Author Archives: eamech

Explosion of PPI Use in Young Children

Members of the FDA’s Pediatric Advisory Committee were surprised by the exponential increase in proton pump inhibitor (PPI) prescriptions dispensed for young children over the past few years, after hearing an FDA presentation on pediatric adverse event reports for PPIs at a meeting last month. But what really struck them was news that infants under age 1 had the steepest increase of all.   

Photo courtesy bbaunach at Creative Commons (flickr)

In her presentation, Dr. Amy Taylor, a medical officer on the pediatric and maternal health staff in the FDA’s Office of New Drugs, presented outpatient prescription data obtained from Vector One for PPIs in children and adolescents between 2002 and 2009.  It showed that for children from birth through age 17, the number of prescriptions increased from 875,000 in 2002 to 2.6 million  in 2009–a threefold increase.  The number of patients prescribed PPIs in this age group increased in the same proportion, from 332,000 in 2002 to 885,000 in 2009. 

Now here are the really striking numbers: In children under age 1, PPI prescriptions grew from 37,000 to 403,000 in the same period–an 11-fold increase. The number of patients in this age group prescribed a PPI increased from 18,000 to 145,000, an 8-fold increase. 

But none of the PPIs approved in the United States are approved for use in children younger than 1 year. (Esomeprazole, lansoprazole, and omeprazole are approved for gastroesophageal reflux disease [GERD], erosive esophagitis, and/or maintenance of healing of erosive esophagitis in children ages 1 and older; rabeprazole is approved for GERD in ages 12-17 years.)  

Pediatric use of PPIs and the effectiveness of these drugs in pediatric populations is a topic that the FDA is looking at more closely. During the discussion, Dr. Joyce Korvick, deputy director for safety in the FDA’s division of gastroenterology products, informed the panel that the agency is planning an advisory panel meeting on clinical trials on the effficacy of PPIs in pediatric patients in November. Dr. Dianne Murphy, director of the FDA’s Office of Pediatric Therapeutics,  remarked that when she saw the prescription use data, “I just about fell out of my chair,”  and said that one of the reasons the meeting is planned is “we’re learning how much we don’t know” about the use of PPIs in pediatrics. 

 They both indicated that questions raised by panelists during the discussion-which included how efficacy in older children is extrapolated to those under age 1, the differences in reflux disease across age groups, and the use of PPIs in premature babies–will be addressed at that meeting. 

The meeting will probably be a joint meeting of the Pediatric Advisory Committee  and the Gastrointestinal Drugs Advisory Committee 

–Elizabeth Mechcatie (twitter: @elizmech)

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Filed under Drug And Device Safety, Family Medicine, Gastroenterology, Hospital and Critical Care Medicine, IMNG, Pediatrics, Practice Trends, Primary care

Safety and Efficacy First

From the meeting of the FDA Cardiovascular and Renal Drugs Advisory Committee, Adelphi, Md. 

Like cost-effectiveness, convenience is on the list of topics that cannot be taken into account when a Food and Drug Administration advisory panel decides whether or not to recommend approval of a drug. But for the oral anticoagulant rivaroxaban, under review for the prevention of deep vein thromboses and pulmonary emboli in patients who have had hip or knee replacement surgery, the topic was hard to avoid during extensive discussion of the drug’s risks and benefits. That’s because, if approved, rivaroxaban would be the first oral anticoagulant to become available since warfarin was approved over 40 years ago. And unlike warfarin, rivaroxaban is not titrated and patients on the drug do not need regular blood draws to check INR.

Panel members commented that if approved rivaroxaban could help improve compliance with the American College of Chest Physicians and American Academy of Orthopedic Surgeon guidelines for prophylaxis of DVT and PE after hip and knee surgery, and that having an oral option would be a significant advantage.

But Dr. Richard Pazdur, director of the FDA office of oncology drug products, reminded panelists that safety and efficacy of a drug should come first, then convenience can be discussed. “It’s not about convenience, it’s about safety and efficacy that has to be demonstrated first, then a discussion of convenience can be entertained,” he said. If convenience was considered over uncertainty over safety, the FDA would “simply approve more convenient toxic placebos.”

Most of the panel supported approval, despite reservations about more cases of excess bleeding and elevated liver enzymes in patients treated with the drug in trials than in patients on enoxaparin. But they agreed that the benefits exceeded those potential risks, and recommended that the potential for severe hepatotoxicity be followed closely.

Panel members also expressed concern that once the drug becomes available, clinicians would prescribe it off-label for periods longer than the short-term use studied in the trials (35 days after hip surgery and 14 days after a hip replacement).

The FDA’s deadline for an approval decision is May 28 and approval is likely, since the FDA usually follows the advice of its advisory panels.

Pharma giant Johnson & Johnson also is studying rivaroxaban for indications that will be treated for extended periods of time (including acute coronary syndromes and secondary prevention of DVT/PE) and those studies are expected to provide more useful data about the potential hepatoxicity issue.

—Elizabeth Mechcatie
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Filed under Cardiovascular Medicine, Hospital and Critical Care Medicine, Orthopedic Surgery, Surgery