BOTOX^® (botulinum toxin type A)

Please refer to the Summary of Product Characteristics (SmPC) before prescribing.

PRESENTATION: Botulinum toxin type A (from clostridium botulinum), 50, 100 & 200 Allergan Units/vial. INDICATIONS: Management of Neurologic disorders: blepharospasm, hemifacial spasm and associated focal dystonias, cervical dystonia (spasmodic torticollis). BOTOX is indicated for the symptomatic treatment of focal spasticity of the ankle and foot in ambulant paediatric cerebral palsy patients two years or older as an adjunct to rehabilitative therapy. Focal spasticity of the ankle and foot in adult post stroke patients and focal spasticity of the wrist and hand in adult post stroke patients. Symptom relief in adults fulfilling criteria for chronic migraine (defined as headaches on ≥15 days per month of which at least 8 days with migraine) in patients who have responded inadequately or are intolerant of prophylactic migraine medications. Bladder disorders: idiopathic overactive bladder with symptoms of urinary incontinence, urgency and frequency in adult patients who have an inadequate response to, or are intolerant of, anticholinergic medication and urinary incontinence in adults with neurogenic detrusor overactivity resulting from neurogenic bladder due to stable sub-cervical spinal cord injury, or multiple sclerosis. Skin and skin appendage disorder: Persistent severe primary hyperhidrosis of the axillae, which interferes with the activities of daily living and is resistant to topical treatment.

DOSAGE AND ADMINISTRATION: Botulinum toxin Units are not interchangeable from one product to another. In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded. Botox must only be reconstituted with sterile sodium chloride 9 mg/ml (0.9%) solution for injection. Neurologic disorders: Focal Spasticity of the lower limb in paediatric patients: Appropriately sized sterile needle. Needle length should be determined based on muscle location and depth. Localisation of the involved muscles with techniques such as needle electromyographic guidance, nerve stimulation, or ultrasound is recommended. Prior to injection, local anaesthesia or local anaesthesia in combination with minimal or moderate sedation may be used, per local site practice. The safety and efficacy of BOTOX in the treatment of paediatric spasticity has not been evaluated under general anaesthesia or deep sedation/analgesia. The recommended dose for treating paediatric lower limb spasticity is 4 Units/kg to 8 Units/kg body weight divided among the affected muscles. The total dose of BOTOX administered per treatment session in the lower limb should not exceed 8 Units/kg body weight or 300 Units, whichever is lower. (and 10 Units/kg body weight or 340 Units when treating both lower limbs). 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: Inject using a 27-30 gauge/0.40-0.30mm needle. Initially, 1.25–2.5 Units injected into the medial and lateral orbicularis oculi of the upper lid and the lateral orbicularis oculi of the lower lid. Initial dose should not exceed 25 Units per eye. Total dose should not exceed 100 Units every 12 weeks. Hemifacial spasm: Treat as for unilateral blepharospasm. Inject other affected facial muscles as needed. Cervical dystonia: Inject using a 25-30 gauge/0.50-0.30 mm needle. Tailor dosing to individual patient based on muscle mass and degree of hypertrophy or atrophy. Do not inject sternomastoid muscle bilaterally. No more than 200 Units for first course. Subsequently, maximum total dose of 300 Units. Treatment intervals of less than 10 weeks are not recommended. Focal upper limb spasticity associated with stroke in adult: Inject using a sterile 25, 27 or 30 gauge needle. Recommended dose is up to 240 Units, divided among selected muscles. Needle length should be determined based on muscle location and depth. Tailor dose and number of sites based on size, number and location of muscles involved, the severity of spasticity, the presence of local muscle weakness, and the patient response to previous treatment. Re-injections should not occur before 12 weeks. Focal lower limb spasticity associated with stroke in adult: Inject using a sterile 25, 27 or 30 gauge needle. Needle length should be determined based on muscle location and depth. Localisation of the involved muscles with electromyographic guidance or nerve stimulation techniques may be useful. 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. The recommended dose for treating adult lower limb spasticity involving the ankle and foot is 300 - 400 Units divided among up to 6 muscles. Re-injections should not occur before 12 weeks. The maximum recommended dose at one treatment is 400 Units.  Chronic migraine: Inject using 30 gauge, 0.5 inch needle, or 1 inch needle for thicker muscles in neck region if required. Inject 0.1 ml (5 Units) intramuscularly to 31 and up to 39 injection sites, divided across seven specific head/neck muscle areas. Total dose 155 Units -195 Units. Bladder disorders: Overactive bladder: Reconstituted Botox (100 Units/10 ml) is injected approximately 2mm into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone and base. The bladder should be instilled with enough saline to achieve adequate visualisation for the injections, but over-distension should be avoided. 20 injections of 0.5 ml each (total volume 10 ml) should be spaced approximately 1 cm apart. For the final injection, approximately 1 ml of sterile normal saline should be injected so the full dose is delivered. The saline used for bladder wall visualisation should not be drained so that patients can demonstrate their ability to void prior to leaving the clinic. Reinjection should be no sooner than 3 months from the prior bladder injection. Urinary incontinence due to neurogenic detrusor overactivity: Reconstituted BOTOX (200 Units/30 ml) injected into the detrusor muscle via a flexible or rigid cystoscope, avoiding the trigone and base. Needle should be inserted approximately 2 mm into the detrusor, and 30 injections of 1 ml each (total volume 30 ml), spaced approximately 1 cm apart. For final injection, approximately 1 ml of sterile normal saline should be injected so the full dose is delivered. The saline used for bladder wall visualisation should be drained and patient observed for at least 30 minutes post-injection. Reinjection should be no sooner than 3 months from the prior bladder injection. Skin and skin appendage disorder: Primary hyperhidrosis of the axillae: Inject using a sterile 30 gauge needle. Inject 50 Units intradermally into each axilla, evenly distributed in multiple sites approximately 1-2 cm apart. Repeat injections should be administered when clinical effects from previous injections diminishes and treating physician deems it necessary. Injections should not be repeated more frequently than every 16 weeks. All Indications: In treating adult patients, including when treating for multiple indications, the maximum cumulative dose should not exceed 400 Units, in a 12 weeks interval CONTRAINDICATIONS: Known hypersensitivity to any constituent. Pregnancy or lactation. Presence of infection at proposed injection site(s). Bladder disorders: Patients who have urinary tract infection at the time of treatment. Patients with acute urinary retention at the time of treatment, who are not routinely catheterising. Patients who are not willing and/or able to initiate catheterisation post-treatment if required.

SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details. The recommended dosages and frequencies of administration should not be exceeded due to the potential for overdose, exaggerated muscle weakness, distant spread of toxin and the formation of neutralising antibodies. Initial dosing in treatment naïve patients should begin with the lowest recommended dose for the specific indication. Prescribers and patients should be aware that side effects can occur despite previous injections being well tolerated. Side effects related to spread of toxin distant from the site of administration have been reported sometimes resulting in death, which in some cases was associated with dysphagia, pneumonia and/or significant debility. The risk of symptoms is probably greatest in patients who have underlying conditions and comorbidities, including children and adults treated for spasticity or those treated with high doses.  Elderly patients with significant medical history and concomitant medications should be treated with caution. There are limited clinical data in patients older than 65 years treated for post-stroke spasticity of the upper and lower limb. Dysphagia has also been reported following injection to sites other than the cervical musculature. Caution in patients with subclinical or clinical evidence of defective neuromuscular transmission, with underlying neurological disorders and with a history of dysphagia and aspiration. Patients or caregivers should be advised to seek immediate medical care if swallowing, speech or respiratory disorders arise. Sedentary patients should be cautioned to resume activity gradually. The relevant anatomy, and any alterations to the anatomy due to prior surgical procedures, must be understood prior to administration and injection into vulnerable anatomic structures must be avoided. Pneumothorax associated with injection procedure has been reported. Serious adverse events including fatal outcomes have been reported in patients who had received off-label injections directly into salivary glands, the oro-lingual-pharyngeal region, oesophagus and stomach. If serious hypersensitivity reactions occur, further injection should be discontinued and appropriate medical therapy, such as epinephrine, immediately instituted.  Procedure-related injury could occur. Caution should be exercised in the presence of inflammation at the proposed injection site(s) or when excessive weakness or atrophy is present in the target muscle. There have also been reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. New onset or recurrent seizures have been reported, typically in patients, who are predisposed to experiencing these events. Injections at more frequent intervals or at higher doses may lead to greater incidence of antibody formation. Clinical fluctuations during the repeated use (as with all botulinum toxins) may be a result of different vial reconstitution procedures, injection intervals, muscles injected and slightly differing potency values given by the biological test method used. Paediatric Use: The safety and efficacy in indications other than those described for the paediatric population has not been established. There have been rare spontaneous reports of death sometimes associated with aspiration pneumonia in children with severe cerebral palsy after treatment with botulinum toxin, including following off-label use (e.g. neck area). Extreme caution should be exercised when treating paediatric patients who have significant neurologic debility, dysphagia, or have a recent history of aspiration pneumonia or lung disease. BOTOX should only be administered by physicians who are experienced in the assessment and treatment of paediatric focal spasticity and as part of a structured program of rehabilitation. Neurologic disorders: Focal spasticity of the ankle and foot associated with paediatric cerebral palsy and focal spasticity of the ankle, foot, wrist and hand in adult post-stroke patients: BOTOX is a treatment of focal spasticity that has only been studied in association with usual standard of care regimens, and is not intended as a replacement for these treatment modalities.  BOTOX is not likely to be effective in improving range of motion at a joint affected by a fixed contracture and should not be used for the treatment of focal spasticity of upper limb (hand and wrist) and lower limb (ankle and foot) in adult post-stroke patients if muscle tone reduction is not expected to result in improved function (e.g. improvement in walking), or improved symptoms (e.g. reduction in pain), or to faciliate care. For lower limb spasticity, improvement in active function may be limited if treatment is initiated longer than 2 years post-stroke or in patients with less severe ankle spasticity (Modified Ashworth Scale (MAS) < 3). Caution should be exercised when treating adult patients with post-stroke spasticity who may be at increased risk of fall. Blepharospasm: Reduced blinking following botulinum toxin injection into the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and corneal ulceration, especially in patients with VII nerve disorders. Careful testing of corneal sensation in eyes previously operated upon, avoidance of injection into the lower lid area to avoid ectropion, and vigorous treatment of any epithelial defect should be employed. Ecchymosis occurs easily in the soft eyelid tissues. Because of the anticholinergic activity of botulinum toxin, caution should be exercised when treating patients at risk for angle closure glaucoma, including patients with anatomically narrow angles. Cervical dystonia: Patients can experience dysphagia which may be very mild, but could be severe. Dysphagia may persist for two to three weeks after injection, but has been reported to last up to five months post-injection. Consequent to the dysphagia there is the potential for aspiration, dyspnoea and occasionally the need for tube feeding. Limiting the dose injected into the sternocleidomastoid muscle to less than 100 Units may decrease the occurrence of dysphagia. Patients with smaller neck muscle mass, or patients who receive bilateral injections into the sternocleidomastoid muscle, have been reported to be at greater risk of dysphagia. Chronic migraine: Safety and efficacy have not been established in prophylaxis of headaches in patients with episodic migraine (headaches on <15 days per month) or chronic tension type headache. Safety and efficacy in patients with medication overuse headache (secondary headache disorder) has not been studied. Bladder Disorders: Appropriate medical caution should be exercised when performing a cystoscopy. In patients who are not catheterising, post-void residual urine volume should be assessed within 2 weeks post-treatment and periodically as medically appropriate up to 12 weeks. Patients should be instructed to contact their physician if they experience difficulties in voiding as catheterisation may be required. Overactive bladder: Men with overactive bladder and signs or symptoms of urinary obstruction should not be treated with BOTOX. Urinary incontinence due to neurogenic detrusor overactivity: Autonomic dysreflexia associated with the procedure can occur. Prompt medical attention may be required. Skin and Skin Appendage Disorder: Primary hyperhidrosis of the axilla:  Medical history and physical examination, along with specific additional investigations as required, should be performed to exclude potential causes of secondary hyperhidrosis (e.g. hyperthyroidism, phaeochromocytoma).

INTERACTIONS: Theoretically, effect may be potentiated by aminoglycoside antibiotics or spectinomycin, or other drugs that interfere with neuromuscular transmission.

UNDESIRABLE EFFECTS: See SmPC for full details on adverse reactions including details on frequencies. In general, adverse reactions usually occur within the first few days following injection and are generally transient, but may persist for several months or longer. Local muscle weakness represents the expected pharmacological action of botulinum toxin in muscle tissue. However, weakness of adjacent muscles and/or muscles remote from the site of injection has been reported. Localised pain, inflammation, paraesthesia, hypoaesthesia, tenderness, swelling/oedema, erythema, localised infection, bleeding and/or bruising have been associated with the injection. Needle-related pain and/or anxiety have resulted in vasovagal responses, including transient symptomatic hypotension and syncope. Fever and flu syndrome have also been reported after injections of botulinum toxin. Neurologic Disorders: Focal spasticity of the lower limb in paediatric patients: Common (>1/100 to <1/10) rash, ligament sprain, skin abrasion, gait disturbance, injection site pain. Focal upper and lower limb spasticity associated with stroke in adult: Common (>1/100 to <1/10) nausea, pain in extremity, muscle weakness, fatigue, rash,  arthralgia, musculoskeletal stiffness, oedema peripheral, fall. Blepharospasm, hemifacial spasm and associated dystonias: Very Common (>1/10) eyelid ptosis. Common (>1/100 to <1/10)  punctate keratitis, lagophthalmos, dry eye, photophobia, eye irritation, lacrimation increase, ecchymosis, irritation, face oedema. Cervical dystonia: Very Common (>1/10) dysphagia, muscular weakness, pain, Common (>1/100 to <1/10) Rhinitis, upper respiratory tract infection, dizziness, hypertonia, hypoaesthesia, somnolence, headache, dry mouth, nausea, musculoskeletal stiffness, soreness,  asthenia, influenza-like illness, malaise. Chronic Migraine: Common (>1/100 to <1/10) headache, migraine, facial paresis, eyelid ptosis, pruritis, rash, neck pain, myalgia, musculoskeletal pain, musculoskeletal stiffness, muscle spasms, muscle tightness, muscular weakness, injection site pain. Bladder disorders: Adult Overactive Bladder: Very Common (>1/10) urinary tract infection, dysuria. Common (>1/100 to <1/10) bacteriuria, urinary retention, residual urine volume, pollakiuria, leukocyturia. Paediatric overactive bladder: Common (>1/100 to <1/10) urinary tract infection, dysuria*, urethral pain*, abdominal pain, abdominal pain lower. Adult urinary incontinence due to neurogenic detrusor overactivity: Very Common (>1/10) urinary tract infection, urinary retention, bacteriuria, residual urine volume. Common (>1/100 to <1/10) insomnia, constipation, muscular weakness, muscle spasm, haematuria*, dysuria*, bladder diverticulum, fatigue, gait disturbance, autonomic dysreflexia*, fall. Paediatric neurogenic detrusor overactivity: Very Common (>1/10) bacteriuria. Common (>1/100 to <1/10) urinary tract infection, leukocyturia, haematuria, bladder pain*. Skin and skin appendage disorder: Primary hyperhydrosis of the axillae: Very Common (>1/10) injection site pain. Common (>1/100 to <1/10) headache, paraesthesia, hot flushes, hyperhidrosis (non-axillary sweating), skin odour abnormal, pruritus, subcutaneous nodule, alopecia, pain in extremity, pain, injection site oedema, injection site haemorrhage, injection site hypersensitivity, injection site irritation, asthenia, injection site reactions. (*procedure-related).

Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; website: www.hpra.ie.

LEGAL CLASSIFICATION: POM (S1A)

MARKETING AUTHORISATION HOLDER: AbbVie Limited, Citywest Business Campus, Dublin 24, Ireland.  

MARKETING AUTHORISATION NUMBERS: BOTOX 50 Units PA1824/17/2; BOTOX 100 Units PA 1824/17/1; BOTOX 200 Units PA1824/17/3

Further information is available from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, D24XN32.

DATE OF REVISION: June 2024 PI/17/003