Section 4 Plastic and Reconstructive Problems

HANDL I NG BOTUL I NUM TOX I NS

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. 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. Conclusion and Summary There are several different preparations of BoNT licensed worldwide and others to come. Formula- tions are neither identical nor interchangeable.

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. 1. Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabis- mus 1980;17:21–5. 2. Carruthers A, Carruthers J. Botulinum toxin products overview. Skin Therapy Lett 2008;13:1–4. 3. Aoki RK. Pharmacology and immunology of botulinum neuro- toxins. Int Ophthalmol Clin 2005;45:25–37. 4. Parsa AA, Lye KD, Parsa FD. Reconstituted botulinum type A neurotoxin: clinical efficacy after long-term freezing before use. Aesth Plast Surg 2007;31:188–91. 5. Poulain B, Popoff M, Molgo J. How do the botulinum neurotoxins block neurotransmitter release: from botulism to the molecular mechanism of action. Botulinum J 2008;1: 14–87. 6. Chen F, Kuziemko GM, Stevens RC. Biophysical characterization of the stability of the 150-kilodalton botulinum toxin, the non- toxic component, and the 900-kilodalton botulinum toxin com- plex species. Infect Immun 1998;66:2420–5. 7. Sharma SK, Singh BR. Hemagglutinin binding mediated protec- tion of botulinum neurotoxin from proteolysis. J Nat Toxins 1998;7:239–53. 8. Sattler G. Current and future botulinum neurotoxin type A preparations in aesthetics: a literature review. J Drugs Dermatol 2010;9:1065–71. 9. Binz T, Rummel A. Cell entry strategy of clostridial neurotoxins. J Neurochem 2009;109:1584–95. 10. Chen S, Kim JJ, Barbieri JT. Mechanism of substrate recongnition by botulinum neurotoxin serotype A. J Biol Chem 2007;282: 9621–7. 11. Parrish J. Commercial preparations and handling of botulinum toxin type A and type B. Clin Dermatol 2003;21:481–4. 12. Klein AW. Dilution and storage of botulinum toxin. Dermatol Surg 1998;24:1179–80. 13. De Boulle K, Fagien S, Sommer B, Glogau R. Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: a re- view of the science, the clinical data, and patient satisfaction. Clin Interv Aging 2010;5:101–18. References

With regard to the best dilution to be used, when treating limb muscles, perhaps as a result of greater

DERMATOLOG I C SURGERY