The consumer group Public Citizen (Washington) said it wants stronger warnings of side effects tied to Allergan’s (Irvine, California) cosmetic and drug Botox and a similar product, Myobloc, which is made by Solstice Neurosciences (South San Francisco, California).

Public Citizen said it filed a petition with the FDA seeking a tough so-called “black box” warning on Botox and Myobloc about side effects that can include difficulty swallowing, pneumonia and, in rare cases, death from aspiration pneumonia. The petition was filed following reports of at least 16 deaths after the botulinum toxin spread inside the body.

“The FDA should immediately increase its warnings and directly warn patients and doctors about the use of botulinum toxin – available as Botox and Myobloc – because of serious adverse reactions, including deaths, linked to the drug,” Public Citizen said in a petition filed with the agency.

It said that unlike drug regulatory agencies in Europe, the FDA has not issued any warnings to patients or doctors about the dangers of using the toxin, which is commonly used in therapeutic and cosmetic procedures.

The petition noted that the European Union has posted a series of warnings concerning botulinum toxin on its web site, the latest in March 2007, alerting physicians in its 27 member states about the need to monitor for signs of botulinum toxin adverse events. The U.K. and Germany amplified the EU warning with “Dear Doctor Letters,” but no similar official warnings have been forthcoming from the FDA, the petition said.

While Public Citizen’s actions are laudable, the group’s general director Peter Lurie, MD, told Medical Device Daily that so far, there is no hard proof in Europe that the new regulations have made any kind of significant impact. However, he argued rather persuasively that even if the data backing up heightened warning for the drug is not available “people have a right to know,” about potential side effects. “These significantly improved warnings to doctors and patients would increase the likelihood of earlier medical intervention when symptoms of adverse reactions to botulinum toxin first appear and could prevent more serious complications, including death,” Wolfe said. “Nobody should be dying from injected botulinum toxin. Educating physicians and patients about what adverse symptoms to look for and when to seek immediate medical attention will save lives.”

A Public Citizen analysis of FDA data found that makers of the drug have reported 180 U.S. cases of people developing these sometimes life-threatening conditions after receiving injections, including 16 deaths; four of the deaths occurred in children less than 18 years of age. The FDA data come from voluntary reports, which have been estimated to account for only 10% of actual cases, meaning the number of incidents could be much higher.

Public Citizen said that the FDA has approved the use of botulinum toxin for a limited number of “therapeutic” conditions, including uncontrollable neck and shoulder muscle contractions, crossed eyes, spasmodic blinking of the eyes and excessive underarm sweating. The only approved cosmetic use is for temporary smoothing of wrinkles between the eyebrows. Most cosmetic uses of botulinum toxin are unapproved, it noted.

The FDA should send a warning letter directly to doctors alerting them to the problems associated with the toxin, including cases of hospitalization and death, Public Citizen’s petition said. The petition also asks the FDA to label the products with a black box warning, the strongest warning the agency can make, and require doctors to give patients a medication guide at the time of the injection warning them of possible symptoms of adverse reactions, as well as other information about the drug.

The group said that early symptoms include dry mouth, difficulty swallowing, difficulty breathing, slurred speech, drooping eyelids and muscle weakness.

The Public Citizen analysis of FDA data found that between Nov. 1, 1997, and Dec. 31, 2006, there were 658 reported cases of people suffering adverse effects from injections of botulinum toxin. Of these, 180 were associated with aspiration (fluid in the lungs), dysphagia and/or pneumonia; 87 required hospitalization.

In fact, cases of dysphagia were common in pre-approval studies of botulinum toxin for therapeutic uses. Although most cases were mild, severe cases did occur, even with the limited number of people exposed in these studies.

In a statement, Allergan which did not return calls to Medical Device Daily before press time, said that “there are no safety issues raised in the petition that are not already addressed in the labeling for Botox” The company added that it “takes its FDA-mandated labeling obligations very seriously.” The company added that it is “in frequent dialog with the FDA” to ensure proper labeling for its products and also submits information on all adverse events that are received whether or not they are considered related to the drug. It also noted that the product has a “long-established safety profile and has been approved by the FDA for more than 17 years to treat a variety of medical conditions, as well as for aesthetic use (glabellar lines) since 2002.”

Solstice Neurosciences, which was also not available for comment, said in a statement that it recently submitted safety data to the FDA and it stood behind the current prescribing information.