Class
- Neurotoxin
Botulinum Toxin Type A
Commonly Prescribed for
(FDA approved in bold)
- Cervical dystonia (CD)
- Glabellar lines
- Axillary hyperhidrosis (Onabotulinum toxin A only)
- Strabismus and blepharospasm associated with dystonia (Onabotulinum toxin A only)
- Upper limb spasticity in adults
- Hemifacial spasm
- Spasmodic torticollis
- Spasmodic dysphonia (laryngeal dystonia)
- Writer’s cramp and other task-specific dystonias
- Spasticity associated with stroke
- Dynamic muscle contracture in cerebral palsy
- Acquired nystagmus
- Oscillopsia
- Sialorrhea (drooling)
- Headache
- Temporomandibular joint dysfunction
- Diabetic neuropathic pain
- Myofascial pain
- Detrusor sphincter dyssynergia
- Palmar hyperhidrosis
- Tics
- Cosmesis
- Incontinence due to overactive or neurogenic bladder
- Achalasia (esophageal motility disorder)
Botulinum Toxin Type A
How the Drug Works
- Blocks neuromuscular transmission by cleaving SNAP-25 protein, which inhibits the vesicular release of acetylcholine from nerve terminals
- In CD and other dystonias, produces partial denervation of muscle and localized reduction in muscle activity. In hyperhidrosis, produces chemical denervation of sweat gland
- Also appears to inhibit release of neurotransmitters involved in pain transmission (including glutamate, calcitonin gene-related peptide, and substance P) and may enter CNS via retrograde axonal transport
Botulinum Toxin Type A
How Long Until It Works
- Usually 2–3 days, with peak effect beginning at 2–3 weeks. Effect is quicker in blepharospasm compared to CD
Botulinum Toxin Type A
If It Works
- Continue to use as long as effective, but monitor for clinical effects
Botulinum Toxin Type A
If It Doesn’t Work
- Increase dose or change injection technique. Some pain disorders may respond better to oral medications
- Patients can develop neutralizing antibodies from prior exposure. Response to a test dose of 15 units (u) in the frontalis muscle indicates a physiologic response. Antibody formulation has not been reported with newer type-A formulations
Botulinum Toxin Type A
Best Augmenting Combos for Partial Response or Treatment-Resistance
- Increase dose, number of injections or change site of location
Botulinum Toxin Type A
Tests
- None
Adverse Effects (AEs)
Botulinum Toxin Type A
How Drug Causes AEs
- Most AEs are related to muscle weakness adjacent to the site of injection. Serious systemic AEs are rare, but injectors should use the lowest dose and be familiar with injection technique to minimize AEs
Botulinum Toxin Type A
Notable AEs
- Injection site pain and hemorrhage, infection, fever, headache, pruritus, and myalgia. Most AEs depend on site of injection
- CD – dysphagia, neck weakness, upper respiratory infection
- Blepharospasm/strabismus – ptosis, diplopia, dry or watery eyes, keratitis (from reduced blinking)
- Spasmodic dysphonia – hypophonia (“breathy” voice)
- Writer’s cramp – hand weakness
Botulinum Toxin Type A
Life-Threatening or Dangerous AEs
- Rarely patients may experience severe dysphagia requiring a feeding tube or leading to aspiration pneumonia
- Use with caution in patients with motor neuropathies or neuromuscular junctional disorders. These patients may be at greater risk for systemic weakness or respiratory problems
Botulinum Toxin Type A
Weight Gain
- Unusual
Botulinum Toxin Type A
Sedation
- Unusual
Botulinum Toxin Type A
What to Do About AEs
- Most AEs will improve with time (weeks)
Botulinum Toxin Type A
Best Augmenting Agents for AEs
- Most AEs cannot be improved with an augmenting agent
Dosing and Use
Botulinum Toxin Type A
Usual Dosage Range
- The following units are for Botox formulation. The appropriate conversion from Botox to Dysport is unknown, but studies of CD suggest a ratio of 1:3 or less (100 u Botox less than or equal to 300 u Dysport). Xeomin has a similar strength to Botox
- CD – Botox mean dose 236 u (usually 150–300). Per muscle: sternocleidomastoid 12.5–70 u, trapezius 25–100 u, levator scapulae 25–60 u, splenius 20–100 u, scalenus 15–50 u
- Dysport – typical dose 250–1000 u
- Blepharospasm – 1.25–5 u at each site (15–100 u total)
- Oromandibular dystonia – Masseter 10–75 u, temporalis 5–50 u, medial and lateral pterygoids 5–40 u each
- Spasmodic dysphonia – 2.5–5 u
- Sialorrhea – 7.5–40 u
- Limb dystonia – Intrinsic hand muscles 2.5–12.5 u, arm 5–45 u, intrinsic hand muscles 35–85 u, leg muscles 50–200 u
- Primary axillary hyperhidrosis – 50 u per axilla
- Headache – 50–200 u
- Upper limb spasticity – 75–360 u
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