Reconstitution is key to optimizing neurotoxin results

April 1, 2014

Suboptimal reconstitution of botulinum toxin type A preparations can diminish the efficacy of neuromodulators for cosmetic use.

Montreal - IncobotulinumtoxinA (Xeomin, Merz) is equivalent to onabotulinumtoxinA (Botox, Allergan) in efficacy and safety, but the former product needs to be reconstituted in a different fashion from onabotulinumtoxin A to achieve equivalent efficacy.

"Although more than 3,000 patients in numerous studies show that both products are comparable, a small number of studies have shown incobotulinumtoxinA to be inferior to onabotulinumtoxinA," said Wayne Carey M.D., F.R.C.P.C., associate professor of dermatology at McGill University, Montreal, speaking at a dermatology symposium here.

"The reason for this inferiority is because the product was most likely mixed the same way that onabotulinumtoxinA was. If you reconstitute incobotulinumtoxinA, the way you would onabotulinumtoxinA, you will have a significant loss of product (incobotulinumtoxin A)," Dr. Carey says.

Product differentiation

Anecdotal reports in his own practice, of patients complaining about a lack of duration of effect with incobotulinumtoxinA when injected around the corrugator muscles to treat glabellar frown lines, prompted Dr. Carey to look deeper into the issue of equivalence and efficacy between the two products.

Dr. Carey inadvertently changed his reconstitution technique for a method that allows for a more complete reconstitution. As a result of this technique, both patients and Dr. Carey notes that the efficacy and safety of incobotulinumtoxinA versus onabotulinumtoxinA is equivalent. Dr. Carey continues to use incobotulinumtoxinA in his practice today and emphasizes that patients are more concerned with outcomes rather than the brand they are being injected with.

"Essentially, we are the brand, and as physicians, we decide which treatment is optimal for our patients," he says.

A key difference between the two products is the presence of additional bacterial proteins, such as complexing proteins in onabotulinumtoxinA, Dr. Carey says. IncobotulinumtoxinA, the naked toxin, is completely pure and contains only what is necessary for the mechanism of action, according to Dr. Carey, adding that research suggests the presence of complexing proteins do not offer any added therapeutic benefit. (Eisele KH1, Fink K, Vey M, Taylor HV. Toxicon. 2011;57(4):555-565).

An advantage of incobotulinum toxinA is that it does not require refrigeration where onabotulinumtoxinA does, according to Dr. Carey.

 

 

Volume equivalence   

Understanding volume equivalence across the neurotoxins that are available in North America will allow dermatologists using the products for cosmetic purposes to develop comfort in choosing from any of the three toxins, according to Andrei Metelitsa, M.D., F.R.C.P.C., medical co-director of the Institute for Skin Advancement, Calgary, Alberta, and assistant professor of dermatology, University of Calgary.

"There are subtle differences between these neuromodulators," Dr. Metelitsa says. "The units are not interchangeable. They should be viewed as siblings and not as identical triplets."

Still, despite the differences of the neurotoxins, owing to the manufacturing process, clinicians should aim to produce aesthetic outcomes that are comparable with each.

"They should create more or less an equal result," Dr. Metelitsa says. "The active molecule is the same."

Dr. Metelitsa points to evidence-based aesthetic consensus recommendations that state the unit size of abobotulinumtoxinA (Dysport, Medicis) is smaller than the unit size of onabotulinumtoxinA. The consensus recommendations state also that one unit of onabotulinumtoxinA is equivalent to 2.5 units of abobotulinumtoxinA (Maas C, Kane MA, Bucay VW, et al. Aesthetic Surgery Journal. 2012;32(1 Suppl):8S-29S). 

There is some interoperator variability in how clinicians reconstitute neuromodulators, but regardless of whether clinicians reconstitute the 100-unit onabotulinumtoxinA in 1 mL, 2 mL, or 2.5 mL of saline, they should be able to easily switch to abobotulinumtoxinA using a simplified off-label conversion method, which Dr. Metelitsa developed with other clinicians during his fellowship in Boston.

"Off-label, we recommend that clinicians add 20 percent more volume of saline to a 300-unit vial of abobotulinumtoxinA as compared to their typical reconstitution volume with a 100 unit vial of onabotulinumtoxinA," Dr. Metelitsa says. "This rule is applicable regardless of the reconstitution technique (with onabotulinumtoxinA or incobotulinumtoxinA)."

Dr. Metelitsa recommends that dermatologists label their syringes, indicating the neuromodulator contained in each.

Navigating to optimize the use of the neurotoxins will expand choice for physicians and patients, he says.

"From a clinical standpoint, it is nice to have a variety of options," Dr. Metelitsa says.

Disclosures: Dr. Carey has been a speaker for Merz Pharma Canada. Dr. Metelitsa has been an investigator and consultant for Allergan and Valeant.