Safety of drotrecogin alfa (activated) in severe sepsis: data from adult clinical trials and observational studies.

Drotrecogin alfa (activated) (DrotAA), or recombinant human activated protein C, represents the only Food and Drug Administration-approved therapy for mortality reduction in adult patients with severe sepsis. Drotrecogin alfa (activated) has properties that address microvascular injury in severe sepsis through its direct effects on endothelial cells and leukocytes while also having antithrombotic and indirect profibrinolytic properties. Sepsis bundle and guideline implementation has been associated with improved survival and includes DrotAA administration in appropriate patients. Several DrotAA postapproval clinical studies have yielded additional outcome and safety data, better defining its benefit/risk profile. Bleeding is more common in DrotAA-treated patients; therefore, a careful assessment of bleeding risk and an understanding of the safety profile is required. This summary provides a detailed review of safety data and outcomes of patients treated with DrotAA in recent clinical studies enrolling more than 7000 adult patients.