An FDA advisory committee has given a second—and very different—opinion on the need for new warnings on attention deficit hyperactivity disorder (ADHD) drugs. The Pediatric Advisory Committee recommended that the FDA require additional label language on these drugs to warn about potential cardiovascular risks to children with preexisting heart problems and the rare risk of psychotic events. At the same time, the committee rejected the recommendation, made 1 month previously by the FDA's Drug Safety and Risk Management advisory committee, to require a black box warning on ADHD drugs concerning cardiovascular risks.
The Pediatric Advisory Committee looked at evidence that those drugs caused excessive psychotic and cardiovascular adverse events in children and adolescents. A March 3 memo by 2 psychiatric drug reviewers in the agency's Office of Drug Safety stated that since January 1, 2000, the agency and drug companies had received hundreds of reports of psychosis or manic behavior, particularly hallucinations, in patients with no known risk factors who took the usual dose of an ADHD medication. Current approved labeling for ADHD drugs does not clearly address the risk of drug-induced psychosis or symptoms of mania in such patients, medical epidemiologist Kate Gelperin, MD, MPH, and safety evaluator Kate Phelan wrote. “We recommend that these issues be addressed,” they added.
Any new labeling requirement advanced by the FDA will take into account the softer recommendation of the Pediatric Committee, which was based on testimony provided by both psychiatrists and pharmaceutical companies.
Darrel A. Regier, MD, MPH, research director for the American Psychiatric Association, emphasized the risk of limiting access to these “valid and effective treatments . . . when the FDA is asked to use non-research standards for warnings.”
McNeil Consumer & Specialty Pharmaceuticals submitted data on methylphenidate(Drug information on methylphenidate) (Concerta) that showed an estimated rate of sudden cardiac death of 0.19 per 100,000 patient-years in those using the drug. The rate of sudden cardiac death in children and young adults in the general population is approximately 1.3 to 8.5 per 100,000 persons. Regarding psychiatric events, a postmarketing safety review for methylphenidate found the rate of suicidal ideation to be 0.65 cases per 100,000 patient-years. The company stated that even with a correction for under-reporting, the observed rate of suicidal ideation is lower than the rate of suicidal ideation in the general population.
“We appreciate the careful and informative dialogue demonstrated by the committee and agree with the committee's suggestion to the FDA that heightened awareness around adverse events is important but that the data do not support the need for a black box–type of warning,” said Matt Cabrey, spokesman for Shire Pharmaceuticals.
