FDA Delays Changes to Concerta Label Until 2006

ROCKVILLE, MD. — A Food and Drug Administration panel has decided to postpone changes to safety warnings in the label for Concerta, a stimulant widely prescribed for attention-deficit hyperactivity disorder.

The FDA's Pediatric Advisory Committee recommended that agency officials delay any possible changes until data on adverse events associated with all methylphenidates (including Ritalin, Methylin, and Metadate) have been analyzed. Some committee members said they were unsure whether certain events were caused by the drugs or by underlying conditions. That review probably won't be complete until early 2006, according to Anne Trontell, M.D., deputy director of the FDA's Office of Drug Safety.

The FDA's legally required 1-year postexclusivity data review for Concerta examined reports of adverse psychiatric and cardiovascular events, including hallucinations, suicidal ideation, psychotic behavior, hypertension, and arrhythmias.

Although FDA officials and members of the Pediatric Advisory Committee agreed that these reports don't give new or unusual information, most also noted that existing warnings about possible adverse events could be better presented on the Concerta label, which now includes information in seven different places.

The FDA wants to update safety information on the labels on Concerta and other methylphenidates because prescribing practices have changed drastically since the first such drug (Ritalin) entered the market in 1955, said Paul J. Andreason, M.D., of the FDA's division of neuropharmacological drug products.

Calling methylphenidates “remarkably effective,” Richard Gorman, M.D., representative for the American Academy of Pediatrics, noted the public perception that methylphenidates are dangerous.

“Nothing I've heard today about these medications makes me particularly concerned,” said pediatric epidemiologist Thomas B. Newman, M.D., of the University of California, San Francisco.

Most committee members also urged FDA officials to let physicians and the public know why the FDA is postponing changes to safety information on the Concerta label and that the FDA is continuing to monitor methylphenidate problems.

Michael E. Fant, M.D., a neonatologist and biochemist at the University of Texas, Houston, also suggested studying the drug's effects on younger children.

Dianne Murphy, M.D., director of the FDA's Office of Pediatric Therapeutics, added that exclusivity trials showed differences in metabolism and clearance among 3- to 8-year-olds, and added that exclusivity studies did not involve younger children.

FDA committee members also considered information from a small study of Ritalin that suggests it is associated with chromosome aberrations in peripheral blood lymphocytes, an independent risk factor for cancer.

That study by Randa A. El-Zein, M.D., and colleagues, published earlier this year in Cancer Letters, was the topic of an on-site evaluation by officials at the FDA and other federal agencies. They determined the study had methodology flaws, including a lack of placebo controls and unusual data presentation, said David Jacobson-Kram, Ph.D., of the FDA's Office of New Drugs.

He added that researchers don't know how the drug can damage DNA.

The Texas researchers are seeking funding to perform a larger study, while the FDA, the National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, and Duke University, Durham, N.C., are collaborating to replicate the study by Dr. El-Zein and colleagues, according to Dr. Jacobson-Kram.

“If these data are reproducible, it would be very concerning,” he said, adding that studies similar to Dr. El-Zein's won't yield results for at least a year.

ROCKVILLE, MD. — A Food and Drug Administration panel has decided to postpone changes to safety warnings in the label for Concerta, a stimulant widely prescribed for attention-deficit hyperactivity disorder.

The FDA's Pediatric Advisory Committee recommended that agency officials delay any possible changes until data on adverse events associated with all methylphenidates (including Ritalin, Methylin, and Metadate) have been analyzed. Some committee members said they were unsure whether certain events were caused by the drugs or by underlying conditions. That review probably won't be complete until early 2006, according to Anne Trontell, M.D., deputy director of the FDA's Office of Drug Safety.

The FDA's legally required 1-year postexclusivity data review for Concerta examined reports of adverse psychiatric and cardiovascular events, including hallucinations, suicidal ideation, psychotic behavior, hypertension, and arrhythmias.

Although FDA officials and members of the Pediatric Advisory Committee agreed that these reports don't give new or unusual information, most also noted that existing warnings about possible adverse events could be better presented on the Concerta label, which now includes information in seven different places.

The FDA wants to update safety information on the labels on Concerta and other methylphenidates because prescribing practices have changed drastically since the first such drug (Ritalin) entered the market in 1955, said Paul J. Andreason, M.D., of the FDA's division of neuropharmacological drug products.

Calling methylphenidates “remarkably effective,” Richard Gorman, M.D., representative for the American Academy of Pediatrics, noted the public perception that methylphenidates are dangerous.

“Nothing I've heard today about these medications makes me particularly concerned,” said pediatric epidemiologist Thomas B. Newman, M.D., of the University of California, San Francisco.

Most committee members also urged FDA officials to let physicians and the public know why the FDA is postponing changes to safety information on the Concerta label and that the FDA is continuing to monitor methylphenidate problems.

Michael E. Fant, M.D., a neonatologist and biochemist at the University of Texas, Houston, also suggested studying the drug's effects on younger children.

Dianne Murphy, M.D., director of the FDA's Office of Pediatric Therapeutics, added that exclusivity trials showed differences in metabolism and clearance among 3- to 8-year-olds, and added that exclusivity studies did not involve younger children.

FDA committee members also considered information from a small study of Ritalin that suggests it is associated with chromosome aberrations in peripheral blood lymphocytes, an independent risk factor for cancer.

That study by Randa A. El-Zein, M.D., and colleagues, published earlier this year in Cancer Letters, was the topic of an on-site evaluation by officials at the FDA and other federal agencies. They determined the study had methodology flaws, including a lack of placebo controls and unusual data presentation, said David Jacobson-Kram, Ph.D., of the FDA's Office of New Drugs.

He added that researchers don't know how the drug can damage DNA.

The Texas researchers are seeking funding to perform a larger study, while the FDA, the National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, and Duke University, Durham, N.C., are collaborating to replicate the study by Dr. El-Zein and colleagues, according to Dr. Jacobson-Kram.

“If these data are reproducible, it would be very concerning,” he said, adding that studies similar to Dr. El-Zein's won't yield results for at least a year.

ROCKVILLE, MD. — A Food and Drug Administration panel has decided to postpone changes to safety warnings in the label for Concerta, a stimulant widely prescribed for attention-deficit hyperactivity disorder.

The FDA's Pediatric Advisory Committee recommended that agency officials delay any possible changes until data on adverse events associated with all methylphenidates (including Ritalin, Methylin, and Metadate) have been analyzed. Some committee members said they were unsure whether certain events were caused by the drugs or by underlying conditions. That review probably won't be complete until early 2006, according to Anne Trontell, M.D., deputy director of the FDA's Office of Drug Safety.

The FDA's legally required 1-year postexclusivity data review for Concerta examined reports of adverse psychiatric and cardiovascular events, including hallucinations, suicidal ideation, psychotic behavior, hypertension, and arrhythmias.

Although FDA officials and members of the Pediatric Advisory Committee agreed that these reports don't give new or unusual information, most also noted that existing warnings about possible adverse events could be better presented on the Concerta label, which now includes information in seven different places.

The FDA wants to update safety information on the labels on Concerta and other methylphenidates because prescribing practices have changed drastically since the first such drug (Ritalin) entered the market in 1955, said Paul J. Andreason, M.D., of the FDA's division of neuropharmacological drug products.

Calling methylphenidates “remarkably effective,” Richard Gorman, M.D., representative for the American Academy of Pediatrics, noted the public perception that methylphenidates are dangerous.

“Nothing I've heard today about these medications makes me particularly concerned,” said pediatric epidemiologist Thomas B. Newman, M.D., of the University of California, San Francisco.

Most committee members also urged FDA officials to let physicians and the public know why the FDA is postponing changes to safety information on the Concerta label and that the FDA is continuing to monitor methylphenidate problems.

Michael E. Fant, M.D., a neonatologist and biochemist at the University of Texas, Houston, also suggested studying the drug's effects on younger children.

Dianne Murphy, M.D., director of the FDA's Office of Pediatric Therapeutics, added that exclusivity trials showed differences in metabolism and clearance among 3- to 8-year-olds, and added that exclusivity studies did not involve younger children.

FDA committee members also considered information from a small study of Ritalin that suggests it is associated with chromosome aberrations in peripheral blood lymphocytes, an independent risk factor for cancer.

That study by Randa A. El-Zein, M.D., and colleagues, published earlier this year in Cancer Letters, was the topic of an on-site evaluation by officials at the FDA and other federal agencies. They determined the study had methodology flaws, including a lack of placebo controls and unusual data presentation, said David Jacobson-Kram, Ph.D., of the FDA's Office of New Drugs.

He added that researchers don't know how the drug can damage DNA.

The Texas researchers are seeking funding to perform a larger study, while the FDA, the National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, and Duke University, Durham, N.C., are collaborating to replicate the study by Dr. El-Zein and colleagues, according to Dr. Jacobson-Kram.

“If these data are reproducible, it would be very concerning,” he said, adding that studies similar to Dr. El-Zein's won't yield results for at least a year.