The stronger warning also could undermine the growth of the $3.62 billion U.S. market for ADHD drugs, with particular impact in Philadelphia. The region is home to companies that market the two top-selling ADHD drugs, Adderall XR and Concerta, which account for half of U.S. sales.
The 16-member panel in Gaithersburg, Md., agreed that physicians and parents were largely unaware of the risks and may be overusing the prescription drugs, which include Adderall XR, Concerta, Ritalin, and generic versions called methylphenidate.
"We've got to warn people," Steven Nissen, vice chairman of cardiology at the Cleveland Clinic Foundation, told committee members. "We could learn four to five years from now that it increases risks of heart attack. And we will have known that we sat here and did nothing."
ADHD medications, most of which are classified as stimulants and regulated like narcotics, have been the focus of concern because of misdiagnosis, abuse, addiction and suicide. An FDA review in 2004 found 25 reports of deaths among users of ADHD drugs between 1999 and 2003, including 19 children. Some of these patients had pre-existing heart conditions or hypertension.
"There's smoke. Does that mean there's fire?" asked David Graham, a medical officer at the FDA's Center for Drug Evaluation and Research.
"We wouldn't be going through this exercise if we didn't think there was a real possibility of increased risk," Graham told reporters.
Advocates for the drugs criticized the recommendation as an overreaction to unproven fears that overlooks a huge benefit.
"The main problem is not the complications of the medications, but it's the failure to treat this devastating condition," said M. Christopher Griffith, a psychiatry professor at Morehouse School of Medicine representing the industry-supported patient group Children and Adults With Attention Deficit/Hyperactivity Disorder.
The advisory panel also recommended that the drugs include a medication guide for patients and parents. That vote was 15-0, with one abstention.
Panel members voted by 8-7 to require the "black box" warning, also with one abstention. FDA officials traditionally abide by the recommendations of the outside advisers. However, the panel's vote was close, and two FDA officials rose to try to dissuade the panel.
The agency's analysis of the reports of death and injury only suggests a possible link between the drugs and cardiovascular problems, said Kate Gelperin, a medical officer in the agency's Office of Drug Safety.
Gerald DalPan, a division director in the FDA's Center for Drug Evaluation and Research, said the drugs already carried warnings related to the possible risk they could pose to patients with heart defects.
"We feel this warning is appropriate given our current knowledge of these drugs," DalPan said.
About 2.5 million children between ages 4 and 17 take ADHD drugs, according to federal survey data cited by Andrew Mosholder, a medical officer in the Office of Drug Safety. About 1.5 million adults take the drugs.
"Because adults have a higher risk of heart disease and stroke to begin with, any increase in risk caused by these drugs could affect a large number of people," Graham said.
The FDA said the few studies that had looked at longer-term use of ADHD drugs provided little information on those risks.
The Drug Safety and Risk Management Committee was initially called to review plans for more safety studies but went further. The FDA's pediatric committee will meet on March 22 to discuss suicides associated with ADHD drugs.
Shire P.L.C., the maker of Adderall XR whose North American headquarters is in Wayne, said in a statement that it "looks forward to working with the FDA to explore ways to ensure that patients and physicians have all the information they need."
Adderall XR already carries a warning label about sudden death or heart attack from "misuse," although not from general appropriate use as the panel demanded. The FDA said it had ordered makers of most other ADHD drugs to put similar "misuse" warnings on their labels.
Matt Cabrey, a spokesman for Shire, which depends on Adderall XR for about half its $1.6 billion in revenues, called the vote a "knee-jerk reaction to misinformation and to information that already has been out there."
Johnson & Johnson, the New Jersey-based parent of McNeil Consumer & Specialty Products, of Fort Washington, maker of Concerta, said in a statement: "McNeil is committed to supporting the FDA in their efforts to ensure that there is appropriate labeling for all medications used to treat ADHD."
Novartis AG, maker of Ritalin, the oldest ADHD drug, issued a statement defending the drug's safety record but promising to "work with the FDA to do what is in the best interest of patients."
Another popular ADHD drug is Strattera, manufactured by Eli Lilly & Co. of Indianapolis. However, Strattera is not classified as a stimulant and would not be covered by the proposed black box warning.
Contact staff writer Thomas Ginsberg at 215-854-4177 or firstname.lastname@example.org.
This article contains information from the Associated Press.
By the Numbers
* Prescriptions for treating ADHD for adults jumped 90 percent from March 2002 to about 1 million filled each month as of June 2005.
* About 2 million prescriptions are filled each month for children.
* Sales of ADHD drugs rose to $3.62 billion last year, from $3.1 billion in 2004 and $1.2 billion in 2001.
SOURCES: FDA researcher Andrew Mosholder; IMS Health Inc.