FDA Approves New, Stronger Warnings For ADHD Drugs

Sudden Deaths, Strokes, And Heart Attacks In Adults At Usual Doses

Several drugs to treat attention deficit hyperactivity disorder (ADHD) -- including GlaxoSmithKline (GSK) Plc's Dexedrine, Novartis AG's Ritalin, Johnson & Johnson's Concerta, and Shire PLC's Adderall -- now carry a warning about the possible risk of sudden death and serious heart problems.

According to an August 21, 2006 Reuters article:

[FDA spokeswoman Susan Bro] could not confirm whether the heart warning was boxed. But a letter from Glaxo made public earlier on Monday advising doctors about the new warnings said the heart caution was a boxed warning.

Regarding that last point, the boxed warning actually addressed the misuse of amphetamines, a more general warning, as read in the June 2006 version of the Dexedrine package insert. 

Meanwhile, in the third week of August 2006 the FDA announced on its web site that GSK recently sent a so-called "Dear Doctor" letter regarding Dexedrine dated August 4, 2006 informing healthcare professionals about changes made to the June 2006 version of the Dexedrine package insert, or label.

The FDA's approval of this new, stronger warning for Dexedrine and some of the other ADHD drugs seems to be the resolution of conflicting opinions issued by two different FDA advisory committees which considered the safety of ADHD drugs in February and March 2006.  The primary distinctions between the recommendations made by these two advisory committees were, to start, the extent of cardiovascular risks associated with Adderall, Concerta, Ritalin, Dexedrine, as well as some other ADHD drugs and, then, whether those risks warranted the addition of a "black-box" warning on the package insert for these controversial stimulants.

In his August 21 article Gardiner Harris, of The New York Times, summarized the concerns of the February 2005 advisory committee:

At a meeting in February, an F.D.A. advisory committee focused attention on stimulants’ risks in adults after a report suggested that the drugs might double the risk of strokes and serious arrhythmias. Such an increase may not be significant in children, whose heart risks are low, but it could cause concern in adults, committee members said.

During the past year-and-a-half the FDA has been criticized for its handling of the cardiovascular safety issue associated with Adderall and other ADHD drugs. In particular, the agency came under increasing scrutiny after Health Canada pulled Adderall XR from the market in February 2005 based on reports that 20 people taking the drug died. Health Canada returned Adderall to the market in August 2005, and in May 2006 issued a safety alert warning against the use of ADHD drugs by people with high blood pressure, heart disease, and certain other medical problems.

An August 21, 2006 piece published on Bloomberg.com brought us the reaction of prominent cardiologist Steven Nissen, chairman of cardiology at the Cleveland Clinic, who served on the February FDA advisory committee:

It's a very strong warning....  It's appropriately worded. It basically lets physicians and patients know that these drugs do have serious cardiovascular side effects.

According to the August 21 Reuters article, the FDA estimates that the number of ADHD drug prescriptions written each month in the U.S. are about 1 million for adults and 2 million for children.

(Posted by: Tom Lamb)