ROCKVILLE, MD. — Panelists on the Food and Drug Administration's Pediatric Advisory Committee strongly urged the FDA to overhaul MedWatch, its voluntary safety information and adverse event reporting program, to make the system less onerous.
Currently, the program entails the submission of a five-page report, and the submission often triggers a follow-up interview via telephone.
“Consider the possibility of streamlining the adverse event reporting system so that people don't mind doing it,” advised Thomas Newman, M.D., of the University of California, San Francisco.
“Create a system that is more specific and less open to interpretation, so that way the data would be stronger and potentially cleaner,” recommended another panel member.
Panelists suggested making the system more user friendly, in addition to having narrative descriptions that are more consistent across categories.
For example, one provider may use a description of “loose stool” while another would use the term “diarrhea.”
“I feel like I'm not serving the general public or the government of the United States, with the current information that I'm receiving. I am not capable of being assured in any way about safety with the [current] passive surveillance system. We have to get better information,” said Mary Glode, M.D., an infectious diseases specialist with the University of Colorado, Denver.
FDA representatives acknowledged that underreporting of adverse events and establishing causality are ongoing challenges under the current MedWatch system.
“There's a lot of missing information. We try to make the most out of this limited information. It's a good system to pick up some rare, serious events,” said an FDA representative.
The panelists also heard data compiled as part of the 1-year postexclusivity adverse event review program mandated by the Best Pharmaceuticals for Children Act.
Information was presented on the following medications:
Benazepril (Lotensin, Lotensin HCT, Lotrel).
▸ Approved: June 25, 1991, manufactured by Novartis.
▸ Indication: This antihypertensive (ACE inhibitor) is used to treat hypertension in patients over 6 years of age.
▸ Pediatric Adverse Events Reported: Three adverse events (AEs) in 1-year period reviewed, and five total since its approval; all were serious, none were fatal. No patterns discernible in the AEs for benazepril monotherapy. No AEs reported for benazepril's combination products.
▸ FDA Recommendation: Return to routine monitoring. The agency recommended routine monitoring of AEs, focusing on serious AEs in all populations, as opposed to giving special attention to all pediatric AEs reported as mandated by the 1-year exclusivity period.
▸ Panel Recommendation: The panel did not concur, and regarded the data presented as too inadequate for a return to routine monitoring. They recommended the FDA “look closely at all case reports for benazepril for yet another year and then report back to the committee,” said panel chair, P. Joan Chesney, M.D., an infectious diseases specialist and director of academic programs at St. Jude Children's Research Hospital, Memphis.
Esmolol (Brevibloc).
▸ Approved: December 31, 1986, manufactured by Baxter Laboratories.
▸ Indication: No pediatric indication. In adults, this β-1-selective (cardioselective) adrenergic receptor blocking agent is used to treat supraventricular tachycardia, intraoperative and postoperative tachycardia and/or hypertension.
▸ Pediatric Adverse Events Reported: During the 1-year postexclusivity period there was one pediatric AE reported. Since its approval there were 13 pediatric AEs reported (9 serious, 3 deaths). No discernible patterns in AEs.
▸ FDA Recommendation: Return to routine monitoring.
▸ Panel Recommendation: The panel did not concur, and regarded the data presented as insufficient. Recommended another year-long exclusivity period.
Orlistat (Xenical).
▸ Approved: April 23, 1999, manufactured by Roche.
▸ Indication: A lipase inhibitor for obesity management in conjunction with weight loss in patients aged 12 years and older with a body mass index greater than 30, or 27 with risk factors (hypertension, diabetes, dyslipidemia). Less than 1% (about 4,000) annual prescriptions for the drug were for pediatric patients.
▸ Pediatric Adverse Events Reported: Twenty-two pediatric AEs were reported (21 serious, no deaths). There was one serious AE reported during the 1-year postexclusivity period.
▸ FDA Recommendation: Return to routine monitoring.
▸ Panel Recommendation: The panel concurred.
Glyburide-Metformin (Glucovance).
▸ Approved: July 31, 2000, manufactured by Bristol-Myers Squibb Co.
▸ Indication: An antihyperglycemic for the adjunct treatment of type 2 diabetes mellitus along with diet and exercise, as well as a second-line treatment for type 2 diabetes if metformin or sulfonylurea fail. The glyburide stimulates release of insulin while the metformin improves glucose tolerance.
▸ Pediatric Adverse Events Reported: No AE reports in this population since Glucovance's approval. Both drugs have minimal use in pediatric patients.
▸ FDA Recommendation: Return to routine monitoring for the drug combo.