BOTOX

What it is

BOTOX is botulinum toxin type A purified neurotoxin complex, available in vials containing 50 units (U), 100 units (U) or 200 units (U) . It is a powder for injection .

Approved indications

BOTOX is indicated for the following therapeutic indications: — Treatment of overactive bladder with symptoms of urinary incontinence, urgency and frequency in adult patients who have an inadequate response to or are intolerant of an anticholinergic medication. — Treatment of urinary incontinence due to neurogenic detrusor overactivity resulting from a defined neurological illness (such as spinal cord injury or multiple sclerosis) in adult patients who have an inadequate response to or are intolerant of an anticholinergic medication. — Prophylaxis of headaches in adults with chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine). — Treatment of strabismus in patients twelve years and over. — Treatment of blepharospasm associated with dystonia, including benign blepharospasm and VIIth nerve disorders (specifically hemifacial spasm) in patients twelve years and over. — Treatment of cervical dystonia (spasmodic torticollis). — Treatment of focal spasticity of the upper and lower limbs, including dynamic equinus foot deformity, due to juvenile cerebral palsy in patients two years and older. — Treatment of severe primary hyperhidrosis of the axillae. — Treatment of focal spasticity in adults. — Treatment of spasmodic dysphonia. BOTOX is also indicated for the following cosmetic indications: — Temporary improvement in the appearance of upper facial rhytides (glabellar lines, crow's feet and forehead lines) in adults. — Temporary improvement in the appearance of platysma continuous bands in healthy adults.

Dosing overview

Dosing of BOTOX is individualised for each patient. BOTOX dosing should always start with the minimal effective dose, and the dosing interval should typically not be more frequent than every three months . For overactive bladder, the recommended dose is 100 U, administered as 0.5 mL (5 U) injections across 20 sites in the detrusor, which is also the maximum recommended dose . For neurogenic detrusor overactivity, the recommended dose is 200 U . For chronic migraine, the recommended dose is 155 U to 195 U administered intramuscularly as 0.1 mL (5 U) injections per site, divided across 7 specific head and neck muscle areas . The recommended re-treatment schedule is every 12 weeks . For blepharospasm, the initial recommended dose is 1.25 U to 2.5 U (0.05 mL to 0.1 mL volume at each site) injected into the medial and lateral pre-tarsal orbicularis oculi of the upper lid and into the lateral pre-tarsal orbicularis oculi of the lower lid . For primary hyperhidrosis of the axillae, 50 U of BOTOX should be injected intradermally and evenly distributed in 10–15 sites approximately 1–2 cm apart within the hyperhidrotic area for each axilla .

Key safety warnings

BOTOX is not therapeutically equivalent to any other botulinum toxin type A preparation, as the potencies of BOTOX and other botulinum toxin type A preparations are based on different assay methods. Extreme caution is required if it should prove necessary to substitute BOTOX by another botulinum type A toxin . Post-marketing safety data suggest that botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms include muscular weakness, ptosis, diplopia, blurred vision, facial weakness, swallowing and speech disorders, constipation, aspiration pneumonia, difficulty breathing and respiratory depression . Swallowing and breathing difficulties can be life threatening, and patients or caregivers should seek immediate medical attention if any of these symptoms occur . BOTOX is contraindicated in patients with myasthenia gravis or Eaton Lambert Syndrome . Patients with neuromuscular junction disorders may be at increased risk of clinically significant systemic effects including severe dysphagia and respiratory compromise from typical doses of BOTOX . Serious and/or immediate hypersensitivity reactions such as anaphylaxis and serum sickness have been rarely reported, as well as other manifestations of hypersensitivity including urticaria, soft tissue oedema and dyspnoea . In patients with overactive bladder, the proportion of subjects who initiated clean intermittent catheterisation for urinary retention following treatment with BOTOX was 6.5% (36 of 552 patients) compared to 0.4% for placebo (2 of 542 patients). Patients with diabetes mellitus treated with BOTOX were more likely to develop urinary retention than those without diabetes, with 12.3% (10 of 81 patients) experiencing urinary retention compared to 6.3% in non-diabetic patients .

Contraindications

BOTOX is contraindicated in individuals with known hypersensitivity to any ingredient in the formulation . BOTOX is contraindicated in patients with myasthenia gravis or Eaton Lambert Syndrome . BOTOX is contraindicated in the presence of infection at the proposed injection site(s) . Intradetrusor injection of BOTOX is contraindicated in patients who have a urinary tract infection and in patients with acute urinary retention who are not routinely catheterising. Due to the risk of urinary retention, intradetrusor injection of BOTOX is also contraindicated in patients who are not willing and/or able to initiate catheterisation post-treatment if required .

PBS listing

BOTOX is registered on the ARTG in three strengths: 50 U vial (first listed 2013-07-01), 100 U vial (first listed 1999-07-09), and 200 U vial (first listed 2011-03-02) . In March 2017, PBAC recommended amendments to add gynaecologists to the specialists able to provide treatment for urinary incontinence due to idiopathic overactive bladder . In July 2017, PBAC recommended removal of methysergide from the list of prophylactic medicines required to be trialed prior to initiating BOTOX for chronic migraine . In November 2019, PBAC recommended extension of the Section 100 Botulinum Toxin Program Authority Required (Streamlined) listing to include spasticity following acute events other than stroke .

Regulatory history

BOTOX 100 U vial was first registered on the ARTG on 9 July 1999 . The 200 U vial was registered on 2 March 2011, and the 50 U vial on 1 July 2013 . An AusPAR was published on 6 August 2013 for the indication of treatment of overactive bladder with symptoms of urinary incontinence, urgency and frequency in adult patients who have an inadequate response to or are intolerant of an anticholinergic medication .