Regulatory Focus™ > News Articles > Public Citizen Petitions FDA to Pull Some IV Solutions

Public Citizen Petitions FDA to Pull Some IV Solutions

Posted 08 February 2017 | By Zachary Brennan 

Public Citizen Petitions FDA to Pull Some IV Solutions

Consumer advocacy organization Public Citizen on Wednesday petitioned the US Food and Drug Administration (FDA) to immediately require the removal of hydroxyethyl starch (HES) intravenous (IV) solutions from the market because their risks outweigh their limited benefits and there are other, safer alternative IV solutions.

According to the petition, there are two main categories of IV solutions: crystalloid and colloid. Colloidal solutions, including HES, have largely the same content as crystalloid solutions but with added protein, starch or other large molecules in varying amounts.

The first HES solution was approved by FDA in 1972, and the petition notes that the “studies that supported its approval would likely have been deemed inadequate by today’s regulatory standards” as they were uncontrolled, with a small number of subjects and short periods of observation (less than 24 hours).

Following that approval, Public Citizen says serious safety concerns, related to coagulation interference and uptake in tissue, were reported. Later in the 1990s, evidence of renal abnormalities linked to HES solutions were also reported and by 2001, French guidelines on HES products had been expanded to include restrictions on dosing and treatment duration, among other measures.

The same year, a randomized trial showed a higher risk of acute kidney failure with HES solutions compared with gelatin-based IV fluids in patients with severe sepsis or septic shock.

And in August 2003, FDA added a warning to the labeling of one HES product, 6% hetastarch (Hespan), advising against using it in cardiopulmonary bypass surgery patients during the intraoperative and immediate post-operative periods because of an increased risk of coagulation abnormalities and bleeding in patients whose coagulation status is already impaired.

“Beginning in 2008, pivotal evidence began to emerge that even more definitively demonstrated the dangers of HES products,” the petition says. “Over the next four years, three large multicenter randomized clinical trials were published showing increased rates of renal failure, bleeding, and mortality associated with HES solution use in critically ill patients, including those with sepsis."

In 2012, the German Federal Institute for Drugs and Medical Devices requested that the European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) review the risks and benefits of using HES.

FDA also held a public workshop in September 2012 to discuss the HES products' risks and benefits, and after reviewing the data, like the EMA’s PRAC, concluded that HES solutions should not be used in critically ill patients, including patients with sepsis and those admitted to an intensive care unit. In June 2013, FDA announced a new boxed warning for all HES products about the risk of mortality and severe renal injury in certain patient populations.

But Public Citizen takes issue with FDA’s decision to keep HES solutions on the market and says the agency “did not offer sufficient justification” in its conclusion that the safety concerns seen in critically ill patients, including those with sepsis, had not been definitively shown to apply to surgical and trauma patients.

“The harms of HES products to patients outweigh their very modest fluid-saving effects, and these solutions should not be used in any patient population, including in surgical, trauma, and pediatric patients. HES products should be immediately removed from the market to prevent further harm to thousands of patients,” the petition concludes.

Public Citizen and two leading medical experts also sent a letter on Wednesday to EMA, urging a ban on HES solutions for the EU market because the solutions cause kidney failure, bleeding, and death and there are safer alternatives available.

Petition to FDA on HES Solutions


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