Section 4 Plastic and Reconstructive Problems

HANDL I NG BOTUL I NUM TOX I NS

Initially, it was believed that BoNTA was fragile and susceptible to surface denaturation. 11,12 A variety of conditions have been postulated to affect the potency of BoNTs, and different authors and manufacturers made many recommendations concerning reconstitution and storage of the agent in order not to interfere with its efficacy or duration. During these more than 20 years of clinical use, some of these initial ideas have changed, and others have remained stable with our growing experience with and knowledge about BoNTs. The objective of this article was to review the medical literature and prescribing information on all of the available products and to update the concept of handling toxins, although this is not a Cochrane type analysis. It will be divided into five sections: preparations, reconstitution, storage, sterility, and dilution. BoNT formulations are not identical or inter- changeable. 13 They possess individual potencies, and attention is required to ensure proper use and avoid errors. In April 2009, the FDA established drug names to reinforce these differences and pre- vent potential serious risks associated with these medications. 14 Currently, only one form of BoNTB (rimabotuli- numtoxinB) is available, under the trade name of Myobloc/Neurobloc (Solstice Neurosciences Inc./ Eisai Co., Ltd.) in the United States and Neurobloc in Europe. The U.S. FDA approved it for cervical dystonia in 2001. Preparations

2. AbobotulinumtoxinA: Dysport (Ipsen Ltd., Berkshire, UK) in the United States, Europe, and Latin America and Azzalure in Europe.

3. BoNTA Prosigne (Lanzhou, China) in Asia and Latin America.

4. BoNTA Neuronox (Medy-Tox Inc., South Korea)

5. IncobotulinumtoxinA: Xeomin, (Merz Pharma, Frankfurt) in Canada, Germany, the United States (for therapeutic use), and Latin America and Bocouture in Europe and Latin America. Another product, BoNTA PureTox (Mentor Corpo- ration, Santa Barbara, CA), similar to Xeomin, is an uncomplexed type A toxin and has completed phase III trials.

BoNTs manufacturer recommendations on supply, dilution, and storage are summarized in Table 1. 15–20

Reconstitution

Published information about variations in reconsti- tution methods, including agitation or foam formation and mixtures of toxins with several substances is reviewed in this section.

Unpreserved Saline

OnabotulinumtoxinA is the most studied type of BoNTA, and as a consequence, the majority of the information about handling BoNTs is found with this brand. Initially, the product was thought to be fragile. 11,12 Later, many studies following anecdotal observations confirmed the persistence of activity of BoNTA in different situations. 21–32

There are five sources of BoNTA available world- wide:

Most manufacturers recommend that BoNTA reconstitution be performed using unpreserved saline. 15–19

1. OnabotulinumtoxinA: Botox/Botox Cosmetic in the United States, Latin America (Allergan, Inc., Irvine, CA), also known as Vistabel in Europe and Vistabex in Italy.

In a recent international consensus on the use of abobotulinumtoxinA, 32 the recommendation was to

DERMATOLOG I C SURGERY