UPDATE: FDA Strengthens Warnings On Allergan's Botox

The U.S. Food and Drug Administration said Thursday it was strengthening warnings on Allergan Inc.'s (AGN) Botox and similar products about the possibility of life-threatening breathing and swallowing problems.

Specifically, the FDA said it would require the agency's toughest boxed warning regarding the risk of adverse events when the effects of the toxin - or the active ingredient used in the products - spread beyond the site where it was injected.

The FDA also said it would require manufacturers to develop a so-called risk evaluation and mitigation strategy or REMS that would provide more information to doctors and patients about risk of botulinum toxin effects and to explain that individual products cannot be interchanged.

Dr. Sef Kurstjens, Allergan's chief medical officer, said the company would "work with the FDA to update the safety labeling for Botox and develop an appropriate REMS program."

An agency safety review of Botox and another product, Myobloc, was touched off by reports of breathing problems and a "handful" of deaths in some patients when the products were being used for an unapproved, off-label use. Most of the deaths and serious problems were reported in children being treated cerebral palsy-associated limb spasticity. Neither product is approved for such use in the U.S.

Botox and Myobloc, made by Solstice Neurosciences Inc., a private firm in Malvern, Pa., are designed to block nerve impulses to certain muscles, causing them to relax. Both products are approved to treat cervical dystonia, or uncontrolled muscle contractions of the neck and shoulder muscles. Botox is also approved for cosmetic use to treat wrinkles between the eyebrows and to help control excessive underarm sweating.

In some cases, the toxic, active ingredient in Botox and Myobloc can affect respiratory muscles and cause difficulty swallowing, a condition known as dysphagia. Both products warn doctors and consumers of that side effect.

However, the FDA said there's evidence that the active ingredient in the drugs can spread from distant parts of the body - such as children's leg muscles - to muscles that affect breathing rather than being just a local event as previously believed.

The warnings and other requirements will also apply to Dysport which was approved Wednesday by the FDA. Medicis Pharmaceutical Corp. (MRX), Scottsdale, Ariz., will market Dysport in the U.S. to treat frown lines while Ipsen (IPN.FR), based in Paris, will market the product to treat cervical dystonia. Medicis said Thursday that it should being shipping Dysport for cosmetic use within the next 30 to 60 days, while Ispen said it anticipated launching the product for cervical dystonia during the second half of the year.

The agency also said it's requiring manufacturers to submit safety data after multiple administrations of the products in a certain number of children and adults with spasticity "to assess the signal of serious risk regarding distant spread of toxin effects."

-By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294; [e-mail]