Hemactiv Adverse Reactions

Studies indicate that recombinant human erythropoietin is generally well tolerated.
The most frequently reported adverse event to the treatment with erythropoietin alpha is increased blood pressure or worsening of preexisting hypertension. Monitoring of blood pressure, especially at the beginning of treatment is recommended. Hypertensive crisis with encephalopathy, which requires immediate medical attention and intensive care in patients with low or normal blood pressure has been reported during treatment with erythropoietin. It is advised to pay special attention to sudden stabbing migraine-like headaches as a possible warning signal.
In patients receiving erythropoiesis-stimulating agents an increased incidence of thrombotic vascular events has been observed.
Hypersensitivity reactions such as rash (including urticaria), anaphylactoid reactions and angioedema have also been reported.
Other most frequently reported events (≥10%) in clinical trials are diarrhea, nausea, vomiting, pyrexia, chills, injection site reactions, headache, and flu-like syndrome (especially at the start of treatment).
Adverse events occurred in more than 5% of patients with chronic renal failure participating in several clinical trials were hypertension, thromboembolism (mainly in patients on dialysis), rash, diarrhea, nausea, vomiting, arthralgia, limbs pain, muscle aches, bone pain, chills, peripheral edema, injection site reactions, flu-like syndrome, pyrexia, hyperkalemia, dizziness, upper respiratory tract infections, cough. In more than 5% of patients with anemia due to cancer chemotherapy treated with erythropoietin in various clinical trials, nausea, vomiting, diarrhea, pyrexia, peripheric edema, headache, cough, embolism and thrombosis, myalgia, arthralgia, stomatitis, cough, weight loss, leukopenia, bone pain, rash, hyperglycemia, insomnia, headache, depression, dysphagia, hypokalemia, and thrombosis and embolism have been described.
Adverse reactions occurred in ≥5% of surgical patients in clinical trials were: nausea, vomiting, diarrhea, chills, itching, injection site reactions, pyrexia, peripheral edema, headache, cough, embolism and thrombosis, deep venous thrombosis, hypertension.
Allergic reactions: There were no reports of serious allergic reactions or anaphylaxis associated with the administration of recombinant human erythropoietin. In patients with chronic renal failure rash and urticaria of moderate and transient nature were rarely observed.
However, if an anaphylactic reaction occurs, therapy with recombinant human erythropoietin should be immediately discontinued and appropriate therapy should be initiated. In HIV-infected patients treated with zidovudine developing urticarial reactions, this event was related to immunosuppression induced by HIV or prior exposure to blood products.
Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity. In patients receiving recombinant human erythropoietin, erythropoietin neutralizing antibodies, in association with recombinant human erythropoietin or severe anemia with or without other cytopenias have been reported.
When reported, the incidence of antibody formation is high depending on the sensitivity and specificity of the assay.
Additionally, the observed incidence of positive antibodies (including neutralizing antibodies) in an assay may be influenced by several factors including assay methodology, sampling, sample collection time, concomitant medications, and underlying disease.
For these reasons the comparison of the incidence of cross-antibodies within this class (erythropoietic proteins) may be an unclear data.
Hypertension: Up to 80% of patients with chronic renal failure have a history of hypertension. The blood pressure may rise during therapy with recombinant human erythropoietin in patients with chronic renal failure (on dialysis or not). During the early phase of treatment when the hematocrit is increasing, approximately 25% of patients on dialysis may require antihypertensive therapy.
Seizures: In patients with chronic renal failure, the relationship between therapy with recombinant human erythropoietin and seizures is uncertain. However, it seems to have a higher rate of seizures during the first 90 days of therapy (occurring in approximately 2.5% of patients), when compared with subsequent periods.
In clinical trials with recombinant human erythropoietin in HIV-infected patients treated with zidovudine, 10 patients experienced seizures. In general, these events seem to be related to an underlying disease such as meningitis or brain neoplasm and not to therapy with recombinant human erythropoietin.
Thrombotic events: During hemodialysis, patients treated with recombinant human erythropoietin may require an increase in heparin anticoagulation. A statistical link between increased hematocrit and rate of thrombotic events has not been established. In patients with chronic renal failure (on dialysis or not) thrombotic events such as myocardial infarction, stroke, and transient ischemic attack have occurred.
Patients with chronic renal failure: In all clinical studies the administration of recombinant human erythropoietin was generally well tolerated, regardless of the route of administration.
Reported events occurred within several hours after administration of recombinant human erythropoietin were rare, mild and transient and included flu-like symptoms such as arthralgia and myalgia. In clinical studies with recombinant human erythropoietin in patients on dialysis, the most frequently reported adverse effects were: Hypertension; headache; tachycardia; nausea/vomiting; clot in vascular access; shortness of breath; hyperkalemia and diarrhea.
Other reported side effects were: Arthralgia; edema; fatigue; chest pain; skin reaction (at the site of administration); asthenia; vertigo; convulsion; stroke; transient ischemic attack, and myocardial infarction.
Patients with cancer on chemotherapy: In double-blind, placebo-controlled studies, although some statistically significant differences between patients treated with recombinant human erythropoietin and those treated with placebo were noted, the overall safety profile of recombinant human erythropoietin appears to be consistent with the process of the advanced cancer disease. The observed adverse effects were pyrexia; diarrhea; nausea; vomiting; edema; asthenia; fatigue; shortness of breath; paresthesia; upper respiratory infection; dizziness and chest pain.
The available data from tumor models in animals and measurements of proliferation of solid tumor cells from clinical biopsy specimens in response to recombinant human erythropoietin, suggest no enhancement of tumor growth. However, as a growth factor, the possibility that human recombinant erythropoietin may enhance the growth of some tumors, particularly myeloid tumors, cannot be excluded.
HIV-infected patients treated with zidovudine: In double-blind, placebo-controlled studies there was no significant difference between treatment groups in the incidence of the events listed as follows: pyrexia, fatigue, headache, cough, diarrhea, rash, respiratory congestion, nausea, shortness of breath, asthenia, skin reaction (at the site of administration), vertigo.
Recombinant human erythropoietin was not associated with significant increases in opportunistic infections or mortality. The serum antigen levels seem not to increase. Preliminary data showed no increase in HIV replication in "in vitro" infected cell lines.
In post-marketing experience, pure red blood cells aplasia, which has been linked to anti-erythropoietin antibodies, was reported very rarely (<1/10,000).