Botulinum Toxin Type A

Registered South African indications:

• Dynamic equinus foot deformity
• Focal spasticity
• Strabismus and blepharospasm associated with dystonia
• Spasmodic torticollis
• Urinary incontinence
• Axillary hyperhidrosis
• Glabellar lines
• Crow's feet lines

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Presence of infection at proposed injection site(s)
• Urinary tract infection at time of treatment (for bladder disorders)
• Acute urinary retention at time of treatment (for bladder disorders)
• Patients who are unwilling or unable to initiate catheterisation post-treatment if required (for bladder disorders)
• Presence of bladder calculi (for bladder disorders)

Cautions

• Pregnancy
• Breastfeeding
• Elderly
• Children
• High doses
• Debilitated patients
• Defective neuromuscular transmission
• Underlying neurological disorders
• History of dysphagia and aspiration
• Sedentary patients
• Alterations to anatomy due to prior surgical procedures
• Injection in proximity to lung or other vulnerable anatomic structures
• Inflammation at proposed injection site
• Excessive weakness or atrophy of target muscle
• Cardiovascular disease
• Predisposition to seizures
• Poor underlying health status
• Patients at risk for angle-closure glaucoma
• Patients with subclinical dysphagia

Forms avail. in SA and covered in this monograph: inj

Focal spasticity
- Upper limb spasticity associated with stroke

• IM: 20-50 U/muscle; Max: 240 U/patient

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Sites of injection should be guided by electromyography

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Clinical improvement can be expected within 2 weeks of administration, with peak effect usually seen within 4-6 weeks

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Readministration should not occur before 12 weeks

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Selected cases of strabismus associated with dystonia

• IM: 1.25-5.0 U/muscle; Max: 200 U/2 months

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Paralysis of injected muscles can be expected within 1-2 days of administration, and lasts for 2-6 weeks

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Selected cases of blepharospasm and hemifacial spasm
- Including benign essential blepharospasm or VII nerve disorders (hemifacial spasm)

• IM: 1.25-2.5 U/muscle; Max: 25 U/eye and 100 U/3 months

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Clinical effect is generally seen within 3 days and reaches a peak at 1-2 weeks post-administration

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Readministration should not occur more frequently than every 12 weeks

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Spasmodic torticollis

• IM: 200 U/patient, as divided doses into the most active neck muscles, every 12-16 weeks; Max: 300 U/patient or 360 U/3 months

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Clinical effect is generally seen within 2 weeks and reaches a peak at approximately 6 weeks post-administration

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Readministration should not occur more frequently than every 10 weeks

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Idiopathic overactive bladder
- In adult female patients who have an inadequate response to, or are intolerant of anticholinergics

• IM: 100 U, in 20 divided doses into detrusor muscle

Urinary incontinence due to neurogenic detrusor overactivity
- Caused by spinal cord injury (SCI) or multiple sclerosis (MS) in
adult patients who are willing and able to perform clean intermittent self-catheterisation

• IM: 200 U, in 30 divided doses into detrusor muscle

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Should be administered by medical practitioners who are experienced in the assessment and treatment of bladder dysfunction such as urologists and urogynaecologists

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Clinical effect is generally seen within 2 weeks post-administration

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Readministration should not occur more frequently than every 12 weeks

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Primary axillary hyperhidrosis

• Intradermally: 50 U/axilla, in divided doses

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Area to be injected should be determined beforehand using the iodine-starch test

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Clinical effect is generally seen within 1 week post-administration

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Readministration should not occur more frequently than every 16 weeks

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Glabellar lines

• IM: 20 U/patient, as 5 divided doses into corrugator and procerus muscles

Crow's feet lines

• IM: 24 U/patients, as 6 divided doses into lateral orbicularis oculi muscles

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Readministration should not occur more frequently than every 12 weeks

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Dosage and units are preparation specific and are not interchangeable with other preparations of botulinum type A toxin

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Optimum dose levels levels and number of injection sites per muscle have not been established, and should be determined by titration

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Should only be administered by doctors with appropriate qualifications and expertise in the treatment and the use of the required equipment

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See additional prescribing points

Paed. forms avail. in SA and covered in this monograph: inj

Dynamic equinus foot deformity in paediatric cerebral palsy patients

Younger than 2 years

• Not established for use

Older than 2 years
- Hemiplegia

• IM: 4 U/kg, as divided doses into the calf muscle of the affected limb; Max: 200 U/patient

- Diplegia 

• IM: 6 U/kg, as divided doses into both calf muscles; Max: 200 U/patient

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Clinical improvement can be expected within 2 weeks of administration

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Administration may be repeated when the clinical effect diminishes, but not more frequently than every 3 months

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Selected cases of blepharospasm and hemifacial spasm
- Including benign essential blepharospasm or VII nerve disorders (hemifacial spasm)

Younger than 12 years

• Not established for use

Older than 12 years

• See adult dosage

Spasmodic torticollis

Younger than 16 years

• Not established for use

Older than 16 years

• See adult dosage

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Dosage and units are preparation specific and are not interchangeable with other preparations of botulinum type A toxin

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Optimum dose levels levels and number of injection sites per muscle have not been established, and should be determined by titration

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Should only be administered by doctors with appropriate qualifications and expertise in the treatment and the use of the required equipment

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See additional prescribing points

Pregnancy

• Caution
• There are no adequate data from the use of onabotulinumtoxinA in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. OnabotulinumtoxinA is not recommended during pregnancy and in women of childbearing potential not using contraception

Breastfeeding

• Caution; not recommended 
• There is no information on whether onabotulinumtoxinA is excreted in human milk. The use of onabotulinumtoxinA during breastfeeding cannot be recommended

Fertility

• There is no adequate data on the effects on fertility from the use of botulinum toxin type A in women of childbearing potential. Studies in male and female rats have shown fertility reductions

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• No dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Initial dosing should begin at the lowest recommended dose for the specific indication

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Somnolence 
• Gait disturbance
• Paraesthesia
• Asthenia
• Depression
• Insomnia
• Hypertonia
• Hypoaesthesia
• Headache
• Incoordination
• Amnesia
• Dizziness
• Facial paresis
• Facial palsy
• Anxiety
• Brachial plexopathy
• Dysarthria
• Myasthenia gravis
• Peripheral neuropathy
• Radiculopathy
• Seizures
• Syncope

Cardiovascular Disorders

• Orthostatic hypotension
• Hot flushes
• Arrhythmia
• Myocardial infarction

Respiratory Disorders

• Rhinitis
• Upper respiratory infection
• Dyspnoea
• Dysphonia
• Aspiration pneumonia
• Respiratory depression
• Respiratory failure

Gastrointestinal Disorders

• Nausea and vomiting
• Oral paraesthesia
• Dysphagia
• Dry mouth
• Constipation
• Diarrhoea

Genitourinary Disorders

• Urinary incontinence
• Bacteriuria
• Dysuria
• Urinary retention
• Pollakiuria
• Leukocyturia
• Haematuria
• Bladder diverticulum

Endocrine and Metabolic Disorders

• Anorexia

Musculoskeletal Disorders

• Myalgia
• Muscular weakness
• Pain in extremity
• Arthralgia
• Bursitis
• Neck pain
• Musculoskeletal pain
• Musculoskeletal stiffness
• Muscle spasms
• Muscle tightness
• Muscle atrophy

Skin and Subcutaneous Tissue Disorders

• Rash
• Dermatitis
• Pruritus
• Peripheral oedema
• Injection site pain
• Hyperhidrosis
• Subcutaneous nodule
• Alopecia
• Erythema
• Photosensitivity reaction
• Dry skin
• Urticaria
• Dermatitis psoriasiform
• Erythema multiforme

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Angioedema
• Serum sickness
• Ecchymosis
• Purpura
• Pyrexia

Sensory Disorders

• Vertigo
• Eyelid ptosis
• Punctate keratitis
• Lagophthalmos
• Dry eye
• Photophobia
• Eye irritation
• Increased lacrimation
• Ectropion
• Diplopia
• Entropion
• Blurred vision
• Eyelid oedema
• Corneal ulceration
• Corneal epithelium defect
• Corneal perforation
• Closed angle glaucoma
• Strabismus
• Hypoacusis
• Tinnitus

Others

• Fall

• Aminoglycosides
• Spectinomycin
• Neuromuscular blocking agents
• Other botulinum neurotoxin serotypes

None routine. Specific cases may require

• Residual urine volume

Dilution instructions

- Dilution table for 50, 100, 200 Unit vials for all indications except bladder disorders

Resulting dose (Units per 0.1ml)	50 Unit vial	100 Unit vial	200 Unit vial
	Amount of diluent* added	Amount of diluent* added	Amount of diluent* added
20 Units	0.25ml	0.5ml	1ml
10 Units	0.5ml	1ml	2ml
5 Units	1ml	2ml	4ml
4 Units	1.25ml	2.5ml	5ml
2.5 Units	2ml	4ml	8ml
1.25 Units	4ml	8ml	N/A

*OnabotulinumtoxinA must only be reconstituted with sterile, non-preserved sodium chloride 9mg/ml (0.9%) solution for injection

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• OnabotulinumtoxinA is denatured by bubbling or similar violent agitation
• Inject the diluent into the vial gently
• Reconstituted OnabotulinumtoxinA should be clear, colourless and particulate free
• Should be stored in a refrigerator 2 to 8 degrees celsius
• Should be administered within 24 hours of reconstitution

- Overactive bladder

• Reconstitute a 100 Unit vial of OnabotulinumtoxinA with 10 ml of 0,9% non-preserved saline solution
• Draw the 10 ml from the vial into a 10 ml syringe
  OR
• Reconstitute two 50 Unit vials of OnabotulinumtoxinA each with 5 ml of 0,9% non-preserved saline solution
• Draw the 5 ml from each of the vials into a single 10 ml syringe
• Resulting dose: 100 Units/10ml

- Urinary incontinence due to neurogenic detrusor overactivity

• Reconstitute two 100 Unit vials of OnabotulinumtoxinA, each with 6 ml of 0,9% non-preserved saline solution
• Draw 4 ml from each vial into each of two 10 ml syringes
• Draw the remaining 2 ml from each vial into a third 10 ml
  syringe
• Complete the reconstitution by adding 6 ml of 0,9% non-preserved saline solution into each of the 10 ml syringes
  OR
• Reconstitute a 200 Unit vial of OnabotulinumtoxinA with 6 ml of 0,9% non-preserved saline solution
• Draw 2 ml from the vial into each of three 10 ml syringes
• Complete the reconstitution by adding 8 ml of 0,9% non-preserved saline solution into each of the 10 ml syringes
  OR
• Reconstitute four 50 Unit vials of OnabotulinumtoxinA, each with 3 ml of 0,9% non-preserved saline solution and mix the vials gently
• Draw 3 ml from the first vial and 1 ml from the second vial into one 10 ml syringe
• Draw 3 ml from the third vial and 1 ml from the fourth vial into a second 10 ml syringe
• Draw the remaining 2 ml from the second and fourth vials into a third 10 ml syringe
• Complete the reconstitution by adding 6 ml of 0,9% non-preserved saline solution into each of the three 10 ml syringes
• Resulting dose: 200 Units/30ml

Clostridium botulinum toxin type A neurotoxin complex blocks peripheral acetylcholine release at presynaptic cholinergic nerve terminals. 

Injection (per vial) 50u

• Botox (Allergan) originator

Injection (per vial) 100u

• Botox (Allergan) originator

Injection (per vial) 200u

• Botox (Allergan) originator