General: In cancer patients and in chronic renal failure patients the most frequent adverse drug reaction during treatment with epoetin alfa is a dose-dependent increase in blood pressure or aggravation of existing hypertension.
Monitoring of the blood pressure should be performed, particularly at the start of therapy (see Precautions).
Other common adverse drug reactions observed in clinical trials of epoetin alfa are deep vein thrombosis, pulmonary embolism, seizures, diarrhoea, nausea, headache, influenza-like illness, pyrexia, rash, and vomiting. Influenza-like illness including headaches, arthralgia, myalgia, and pyrexia may occur especially at the start of treatment. Frequencies may vary depending on the indication (see table as follows).
Serious adverse drug reactions include venous and arterial thromboses and embolism (including some with fatal outcomes), such as deep venous thrombosis, pulmonary emboli, arterial thrombosis (including myocardial infarction and myocardial ischaemia), retinal thrombosis, and shunt thrombosis (including dialysis equipment). Additionally, cerebrovascular accidents (including cerebral infarction and cerebral haemorrhage) and transient ischaemic attacks have been reported in clinical trials of epoetin alfa. Aneurysms have been reported.
Hypersensitivity reactions, including cases of rash, urticaria, anaphylactic reaction, and angioneurotic oedema have been reported.
Hypertensive crisis with encephalopathy and seizures, requiring the immediate attention of a physician and intensive medical care, have occurred also during epoetin alfa treatment in patients with previously normal or low blood pressure. Particular attention should be paid to sudden stabbing migraine-like headaches as a possible warning signal.
Antibody-mediated pure red cell aplasia has been very rarely reported in < 1/10,000 cases per patient year after months to years of treatment with epoetin alfa (see Precautions).
The overall safety profile of epoetin alfa was evaluated in 142 subjects with chronic renal failure and in 765 subjects with cancer who participated in placebo-controlled, double-blind clinical registration trials.
Adverse drug reactions reported by ≥ 0.2% of epoetin alfa-treated subjects from these trials, additional clinical trials and from post-marketing experience are listed as follows by system organ class and frequency.
Frequencies are defined: Very common (≥ 1/10), Common (≥ 1/100, < 1/10), Uncommon (≥ 1/1,000, < 1/100), Rare (≥ 1/10,000, < 1/1,000), Very rare (< 1/10,000), Not Known - if the adverse drug reaction was not reported in the placebo-controlled, double-blind clinical registration trials or when the frequency cannot be estimated from other available data.
Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. (See Table 2.)
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Chronic renal failure patients: In chronic renal failure patients, haemoglobin levels greater than 12 g/dl may be associated with a higher risk of cardiovascular events, including death (see Precautions).
Shunt thromboses have occurred in haemodialysis patients, especially in those who have a tendency to hypotension or whose arteriovenous fistulae exhibit complications (e.g. stenoses, aneurysms, etc.) (see Precautions).
Cancer patients: An increased incidence of thromboembolic events has been reported in cancer patients receiving ESAs, including epoetin alfa (see Precautions).
Surgery patients: In patients scheduled for major elective orthopaedic surgery, with a baseline haemoglobin of 10 to 13 g/dl, the incidence of thrombotic/vascular events (most of which were deep vein thrombosis) in the overall patient population of the clinical trials appeared to be similar across the different epoetin alfa dosing groups and placebo group, although the clinical experience is limited.
Moreover, in patients with a baseline haemoglobin of > 13 g/dl, the possibility that epoetin alfa treatment may be associated with an increased risk of postoperative thrombotic/vascular events cannot be excluded.
Zidovudine-treated HIV-infected patients: Allergic reactions and urticaria have been reported within 48 hours of epoetin alfa administration. There have also been reports of seizures in patients treated conjunctly with zidovudine and erythropoietin. These conditions appear to be related to underlying disease such as meningitis or cerebral neoplasia and not with epoetin alfa treatment.