Data from both unpublished and published clinical studies suggest an increased risk of serious cardiovascular complications in patients with chronic renal failure and a possible effect on tumour progression in cancer patients, said the agency in a statement. It did concede that some of the results included cases where epoetins were used outside their approved indications or dosing recommendations.

Data from the studies are currently being carefully analysed by the EMEA's Committee for Medicinal Products for Human Use (CHMP), to determine whether updates of the product information will be required.

In the meantime, the EMEA is urging physicians to "exercise caution when considering raising haemoglobin concentrations above 12 g/dL" and ensure that epoetins are only used "strictly in accordance with their approved Summaries of Product".

Epoetins are primarily used for the treatment of anaemia in patients with chronic renal failure and in patients with non-myeloid malignancies receiving chemotherapy. Several big pharma firms have epoetins on the market, such as Amgen's Aranesp (darbepoetin alfa) and Epogen (epoetin alfa); Ortho Biotech's Eprex (epoetin alfa); and Roche's NeoRecormon (epoetin beta). 'Generic' or biosimilar drugmakers are also eyeing these lucrative products.

However, this is not the first instance that the safety of epoetins has been brought into question.

They were previously reviewed by the EMEA in 2004, which resulted in revised dosing recommendations for cancer patients undergoing chemotherapy. In addition, the product information for all epoetins, in all indications, was revised to include a harmonised warning on

possible stimulating effects on tumour progression, and a summary of the available evidence on survival and tumour progression.

The EMEA is not the only agency keeping a close eye on these products either. In November last year, the US Food and Drug Administration (FDA) issued an alert, which has since been updated in February and March, to provide new safety information for erythropoiesis-stimulating agents (ESAs) marketed in the US (Aranesp, Epogen, and Procrit, which is known as Eprex outside the US).

"Analyses of four new studies in patients with cancer found a higher chance of serious and life-threatening side effects and/or death with the use of ESAs. These research studies were evaluating an unapproved dosing regimen, a patient population for which ESAs are not approved, or a new unapproved ESA. In another study, patients scheduled for orthopedic surgery had a higher rate of deep venous thrombosis when treated with Procrit at the approved dose," said the FDA's public statement.

The agency said this new information is consistent with risks found in two clinical studies in patients with chronic renal failure treated with an unapproved regimen of an ESA that were reported in November 2006.

"All ESAs have the same mechanism of action. As a result, FDA believes these new concerns apply to all ESAs and is re-evaluating how to safely use this product class."

As a preliminary measure, the FDA and the manufacturers of the products have changed the full prescribing information for these drugs. The new product labelling includes a new boxed warning, updated warnings, and a change to the dosage and administration sections for all ESAs.