Botulinum toxin type a parenteral 100unit, 125unit, 200unit and 50unit
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of botulinum toxin type A.
Drugs List
Therapeutic Indications
Uses
Ankle and foot disability with lower limb spasticity in adults post stroke
Arm symptoms associated with focal spasticity
Blepharospasm and hemifacial spasm
Dynamic equinus foot deformity in cerebral palsy paed. patients 2yrs & over
Hypersalivation
Migraine (prophylaxis)
Severe hyperhidrosis of the axillae unresponsive to topical treatment
Temporary improvement of forehead lines,glabellar frown lines or crows feet
Treatment of cervical dystonia (torticollis)
Urinary incontinence not adequately managed with anticholinergics
Wrist/hand disability due to upper limb spasticity, post stroke in adults
Treatment of blepharospasm and hemifacial spasm.
Treatment of cervical dystonia (spasmodic torticollis).
Management of severe hyperhidrosis of the axillae, which does not respond to topical treatment with antiperspirants or antihidrotics.
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).
Focal spasticity, including the treatment of:
Dynamic equinus foot deformity due to spasticity in ambulant paediatric cerebral palsy patients, two years of age or older;
Post-stroke spasticity of the upper limb presenting with wrist and hand disability in adults;
Post stroke spasticity of the lower limb presenting with ankle and foot disability in adults.
Temporary improvement in the appearance of:
Moderate to severe horizontal forehead lines seen at maximum eyebrow elevation;
Moderate to severe vertical lines between the eyebrows seen at maximum frown (glabellar lines) and/or;
Moderate to severe crow's feet lines seen at maximum smile (lateral canthal lines);
In adults up to the age of 75 years where the severity of these lines has an important psychological impact for the patient.
Management of bladder dysfunctions in adult patients who are not adequately managed with anticholinergics, including:
Overactive bladder with symptoms of urinary incontinence, urgency and frequency;
Neurogenic detrusor overactivity with urinary incontinence due to subcervical spinal cord injury (traumatic or non-traumatic), or multiple sclerosis.
Dosage
Adults
Blepharospasm
Initial dose is 1.25 to 2.5 units injected into the medial and lateral orbicularis oculi muscle of the upper lid and the lateral orbicularis oculi muscle of the lower lid.
Additional sites in the brow area, the lateral orbicularis oculi muscle and in the upper facial area may also be injected if spasms here interfere with vision. Avoid injecting near the levator palpebrae superioris to reduce the occurrence of ptosis. Avoiding medial lower lid injections and thereby reducing diffusion into the inferior oblique, may reduce the complication of diplopia.
An effect is usually seen within 3 days and peaks at 1 to 2 weeks post treatment. Each treatment lasts approximately 3 to 4 months and can be repeated if required. Repeat treatment doses may be increased up to two-fold if the response from the initial treatment is considered insufficient. Little benefit has been seen from injecting more than 5units per site.
Maximum dose 25 units per eye. No additional benefit has been seen by treating more frequently than every 3 months. Total dosing should not exceed 100 units every 12 weeks.
Hemifacial spasm
Patients with hemifacial spasm or VIIth nerve disorders should be treated as for unilateral blepharospasm, with other affected facial muscles being injected as needed. Electromyographic control may be necessary to identify affected small circumoral muscles.
Cervical dystonia (spasmodic torticollis)
Botulinum toxin type A is usually injected into the sternocleidomastoid, levator scapulae, scalenus, splenius capitis, and/or trapezius muscle(s). This list is not exhaustive as any of the muscles responsible for controlling head position may be involved and therefore require treatment. Electromyographic guidance and/or ultrasound may be required. Muscle activation patterns may change spontaneously without a change in clinical presentation.
No more than 200 units in total should be administered for the first treatment, with adjustments made on subsequent treatments according to the initial response. Maximum dose 300 units in one treatment session and maximum 50 units at any one injection site.
Dosing must be tailored to the individual patient based on the patient's head and neck position, location of pain, muscle hypertrophy, patient's bodyweight, and patient response to the injection. The muscle mass and the degree of hypertrophy or atrophy are factors to be taken into consideration when selecting the appropriate dose. For some products specific dose ranges are provided by the manufacturer depending on the type of dystonia and affected muscles. Consult product literature for details.
No more than 100 units should be injected in to the sternocleidomastoid muscle bilaterally due to an increased risk of adverse effects (in particular dysphagia).
Multiple injection sites allow more uniform contact with the innervated areas of the dystonic muscle and are especially useful in larger muscles. The optimal number of injection sites is dependent upon the size of the muscle to be chemically denervated.
The median first onset of effect is observed within 7 days of injection. The effect of each treatment generally lasts approximately 3 to 4 months, but may be significantly longer or shorter. The period between each treatment session should be at least 10 weeks.
Hyperhidrosis of the axillae
Initial dose of 50 units injected intradermally to each axilla, evenly distributed in multiple sites approximately 1 to 2 centimetres apart. The hyperhidrotic area to be injected may be defined by using standard staining techniques, e.g. Minor's iodine-starch test.
Clinical improvement generally occurs within the first week after injection and persists for 4 to 7 months. Repeat injections can be administered when the effects from previous injections subside. Do not repeat more frequently than every 16 weeks.
Focal spasticity associated with stroke
The exact dosage and number of injection sites may be tailored to the individual based on the size, number and location of the muscles involved, the severity of spasticity, the presence of local muscle weakness and response to previous treatment.
Localisation of affected muscles by electrophyographic guidance, nerve stimulation or ultrasound is recommended.
Upper limb
The dose is specific to each individual preparation and is not interchangeable. Consult product literature for details.
Repeat treatments can be administered at intervals of not less than 12 weeks.
Lower limb
300 units to 400 units divided among up to 6 muscles.
Specific dose ranges are recommended dependent on the target muscle. Consult product literature for details.
Repeat treatment can be administered at intervals of not less than 12 weeks.
Chronic migraine
Initial dose is 155 units to 195 units administered intramuscularly at 31 to 39 sites.
Divide injections across 7 specific head or neck muscle areas as advised in the product literature. In the case of predominant pain location(s), additional injections to one or both sides may be administered in up to 3 specific muscle groups (occipitalis, temporalis, and trapezius), up to the maximum dose per muscle, as quoted in the product literature.
The recommended retreatment schedule is every 12 weeks.
Glabella lines
The dose is specific to each individual preparation and is not interchangeable. Consult product literature.
Lateral canthal (crow's feet) lines
The dose is specific to each individual preparation and is not interchangeable. Consult product literature.
Forehead lines
The dose is specific to each individual preparation and is not interchangeable. Consult product literature.
Overactive bladder
Recommended dose of 100 units split into 20 separate injections, administered into the detrusor muscle at various sites.
The injections should be administered via a flexible or rigid cystoscope (avoiding the trigone and base) as advised in the product literature.
Patients should be considered for reinjection when the clinical effect of the previous injection has diminished, but no sooner than 3 months post treatment.
Urinary incontinence due to neurogenic detrusor overactivity
Recommended dose of 200 units split into 30 separate injections, administered into the detrusor muscle at various sites.
The injections should be administered via a flexible or rigid cystoscope (avoiding the trigone and base) as advised in the product literature.
Patients should be considered for reinjection when the clinical effect of the previous injection has diminished, but no sooner than 3 months post treatment.
Elderly
Consult the product literature for brand specific age advice regarding the treatment.
Botulinum A toxin is not recommended for the temporary improvement of facial lines in patients over 75 years of age.
For other indications the lowest effective dose and the longest clinically indicated interval between injections is recommended. There have not been adequate studies performed on dosing in the elderly.
Children
Blepharospasm and hemifacial spasm, cervical dystonia and hyperhidrosis of the axilae.
Children aged 12 to 18 years:
Consult product literature. Not all products are licensed in children.
Dynamic equinus foot deformity caused by spasticity in ambulant paediatric cerebral palsy in children 2 years and older
Hemiplegia: The initial dose is 4 units per kg bodyweight in the affected limb.
Diplegia: The initial dose is 6 units per kg bodyweight divided between the affected limbs.
Maximum dose 200 units total or 6 units per kg bodyweight, whichever is lower, in a 3 month interval.
Clinical improvement generally occurs within the first 2 weeks after injection. Repeat injections should be administered when the clinical effect of a previous injection diminishes but not more frequently than every 3 months.
Additional Dosage Information
Treatment failure
If no treatment effect occurs within one month after the initial injection analyse potential causes of failure e.g. too low dose, poor isolation of target muscles, poor injection technique, fixed contracture, development of toxin-neutralising antibodies.
Consider clinical verification of the neurotoxin effect on the injected muscle e.g. an electromyographic investigation in a specialised facility.
If no adverse reactions occur during initial treatment, perform an additional course of treatment under the following conditions:
Dose adjustment with regard to analysis of the most recent therapy failure.
The recommended minimum interval between the initial and repeat treatment is followed.
Electromyographic guidance (where appropriate for the condition).
A treatment-naive patient should be regarded as a primary non-responder in cases of first injection failure. In cases of non-response, alternative therapies should be considered.
Administration
All products should be prepared in accordance with the manufacturers instructions for the specific indication being treated.
Blepharospasm, hemifacial spasm, spasmodic torticollis, chronic migraine, glabella lines, focal spasticity due to stroke in adults and paediatric cerebral palsy: Intramuscular use only.
Hyperhidrosis of the axillae: Intradermal use only.
Bladder disorders: Injection into the detrusor muscle only.
Use the smallest injection volume recommended to reduce discomfort and the spread of toxin. This will reduce the effects on nearby muscle groups.
Consult product literature for specific administration advice including recommended needle size.
Contraindications
Administration site infection
Children under 2 years
Amyotrophic lateral sclerosis
Bladder calculi - if treating overactive bladder
Breastfeeding
Myasthenia gravis
Myasthenic Eaton-Lambert syndrome
Urinary retention - if treating overactive bladder
Urinary tract infection - if treating overactive bladder
Precautions and Warnings
Debilitation
Elderly
Inflammation of injection site
Predisposition to aspiration or regurgitation
Predisposition to narrow angle glaucoma
Prolonged bleeding times
Weight below 12kg
Chronic respiratory impairment
Dysphagia
Eyelid disorder
Muscle weakness
Narrow angle glaucoma
Neurological disorder
Neuromuscular disorder
Pregnancy
Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all age groups
Not all available brands are licensed for all indications
Rule out causes of secondary hyperhidrosis before treatment
Contains human albumin
Derived from human blood - transmission of infectious agents possible
Different brands of this product are not interchangeable
Discard any unused portion
Do not inject into blood vessels
For single patient use only
Have adrenaline injection ready for use in case of anaphylaxis
Prepare injection only in accordance with manufacturer's directions
Record name and batch number of administered product
Residual drug, spillage, etc - neutralise with dilute hypochlorite solution
Treatment to be administered by or under supervision of specialist
Avoid deep or misplaced injections
Monitoring of patients with compromised corneas required during use
Advise pt to seek medical attention if diff. swallowing or breathing occurs
Neutralising antibodies may develop that decrease clinical efficacy
Discontinue if hypersensitivity reactions occur
'Unit' of potency is brand specific. Refer to brand data sheet for dose
Consider reducing initial dose in the elderly
Do not exceed recommended dosages and frequency of administration
Not licensed for all indications in all age groups
Female: Ensure adequate contraception during treatment
Advise patient to resume normal activities gradually
Procedure related injury can occur. Injections may result in localised infection, pain, inflammation, paraesthesia, hypoaesthesia, tenderness, swelling, erythema, and/or bleeding/bruising. Care should be taken when injecting near vulnerable anatomical structures particularly the pleural apices and oesophagus. The relevant anatomy, and any alterations to the anatomy due to prior surgical procedures, must be understood prior to administration.
The effect of administering different botulinum toxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of previously administered botulinum toxin.
Undesirable effects (including paralysis) may occur as a result of the spread of botulinum toxin type A to sites distant from the injection site or following misplaced injections. Administration at therapeutic doses can lead to exaggerated muscle weakness including swallowing and breathing difficulties and can result in death. Symptoms may present hours to weeks after treatment. Risk is greatest in patients with underlying conditions which predispose them to aspiration including a history of aspiration or dysphagia, in particular children and adults treated for spasticity, those receiving high doses and patients with defective neuromuscular transmission.
Cardiovascular adverse effects (including arrhythmia and myocardial infarction) and seizures have been reported following the use of botulinum toxin type A.
Some botulinum toxin type A products might be used in patients with subclinical or clinical evidence of defective neuromuscular transmission (myasthenia gravis, Lambert-Eaton Syndrome) or in patients with peripheral motor neuropathic diseases (amyotrophic lateral sclerosis, motor neuropathy) but only with extreme caution and under close supervision when the benefit of treatment outweighs the risk. The appropriate manufacturer product literature should be consulted.
Blepharospasm
Reduced blinking following injection of botulinum A toxin into the orbicularis muscle, can lead to corneal exposure, persistent epithelial defects and corneal ulceration, especially in patients with cranial nerve disorders. Careful testing of corneal sensation should be performed in patients with previous eye operations. Avoid injections into the lower lid area to prevent ectropion, and treat any epithelial defects. Ecchymosis occurs easily in the soft eyelid tissues, this can be minimised by applying gentle pressure at the injection site immediately after injection.
Cervical dystonia (spasmodic torticollis)
The risk of dysphagia is more pronounced when treating cervical dystonia due to the spread of toxin from oesophageal musculature and can be minimised by limiting the dose injected into the sternocleidomastoid muscle to less than 100 units. This risk is further increased in patients with smaller neck muscle mass and in patients receiving bilateral injections into the sternocleidomastoid muscle.
Focal spasticity
Botulinum A toxin injection is not likely to be effective in improving range of motion at a joint affected by a fixed contracture. Take caution when treating adult patients with post stroke spasticity at increased risk of fall.
Urinary incontinence
In patients who are not regularly practising catheterisation, post-void residual urine volume should be assessed within 2 weeks post-treatment and periodically as medically appropriate. Patients should be instructed to contact their physician if they experience difficulties in voiding as catheterisation may be required.
Patients with asymptomatic bacturiuria or sterile urine may require prophylactic antibiotics. Treatment should follow local protocols.
Pregnancy and Lactation
Pregnancy
Use botulinum toxin type A with caution in pregnancy.
Some manufacturers recommend not using botulinum toxin type A during pregnancy and in women of childbearing potential not using contraception. Others recommend only using botulinum toxin type A when clearly necessary and the potential benefit outweighs the risk. There is limited data regarding the use of botulinum toxin type A in pregnant women. Animal studies have shown reproductive toxicity.
Lactation
Botulinum toxin type A is contraindicated in breastfeeding.
The manufacturers do not recommend breastfeeding whilst using botulinum type A products. There is no data regarding the use of botulinum toxin type A during breastfeeding and it is not known whether botulinum A toxin is excreted in human breast milk.
Side Effects
Alopecia
Amnesia
Anaphylactic reaction
Anaphylaxis
Angioedema
Anorexia
Antibody formation
Anxiety
Arrhythmias
Arthralgia
Arthropathy
Aspiration pneumonia
Asthenia
Asthenopia
Brachial plexopathy
Bursitis
Corneal disorders
Depression
Dermatitis
Diplopia
Dizziness
Dry mouth
Dryness and irritation of eyes
Dysarthria
Dysphagia
Dysphonia
Dyspnoea
Ecchymosis
Ectropion
Electrophysiological jitter in distant muscles
Entropion
Erythema
Erythema multiforme
Exacerbation of myasthenia gravis
Eye disorder
Eyelid oedema
Facial oedema
Facial paralysis
Falls
Fatigue
Fever
Gait abnormality
Gastrointestinal disorder
Glaucoma (closed angle)
Haematoma
Haematuria
Headache
Hot flushes
Hypersensitivity reactions
Hypertonia
Hypoacusis
Hypoaesthesia
Inco-ordination
Infections
Influenza-like symptoms
Injection site reactions
Insomnia
Madarosis
Malaise
Migraine
Muscle spasm
Muscle twitch
Muscle weakness
Myalgia
Myocardial infarction
Nausea
Neck pain
Oedema
Orthostatic hypotension
Pain
Painful extremities
Paraesthesia
Paralysis in muscles distant to the injection site
Perceived increase in non axillary sweating
Peripheral neuropathy
Photosensitivity
Presyncope
Pruritus
Ptosis
Purpura
Pyrexia
Radiculopathy
Rash
Respiratory depression
Seizures
Serum sickness
Skin disorder
Somnolence
Stiffness
Syncope
Tinnitus
Upper respiratory tract infection
Urinary dysfunction
Urinary incontinence
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last full review date: February 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Azzalure. Galderma UK Ltd. Revised July 2018.
Summary of Product Characteristics: Bocouture 50 units. Merz Pharma Ltd. Revised October 2018.
Summary of Product Characteristics: Bocouture 100 units. Merz Pharma Ltd. Revised October 2018.
Summary of Product Characteristics: Botox 50 units. Allergan Ltd. Revised July 2020.
Summary of Product Characteristics: Botox 100 units. Allergan Ltd. Revised July 2020.
Summary of Product Characteristics: Botox 200 units. Allergan Ltd. Revised July 2020.
Summary of Product Characteristics: Letybo 50 units powder for solution for injection. Croma Pharma Ltd. Revised March 2022.
Summary of Product Characteristics: Xeomin 50 units. Merz Pharma UK Ltd. Revised September 2017.
Summary of Product Characteristics: Xeomin 100 units. Merz Pharma UK Ltd. Revised September 2017.
Summary of Product Characteristics: Xeomin 200 units. Merz Pharma UK Ltd. Revised September 2017.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 09 June 2022
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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