FDA Orders New Boxed Warning for Hydroxyethyl Starch
- By BSTQ Staff
The U.S. Food and Drug Administration (FDA) has determined that hydroxyethyl starch (HES) solutions should not be used in critically ill adult patients, including patients with sepsis and those admitted to the intensive care unit (ICU). Data analyzed from numerous randomized controlled trials (RCTs), meta-analyses and observational studies document that HES use is associated with increased mortality and/or renal injury requiring renal replacement therapy (RRT), according to an FDA Safety Communication. The FDA has instructed manufacturers of all HES products* to add a Boxed Warning to the labeling, identifying these increased mortality and severe renal injury risks. Based on the totality of the evidence, the FDA considers these serious adverse outcomes in critically ill adult patients, including those with sepsis and those admitted to the ICU, to be HES class effects.
Health professionals are additionally advised to avoid use of HES products in patients with pre-existing renal dysfunction and to discontinue use of HES at the first sign of renal injury or coagulopathy. As the need for RRT has been reported up to 90 days after HES administration, renal function monitoring is recommended for 90 days in all patients.
The FDA has additionally ordered manufacturers of HES solutions to add new safety information to the Warning and Precautions Section of the package insert, identifying the risk of excess bleeding in patients undergoing open heart surgery in association with cardiopulmonary bypass. A meta-analysis of 18 RCTs reviewed by the agency found that increased bleeding occurred irrespective of molecular weight or degree of molar substitution. Again, the FDA indicated that it considers excess bleeding in this particular treatment setting to be a HES class effect.
*HESPAN (6% HES 450/0.7 in Sodium Chloride Injection; B. Braun Medical Inc.), Hetastarch (6%) in 0.9% Sodium Chloride Injection (generic equivalent to HESPAN; Teva Pharmaceuticals USA), HEXTEND (6% HES 450/0.7 in physiological solution; BioTime Inc.) and Voluven (6% HES 130/0.4 in normal saline; Fresenius Kabi USA, LLC).
