FDA Panel Discusses Role of Proton Pump Inhibitors in Infants

Emma Hitt, PhD

November 09, 2010

November 9, 2010 — A US Food and Drug Administration (FDA) Gastrointestinal Drugs Advisory Committee convened on November 5 to discuss the role of proton pump inhibitors (PPIs) in infants.

According to background material on the FDA Web site, the purpose of the meeting was to discuss results from clinical trials of PPIs in patients younger than 1 year; the meeting was conducted in response to a request by manufacturers under the Best Pharmaceuticals for Children Act and Pediatric Research Equity Act commitment.

Although they cast no vote, the committee agreed that when PPIs are approved for the treatment of symptomatic gastroesophageal reflux disease (GERD) in an adult population, they should also be studied separately in infants with GERD.

None of the 4 PPIs (esomeprazole, lansoprazole, pantoprazole, or omeprazole) has been approved for use in infants. The studies of esomeprazole, lansoprazole, and pantoprazole failed to demonstrate efficacy in infants, and the omeprazole trial, which lacked a control group, resulted in changing the label to indicate that toddlers older than 12 months could be given omeprazole.

In response to the question, "Is the pathophysiology of GERD the same in patients ages 1 month to less than 1 year and adults?" panelist Alexander Rakowsky, MD, from the Nationwide Children's Hospital in Columbus, Ohio, noted that there is probably a subclass of symptomatic infants who have a pH-induced problem that could be identical to adults, "but there is also a large percentage of infants who may have some other mechanism causing those symptoms — so a categorical 'no.' " The other panelist responses echoed this sentiment.

Regarding the population of premature infants, Richard Martin, MD, from the Rainbow Babies & Children's Hospital, in Cleveland, Ohio, noted that it is difficult to get the preliminary data needed to study these medications further. Furthermore, of the 40,000 very-low-birth-weight premature babies, "25% are going home on antireflux medication, and the problem is compounded because they tend to stay on these medications," he added.

"If we are going to use [these agents in infants,] let's at least do it in a way that is safe," said Michael Reed, PharmD, from the Children's Hospital Medical Center of Akron, in Ohio.

However, others on the panel stated that using these agents "off-label" in infants may help far more than they hurt, and the challenge of getting a specific indication in this setting may be unwarranted.

Panel chair Jean-Pierre Raufman, MD, from the University of Maryland School of Medicine in Baltimore, noted that 10 years ago, PPIs were considered absolutely safe, and now "we are seeing side effects such as changes in bone metabolism and intestinal bacterial flora," he said. "If you have drugs that are potentially harmful, and with a side effect profile that is not completely understood, then you would have to show efficacy in this age group before approving their use in these infants."

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