BETHESDA, MD 30 April 2009—FDA announced today that the makers of botulinum toxin products must add a boxed warning to their labeling about the risk of neurologic effects typical of the toxin, such as unexpected muscle weakness, developing in areas distant from the site of injection.
The agency also announced that the companies must develop a medication guide for patients to receive along with the product.
FDA`s decision to require a boxed warning and medication guide affects three injectable products: botulinum toxin type A, sold as Botox and Botox Cosmetic by Allergan Inc.; botulinum toxin type B, sold as Myobloc by Solstice Neurosciences, Inc.; and abobotulinumtoxin A, to be sold as Dysport by Medicis Pharmaceutical Corporation and Ipsen.
Abobotulinumtoxin A was approved for marketing on Wednesday, said Ellis F. Unger, acting deputy director for the FDA office responsible for neurology products, during a media briefing.
This newest botulinum toxin product will become available within the next 60 days, when Medicis starts marketing Dysport as a means to temporarily improve the appearance of moderate to severe lines in the area between the eyebrows of adults younger than age 65 years. Ipsen said it will start marketing the product for the treatment of cervical dystonia in adults in the second half of 2009.
Unger said most of the known instances in which a botulinum toxin product`s effects spread beyond the injection site involved children with cerebral palsy who received the drug to treat muscle spasticity—an off-label use.
He added, however, that spread of the toxin`s effects beyond the injection site has also been reported in adults. The affected adults had received a botulinum toxin product for any of several reasons, some of which are not described in the FDA-approved labeling.
"We`ve not seen any definitive, serious adverse-event reports of distant spread of toxin associated with dermatologic use of Botox when it`s given the way the label says it should be given," Unger said.
FDA said the medication guide is part of the risk evaluation and mitigation strategy that all makers of botulinum toxin products must develop and implement. Another part of the strategy is a communication plan to provide more information about the risk of toxin-related neurologic effects developing distant to the injection site as well as inform health care providers that botulinum toxin products are not interchangeable.
"There are now three products approved in the United States . . . and they have different dosing units and the units cannot be interchanged," Unger said. "So, by switching a patient from one product to another, there would be a risk of underdosing or, more importantly, overdosing."
When questioned whether office-based physicians who administer botulinum toxin products must give the medication guide to patients, Unger said yes.
Today`s announcement was not based on new scientific information. Rather, Unger said,, FDA had become more certain about a "signal" that had been detected through an earlier safety review.
The announcement coincided with the release of a letter (PDF) explaining that FDA agreed in part to requests made by Public Citizen Health Research Group in February 2008.