United States of America - The manufacturer of drotrecogin alfa (activated) (Xigris®) has communicated new safety information on drotrecogin alfa, a biological therapeutic product indicated for the treatment of adult patients with severe sepsis who are at high risk of death. The warning is based upon exploratory analyses of the ADDRESS clinical trial database and subsequent reanalysis of the PROWESS (Phase III registration) clinical trial database.

Among the small number of patients enrolled in PROWESS with single organ dysfunction and recent surgery (surgery within 30 days prior to study treatment) all-cause mortality was numerically higher in the drotrecogin alfa group compared to the placebo group.

In a preliminary analysis of the subset of patients with single organ dysfunction and recent surgery from a separate, randomized, placebo-controlled study (ADDRESS) of septic patients at lower risk of death, all-cause mortality was also higher in the drotrecogin alfa group. Patients with single organ dysfunction and recent surgery may not be at high risk of death and therefore may not be among the indicated population. Drotrecogin alfa should be used in these patients only after careful consideration of the risks and benefits.

This observation underscores the importance of accurate severe sepsis diagnosis and assessment of risk of death when considering patients for drotrecogin alfa treatment.

Reference: Communication from Ely Lilly on http://www.fda.gov/medwatch.