Botox Technical Information
This Botox Technical Information Is For Medical Professionals
1. Name of the medicinal product: BOTOX
50 Allergan Units
Powder for solution for injection
2. Qualitative and quantitative composition
Botulinum toxin* type A, 50 Allergan Units/vial.
* from Clostridium botulinum
Botulinum toxin units are not interchangeable from one product to another.
For a full list of excipients, see section 6.1.
3. Pharmaceutical form
Powder for solution for injection.
BOTOX product appears as a thin white deposit that may be difficult to see on the base of the vial.
4. Clinical particulars
4.1 Therapeutic indications
BOTOX is indicated for:
Neurologic disorders:
• treatment of focal spasticity, including:
dynamic equinus foot deformity due to spasticity in ambulant paediatric cerebral palsy patients, two years of age or older
wrist and hand disability due to upper limb spasticity associated with stroke in adults
ankle and foot disability due to lower limb spasticity associated with stroke in adults
• symptomatic relief of blepharospasm, hemifacial spasm and idiopathic cervical dystonia (spasmodic torticollis)
• 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)
Bladder disorders:
• management of bladder dysfunctions in adult patients who are not adequately managed with anticholinergics
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
Skin and skin appendage disorders
• management of severe hyperhidrosis of the axillae, which does not respond to topical treatment with antiperspirants or antihidrotics
• temporary improvement in the appearance of:
moderate to severe vertical lines between the eyebrows seen at maximum frown (glabellar lines) and/or,
moderate to severe lateral canthal lines (crow’s feet lines) seen at maximum smile and/or,
moderate to severe forehead lines seen at maximum eyebrow elevation
when the severity of the facial lines has an important psychological impact in adult patients.
4.2 Posology and method of administration
Posology
Botulinum toxin units are not interchangeable from one product to another. Doses recommended in Allergan Units are different from other botulinum toxin preparations.
Elderly patients
Dosages for elderly patients are the same as for younger adults. Initial dosing should begin at the lowest recommended dose for the specific indication. Elderly patients with significant medical history and concomitant medications should be treated with caution.
There is limited data in patients older than 65 years managed with BOTOX for urinary incontinence with neurogenic detrusor overactivity, ankle and foot disability due to lower limb spasticity associated with stroke, and for facial lines (see section 5.1).
Paediatric population
The safety and efficacy of BOTOX in indications other than those described for the paediatric population in section 4.1 have not been established. No recommendation on posology can be made for indications other than focal spasticity associated with paediatric cerebral palsy. Currently available data per indication are described in section 4.2, 4.4, 4.8 and 5.1, as shown in the table below.
• Focal spasticity associated with paediatric cerebral palsy
2 years (see section 4.2, 4.4 and 4.8)
• Blepharospasm/Hemifacial spasm/ Idiopathic Cervical dystonia
12 years (see section 4.4 and 4.8)
• Primary hyperhidrosis of the axillae
12 years (limited experience in adolescents between 12 and 17 years, see sections 4.4, 4.8 and 5.1)
Botox Technical Information: Method of Administration
BOTOX should only be administered by physicians with appropriate qualifications and expertise in the treatment and the use of the required equipment.
This product is for single use only and any unused solution should be discarded. The most appropriate vial size should be selected for the indication.
An injection volume of approximately 0.1 ml is recommended. A decrease or increase in the BOTOX dose is possible by administering a smaller or larger injection volume. The smaller the injection volume the less discomfort and less spread of toxin in the injected muscle occurs. This is of benefit in reducing effects on nearby muscles when small muscle groups are being injected.
For instructions on reconstitution of the powder for solution for injection, handling and disposal of vials please refer to section 6.6.
Refer to specific guidance for each indication described below.
Generally valid optimum dose levels and number of injection sites per muscle have not been established for all indications. In these cases, individual treatment regimens should therefore be drawn up by the physician. Optimum dose levels should be determined by titration but the recommended maximum dose should not be exceeded.
NEUROLOGIC DISORDERS
Focal spasticity associated with paediatric cerebral palsy
Recommended needle:
Sterile 23-26 gauge/0.60-0.45 mm needle.
Administration guidance:
To be administered as a divided dose through single injections into the medial and lateral heads of the affected gastrocnemius muscle.
Recommended dose:
Hemiplegia: the initial recommended total dose is 4 Units/kg body weight in the affected limb.
Diplegia: the initial recommended total dose is 6 Units/kg body weight divided between the affected limbs.
Maximum dose:
200 Units in total or 6.0 Units/kg body weight, whichever is lower, in a 3-month interval.
Additional information:
Clinical improvement generally occurs within the first two weeks after injection. Repeat doses should be administered when the clinical effect of a previous injection diminishes but not more frequently than every three months. It may be possible to adapt the dosage regimen to obtain an interval of at least six months between treatment sessions.
Focal upper limb spasticity associated with stroke
Recommended needle:
Sterile 25, 27 or 30 gauge needle. Needle length should be determined based on muscle location and depth.
Administration guidance:
Localisation of the involved muscles with techniques such as electromyographic guidance, nerve stimulation, or ultrasound is recommended. Multiple injection sites may allow BOTOX to have more uniform contact with the innervation areas of the muscle and are especially useful in larger muscles.
Botox Technical Information
Recommended dose:
The exact dosage and number of injection sites may be tailored to the individual based on the size, number and location of muscles involved, the severity of spasticity, the presence of local muscle weakness, and the patient response to previous treatment.
The following doses are recommended:
Muscle
Total Dosage;
Number of Sites
Flexor digitorum profundus
15 – 50 Units; 1-2 sites
Flexor digitorum sublimis
15 – 50 Units; 1-2 sites
Flexor carpi radialis
15 – 60 Units; 1-2 sites
Flexor carpi ulnaris
10 – 50 Units; 1-2 sites
Adductor Pollicis
20 Units; 1-2 sites
Flexor Pollicis Longus
20 Units; 1-2 sites
Maximum dose:
Between 200 and 240 Units divided among selected muscles.
Additional information:
If it is deemed appropriate by the treating physician, the patient should be considered for re-injection when the clinical effect of the previous injection has diminished. Re-injections should occur no sooner than 12 weeks after the previous injection. The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose of BOTOX and muscles to be injected. The lowest effective dose should be used.
Focal lower limb spasticity associated with stroke
Recommended needle:
Sterile 25, 27 or 30 gauge needle. Needle length should be determined based on muscle location and depth.
Administration guidance:
Localisation of the involved muscles with techniques such as electromyographic guidance, nerve stimulation, or ultrasound is recommended. Multiple injection sites may allow BOTOX to have more uniform contact with the innervation areas of the muscle and are especially useful in larger muscles.
Recommended dose:
300 Units to 400 Units divided among up to 6 muscles, as listed in the following table.
Muscle
Recommended Dose
Total Dosage; Number of Sites
Gastrocnemius
Medial head
Lateral head
75 Units; 3 sites
75 Units; 3 sites
Soleus
75 Units; 3 sites
Tibialis Posterior
75 Units; 3 sites
Flexor hallucis longus
50 Units; 2 sites
Flexor digitorum longus
50 Units; 2 sites
Flexor digitorum brevis
25 Units; 1 site
Maximum dose:
400 Units in total
Additional information:
If it is deemed appropriate by the treating physician, the patient should be considered for re-injection when the clinical effect of the previous injection has diminished, no sooner than 12 weeks after the previous injection.
Blepharospasm/hemifacial spasm
Recommended needle:
Sterile, 27-30 gauge/0.40-0.30 mm needle.
Administrative guidance:
Electromyographic guidance is not necessary.
Recommended dose:
The initial recommended dose is 1.25-2.5 Units (0.05-0.1 ml volume at each site) injected into the medial and lateral orbicularis oculi of the upper lid and the lateral orbicularis oculi of the lower lid. Additional sites in the brow area, the lateral orbicularis and in the upper facial area may also be injected if spasms here interfere with vision.
The following diagrams indicate the possible injection sites:
Maximum dose:
The initial dose should not exceed 25 Units per eye. In the management of blepharospasm total dosing should not exceed 100 Units in total every 12 weeks.
Additional information:
Avoiding injection near levator palpebrae superioris may reduce the complication of ptosis. Avoiding medial lower lid injections, and thereby reducing diffusion into the inferior oblique, may reduce the complication of diplopia.
In general, the initial effect of the injections is seen within three days and reaches a peak at one to two weeks post-treatment. Each treatment lasts approximately three months, following which the procedure can be repeated indefinitely. Normally no additional benefit is conferred by treating more frequently than every three months.
At repeat treatment sessions, the dose may be increased up to two-fold if the response from the initial treatment is considered insufficient – usually defined as an effect that does not last longer than two months. However, there appears to be little ben