Botulinum neurotoxin formulations: overcoming the confusion

Figures & data

Table 1 Some of the clinical uses of botulinum toxin A

Cosmetic	Therapeutic
	Ophthalmology	Neurology	Otolaryngology	Pain	Autonomic dysfunction	Gastrointestinal	Cardiovascular diseases	Other
Hyperfunctional facial lines: glabellar frown lines, crow’s feet, forehead lines, lateral oblique forehead lines, perioral lines, platysmal bands	Strabismus	Hemifacial spasm	Vocal tics	Migraine	Frey’s syndrome	Gastroparesis	Restenosis	Refractory vaginismus
Brow ptosis, brow repositioning	Blepharospasm	Facial asymmetry	Stuttering	Tension headaches	Sialorrhea	Delayed gastric emptying	Atrial fibrillation	Chronic pain and pelvic floor spasm
Hyperhidrosis: palmar, axillary	Nystagmus	Oromandibular dystonia	Spasmodic dysphonia	Knee, shoulder, neuropathic pain	Rhinorrhea	Chronic anal fissure	Cardiac arrhythmias	Vulvodynia
Facial contouring	Concomitant and non-concomitant misalignment	Cervical dystonia	Oromandibular dystonia	Chronic lower back pain		Achalasia		Erectile dysfunction
Reducing excessive columellar show	Primary or secondary esotropia or exotropia	Spasmodic torticollis	Cricopharyngeal achalasia	Lateral epicondylitis				Urethral and bladder dysfunctions
Excessive gingiva display	Duane’s syndrome	Achalasia	Hemifacial spasm
Scars and keloid revision/improvement		Gustatory sweating Synkinesia Hyperlacrimation Neurogenic detrusor overactivity Chronic migraine Neurogenic incontinence	Temporomandibular joint disorders

Table 2 Properties of different therapeutic botulinum toxin preparations^{5,58,59,114,123,124}

Brand name	Toxin	Manufacturer	Country of production	Pharmaceutical preparation	Storage conditions	Shelf life un-reconstituted	Excipients	Viability after reconstitution
Botox^®/Vistabel^®	Onabotulinum toxin A	Allergan Inc. (Allergan Pharmaceuticals)	Westport, Ireland	Powder	Below 8°C	24 months	Human serum albumin, NaCl	Refrigerated within 24 hours
Dysport^®/Azzalure^®	Abobotulinum toxin A	Ipsen Biopharm Limited	Wrexham, UK	Powder	Below 8°C	24 months	Human serum albumin, lactose	Refrigerated within 24 hours
Xeomin^®/Bocouture^®	Incobotulinum toxin A	Merz Pharmaceuticals	Frankfurt, Germany	Powder	Below 25°C	36 months	Human serum albumin, sucrose	Refrigerated within 24 hours

Figure 1 Botulinum neurotoxin consists of two amino acid chains connected by a disulfide bridge: a heavy amino acid chain with a molecular weight of 100 kDa and a light amino acid chain with a molecular weight of 50 kDa.²⁰

Figure 2 Simplified contents of therapeutic botulinum toxin preparations.

Figure 3 Glabellar complex muscles and position of levator palpebrae superioris muscle.

Note: Top right hand image provided courtesy of Allergan and top left hand image and bottom image acquired from Shutterstock.

Table 3 Correct definitions to apply to botulinum toxin products for clinical administration

Term	Definition
Spread	Physical movement of toxin (caused by, for example, volume of injection)
	Fast and active process
Diffusion	Kinetic dispersion of toxin
	Dispersion beyond the injection site (for example, movement to receptors)
	Slow and passive process
Migration	Distal effects, or the “retrograde transport” phenomena

Table 4 Immunogenicity vs primary nonresponse vs secondary nonresponse

Immunogenicity, and primary and secondary nonresponse
Immunogenicity	The ability of a protein product to elicit antibody formation
Primary nonresponse	Failure to respond to the first and any subsequent administration
Secondary nonresponse	Initial response to treatment, loss of clinical responsiveness over time with repeated treatments

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