- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyThe recommended dose is 1000 units in total, distributed amongst the following five muscles:
|Biceps brachii (BB)||Flexor digitorum profundus (FDP)||Flexor digitorum superficialis (FDS)||Flexor carpi ulnaris (FCU)||Flexor carpi radialis (FCR)||Total Dose|
|300-400 units (0.6-0.8mL)||150 units (0.3mL)||150-250 units (0.3-0.5mL)||150 units (0.3mL)||150 units (0.3mL)||1000 units (2.0mL)|
Method of administrationWhen treating arm spasticity, Dysport 300U vial is reconstituted with 0.6mL of sodium chloride injection B.P. (0.9%) and Dysport 500U vial with 1.0mL of sodium chloride injection B.P. (0.9%) to yield a solution with a concentration equivalent to 500 units per mL of Dysport. Dysport is administered by intramuscular injection into the five muscles detailed above when treating arm spasticity.
Paediatric cerebral palsy spasticity
PosologyThe initial recommended dose is 20 units/kg body weight given as a divided dose between both calf muscles. If only one calf is affected, a dose of 10 units/kg body weight should be used. Consideration should be given to lowering this starting dose if there is evidence to suggest that this dose may result in excessive weakness of the target muscles, such as for patients whose target muscles are small or patients who require concomitant injections to other muscle groups. 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 30 units/kg or 1000 units, whichever is the lower.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 two weeks after injection. Injections may be repeated approximately every 16 weeks or as required to maintain response, but not more frequently than every 12 weeks.
Method of administrationWhen treating paediatric cerebral palsy spasticity, Dysport 300U vial is reconstituted with 0.6mL of sodium chloride injection B.P. (0.9%) and Dysport 500U vial with 1.0mL of sodium chloride injection B.P. (0.9%) to yield a solution with a concentration equivalent to 500 units per mL of Dysport.Dysport is administered by intramuscular injection into the calf muscles when treating spasticity.
PosologyThe 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.The initial recommended dose for the treatment of spasmodic torticollis is 500 units per patient given as a divided dose and administered to the two or three 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 electromyographic (EMG) findings. Where injections of three muscles are required, distribute the 500 units as follows, 300 units splenius capitis, 100 units sternomastoid and 100 units to the third muscle.• For retrocollis distribute the 500 units by administering 250 units into each of the splenius capitis muscles. 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 non complex 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. The maximum dose administered must not exceed 1000 units.The relief of symptoms of torticollis may be expected within a week after the injection. Injections may be repeated approximately every 16 weeks or as required to maintain a response, but not more frequently than every 12 weeks.Children: The safety and effectiveness of Dysport in the treatment of spasmodic torticollis in children have not been demonstrated.
Method of administrationWhen treating spasmodic torticollis, Dysport 300U vial is reconstituted with 0.6mL of sodium chloride injection B.P. (0.9%) and Dysport 500U vial with 1.0mL of sodium chloride injection B.P. (0.9%) to yield a solution with a concentration equivalent to 500 units per mL of Dysport.Dysport is administered by intramuscular injection as above when treating spasmodic torticollis.
Blepharospasm and hemifacial spasm
PosologyIn a dose ranging clinical trial on the use of Dysport for the treatment of benign essential blepharospasm, a dose of 40 units per eye was significantly effective. Doses of 80 units and 120 units per eye resulted in a longer duration of effect. However, the incidence of local adverse events, specifically ptosis, was dose related. In the treatment of blepharospasm and hemifacial spasm, the maximum dose used must not exceed a total dose of 120 units per eye. An injection of 10 units (0.05 ml) medially and 10 units (0.05 ml) laterally should be made laterally into the junction between the preseptal and orbital parts of both the upper (3 and 4) and lower orbicularis oculi muscles (5 and 6) of each eye. In order to reduce the risk of ptosis, injections near the levator palpebrae superioris should be avoided.For injections into the upper lid the needle should be directed away from its centre to avoid the levator muscle. A diagram to aid placement of these injections is provided. The relief of symptoms may be expected to begin within two to four days with maximal effect within two weeks.Injections should be repeated approximately every twelve weeks or as required to prevent recurrence of symptoms but not more frequently than every twelve weeks. On such subsequent administrations, if the response from the initial treatment is considered insufficient, the dose per eye may need to be increased to 60 units: 10 units (0.05mL) medially and 20 units (0.1mL) laterally, 80 units: 20 units (0.1mL) medially and 20 units (0.1mL) laterally or up to 120 units: 20 units (0.1mL) medially and 40 units (0.2mL) laterally above and below each eye in the manner previously described. Additional sites in the frontalis muscle above the brow (1 and 2) may also be injected if spasms here interfere with vision. 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.
Method of administrationWhen treating blepharospasm and hemifacial spasm, Dysport 300U vial is reconstituted with 1.5mL of sodium chloride injection B.P. (0.9%) and Dysport 500U vial with 2.5mL of sodium chloride injection B.P. (0.9%) to yield a solution containing 200 units per mL of Dysport.Dysport is administered by subcutaneous 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.
GeneralIn the clinical trial programme, approximately 28% of the patients treated with Dysport experienced an adverse event.The following adverse reactions were seen in patients treated across a variety of indications including blepharospasm, hemifacial spasm, torticollis and spasticity associated with either cerebral palsy or stroke:
Nervous system disordersRare: Neuralgic amyotrophy
Skin and subcutaneous tissue disordersUncommon: Itching Rare: Skin rashes
General disorders and administration site conditionsCommon: Generalised weakness, fatigue, flu-like syndrome, pain / bruising at injection siteIn addition, the following adverse reactions specific to individual indications were reported:
Gastrointestinal disordersCommon: Dysphagia
Musculoskeletal and connective tissue disordersCommon: Arm muscle weakness
Injury, poisoning and procedural complicationsCommon: Accidental injury/falls
Paediatric cerebral palsy spasticity
Gastrointestinal disordersCommon: Diarrhoea
Musculoskeletal and connective tissue disordersCommon: Leg muscle weakness, muscle pain
Renal and urinary disordersCommon: Urinary incontinence
General disorders and administration site conditionsCommon: Abnormal gait
Injury, poisoning and procedural complicationsCommon: Accidental injury due to fallingAccidental injury due to falling and abnormal gait may have been due to the over-weakening of the target muscle and / or the local spread of Dysport to other muscles involved in ambulation and balance.
Nervous system disordersCommon: Headache, dizziness, facial paresis
Eye disordersCommon: Blurred vision, reduced visual acuity Uncommon: Diplopia, ptosis
Respiratory, thoracic and mediastinal disordersCommon: Dysphonia, dyspnoeaRare: Aspiration
Gastrointestinal disordersVery common: Dysphagia, dry mouth
Musculoskeletal and connective tissue disordersVery Common: Muscle weaknessCommon: Neck pain, musculoskeletal pain, myalgia, pain in extremity, musculoskeletal stiffness Uncommon: Muscle atrophy, jaw disorderDysphagia 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 two to four weeks.Blepharospasm and hemifacial spasm
Nervous system disordersCommon: Facial muscle weakness Uncommon: Facial paralysis
Eye disordersVery common: Ptosis Common: Diplopia, dry eyes, tearing Rare: Ophthalmoplegia
Skin and subcutaneous tissue disordersCommon: Eyelid oedema Rare: EntropionSide effects may occur due to deep or misplaced injections of Dysport temporarily paralysing other nearby muscle groups.
Post-marketing experienceThe profile of adverse reactions reported to the company during post-marketing use reflects the pharmacology of the product and those seen during clinical trials. In addition, hypersensitivity reactions have been reported.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
|Visit||Dysport 40 Units (N=30)||Dysport 80 Units (N=31)||Dysport 120 Units (N=31)|
|Week 4: Difference between the median of the changes in PNA values from baseline in the active group and the median of the changes in PNA values from baseline in the placebo group||31.2 %||41.3 %||48.5 %|
|Week 8: Difference between the median of the changes in PNA values from baseline in the active group and the median of the changes in PNA values from baseline in placebo group||36.0 %||48.3 %||55.0 %|
|Week 12: Difference between the median of the changes in PNA values from baseline in the active group and the median of the changes in PNA values from baseline in placebo group||36.0 %||36.3 %||50.0 %|
|Week 16: Difference between the median of the changes in PNA values from baseline in the active group and the median of the changes in PNA values from baseline in placebo group||10.5 %[a]||24.2 %||31.3 %|
|Statistic||Placebo (N=26)||Dysport 40 Units (N=31)||Dysport 80 Units (N=31)||Dysport 120 Units (N=31)|
|Patients with related TEAEs||n (%)||3 (12)||19 (61)||23 (74)||26 (84)|
|Patients with related eye TEAEs||n (%)||3 (12)||16 (52)||23 (74)||26 (84)|
Unopened vial:24 months
Reconstituted solution:Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C.From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
Unopened vial:Store in a refrigerator (2°C - 8°C).Do not freeze.
Reconstituted solution:For storage conditions after reconstitution of the medicinal product, see section 6.3.
Nature of container/closure:Type 1 glass vials with 3mL capacity. 13mm bromobutyl freeze-drying closures oversealed by 13mm aluminium overseals with centre hole, crimped over.
Contents of container:A white lyophilised powder for reconstitution.
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