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abobotulinumtoxinA group, but after analyzing
other interindividual variations, the authors consid-
ered differences between the several dilutions to be
clinically irrelevant.
92
Reviewing all published studies where a fixed dose of
BoNTA was reconstituted with different volumes,
five were favorable to greater diffusion or enhanced
effect with higher volumes, whereas nine found no
difference in efficacy. Three studies reported more
discomfort with higher dilutions, even though they
were not statistically significant. Controversy re-
mains. For small muscles such as those located in the
face or hand, it seems that there is no difference in
results with greater dilutions. For large muscles of
the limbs, greater volume might be advantageous.
More studies with larger samples are necessary
to clarify this.
Conclusion and Summary
There are several different preparations of BoNT
licensed worldwide and others to come. Formula-
tions are neither identical nor interchangeable.
Prescribing information on all available products
recommend reconstitution in unpreserved saline, but
studies in the literature cited suggest that other
solutions can be used, such as preserved saline,
anesthetics (lidocaine or bupivacaine) with or with-
out epinephrine, and albumin. According to in vivo
studies, onabotulinumtoxinA is not as fragile as
originally thought, and foam during reconstitution
does not inactivate the toxin.
Although manufacturers recommend storage at 2
1
C
to 8
1
C in the refrigerator, toxin administration
within 4 to 24 hours, and not freezing after recon-
stitution, it appears that some products can be stored
for longer periods of time after reconstitution, in the
refrigerator or the freezer, without loss of efficacy or
contamination.
With regard to the best dilution to be used, when
treating limb muscles, perhaps as a result of greater
dispersion of the toxin, higher dilutions might be
beneficial. For facial muscles, more-concentrated
dilutions are preferred, because they produce less
discomfort for patients.
Many of the precautions around BoNT use,
often recommended by the manufacturers, are
described in the clinical literature as too restrictive.
The literature suggests that toxins may be sturdier
and more resistant to degradation than previously
understood.
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DERMATOLOG I C SURGERY
HANDL I NG BOTUL I NUM TOX I NS