Prescribing Information

DYSPORT® 300 or 500 units (Clostridium botulinum type A toxin-haemagglutinin complex) Powder for solution for injection

See full Summary of Product Characteristics (SmPC) before prescribing. Available at www.medicines.org.uk. Presentation: Vials of 300 or 500 units (U) of Clostridium botulinum type A toxin-haemagglutinin complex. Powder for solution for injection. Indications: Symptomatic treatment of focal spasticity of: Upper limbs in adults, Lower limbs in adults affecting the ankle joint. Dynamic equinus foot deformity in ambulant paediatric cerebral palsy patients ≥ 2 years, Upper limbs in paediatric cerebral palsy patients ≥ 2 years. Symptomatic treatment in adults of: Spasmodic torticollis, Blepharospasm, Hemifacial spasm, Severe primary hyperhidrosis of the axillae (not responding to topical treatment with antiperspirants or antihidrotics). Management of urinary incontinence in adults with neurogenic detrusor overactivity due to spinal cord injury (traumatic or non-traumatic) or multiple sclerosis, who are regularly performing clean intermittent catheterisation. Administration: Dysport should only be administered by an appropriately qualified healthcare practitioner with expertise in the treatment of the relevant indication and the use of the required equipment, in accordance with national guidelines. Reconstitute with preservative-free sodium chloride 0.9% w/v injection to yield a concentration as follows: Adult Upper or Lower Limb spasticity: 100/200/500U per ml; Focal spasticity in children ≥ 2 years of age (Dynamic equinus foot deformity or upper limb spasticity associated with cerebral palsy or a combination of both): 100/200/500U per ml (further dilutions may be required); Blepharospasm, Hemifacial spasm: 200U per ml; Neurogenic Detrusor Overactivity: 600/800U per ml (specific instructions may be required). Spasmodic torticollis: 500U per ml. Axillary hyperhidrosis: 200U per ml. For further instruction on reconstitution see SmPC. The units (U) of Dysport are specific to the preparation and are not interchangeable with other preparations of botulinum toxin. Posology: Dosing in initial and sequential treatment sessions should be tailored to the individual. Injection guiding techniques recommended to target injection sites. Degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in dose and muscles to be injected. Adult Upper and/or Lower Limb spasticity: No more than 1 ml administered at any single injection site. Injections may be repeated every 12-16 weeks or as required to maintain response, but not more frequently than every 12 weeks. If treating both upper and lower limbs during the same treatment session, the dose of Dysport to be injected in each limb should be tailored to the individual’s need, without exceeding a total dose of 1500U. Upper Limb: In clinical trials, intramuscular (IM) injections of 500U and 1000U doses were divided among selected muscles at a given treatment session (see SmPC). Total dose should not exceed 1000U. Clinical improvement may be expected 1 week after injection and may last up to 20 weeks. Lower Limb: In clinical trials, IM injections of 1000U and 1500U doses were divided among selected muscles (see SmPC). Total dose should not exceed 1500U. Paediatric cerebral palsy spasticity: Total dose should be divided between affected spastic muscles of upper and/ or lower limb(s). If possible, the dose should be distributed across more than 1 injection site in any single muscle. For treatment initiation, consider starting with a lower dose. No more than 0.5 ml should be administered in any single injection site (see SmPC for full details). Paediatric Dynamic equinus foot deformity due to focal spasticity: Max. total dose for unilateral lower limb injections must not exceed 15U/kg or 30U/kg for bilateral injections, per treatment session. Total dose per treatment session must not exceed 30U/kg or 1000U, whichever is lower. Clinical improvement may be expected within 2 weeks after injection. Repeat treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection. A majority of patients in clinical studies were re-treated between 16-22 weeks; however, some patients had a longer duration of response, i.e. 28 weeks. Focal spasticity of paediatric cerebral palsy in upper limbs: For each treatment session, max. total dose for unilateral upper limb injections must not exceed 16U/kg or 640U, whichever is lower. For bilateral injections, maximum dose must not exceed 21 U/kg or 840 U whichever is lower. Repeat treatment should be administered when the effect of a previous injection has diminished, but no sooner than 16 weeks after the previous injection. A majority of patients in clinical studies were re-treated between 16-28 weeks; however, some patients had a longer duration of response, i.e. 34 weeks or more. Focal spasticity of paediatric cerebral palsy upper and lower limbs: refer to posology section for individual indications above. Concomitant treatment should not exceed total dose per treatment session of 30U/kg or 1000U, whichever is lower. Retreatment of the upper and lower limbs combined considered no sooner than 12 to 16 weeks after the previous treatment session. The optimal time to retreatment should be selected based on an individual’s progress and treatment response. Urinary incontinence due to neurogenic detrusor overactivity: Recommended dose is 600 U. In case of insufficient response, such as in patients with a severe disease presentation, a dose of 800 U may be used. Should be administered to patients who are regularly performing clean intermittent catheterisation. The total dose should be divided across 30 intradetrusor injections evenly distributed throughout the detrusor muscle, avoiding the trigone. Dysport is injected via a flexible or rigid cystoscope and each injection should be to a depth of approximately 2 mm with the delivery of 0.5 ml to each site. For the final injection, approximately 0.5 ml of sterile normal saline should be injected to ensure that the full dose is delivered. Spasmodic torticollis: Initial recommended dose is 500U IM as a divided dose into the 2 or 3 most active neck muscles. The split amongst muscles will vary according to type of torticollis diagnosed (see SmPC). Lower dose may be appropriate in markedly underweight patients or the elderly, where reduced muscle mass may exist. Subsequent doses may be adjusted according to clinical response and side-effects observed. Doses within the range of 250-1000U are recommended, although the higher doses may be accompanied by an increase in side effects, particularly dysphagia. Max. dose must not exceed 1000U. Symptom relief may be expected within 1 week after injection. Injections may be repeated approx. every 16 weeks, but not more frequently than every 12 weeks. Safety and efficacy in children not demonstrated for this indication. Blepharospasm and hemifacial spasm: Initial recommended dose is 40U per affected eye. Subsequently, if the response is insufficient from the initial treatment, the dose may be increased to 60U, 80U or up to 120U/eye. However, the incidence of local adverse events, specifically ptosis, was dose related. Max. dose must not exceed 120U/eye. Injections are given subcutaneously, medially and laterally into the junction between the preseptal and orbital parts of both upper and lower orbicularis oculi muscles of each eye. In order to reduce the risk of ptosis, injections near the levator palpebrae superioris should be avoided. Relief of symptoms may be expected within 2-4 days with maximal effect within 2 weeks. Repeat injections as required to prevent symptoms recurrence, but not more frequently than every 12 weeks. Safety and efficacy in children not demonstrated for this indication. Axillary hyperhidrosis: The initial recommended dose is 100U per axilla (10U to 10 sites), given intradermally. If desired effect is not attained with this dose, up to 200U/axilla can be administered, for subsequent injections. Max. dose must not exceed 200U/axilla. The maximum effect should be seen by week 2 after injection. Injections should not be repeated more frequently than every 12 weeks. Safety and efficacy in children not demonstrated for this indication. See SmPC for full dosing information. Contraindications: Known hypersensitivity to the active substance or to any of the excipients. Urinary tract infection at the time of treatment for the management of urinary incontinence due to neurogenic detrusor overactivity. Warnings and precautions: Side effects related to the spread of toxin, distant from the injection site have been reported which, in some cases, was associated with dysphagia, pneumonia and/or significant debility resulting, very rarely, in death. Patients treated with therapeutic doses may present with excessive muscle weakness. Risk of occurrence of such side effects may be reduced by using the lowest effective possible dose and by not exceeding the maximum recommended dose. Exercise caution, with close medical supervision, in patients with subclinical/clinical evidence of marked defective neuromuscular transmission (e.g. myasthenia gravis), where excessive muscle weakness may occur with Dysport therapeutic doses. Increased risk of this side effect in patients with underlying neurological disorders. Exercise caution when treating lower limb spasticity in adults especially in elderly patients, who may be at increased risk of fall. Dry eye has been reported with the use of Dysport in the treatment of blepharospasm and hemifacial spasm. Reduced tear production, reduced blinking, and corneal disorders may occur. Very rare cases of death, occasionally in the context of dysphagia, pneumopathy (including but not limited to dyspnoea, respiratory failure, respiratory arrest) and/or in patients with significant asthenia, have been reported following treatment with botulinum toxin A or B. Patients with disorders resulting in defective neuromuscular transmission, difficulty in swallowing or breathing are more at risk of experiencing these effects. In these patients, treatment must be administered under the control of a specialist and only if the benefit of treatment outweighs the risk. Administer with caution to patients with pre- existing swallowing/breathing problems which can worsen following the distribution of the effect of toxin into the relevant muscles. Aspiration has occurred in rare cases and is a risk when treating patients who have a chronic respiratory disorder. Do not exceed recommended Dysport posology and administration frequency. Warn patients and their care-givers to seek immediate medical treatment in cases of swallowing, speech or respiratory problems. Do not use to treat spasticity in patients who have developed a fixed contracture. In patients with prolonged bleeding times, infection/inflammation at the proposed injection site, only use if strictly necessary. Autonomic dysreflexia associated with the treatment procedure for neurogenic detrusor overactivity can occur. Prompt medical attention may be required. Exercise caution where the targeted muscle shows excessive weakness or atrophy. Dysport should only be used to treat a single patient during a single session. Antibody formation to botulinum toxin has been noted rarely in patients receiving Dysport. Clinically, neutralising antibodies might be suspected by substantial deterioration in response to therapy and/or the need for consistent use of increased doses. Consider carefully before injecting patients with history of allergic reaction to a product containing botulinum toxin type A. Paediatric use: For the treatment of spasticity associated with cerebral palsy in children, Dysport should only be used in children of 2 years of age or over. Post-marketing reports of possible distant spread of toxin have been very rarely reported in paediatric patients with comorbidities, predominantly with cerebral palsy. In general, the dose used in these cases was in excess of that recommended. 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 with significant neurologic debility, dysphagia, or have a recent history of aspiration pneumonia or lung disease. Treatment in patients with poor underlying health status should be administered only if the potential benefit to the individual patient outweighs the risks. Traceability: the name and the batch number of the administered product should be clearly recorded. Interactions: Drugs affecting neuromuscular transmission (e.g. aminoglycosides, curare-like non-depolarising blockers, muscle relaxants) may potentiate the effect of botulinum toxin, use with caution. Fertility, pregnancy and lactation: Safety in pregnancy has not been demonstrated; Dysport should only be used if the benefit justifies any potential risk to the foetus. Exercise caution when prescribing to pregnant women. Use during lactation cannot be recommended. Studies in male and female rats have shown effects on fertility (see SmPC). Effects on ability to drive and use machines: May temporarily impair the ability to drive or operate machinery in the case of adverse reactions such as muscle weakness and visual disturbances. Undesirable effects: Side effects related to spread of toxin distant from the injection site have been reported, such as dry mouth, exaggerated muscle weakness, dysphagia, aspiration/aspiration pneumonia, with fatal outcome (death) in some very rare cases. Hypersensitivity reactions have also been reported post-marketing. In general, the following adverse reactions were reported in clinical trials, across all indications: Common: asthenia, fatigue, influenza like illness, injection site reactions (e.g. pain, bruising, pruritus, oedema). Rare: includes neuralgic amyotrophy and rash. Adverse reactions vary across the indications. Adult Upper Limb spasticity: Common: muscular weakness, musculoskeletal pain, pain in the extremity. Adult Lower Limb spasticity: Common: dysphagia, muscular weakness, myalgia, asthenia, fatigue, influenza-like illness, injection site reactions (pain, bruising, rash, pruritus), fall. Dynamic equinus foot deformity due to focal spasticity in ambulant paediatric cerebral palsy: Common: myalgia, muscular weakness, urinary incontinence, influenza-like illness, injection site reaction (e.g. pain, erythema, bruising etc.), gait disturbance, fatigue, fall. Focal spasticity of paediatric cerebral palsy in upper limbs: Common: muscular weakness, pain in extremity, influenza-like illness, asthenia, fatigue, injection site bruising, rash. Concomitant treatment of upper and lower limbs in paediatric cerebral palsy patients: When treating upper and lower limbs concomitantly at a total dose of up to 30U/kg or 1000U whichever is lower, there are no safety findings in addition to treating either upper limb or lower limb muscles alone. Neurogenic Detrusor Overactivity: Very Common: Urinary tract infection; Common: Bacteriuria, Constipation, Erectile dysfunction, Haematuria; In the pivotal double blind placebo-controlled studies, over the first 12 weeks of treatment, urinary tract infections were reported in 15.8% of Dysport treated patients and 17.4% of placebo treated patients. Spasmodic torticollis: Very common: dysphagia, dry mouth, muscle weakness; Common: dysphonia, dyspnoea, headache, dizziness, facial paresis, vision blurred, visual acuity reduced, neck pain, musculoskeletal pain, musculoskeletal stiffness, myalgia, pain in extremity; Rare: includes aspiration. Dysphagia appeared to be dose related and occurred most frequently following injection into the sternomastoid muscle. A soft diet may be required until symptoms resolve. These side effects may be expected to resolve within 2-4 weeks. Blepharospasm and hemifacial spasm: Very common: ptosis; Common: facial paresis, diplopia, dry eye, lacrimation increased, eyelid oedema; Uncommon: includes VIIth nerve paralysis, Rare: includes ophthalmoplegia Side effects may occur due to deep or misplaced injections of Dysport temporarily paralysing other nearby muscle groups. Axillary hyperhidrosis: Common: compensatory sweating. Post-marketing experience: Not known: hypersensitivity, hypoaesthesia, muscle atrophy. See SmPC for full side-effect profile including all uncommon and rare events for each indication. Overdose: Respiratory support may be required where excessive doses cause paralysis of respiratory muscles. General supportive care is advised. Symptoms of overdose may not present immediately following injection. Monitor patients for several weeks for symptoms of systemic weakness or muscle paralysis, should accidental injection or oral ingestion occur. Pharmaceutical precautions: Unopened vials: Store at 2°C – 8°C. Do not freeze. Refer to the SmPC for further details on the reconstituted solution. Legal category: POM. Basic NHS Cost:£92.40 per single 300U vial, £308.00 per pack of two 500U vials. Marketing authorisation numbers: 300U: PL 34926/0014; 500U: PL 34926/0001. MA Holder: Ipsen Limited, 190 Bath Road, Slough, UK, SL1 3XE. Tel: + 44 (0) 1753 627777. Dysport® is a registered trademark. Date of PI preparation: October 2023. Ref. DYS-UK-007529