INTRODUCTION
Botulinum neurotoxin (BoNT) is the most potent neurotoxin in existence.1 BoNT is derived from Clostridium botulinum, a gram positive, anaerobic, spore-forming bacteria.2 C. botulinum produces many subtypes of toxin, denoted A through G. However, only subtypes A, B, E, and F have demonstrated effects in humans.2,3 Botulinum toxin cleaves SNARE proteins responsible for the presynaptic release of acetylcholine.4 Inhibition of acetylcholine release prevents depolarization of the postsynaptic muscle fiber and subsequent skeletal muscle contraction.3 This produces a classical flaccid paralysis. This effect is harnessed clinically in the treatment of a variety of conditions. Botulinum toxin subtypes A and B are the only subtypes currently used in clinical formulations.2
The first known clinical use of BoNT was for the treatment of strabismus. Dr Alan B. Scott, an ophthalmologist, first published his use of an intramuscular injection of an A-toxin containing formulation in 1980.5 He named his formulation Oculinum, and later sold it to Allergan.2 The first FDA-approved botulinum toxin formulation, Allergan's Botox, was approved in 1989 for strabismus, blepharospasm, and hemifacial spasm.3 In 2002, Botox was approved for its renowned use in the treatment of glabellar rhytides.2 Botulinum toxin is now available in a variety of formulations and has been approved for a variety of indications.
The first known clinical use of BoNT was for the treatment of strabismus. Dr Alan B. Scott, an ophthalmologist, first published his use of an intramuscular injection of an A-toxin containing formulation in 1980.5 He named his formulation Oculinum, and later sold it to Allergan.2 The first FDA-approved botulinum toxin formulation, Allergan's Botox, was approved in 1989 for strabismus, blepharospasm, and hemifacial spasm.3 In 2002, Botox was approved for its renowned use in the treatment of glabellar rhytides.2 Botulinum toxin is now available in a variety of formulations and has been approved for a variety of indications.
Different formulations of BoNT are available. Those FDA-approved and currently on the market in the United States include Botox (onabotulinumtoxin A), Xeomin (incobotulinumtoxin A), Dysport (abobotulinumtoxin A), and Myobloc (rimabotulinumtoxin B). Botox is indicated for cosmetic treatment of rhytides of the glabella, lateral canthus, and forehead.6 Xeomin is indicated for cosmetic treatment of rhytides of the glabella in adults.7 Dysport is indicated for cosmetic treatment of rhytides of the glabella in patients less than 65 years old.8 Myobloc is not indicated for cosmetic use and its on-label FDA-approved uses will be described later in this paper.9
These formulations differ in their toxin concentration, which directly impacts the units administered for treatment. Most formulations, other than Myobloc, require reconstitution with saline. Xeomin notably does not require refrigeration. The different formulations also demonstrate variable durations of effect. For example, Dysport has been noted to have a longer duration of action than Botox, possibly due to higher toxin concentrations.3
Xeomin contains the least human serum albumin (HSA) content of the available formulations.3 HSA is used as an excipient stabilizer in all commercially available
