Dysport

Dysport

Manufacturer:

Ipsen

Distributor:

DCH Auriga - Healthcare
Full Prescribing Info
Contents
Clostridium botulinum type A toxin-haemagglutinin complex.
Description
Each vial also contains albumin 20% solution 125 mcg and lactose 2.5 mg.
One (1) unit is defined as the median lethal intraperitoneal dose in mice.
Action
Pharmacology: Pharmacodynamics: Clostridium botulinum type A toxin-haemagglutinin complex blocks peripheral cholinergic transmission at the neuromuscular junction by a presynaptic action at a site proximal to the release of acetylcholine. The toxin acts within the nerve ending to antagonise those events that are triggered by calcium (Ca2+) which culminate in transmitter release. It does not affect postganglionic cholinergic or postganglionic sympathetic transmission. The action of toxin involves an initial binding step whereby the toxin attaches rapidly and avidly to the presynaptic nerve membrane. Secondly, there is an internalisation step in which toxin crosses the presynaptic membrane, without causing onset of paralysis. Finally, the toxin inhibits the release of acetylcholine by disrupting the Ca2+-mediated acetylcholine release mechanism, thereby diminishing the endplate potential and causing paralysis.
Recovery of impulse transmission occurs gradually as new nerve terminals sprout and contact is made with the postsynaptic motor endplate, a process which takes 6-8 weeks in the experimental animal.
Pharmacokinetics: Pharmacokinetic studies with botulinum toxin pose problems in animals because of the high potency, the minute doses involved, the large molecular weight of the compound and the difficulty of labelling toxin to produce sufficiently high-specific activity.
Studies using I125-labelled toxin have shown that the receptor-binding is specific and saturable, and the high density of toxin receptors is a contributory factor to the high potency. Dose and time responses in monkeys showed that at low doses, there was a delay of 2-3 days with peak effect seen 5-6 days after injection. The duration of action, measured by changes of ocular alignment and muscle paralysis varied between 2 weeks and 8 months. This pattern is also seen in man, and is attributed to the process of binding, internalisation and changes at the neuromuscular junction.
Indications/Uses
Treatment of spasticity of the arm in adults following a stroke. Treatment of dynamic equinus foot deformity due to spasticity in ambulant paediatric cerebral palsy patients ≥2 years, only in hospital specialist centres with appropriately trained personnel. Treatment of spasmodic torticollis, blepharospasm, hemifacial spasm and glabellar lines in adults.
The safety and effectiveness of Dysport in the treatment of arm spasticity post-stroke, spasmodic torticollis, blepharospasm or hemifacial spasm in children have not been demonstrated.
Dosage/Direction for Use
The units of Dysport are specific to the preparation and are not interchangeable with other preparations of botulinum toxin.
Adult Spasticity of the Arm Post-Stroke: Recommended Dose: 1000 units, distributed amongst the following 5 muscles: Flexor digitorum profundus (FDP), flexor digitorum superficialis (FDS), flexor carpi ulnaris (FCU), flexor carpi radialis (FCR) and biceps brachii (BB). The sites of injection should be guided by standard locations used for electromyography, although actual location of the injection site will be determined by palpation. All muscles except BB will be injected at 1 site, while the biceps will be injected at 2 sites. The recommended distribution of dose is given as follows: BB: 300-400 units; FDP: 150 units; FDS: 150-250 units; FCU: 150 units; FCR: 150 units. Total Dose: 1000 units.
The starting dose should be lowered if there is evidence to suggest that this dose may result in excessive weakness of the target muscle eg, for patients whose target muscles are small, where the BB muscle is not to be injected or patients who are to be administered multi-level injections. Clinical improvement may be expected within 2 weeks after injection. Injections may be repeated approximately every 16 weeks or as required to maintain response, but not more frequently than every 8 weeks.
The exposed central portion of the rubber stopper should be cleaned with alcohol immediately prior to piercing the septum. A sterile 23 or 25 gauge needle should be used.
Dysport is reconstituted with 0.9% sodium chloride 1 mL injection to yield a solution containing Dysport 500 units/mL. Dysport is administered by IM injection into the 5 muscles detailed in previous text when treating arm spasticity.
Paediatric Cerebral Palsy Spasticity: Recommended Dose: Initially, 20 units/kg bodyweight given as a divided dose between both calf muscles. If only 1 calf is affected, a dose of 10 units/kg bodyweight should be used. Consideration should be given to lowering the starting dose if there is evidence to suggest that this dose may result in excessive weakness of the target muscles eg, for patients whose target muscles are small or patients who require concomitant injections to other muscle group. Following evaluation of response to the starting dose, subsequent treatment may be titrated within the range 10 units/kg and 30 units/kg divided between both legs. The maximum dose administered must not exceed 1000 units/patient. Administration should primarily be targeted to the gastrocnemius, although injections of the soleus and injection of the tibialis posterior should also be considered. The use of electromyography (EMG) is not routine clinical practice but may assist in identifying the most active muscles. Clinical improvement may be expected within 2 weeks after injection. Injections may be repeated approximately every 16 weeks or as required to maintain response, but not more frequently than every 8 weeks.
The exposed central portion of the rubber stopper should be cleaned with alcohol immediately prior to piercing the septum. A sterile 23 or 25 gauge needle should be used. When treating paediatric cerebral palsy spasticity, Dysport is reconstituted with 0.9% sodium chloride 1 mL injection to yield a solution containing Dysport 500 units/mL. Dysport is administered by IM injection into the calf muscles when treating spasticity.
Spasmodic Torticollis: Adults and Elderly: The doses recommended for torticollis are applicable to adults of all ages providing the adults are of normal weight with no evidence of low neck muscle mass.
A reduced dose may be appropriate if the patient is markedly underweight or in the elderly, where reduced muscle mass may exist. Initial Recommended Dose: 500 units/patient given as a divided dose and administered to the 2 or 3 most active neck muscles. For rotational torticollis, distribute the 500 units by administering 350 units into the splenius capitis muscle, ipsilateral to the direction of the chin/head rotation and 150 units into the sternomastoid muscle, contralateral to the rotation.
For laterocollis, distribute the 500 units by administering 350 units into the ipsilateral splenius capitis muscle and 150 units into the ipsilateral sternomastoid muscle. In cases associated with shoulder elevation, the ipsilateral trapezoid or levator scapulae muscles may also require treatment, according to visible hypertrophy of the muscle or EMG findings. Where injections of 3 muscles are required, distribute the 500 units as follows, 300 units to the splenius capitis, 100 units to the sternomastoid and 100 units to the 3rd muscle. For retrocollis, distribute the 500 units by administering 250 units into each of the splenius capitis muscles. This may be followed by bilateral trapezius injections (up to 250 units/muscle) after 6 weeks, if there is insufficient response. Bilateral splenii injections may increase the risk of neck muscle weakness. All other forms of torticollis are highly dependent on specialist knowledge, and EMG to identify and treat the most active muscles. EMG should be used diagnostically for all complex forms of torticollis, for reassessment after unsuccessful injections in noncomplex cases, and for guiding injections into deep muscles or in overweight patients with poorly palpable neck muscles. On subsequent administration, the doses may be adjusted according to the clinical response and side effects observed. Doses within the range of 250-1000 units are recommended, although the higher doses may be accompanied by an increase in side effects, particularly dysphagia. Doses >1000 units are not recommended. The relief of symptoms of torticollis may be expected within a week after the injection. Injections should be repeated approximately every 8-12 weeks or as required to prevent recurrence of symptoms.
Children: The safety and effectiveness of Dysport in the treatment of spasmodic torticollis in children have not been demonstrated.
The exposed central portion of the rubber stopper should be cleaned with alcohol immediately prior to piercing the septum. A sterile 23 or 25 gauge needle should be used. When treating spasmodic torticollis, Dysport is reconstituted with 0.9% sodium chloride 1 mL injection to yield a solution containing Dysport 500 units/mL. Dysport is administered by IM injection as previously mentioned when treating spasmodic torticollis.
Blepharospasm and Hemifacial Spasm: Adults and Elderly: In the treatment of bilateral blepharospasm, the recommended initial dose is 120 units/eye. Injection of 0.1 mL (20 units) should be made medially, and of 0.2 mL (40 units) should be made laterally into the junction between the preseptal and orbital parts of both the upper and lower orbicularis oculi muscles of each eye. For injections into the upper lid, the needle should be directed away from its centre to avoid the levator muscle. The relief of symptoms may be expected to begin within 2-4 days with maximal effect within 2 weeks. Injections should be repeated approximately every 8 weeks or as required to prevent recurrence of symptoms. On such subsequent administrations, the dose may need to be reduced to 80 units/eye such that 0.1 mL (20 units) medially, and 0.1 mL (20 units) laterally above and below each eye in the manner previously described. The dose may be further reduced to 60 units/eye by omitting the medial lower lid injection.
In cases of unilateral blepharospasm, the injections should be confined to the affected eye. Patients with hemifacial spasm should be treated as for unilateral blepharospasm. The doses recommended are applicable to adults of all ages including the elderly.
Children: The safety and effectiveness of Dysport in the treatment of blepharospasm and hemifacial spasm in children have not been demonstrated.
The exposed central portion of the rubber stopper should be cleaned with alcohol immediately prior to piercing the septum. A sterile 23 or 25 gauge needle should be used. When treating blepharospasm and hemifacial spasm, Dysport is reconstituted with 0.9% sodium chloride 2.5 mL injection to yield a solution containing Dysport 200 units/mL. Dysport is administered by SC injection medially and laterally, into the junction between the preseptal and orbital parts of both the upper and lower orbicularis oculi muscles of the eyes.
Glabellar Lines: Prior to injection, Dysport should be reconstituted. Remove any make-up and disinfect the skin with a local antiseptic. IM injections should be performed at right angles to the skin using a sterile 29-30 gauge needle.
The recommended dose is Dysport 50 Speywood units (0.25 mL of reconstituted solution) to be divided into 5 injection sites. Ten (10) Speywood units (0.05 mL of reconstituted solution) are to be administered IM into each of the 5 sites: 2 injections into each corrugator muscle and 1 into the procerus muscle near the nasofrontal angle.
The anatomical landmarks can be more readily identified if observed and palpated at maximal frown. Before injection, place the thumb or index finger firmly below the orbital rim in order to prevent extravasation below the orbital rim. The needle should be pointed upward and medially during the injection. In order to reduce the risk of ptosis, avoid injections near the levator palpebrae superioris muscle, particularly in patients with larger brow-depressor complexes (depressor supercilii). Injections in the corrugator muscle must be made into the central part of that muscle, at least 1 cm above the orbital rim.
The treatment interval depends on the individual patient's response after assessment. In clinical studies, an optimal effect was demonstrated for up to 4 months after injection. Some patients were still responders at 5 months. Treatment intervals should not be more frequent than every 3 months.
In the event of treatment failure or diminished effect following repeat injections, alternative treatment methods should be employed. In case of treatment failure after the 1st treatment session, the following approaches may be considered: Analysis of the causes of failure eg, incorrect muscles injected, injection technique and formation of toxin-neutralising antibodies; reevaluation of the relevance of treatment with Dysport.
Children: The safety and effectiveness of Dysport in treating glabellar lines in individuals <18 years have not been demonstrated.
Overdosage
Excessive doses may produce distant and profound neuromuscular paralysis. Respiratory support may be required where excessive doses cause paralysis of respiratory muscles. There is no specific antidote; antitoxin should not be expected to be beneficial and general supportive care is advised.
Contraindications
Dysport is contraindicated in pregnancy.
Special Precautions
For the treatment of spasmodic torticollis, paediatric cerebral palsy and adult post-stroke spasticity, Dysport should only be injected by specialists experienced in the diagnosis and management of these conditions and who have received training on the administration of Dysport.
Careful consideration should be given before the reinjection of patients who have experienced a previous allergic reaction. The risk of a further allergic reaction must be considered in relation to the benefit of treatment.
Dysport should only be used with caution under close supervision in patients with subclinical or clinical evidence of marked defective neuromuscular transmission. Such patients may have an increased sensitivity to agents eg, Dysport, which may result in excessive muscle weakness.
Training: Ipsen will facilitate training in administration of Dysport injections.
There are no reports of any immune response after the local administration of Clostridium botulinum type A toxin-haemagglutin in complex in accordance with the doses recommended when treating blepharospasm and hemifacial spasm. Antibody formation to botulinum toxin has been noted in a small number of torticollis patients and in 1 paediatric cerebral palsy patient receiving therapy with Dysport. Clinically, this has been detected by substantial deterioration in response to therapy or a need for consistently increasing doses.
Dysport contains a small amount of human albumin. The risk of transmission of viral infection cannot be excluded with absolute certainty following the use of human blood or blood products.
Effects on the Ability to Drive or Operate Machinery: None known.
Use in pregnancy & lactation: Teratological and other reproductive studies have not been performed with Dysport. The safety of its use in pregnancy or lactating women has not been demonstrated.
Use In Pregnancy & Lactation
Use in pregnancy & lactation: Teratological and other reproductive studies have not been performed with Dysport. The safety of its use in pregnancy or lactating women has not been demonstrated.
Adverse Reactions
Adult Spasticity of the Arm Post-Stroke: Muscle weakness is the most commonly reported adverse event in clinical studies and in the literature, for this patient population. In the 2 pivotal studies using Dysport for arm spasticity post-stroke, the most frequent adverse events were infection (8.2%), flu syndrome (6.1%), dry mouth, myasthenia, pain, constipation, diarrhoea, pharyngitis and somnolence (each with an incidence of 4.1%). The majority of events resolved within 2 weeks.
Dysphagia has been reported at doses in excess of 2700 units given in 1 dose or when given as a divided dose 12 weeks apart. No cases were reported in pivotal studies.
Paediatric Cerebral Palsy Spasticity: Adverse event incidence has been assessed by 3 prospective studies involving 142 patients treated with Dysport and 75 patients treated with placebo. Adverse events with an incidence of ≥5% following Dysport treatment were leg pain (8%), pharyngitis (8%), accidental injury (7%), bronchitis (6%) and fever (6%). Those with an incidence of 1-5% were viral infection (5%), infection (4%), rhinitis (4%), convulsion (4%), upper respiratory tract infection (4%), asthenia (3%), asthma (3%), cough (3%), vomiting (3%), cold (2%), diarrhoea (2%), urinary incontinence (2%), abnormal gait (1%), gastroenteritis (1%), laryngitis (1%) and somnolence (1%).
The incidence of many of these adverse events (pharyngitis, bronchitis, fever, viral infection, rhinitis, upper respiratory tract infection, cough, vomiting, cold) was similar in placebo-treated patients and probably indicates the typical spectrum of illness in a paediatric population. Also, the incidence of convulsions was identical in placebo-treated patients and reflects one of the most frequent concomitant problems associated with cerebral palsy.
The incidence of accidental injury (falls) demonstrated the biggest difference with placebo-treated patients (1%), and it is likely that these adverse events are due to overweakening of the target muscle and/or the local spread of Dysport to other muscles involved in ambulation and balance. The reports of abnormal gait may also be the result of such an effect. Another local side effect was leg pain, predominantly, calf pain. Although this pain appears to be distinct from any pain experienced from the injection itself, it was also reported for 5% of placebo treatments. Asthenia and urinary incontinence were associated with higher doses of Dysport (20-30 units/kg) and may be the result of systemic spread of the toxin.
Spasmodic Torticollis: Side effects may occur mainly from deep or misplaced injections temporarily paralysing other nearby muscle groups. The injections have been associated with a burning sensation which lasts for 1-2 min after injection. In patients treated for torticollis, dysphagia is the most frequently reported adverse event. In a double-blind, placebo-controlled trial, the incidence of dysphagia was 29% following treatment with Dysport 500 units and 10% in the placebo group. This appears to be dose-related and occurs most frequently following injection into the sternomastoid muscle. A soft diet may be required until symptoms resolve. In those patients severely affected, laryngoscopy has identified pooling of saliva. Aspiration may occur rarely and be of potential concern in those patients with preexisting respiratory problems. Less frequently reported events include weakness of the neck muscles, dryness of mouth and voice changes. A more generalised weakness and visual disturbances (including diplopia and blurred vision) have occasionally been reported. Respiratory difficulties have been noted on rare occasions in association with high doses. These side effects may be expected to resolve within 2-4 weeks. Allergic reactions eg, skin rashes and influenza-like symptoms have occasionally been noted.
Blepharospasm and Hemifacial Spasm: Side effects may occur from deep or misplaced injections of Dysport, temporarily paralysing other nearby muscle groups. They may also occur from exacerbation of preexisting eyelid abnormalities or from an initial overcorrection. Ptosis is the most common unwanted effect.
A few patients may also experience diplopia or symptoms from spread of the paralytic effect to midfacial muscles.
These side effects may be expected to resolve within 2-4 weeks. Keratitis and dry eyes due to reduced blinking have also been reported for which the use of artificial tears could be considered. Minor bruising and lid swelling may occur but are short-lived. Reversible external ophthalmoplegia has been reported after excessive dosing. The injections have been associated with a burning sensation which lasts for 1-2 min after injection. Allergic reactions eg, skin rashes and influenza-like symptoms have occasionally been noted.
Drug Interactions
No interactions of clinical significance have been reported.
Incompatibilities: None known.
Caution For Usage
Instructions for Use/Handling: Once reconstituted, Dysport should only be used to treat a single patient during a single session. Immediately after treatment of the patient, any residual Dysport which may be present in either vial or syringe should be inactivated with dilute hypochlorite solution (1% available chlorine). Thereafter, all items should be disposed of in accordance with standard hospital practice. Spillage of Dysport should be wiped up with an absorbent cloth soaked in dilute hypochlorite solution.
Storage
Unopened vials must be maintained at temperatures between 2°C and 8°C. Dysport must be stored in a refrigerator at the hospital where the injections are to be carried out and should not be given to the patient to store. Reconstituted Dysport may be stored in a refrigerator (2°-8°C) for up to 8 hrs prior to use, provided reconstitution has taken place in controlled and aseptic conditions. Dysport should not be frozen.
Shelf-Life: Dysport may be stored for up to 8 hrs at 2°-8°C following reconstitution has taken place in controlled and aseptic conditions. Since Dysport does not contain an antimicrobial agent, from a microbiological point of view, it is recommended that Dysport should be used immediately following reconstitution.
MIMS Class
ATC Classification
M03AX01 - botulinum toxin ; Belongs to the class of other agents used as peripherally-acting muscle relaxants.
Presentation/Packing
Powd for inj (vial) 500 units (white, lyophilised powd for reconstitution) x 1's.
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