FDA: Botox Black-Box Warnings

By Margarita Nahapetyan

According to the latest order from the U.S. Food and Drug Administration, Allergan Inc.'s (AGN) Botox and other similar anti-wrinkle products from now on must change labeling and start carrying boxed warnings, the most serious type of label warning, about the possibility of life-threatening breathing and swallowing problems.

Requiring a product to carry a black-box warning is one of the strongest safety actions the F.D.A. can take. Black boxes are generally reserved for medications that may pose serious or hazardous threats for life. Antidepressant drugs, for instance, carry black boxes that caution about the increased danger of suicidal thoughts and attempts. The agency released the order the day after the approval of a new anti-wrinkle drug, Dysport, that is expected to be the first real challenger to Botox in the United States. Similarly as Botox, Dysport is a drug that is derived from the paralytic agent botulinum toxin and administered to the skin through injection.

According to the F.D.A., drugs such as Botox must carry warning labels which should state that the product has the potential to spread from the injection site to distant parts of the body - with the risk of serious difficulties, like problems with swallowing or breathing. The F.D.A. also said that Botox and some other injections carry risks of rare botulism symptoms, particularly when administered to children in order to help relax uncontrollable muscle movements associated with cerebral palsy. That use is not approved in the Unites States, though regulators say it is still legitimate.

"These are patients who have a significant disability because of spasticity and these products provide a very effective means to relieve that significant problem," said Dr. Ellis Unger, M.D., the FDA's acting deputy director of the Office of Drug Evaluation I, at the Center for Drug Evaluation and Research,. "We do not want to discourage that use, but people need to understand the risks involved."

Most of the problems associated with the product, seen in adults, came after treatment for muscle spasms, migraine headaches and cervical dystonia, a type of neck contraction for which the drugs are approved. Some of those patients had to be hospitalized and put on mechanical ventilation in order to be able to breath. While the agency said that there have been reports of botulism symptoms in patients taking the drug for cosmetic, anti-wrinkle purposes, none of those cases have been confirmed yet. Dr. Unger noted that patients getting injections for cosmetic use are being administered much smaller doses compared to those who are treated for spasms. However, the agency is still demanding the same label for all products and uses, Unger said.

There are now three botulinum toxin products that are approved by the F.D.A.: Botox and Botox Cosmetic made by Allergan, Myobloc made by Solstice Neurosciences, and Dysport by Ipsen. Botulinum toxin products have been approved by the agency for one or more of the following uses - temporary improvement in the appearance of frown lines, treatment of strabismus, blepharospasm, cervical dystonia, and primary axillary hyperhidrosis. For the treatment of these conditions, botulinum toxin is administered to the skin or into muscle tissue.

The F.D.A. also said it would require manufacturers to develop a so-called risk evaluation and mitigation strategy, or REMS, that would provide physiciand and patients with more information about risk factors associated with botulinum toxin effects and to explain that individual products cannot be interchanged. "Updating labeling will help patients and health-care professionals better understand the risks and benefits," Dr. Unger said. "These drugs have benefits, but they also can cause serious problems," he concluded.