Medication Adverse Event Alert

November 20, 2006

MEDICATION: Erythropoiesis Stimulating Agents
Epoetin alfa (marketed as Procrit, Epogen)
Darbepoetin alfa (marketed as Aranesp)

Dosage Forms:	injectible solution
Manufacturers:	Amgen (Epogen, Aranesp), Ortho Biotech (Procrit)
Strength:	epoetin alfa - 2000, 3000, 4000, 10000, 20000, 40000 units/ml

darbepoetin alfa - 25, 40, 60, 100, 150, 200, 300, 500mcg/ml
- 40mcg/0.4ml, 60mcg/0.3ml, 100mcg/0.5ml
- 150mcg/0.3ml, 200mcg/0.4ml, 300mcg/0.6ml

The following FDA Alert was released on November 16, 2006:
"FDA notified healthcare professionals of a newly published clinical study showing that patients treated with an erythropoiesis-stimulating agent (ESA) and dosed to a target hemoglobin concentration of 13.5 g/dL are at a significantly increased risk for serious and life threatening cardiovascular complications, as compared to use of the ESA to target a hemoglobin concentration of 11.3 g/dL. The "Correction of Hemoglobin and Outcomes in Renal Insufficiency" study, published November 16, 2006 in the New England Journal of Medicine, reports the adverse cardiovascular complications as a composite of the occurrence of one of the following events: death, myocardial infarction, hospitalization for congestive heart failure, or stroke. The study findings underscore the importance of following the currently approved prescribing information for Procrit, Epogen, and Aranesp, including the dosing recommendation that the target hemoglobin not exceed 12 g/dL."

Recommendations: The FDA Alert offers the following considerations for dosing and monitoring

"Physicians and other healthcare professionals should consider the following when using erythropoiesis stimulating agents:

• For all patients:
• Adhere to dosing to maintain the recommended target hemoglobin range of 10 to12 g/dL
• Measure hemoglobin twice a week for 2 to 6 weeks after any dosage adjustment to ensure that hemoglobin has stabilized in response to the dose change
• Decrease the dose of the ESA if the hemoglobin increase exceeds 1g/dL in any 2 week period
• For chronic renal failure (CRF) patients: Measure hemoglobin twice a week after initiating treatment until hemoglobin has stabilized
• For cancer patients and zidovudine-treated HIV patients: Measure hemoglobin once a week after initiating treatment until hemoglobin has stabilized
• For patients with a history of cardiovascular disease or hypertension: Closely monitor and control blood pressure