mg/dL.
Additionally, reduced locoregional control in patients with advanced tumors of head and neck treated with radiation therapy, when given hematopoiesis stimulants agents with a target of hemoglobin higher than 14 mg/dl was reported.
Another erythropoiesis stimulating molecule was shown to increase the risk of death when administered to achieve a hemoglobin level of 12 mg/dl in patients with active malignancy, receiving neither chemotherapy nor radiation therapy.
Considering the previously mentioned, the decision to administer the recombinant erythropoietin treatment should be based on the benefit-risk assessment with the participation of the patient, taking into account the specific clinical setting. Among the factors to be considered for the evaluation are the type of tumor and its stage, extent of anemia, life expectancy, the setting of treatment and the patient's opinion.
Hemactiv should only be administered to treat patients with cancer when anemia has appeared after concomitant chemotherapy. A level of hemoglobin of 12 mg/dL should not be exceeded.
Use in patients with chronic renal failure: In patients with chronic renal failure (CRF) a complete blood count (with hemoglobin concentration) should be performed regularly, until a stable level is achieved and periodically thereafter.
In patients with CRF the rate of increase in hemoglobin should be approximately 1 mg/dl and should not exceed 2 mg/dl to minimize the risk of hypertension. The dose should be reduced where hemoglobin approaches to 12 mg/dL.
In two clinical studies, patients with CRF experienced greater risk of death and serious cardiovascular events when erythropoiesis stimulating agents were administered and higher hemoglobin levels were reached.
Patients with CRF with insufficient response to colony-stimulating agents (deficient hemoglobin concentrations) may be at greater risk of cardiovascular events, including death, than other patients. Shunt thrombosis in patients on hemodialysis has been reported, especially in patients prone to hypotension or whose arteriovenous fistula has complications (e.g., stenosis, aneurysms, etc.). In these patients an early shunt inspection and thrombosis prophylaxis administering a drug such as acetylsalicylic acid is recommended.
In isolated cases, hyperkalemia has been observed, although the causality has not been established. In patients with chronic renal failure monitoring of serum electrolytes is required. If high or increased serum potassium level is observed, then in addition to appropriate treatment of hyperkalemia, the discontinuation of erythropoietin alpha until the serum potassium level has been corrected should be considered.
During therapy with erythropoietin an increase in the dose of heparin during hemodialysis due to the increased volume of the cell mass is often required. If heparinization is not optimal a potential blockage in the dialysis system may occur. Adjustment may be required to prevent the clogging of the extracorporeal circuit during hemodialysis. In some women with CRF, menses have restarted after therapy with EPO alpha, so the possibility of pregnancy should be discussed and the need for contraception should be evaluated. Based on the information available to date, correction of anemia with EPO alpha in adult patients with chronic renal failure not yet undergoing dialysis does not accelerate the rate of progression of renal failure.
Surgical patients included in an autologous pre-donation program: All warnings and special precautions associated with autologous pre-donation programs, especially those related to routine volume replacement, should be followed.
Patients scheduled for elective surgery: There is increased risk of postoperative thrombotic events in patients with hemoglobin greater than 13mg/dL.
In patients scheduled for elective surgery the cause of anemia should be determined and treated, if possible, before initiating treatment with recombinant erythropoietin. Thrombotic events can be a risk in this population, so they should be weighed carefully.
Hypertension: Blood pressure should be controlled before initiation of therapy with recombinant human erythropoietin and during treatment.
Patients with uncontrolled hypertension should not be treated with recombinant human erythropoietin (see Contraindications).
Blood pressure may increase during treatment of anemia with EPO. Seizures and encephalopathy have been observed.
Patients should be advised of the importance of compliance with antihypertensive therapy and dietary restrictions. If the blood pressure is difficult to control with the initial appropriate measures, may be necessary to reduce the dose of recombinant human erythropoietin or discontinue the therapy until the hemoglobin concentration begins to descend.
Seizures: Seizures in patients receiving recombinant human erythropoietin have occurred. Use cautiously in patients with epilepsy, a history of seizures, conditions associated with predisposition to seizure activity as central nervous system infections or brain metastases.
Pure red blood cells aplasia: Cases of red blood cells aplasia and severe anemia, with or without cytopenias, mostly associated with neutralizing antibodies to erythropoietin has been reported.
It has been reported predominantly in patients with pure red cell aplasia receiving erythropoietin subcutaneously. It was rarely reported after months or years of treatment with erythropoietin, there were also rare cases in patients with hepatitis C treated with ribavirin and interferon concomitantly to erythrocytes stimulating agents. The use of hematopoiesis-stimulating agents in patients with anemia associated with hepatitis C is not approved.
Any patient having decreased therapeutic response to erythropoietin should be evaluated for the etiology of loss of therapeutic effect, including typical causes of non-response. If no cause is identified, examination of bone marrow should be considered. If pure red blood cells aplasia is diagnosed, Hemactiv should be discontinued immediately and antibody detection should be considered.
If erythropoietin and other erythropoietic products antibodies are detected, erythropoietin should be discontinued permanently, and switching to another erythropoiesis stimulant agent should not be performed, as there maybe cross-reactive antibodies.