Botulinum toxin

From Ganfyd

Toxin produced by the anaerobic bacterium Clostridium botulinum. It is a neurotoxin and causes inhibition of the neuromuscular junctions by preventing acetylcholine release (see review ^[1]). Its effects were first described by Justinus Kerner in 1793.

It has been harnessed medically as a treatment for almost any condition postulated to be complicated by muscle spasm.

Licensed indications vary across products and jurisdictions. There may be a reasonable evidence base for clinical efficacy in the rarer out of license indications where the cost of procuring a license makes licensing unlikely. As of 2010 the resource effectiveness for use in some indications such as chronic migraine is unclear. Different products are not equivalent and indeed the units of activity vary with each manufacturer.

Indications include (please see SPCs for qualifications):

• Blepharospasm
• Hemifacial spasm
• Cervical dystonia (spasmodic torticollis)
• Hyperhidrosis
• Chronic migraine
• Specific types of focal spasticity
• Facial lines

indications include (FDA warning:

• Cervical dystonia
• Hyperhidrosis
• Strabismus
• Blepharospasm
• Glabellar lines
• Specific types of focal spasticity

Indications which as of 2010 may have fair clinical evidence of effectiveness include:

• Achalasia^[2]
• Anal fissure
• Frey's syndome
• Masseter hypertrophy
• Painful muscle spasm
• Sialorrhea
• Overactive bladder & detrusuor overactivity

Indication stretch is a major problem, not only because some manufacturers have historically been found to have promote out of license use ^[3] but also because it may work indirectly. Thus there are studies in tinnitus due to stapedius myoclonus, headaches, complex regional pain syndrome, postamputation residual limb myokymia, osteoarthritis, dysphagia in multiple sclerosis, trigeminal neuralgia, plastic surgery flap survival, chronic prostate pain, urinary retention, acute radiation proctitis , keloids and hypertrophic scars and even refractory painful total knee arthroplasty amongst other indications.

Issues

• All use where the botulinum toxin could track to paralyze respiratory or throat muscles runs the risk of serious adverse effect.
• Clinical and cost effectiveness needs to be established for the indication at hand
• The preparations are not interchangable and are dangerous if interchanged without consideration of different administration schedules.
  • In America to help prescribers understand this point they were renamed in 2009 as:
    • OnabotulinumtoxinA (Botox^®)
    • AbobotulinumtoxinA (Dysport^®)
    • RimabotulinumtoxinB (NeuroBloc^®)
• Clinical practice has established that dilutional volume issues can be as important as dose in determining toxicity. Variation from the manufacturers recommendations has lead to prolonged PEG feeding and fatal aspiration.
• Patients with pre-existing muscle disorder such as past poliomyelitis, and the physically frail may be extremely sensitive
• Effects such as impairment of swallowing and fatal aspiration pneumonia can come on weeks after an injection. This creates problems in patients who live alone and in physician recognition of the issue where discontinuity of care is likely if a serious complication occurs
• Use in some indications has evidence base problems, but in others there is a strong clinical evidence base. Generalizations are inappropriate but can tend to occur due to perceptual issues. Cost benefit can be underestimated.

References