Favorable risk profile for botulinum toxin A supports expanding applications

February 1, 2012

Even though botulinum toxin type A is one of the most potent neurotoxins known, its injection into muscles for the reduction of hyperfunctional lines is one of the safest procedures being performed in cosmetic dermatology. And the favorable risk-to-benefit profile of the toxin is fueling its use in an expanding number of off-label applications, says Thomas E. Rohrer, M.D.

Key Points

Las Vegas - Even though botulinum toxin type A is one of the most potent neurotoxins known, its injection into muscles for the reduction of hyperfunctional lines is one of the safest procedures being performed in cosmetic dermatology. And the favorable risk-to-benefit profile of the toxin is fueling its use in an expanding number of off-label applications, says Thomas E. Rohrer, M.D.

Also expanding is the number of botulinum toxin products. In July 2011, the Food and Drug Administration granted approval of incobotulinumtoxinA (Xeomin, Merz) for the temporary improvement of glabellar lines, and a fourth investigational product, purified botulinum toxin A (PurTox, Mentor) has completed phase 3 clinical trials.

Speaking at the 30th annual Fall Clinical Dermatology Conference, Dr. Rohrer discussed issues relating to product equivalency and its range of uses. "The bottom line," says Dr. Rohrer, clinical associate professor of dermatology, Brown University School of Medicine, Providence, R.I., "is that patients are being treated with the same active ingredient no matter which botulinum toxin type A product is used, and while there are just limited data from head-to-head comparison trials, available evidence indicates all three FDA-approved products have similar onset of action, efficacy, duration of action, safety profiles, immunogenicity and stability. The availability of several different products just gives patients and physicians more options."

The complexing proteins act to stabilize the active toxin in an acidic environment. With exposure to the higher pH of the body after injection, however, the toxin rapidly dissociates from any complexing proteins within 60 seconds. In fact, 85 percent of the toxin is in its active free form when injected because reconstitution with saline also results in rapid dissociation. With all products, the administered agent is essentially the active ingredient, Dr. Rohrer says.

Understanding units

The idea that there are differences in potency between the various botulinum toxin products is rooted in the fact that the dose may vary, depending on the product. However, Dr. Rohrer says, the "units" used to designate dose represent a miniscule quantity of drug, in the nanogram range.

Furthermore, unit determination is based on manufacturer-specific proprietary assays and animal testing to determine the median lethal dose of an intraperitoneal injection into a standardized mouse model, he says.

"Units do not translate between species, subtype or even application," he says. "However, for dosing purposes in clinical use, one unit of onabotulinumtoxinA is roughly equivalent to one unit of incobotulinumtoxinA and 2.5 or three units of abobotulinumtoxinA."

Dr. Rohrer says a helpful technique to avoid dosing errors if different products are used is to mix the toxin so that equivalent doses are in equivalent volumes. For example, abobotulinumtoxinA is marketed in vials containing 300 units, while vials of onabotulinumtoxinA contain 100 units. Assuming a unit conversion of 3:1 for abobotulinumtoxinA to onabotulinumtoxinA, both products would be mixed using the same diluent volume. For physicians who think 2.5:1 is the proper dose conversion between products, the amount of diluent added to abobotulinumtoxinA would be increased by 20 percent.

Dr. Rohrer says he uses the latter technique and adds 5 mL of diluent to onabotulinumtoxinA and 6 mL to abobotulinumtoxinA, and then he preloads syringes and tags them with the product name and dose.

Product diffusion after injection is more a function of dilution than being product-specific, and the area of spread increases with higher dilution, Dr. Rohrer says.

Disclosures: Dr. Rohrer receives research grants from Allergan, Medicis and Merz.