FDA Orders ADHD Drug Advisories for Patients

ROCKVILLE, Md., Feb. 22 -- The FDA has ordered all drugs approved for attention deficit hyperactivity disorder to carry guides to inform patients about the potential for cardiovascular risks and adverse psychiatric symptoms.

"Medicines approved for the treatment of ADHD have real benefits for many patients but they may have serious risks as well," said Steven Galson, M.D., director of the FDA's Center for Drug Evaluation and Research.

The guides will be aimed at patients, families, and caregivers, and are to be handed out at pharmacies or in clinics where the drugs are dispensed.

The FDA recommended that "children, adolescents, or adults who are being considered for treatment with ADHD drug products work with their physician or other health care professional to develop a treatment plan that includes a careful health history and evaluation of current status, particularly for cardiovascular and psychiatric problems (including assessment for a family history of such problems)."

The patient guides reflected a May 2006 FDA directive to ADHD drug-makers to "revise product labeling for doctors to reflect concerns about adverse cardiovascular and psychiatric events. These changes were based on recommendations from the FDA Pediatric Advisory Committee and the Drug Safety and Risk Management Advisory Committee. To help patients understand these risks, an additional part of this revised labeling process is the creation of a Patient Medication Guide for each individual product."

The FDA said it has received reports of serious cardiovascular adverse events in patients taking standard doses of ADHD medications, including cases of sudden death in patients with underlying cardiac disease or structural cardiac abnormalities.

There have also been reports of stroke and heart attack in adults with certain cardiovascular risk factors, the FDA noted.

In a study of otherwise healthy adults with ADHD who took amphetamine mixed salts extended-release formulations in doses of 20 to 60 mg a day for up to two years, Joseph Biederman, M.D., and colleagues at Harvard Medical School observed significant mean increases from baseline in diastolic and systolic blood pressure, and pulse at the QTc interval, although these changes were deemed not clinically significant. But seven of the 223 patients in the study discontinued the ADHD drugs, five because of hypertension, and two because of tachycardia.

The results of the study were discussed at a hearing of the FDA Drug Safety and Risk Management Advisory last February.

In addition cardiovascular adverse events, drugs for ADHD have been associated with auditory hallucination, paranoia, and manic episodes, even in patients with no prior history of psychiatric problems, the agency reported.

Fifteen products carry the revised labeling and will be accompanied in future by patient handouts. The products are:

• Adderall (mixed salts of a single entity amphetamine product) Tablets
• Adderall XR (mixed salts of a single entity amphetamine product) Extended-Release Capsules
• Concerta (methylphenidate hydrochloride) Extended-Release Tablets
• Daytrana (methylphenidate) Transdermal System
• Desoxyn (methamphetamine HCl) Tablets
• Dexedrine (dextroamphetamine sulfate) Spansule Capsules and Tablets
• Focalin (dexmethylphenidate hydrochloride) Tablets
• Focalin XR (dexmethylphenidate hydrochloride) Extended-Release Capsules
• Metadate CD (methylphenidate hydrochloride) Extended-Release Capsules
• Methylin (methylphenidate hydrochloride) Oral Solution
• Methylin (methylphenidate hydrochloride) Chewable Tablets
• Ritalin (methylphenidate hydrochloride) Tablets
• Ritalin SR (methylphenidate hydrochloride) Sustained-Release Tablets
• Ritalin LA (methylphenidate hydrochloride) Extended-Release Capsules
• Strattera (atomoxetine HCl) Capsules