INTRODUCTION
IncobotulinumtoxinA (INCO; Xeomin® in the United States, Canada / “botulinum toxin A
free of complexing proteins» or Bocouture® in Europe and other parts of the world) is
distributed by Merz Aesthetics Inc. and Merz Pharmaceuticals LLC in Greensboro, NC. INCO has been in approved use in
Europe since 2005, with availability in 20 countries and with over 261,000 patients treated.1
Recently, anecdotal reports from North American aesthetic clinicians
have suggested some variance in efficacy amongst BoNTAproducts2 despite
many studies demonstrating comparable effectiveness of toxins when dosed properly.
Studies of more than 2000 patients have shown comparable dosing, efficacy, and
safety comparing INCO to onabotulinumtoxinA (ONA; Botox®, Allergan, Irvine, CA).3-15
These anecdotal reports raise the issue of variables,
if any, which may be associated with differences in efficacy.
One difference may be related to how INCO is supplied in Europe,
compared to North America. In Europe, INCO appears as a compressed “puck†at the
bottom of its vial. In North America, INCO may appear as a puck with most of the
neuromodulator at the bottom of the vial. However, it is often present as a loose powder,
clustered around and inside the rubber cap, as well as on the sides of the vial, possibly
due to product shifting during overseas transport (Figure 1).2 We wondered whether physical
differences in INCO presentation in its vial would influence reconstitution technique, and
thus account for the anecdotal comments upon differences in efficacy.
Our hypothesis is that, because INCO can be found distributed throughout
the vial rather than solely at the bottom of the vial, failure to invert a
vial of INCO during the addition of saline results in reconstitution of less
than 100 percent of the available neuromodulator,
possibly resulting in diminished efficacy upon injection.
The idea of incomplete reconstitution arose from an inadvertent swirl and
inversion of vials of INCO by the author, rather than the usual simple swirl
reconstitution technique as traditionally used for ONA. The author typically
uses a 2 cc dilution of INCO or ONA. This technique came about when we noticed
that there was no foaming of the ONA solution when saline was injected into the
inverted vial. This technique was continued when we started reusing INCO. When
injected into the patient, the INCO reconstituted from a swirled and inverted
vials resulted in a clinically equivalent effectiveness of neuromuscular paralysis
as compared with ONA injections in our practice. This serendipitous inversion led us
to design an experiment to determine if, by simply altering the reconstitution technique of INCO, optimization of the
clinical effect of decreased motor activity could be demonstrated.
Materials and Methods
Five patients who were naïve to BoNTA injections were selected for this trial.
Vials of INCO were included in the study only if there was visible powder around
and inside the vial cap. Vials that contained INCO in complete or
slightly disrupted puck form were not included in the study (Figure 1).
Reconstitution Method
Step 1. Five vials of INCO were each reconstituted with 2.0 mL of sterile, preserved 0.9% sodium chloride (saline). The vials were
