Off-Label Use of Aranesp Linked to Increased Mortality Risk

Yael Waknine


February 20, 2007

February 20, 2007 — A potential increased mortality risk is associated with unlabeled use of erythropoiesis-stimulating agents (ESAs) in anemic cancer patients not currently receiving chemotherapy, according to a notice from the US Food and Drug Administration (FDA).

The warning was based on data from a randomized phase 3 study of 989 patients showing that use of darbepoetin alfa injection ( Aranesp
, made by Amgen, Inc) in this setting was linked to an increased risk for death compared with placebo at 4.3-month follow-up (hazard ratio = 1.25; 95% confidence interval, 1.04 - 1.51). Moreover, no reduction was observed vs placebo with respect to transfusion requirements.

The study findings may apply to other ESAs such as epoetin alfa ( Epogen
, made by Amgen; Procrit, made by Ortho Biotech) according to an alert sent Friday from MedWatch, the FDA's safety information and adverse event reporting program.

When using ESAs for approved indications, healthcare professionals are reminded to adhere to dosing recommendations for achieving target hemoglobin levels not exceeding 12 g/dL.

The FDA advises that hemoglobin be measured twice weekly for 2 to 6 weeks in all patients receiving adjusted ESA doses; dose reductions are indicated if the hemoglobin rate of increase exceeds 1 g/dL during any 2-week period.

For zidovudine-treated HIV
patients and those with chronic renal failure
(CRF) receiving initial treatment, hemoglobin should be measured once and twice weekly, respectively, until levels have stabilized. Blood pressure should be closely monitored and controlled in patients with a history of cardiovascular disease or hypertension

Darbepoetin alfa and epoetin alfa are indicated for the treatment of CRF-related anemia
and chemotherapy-related anemia in patients with nonmyeloid malignancies. An intravenous route of administration is recommended for patients on hemodialysis.

Epoetin alfa is also indicated for the treatment of anemia in zidovudine-treated HIV patients and to reduce the risk of allogenic blood transfusion in surgery patients. ESAs are not indicated for the treatment of anemia in cancer patients not receiving chemotherapy.

Adverse events potentially related to the use of ESAs should be reported to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at
, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787. 


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