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DYSPORT 500 UNITS POWDER AND SOLVENT FOR SOLUTION FOR INJECTION

Active substance(s): CLOSTRIDIUM BOTULINUM TYPE A TOXIN - HAEMAGGLUTININ COMPLEX

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Proof ONE - 1046736 - TJ

1046736

SUMMARY OF PRODUCT CHARACTERISTICS

Clostridium botulinum type A
toxin-haemagglutinin complex

1 NAME OF THE MEDICINAL PRODUCT
Dysport

2 QUALITATIVE AND QUANTITATIVE
COMPOSITION

Clostridium botulinum type A toxin-haemagglutinin complex 500 units*
* One unit (U) is defined as the median lethal intraperitoneal dose in
mice.
For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM
Injection

4 CLINICAL PARTICULARS
4.1 Therapeutic indications

Dysport is indicated for symptomatic treatment of focal spasticity of:
• Upper limbs in adults
• Dynamic equinus foot deformity in ambulant paediatric cerebral palsy
patients, two years of age or older.
Dysport is indicated in adults for symptomatic treatment of:
• Spasmodic torticollis
• Blepharospasm
• Hemifacial spasm.

4.2 Posology and method of administration

Muscles Injected

Flexor carpi radialis (FCR)
Flexor carpi ulnaris (FCU)
Flexor digitorum profundus (FDP)
Flexor digitorum superficialis (FDS)
Flexor Pollicis Longus
Adductor Pollicis
Brachialis
Brachioradialis
Biceps Brachii (BB)
Pronator Teres
Triceps Brachii (long head)
Pectoralis Major
Subscapularis
Latissimus Dorsi

Recommended Dose
DYSPORT (U)
100-200 U
100-200 U
100-200 U
100-200 U
100-200 U
25-50 U
200-400 U
100-200 U
200-400 U
100-200 U
150-300 U
150-300 U
150-300 U
150-300 U

1
3

400 x 410 mm Component code:
Leaflet-09 PS Presentation:
Component:
ICN:
02385P Territory:
Proof No.:
ONE Language:
Artwork Amend Date:
17/05/2016 Print supplier:
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Colours:
Barcode type:

Black
Datamatrix (1046736)

Front


1046736
Dysport 500U
Pack insert
UK
English
MPS

Perforation:
276 mm from LH edge viewed from front.
Parallel to 410mm dimension

5

6

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 above. 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 (0.05 mL) medially and 20 units (0.1 mL)
laterally, 80 units: 20 units (0.1 mL) medially and 20 units (0.1 mL) laterally
or up to 120 units: 20 units (0.1 mL) medially and 40 units (0.2 mL) 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 administration
When treating blepharospasm and hemifacial spasm, Dysport is
reconstituted with sodium chloride injection B.P. (0.9% w/v) to yield a
solution containing 200 units per mL of Dysport (see section 6.6).
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 as described
above.

4.3 Contraindications

Dysport is contraindicated in individuals with known hypersensitivity to
any components of Dysport.

4.4 Special warnings and precautions for use

Side effects related to spread of toxin distant from the site of
administration have been reported (see section 4.8) 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. The risk of
occurrence of such undesirable effects may be reduced by using the
lowest effective possible dose and by not exceeding the maximum
recommended dose.
Dysport should only be used with caution and under close medical
supervision in patients with subclinical or clinical evidence of marked

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Ipsen Biopharm Ltd,
Ash Road, Wrexham Ind. Est.,
Wrexham, LL13 9UF, UK.
Tel: +44 (0) 1978 661181
Fax: +44 (0) 1978 667569

The effects of botulinum toxin may be potentiated by drugs interfering
either directly or indirectly with neuromuscular function
(e.g. aminoglycosides, curare-like non-depolarising blockers) and such
drugs should be used with caution in patients treated with botulinum
toxin.

4.6 Pregnancy and lactation
Pregnancy:
There are limited data from the use of Clostridium botulinum type A
toxin-haemagglutinin complex in pregnant women. Studies in animals
have shown reproductive toxicity at high doses causing maternal
toxicity (see section 5.3).
Dysport should be used during pregnancy only if the benefit justifies any
potential risk to the foetus. Caution should be exercised when
prescribing to pregnant women.
Lactation:
It is not known whether Clostridium botulinum type A toxinhaemagglutinin complex is excreted in human milk. The excretion of
Clostridium botulinum type A toxin-haemagglutinin complex in milk has
not been studied in animals. The use of Clostridium botulinum type A
toxin-haemagglutinin complex during lactation cannot be recommended.
There is a potential risk of muscle weakness or visual disturbances
which, if experienced, may temporarily impair the ability to drive or
operate machinery.

4.8 Undesirable effects

Document fonts:


4.5 Interaction with other medicinal products and other forms of
interaction

4.7 Effects on ability to drive and use machines

4

Although actual location of the injection sites can be determined by
palpation the use of injection guiding technique, e.g. electromyography,
electrical stimulation or ultrasound is recommended to target the
injection sites.
Clinical improvement may be expected one week after injection and may
last up to 20 weeks. Injections may be repeated every 12-16 weeks or as
required to maintain response, but not more frequently than every
12 weeks. The degree and pattern of muscle spasticity at the time of
re-injection may necessitate alterations in the dose of Dysport and
muscles to be injected.
Children: The safety and effectiveness of Dysport in the treatment of
upper limb spasticity in children have not been demonstrated.
Elderly patients (≥ 65 years): Clinical experience has not identified
differences in response between the elderly and younger adult patients.
In general, elderly patients should be observed to evaluate their
tolerability of Dysport, due to the greater frequency of concomitant
disease and other drug therapy.
Method of administration
When treating focal spasticity affecting the upper limbs in adults,
Dysport is reconstituted with sodium chloride injection B.P. (0.9% w/v) to
yield a solution containing either 100 units per mL, 200 units per mL or
500 units per mL of Dysport (see section 6.6).
Dysport is administered by intramuscular injection into the muscles as
described above.
Dynamic equinus foot deformity due to focal spasticity
Posology
The 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 administration
When treating paediatric cerebral palsy spasticity, Dysport is
reconstituted with sodium chloride injection B.P. (0.9% w/v) to yield a
solution containing 500 units per mL of Dysport (see section 6.6).
Dysport is administered by intramuscular injection into the calf muscles
as described above.

Dimensions:

2

defective neuromuscular transmission (e.g. myasthenia gravis). Such
patients may have an increased sensitivity to agents such as Dysport,
which may result in excessive muscle weakness with therapeutic doses.
Patients with underlying neurological disorders are at increased risk of
this side effect.
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.
Dysport should be administered with caution to patients with preexisting swallowing or breathing problems as these 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.
The recommended posology and frequency of administration for Dysport
must not be exceeded (see section 4.2).
Patients and their care-givers must be warned of the necessity to seek
immediate medical treatment in case of swallowing, speech or
respiratory problems.
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.
Dysport should not be used to treat spasticity in patients who have
developed a fixed contracture.
As with any intramuscular injection, Dysport should only be used where
strictly necessary in patients with prolonged bleeding times, infection or
inflammation at the proposed site(s) of injection.
Dysport should only be used to treat a single patient, during a single
session. Specific precautions must be taken during the preparation and
administration of the product (see section 4.2) and for the inactivation
and disposal of any unused reconstituted solution (see section 6.6).
Antibody formation to botulinum toxin has been noted rarely in patients
receiving Dysport. Clinically, neutralising antibodies might be suspected
by a substantial deterioration in response to therapy and/or the need for
consistent use of increased doses.
Careful consideration should be given before the injection of patients
who have experienced a previous allergic reaction to a product
containing botulinum toxin type A. The risk of a further allergic reaction
must be considered in relation to the benefit of treatment.

For confirmation of Final
Artwork Approval refer to
electronic signature
summary in PALM

General
Side effects related to spread of toxin distant from the site of
administration have been reported, such as exaggerated muscle
weakness, dysphagia, aspiration/aspiration pneumonia, with fatal
outcome in some very rare cases (see section 4.4). Hypersensitivity
reactions have also been reported post-marketing.
The frequency of adverse reactions reported in placebo-controlled trials
after a single administration is defined as follows:
Very common >1/10; Common >1/100, <1/10; Uncommon >1/1000, <1/100;
Rare >1/10 000, < 1/1000.
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:
System Organ Class
Frequency
Nervous system disorders
Rare
Skin and subcutaneous
Uncommon
tissue disorders
Rare
General disorders and
Common
administration site conditions



Adverse Drug Reaction
Neuralgic amyotrophy
Pruritus
Rash
Asthenia, fatigue,
influenza like illness,
injection site pain/
bruising

Frequency of specific adverse reactions by indication
In addition, the following adverse reactions specific to individual
indications were reported:
Focal spasticity affecting the upper limbs
System Organ Class
Gastrointestinal disorders
Musculoskeletal and
connective tissue disorders
General disorders and
administration site conditions

Frequency Adverse Drug Reaction
Uncommon Dysphagia
Common
Muscular weakness
Uncommon Asthenia

Dynamic equinus foot deformity due to focal spasticity
System Organ Class
Frequency
Gastrointestinal disorders
Common
Musculoskeletal and connective Common
tissue disorders
Renal and urinary disorders
Common
General disorders and
Common
administration site conditions
Injury, poisoning and procedural Common
complications

Adverse Drug Reaction
Diarrhoea
Leg muscle weakness,
muscle pain
Urinary incontinence
Abnormal gait
Accidental injury/fall

Accidental injury due to falling and abnormal gait may have been due to
the over-weakening of the target muscle(s) and / or the local spread of
Dysport to other muscles involved in ambulation and balance.

PACKAGE LEAFLET:
INFORMATION FOR THE USER

Clostridium botulinum type A
toxin-haemagglutinin complex

Read all of this leaflet carefully
before you start using this medicine.
• Keep this leaflet. You may need to
read it again.
• If you have further questions, ask
your doctor.
• This medicine has been prescribed
for you. Do not pass it on to others.
It may harm them, even if their
symptoms are the same as yours.
• If any of the side effects become
serious, or if you notice any side
effects not listed in this leaflet,
please tell your doctor.
In this leaflet:
1. What Dysport is and what it is used
for
2. What you need to know before you
use Dysport
3. How Dysport is given
4. Possible side effects
5. How to store Dysport
6. Contents of the pack and other
information

DETACH HERE AND GIVE INFORMATION TO PATIENT

The units of Dysport are specific to the preparation and are not
interchangeable with other preparations of botulinum toxin.
Training: Dysport should only be administered by appropriately trained
physicians.
Ipsen can facilitate training in administration of Dysport injections.
For instructions on reconstitution of the powder for solution for injection,
handling and disposal of vials please refer to section 6.6.
Focal spasticity affecting the upper limbs
Posology
Dosing in initial and sequential treatment sessions should be tailored to
the individual based on the size, number and location of muscles
involved, severity of spasticity, the presence of local muscle weakness,
the patient's response to previous treatment, and/or adverse event
history with Dysport. In clinical trials, doses of 500 Units and 1000 Units
were divided among selected muscles at a given treatment session as
shown below.
No more than 1 mL should generally be administered at any single
injection site.

Spasmodic torticollis
Posology
The doses recommended for torticollis are applicable to adults of all
ages, provided the adults are of normal weight with no evidence of
reduced neck muscle mass. A lower 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 into 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 administration
When treating spasmodic torticollis Dysport is reconstituted with sodium
chloride injection B.P. (0.9% w/v) to yield a solution containing 500 units
per mL of Dysport (see section 6.6).
Dysport is administered by intramuscular injection as described above.
Blepharospasm and hemifacial spasm
Posology
In 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 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.

1. What Dysport is and what it is
used for
Dysport contains the active substance
Clostridium botulinum type A toxinhaemagglutinin complex.
What Dysport is used for:
Dysport is used in adults to treat
muscle spasms:
• Around the eyes
• In the face
• In the neck
• In the arm and shoulders.
Dysport is used in children (aged two
years or older) with cerebral palsy to
treat muscle spasms in the legs, to
improve their walking.
How Dysport works:
Dysport contains a toxin produced by
the bacterium Clostridium botulinum. It
works by stopping your muscles
contracting. It does this by stopping the
release of a chemical which acts
between the nerves and muscles that
makes the muscles contract. This helps
to reduce abnormal muscle
contractions known as spasms.

If you are pregnant or breast-feeding
you should ask your doctor for advice
before taking any medicine.
Use in children:
Dysport should not be used in children
younger than 2 years of age.
Driving and using machines:
Dysport may cause muscle weakness
or problems with your vision.
If you experience any of these effects,
do not drive or use any machines.

3. How Dysport is given
Your doctor will choose your dose of
medicine, and decide how often you
need treatment. This will depend on
what you are being treated for.
A vial of Dysport should be used only
for you and only for a single treatment
session.
For treatment of muscle spasms in your
arm and shoulder:
The dose of Dysport will usually be
between 500 and 1000 units divided
between the affected arm and shoulder
muscles. Your muscle spasms should
normally improve within 1 week.
Injections will usually be given about
every 12 to 16 weeks.
For treatment of muscle spasms in your
neck:
The first dose of Dysport will usually be
500 units divided into a number of
places in the neck, probably into 2 or 3
of the neck muscles most affected by
the condition. A smaller amount may be
given to very underweight or elderly
patients. Your muscle spasms should
improve within 1 week. Further
injections (250-1000 units) will be given
about every 16 weeks depending on
how long the effect lasts or as required
to maintain a response, but not more
frequently than every 12 weeks. The
maximum dose should not exceed
1000 units.
For treatment of muscle spasm around
your eyes:

The first injection will usually be 40 units
per eye. The medicine will be injected
just under the skin at various sites
around the eye. If only one eye is
affected the doctor will only give
injections of Dysport around this eye.
2. What you need to know before you
Injections will be given about every
use Dysport
12 weeks depending on how long the
Do not use Dysport:
effects last. On the next visits the
If you are allergic to botulinum toxin or amount of Dysport given may be
any of the ingredients (See section 6 for increased to a maximum of 120 units per
a list of ingredients).
eye.
Warnings and precautions:
For treatment of muscle spasm in your
There are increased risks of having
face:
Dysport injections under any of these
circumstances.
The doctor will give you injections on the
side of your face that is affected. The
Tell your doctor if:
first injection will usually be 120 units.
• You have problems swallowing
Injections will be given about every
• You have any history of bronchitis,
12 weeks depending on how long the
pneumonia or problems with
effects last. Your next injections of
breathing
• You have had an allergic reaction to Dysport may be reduced to 80 or 60 units.
a botulinum toxin in the past
For treatment of muscle spasms in the
• You have other problems or diseases legs of children with cerebral palsy:
that affect your muscles
The first dose of Dysport will be 20 units
e.g. myasthenia gravis
for each kg of the child’s body weight
• You bleed easily
divided between both lower leg
• You have an infection where the
injection will be given or if that area muscles. If only one leg is affected by
spasms, the doctor will only give
is swollen.
injections of 10 units per kg in this leg.
Other medicines and Dysport:
Injections will be given about every 12 to
Please tell your doctor if you are taking 16 weeks. The dose your doctor gives
any antibiotics for an infection
the child could change depending on
(e.g. aminoglycosides such as
how they respond. The maximum dose
gentamicin or amikacin) or muscle
should not exceed 1000 units.
relaxing drugs. Some of these
medicines may increase the effect of
If you are given more Dysport than you
Dysport.
should
Please tell your doctor or pharmacist if
you are taking or have recently taken any If you are given more Dysport than you
other medicines, including medicines
need, muscles other than the ones that
obtained without a prescription.
were injected may begin to feel weak.
This may not happen straightaway. If
Pregnancy and breast-feeding:
this does happen, speak to your doctor
Dysport is not recommended during
immediately. Seek urgent medical help
pregnancy, unless clearly necessary.
Dysport is not recommended in breast- if you have difficulty breathing,
swallowing or speaking.
feeding women.

Proof ONE - 1046736 - TJ

If you stop taking Dysport
Your muscle spasms will return to the
way they were before treatment.

4. Possible side effects

Uncommon: may affect up to 1 in 100
people
• Loss of muscle tissue
• Jaw problems
• Drooping of the upper eyelid
• Double vision
• Nausea
Rare: may affect up to 1 in 1,000 people
• Lung inflammation caused by
accidentally breathing in food, drink,
saliva or vomit (aspiration pneumonia).

Treatment of muscle spasms in the
eyes or face:
Very common: may affect more than 1
in 10 people
• Drooping of the upper eyelid
Common: may affect up to 1 in 10
people
• Double vision
• Swelling of the eyelid
• Facial muscle weakness
• Dry eyes or more tears than usual
Uncommon: may affect up to 1 in 100
people
• Facial paralysis
Rare: may affect up to 1 in 1,000 people
• Difficulty in moving the eye
• Edge of the eyelid turning in towards
the eyeball (entropion).

What Dysport contains
The active constituent of Dysport is
Clostridium botulinum toxinhaemagglutinin complex (500 units).
Dysport also contains human albumin
and lactose. Before it is injected
Dysport will be dissolved in sodium
chloride for injection (a solution of salt).

Treatment of muscle spasms in the
neck:
Very common: may affect more than 1
in 10 people
• Muscle weakness
• Difficulty in swallowing. This side
effect may be expected to resolve
within 2 to 4 weeks
• Dry mouth
Common: may affect up to 1 in 10
people
• Headache
• Dizziness
• Blurred vision or other problems in
seeing clearly
• Weakness of face muscles
• Stiff muscles
• Shortness of breath
• A change to the tone of the voice
• Neck pain, muscle pain, pain in the
hands and fingers

Manufacturer:
Ipsen Biopharm Limited, Ash Road,
Wrexham Industrial Estate, Wrexham
LL13 9UF.
Is this leaflet hard to see or read?
Please phone +44 (0) 1753 627777 and
ask for help.
This leaflet was last revised in
April 2016.

Dimensions:

What Dysport looks like and contents
of the pack
Dysport is a white powder in a glass
vial. It comes in a pack size of 1 or 2
vials though not all pack sizes may be
marketed.

Colours:
Barcode type:

Marketing authorisation holder:
Ipsen Limited, 190 Bath Road, Slough,
Berkshire, SL1 3XE, UK.



1046736
Dysport 500U
Pack insert
UK
English
MPS

Document fonts:


Univers family,

FrizQuadrata Bold, OCRB

Minimum font size:

SmPC text 8.5pt

SmPC table: 7pt; Patient: 9.5pt
Preliminary Artwork Approval
Final Artwork Approval

see other side

Perforation:
276 mm from LH edge viewed from front.
Parallel to 410mm dimension

Adverse Drug Reaction
Facial paresis
VIIth nerve paralysis
Ptosis
Diplopia, dry eye,
lacrimation increased
Ophthalmoplegia
Eyelid oedema
Entropion

Ipsen Biopharm Ltd,
Ash Road, Wrexham Ind. Est.,
Wrexham, LL13 9UF, UK.
Tel: +44 (0) 1978 661181
Fax: +44 (0) 1978 667569

For confirmation of Final
Artwork Approval refer to
electronic signature
summary in PALM

The Principal Target of Treatment (PTT) of the Disability Assessment
Scale [DAS] was used to investigate the effect of treatment on
functional impairment (passive function). Although some improvement in
the mean change from baseline at Week 4 in the Dysport groups did not
reach statistical significance compared to placebo, the proportion of
DAS score responders (subjects achieving at least a one grade
improvement) for the PTT was significantly higher at the 1000U dose as
shown below.
Treatment Group
Week 4
Week 12

% Responders
% Responders
Dysport 500U
50.0
41.3

n=80
n=76

p = 0.13
p = 0.11
Dysport 1000U
62.0
55.7

n=78
n=76

p = 0.0018
p = 0.0004
Placebo
39.2
32.9

n=79
n=75
*Domains included in DAS are hygiene, limb position, dressing and pain.

In addition, statistically significant improvements in spasticity (grade and
angle) assessed by the Tardieu scale, in the active range of motion of the
fingers, wrist or elbow, and in ease of applying a splint by the subject were
observed, especially at the 1000U dose. However, there was no effect of
treatment shown on the active function, as assessed by the Modified
Frenchay Score, and on quality of life EQ5D or SF-36 questionnaires.
Blepharospasm
Three Dysport doses were investigated over 1 treatment cycle in a
clinical study.
Efficacy was measured by the medians of differences in the Percentage
of Normal Activity (PNA) values (derived from the Blepharospasm
Disability Scale) between each treatment group and placebo. A dosedependent improvement in blepharospasm was evident with increasing
Dysport dose, with all treatment groups being superior to placebo.

Side effects may occur due to deep or misplaced injections of Dysport
temporarily paralysing other nearby muscle groups.
Reporting of suspected adverse reactions
Reporting 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








4.9 Overdose

Excessive doses may produce distant and profound neuromuscular
paralysis. Overdose could lead to an increased risk of the neurotoxin
entering the bloodstream and may cause complications associated with
the effects of oral botulinum poisoning (e.g. dysphagia and dysphonia).
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. In the event of overdose the patient should be medically monitored
for signs and/or symptoms of excessive muscle weakness or muscle
paralysis. Symptomatic treatment should be instigated if necessary.
Symptoms of overdose may not present immediately following injection.
Should accidental injection or oral ingestion occur, the patient should be
medically supervised for several weeks for signs and/or symptoms of
excessive muscle weakness or muscle paralysis.

5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties

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
Visit

Dysport
40 Units
(N=30)

Dysport
80 Units
(N=31)

Dysport
120 Units
(N=31)

Week 4:

31.2 %

41.3 %

48.5 %

Week 8:

36.0 %

48.3 %

55.0 %

Week 12:

36.0 %

36.3 %

50.0 %

Week 16:

10.5 %[a]

24.2 %

31.3 %

[a] p value > 0.001

For the 40 units, 80 units and 120 units Dysport treatment groups, the
medians of the changes from baseline in PNA values were statistically
significantly higher compared to those in placebo group at weeks 4, 8,
and 12.
A statistically significant difference compared to placebo group was
also observed for the 80 units and 120 units Dysport treatment groups at
week 16, indicating a greater duration of response at the 80 units and
120 units doses.
The incidence of related Treatment Emergent Adverse Events (TEAEs),
specifically ptosis, was higher in the Dysport treatment groups than in
the placebo treatment group and was dose-dependent with greater
incidence seen at higher Dysport doses. See table below.
Statistic
Placebo


(N=26)
Patients with
related TEAEs
n (%)
3 (12)
Patients with
related eye TEAEs n (%)

3 (12)

Dysport
40 Units
(N=31)

Dysport
80 Units
(N=31)

Dysport
120 Units
(N=31)

19 (61)

23 (74)

26 (84)

16 (52)

23 (74)

26 (84)

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.

6.5 Nature and contents of container
Nature of container/closure:
Type 1 glass vials with 3 mL capacity. 13 mm bromobutyl freeze-drying
closures oversealed by 13 mm aluminium overseals with centre hole,
crimped over.
Contents of container:
A white lyophilised powder for reconstitution.

6.6 Special precautions for disposal

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.
Each vial is for single use only.
Reconstitution instructions are specific for each of the 300 Unit vial and
the 500 Unit vial. These volumes yield concentrations specific for the use
for each indication.






Resulting Dose
Unit per mL
500 Units
200 Units
100 Units

Diluent* per
500 Unit Vial
1 mL
2.5 mL
5 mL

Diluent* per
300 Unit Vial
0.6 mL
1.5 mL
3 mL

*Preservative-free 0.9% sodium chloride injection

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).
Spillage of Dysport should be wiped up with an absorbent cloth soaked
in dilute hypochlorite solution.
Any unused product or waste material should be disposed of in
accordance with local requirements.
Ipsen Limited
190 Bath Road
Slough
Berkshire
SL1 3XE
United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)
PL 34926/0001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF
THE AUTHORISATION
Date of first authorisation: 09 December 1990
Date of latest renewal: 17 December 2002

10 DATE OF REVISION OF THE TEXT
To be completed upon MHRA approval

5.2 Pharmacokinetic properties

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.

5.3 Preclinical safety data


Week 4

Placebo Dysport Dysport
Placebo

(500 units) (1000 units)

(N=79) (N=80) (N=79)
(N=79)

Week 12
Dysport Dysport
(500 units) (1000 units)
(N=80)
(N=79)

LS Mean Change from
-0.3
-1.2**
-1.4**
Baseline in PTMG
Muscle Tone on the MAS

-0.1
n=75

-0.7**
n=76

-0.8**
n=76

Reproductive toxicity studies in pregnant rats and rabbits given
Clostridium botulinum type A toxin-haemagglutinin complex by daily
intramuscular injection, at doses of 6.6 units/kg (79 units/kg total
cumulative dose) and 3.0 units/kg (42 units/kg total cumulative dose) in
rats and rabbits respectively, did not result in embryo/foetal toxicity.
Implantation losses at maternally toxic doses were observed at higher
doses in both species. Clostridium botulinum type A toxinhaemagglutinin complex demonstrated no teratogenic activity in either
rats or rabbits and no effects were observed in the pre- and postnatal
study on the F1 generation in rats. Fertility of male and female rats was
decreased due to reduced mating secondary to muscle paralysis at
doses of 29.4 units/kg weekly in males and increased implantation loss
at 20 units/kg weekly in females.
In a chronic toxicity study performed in rats up to 12 units/animal, there
was no indication of systemic toxicity. Effects in chronic toxicity nonclinical studies were limited to changes on injected muscles related to
the mechanism of action of Clostridium botulinum type A toxinhaemagglutinin complex. There was no ocular irritation following
administration of Clostridium botulinum type A toxin-haemagglutinin
complex into the eyes of rabbits.

LS Mean PGA of
0.7
1.4*
1.8**
Response to Treatment

0.4
n=75

0.5
n=76

1.0*
n=76

6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients

LS Mean Change from
-0.3
Baseline in Wrist Flexor n=54
Muscle Tone on the MAS

-1.4**
n=57

-1.6**
n=58

-0.3
n=52

-0.7*
n=54

-0.9*
n=56

LS Mean Change from
-0.3
Baseline in Finger Flexor n=70
Muscle Tone on the MAS

-0.9*
n=66

-1.2**
n=73

-0.1
n=67

-0.4*
n=62

-0.6*
n=70

LS Mean Change from
-0.3
Baseline in Elbow Flexor n=56
Muscle Tone on the MAS

-1.0*
n=61

-1.2**
n=48

-0.3
n=53

-0.7*
n=58

-0.8*
n=46

Mean Change from
Baseline in Shoulder
Extensors Muscle Tone
on the MAS (1)

-0.6
n=7

-0.7
n=6

0.0
n=12

-0.9
n=7

0.0
n=6

-0.4
n=12

6.4 Special precautions for storage

7 MARKETING AUTHORISATION HOLDER



Pharmacotherapeutic Group: Other muscle relaxants, peripherally acting
agents.
ATC code: M03AX01
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 Ca2+ which culminate in transmitter release. It does not
affect postganglionic cholinergic transmission 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.
Focal spasticity affecting the upper limbs
The efficacy and safety of Dysport for the treatment of upper limb
spasticity was evaluated in a randomized, multi-centre, double-blind,
placebo-controlled study that included 238 patients (159 Dysport and
79 placebo) with upper limb spasticity who were at least 6 months poststroke (90%) or post-traumatic brain injury (10%). The primary targeted
muscle group (PTMG) was the extrinsic finger flexors (56%), followed by
the elbow (28%) and wrist flexors (16%).
The primary efficacy variable was the PTMG muscle tone at week 4, as
measured by the Modified Ashworth Scale (MAS), a 5 point scale
ranging from 0 (no increase in muscle tone) to 4 (affected in part[s] rigid
in flexion or extension) and the first secondary endpoint was the
Physician Global Assessment (PGA) of response to treatment (a 9 point
scale ranging from -4 [markedly worse], through 0 [no change], to +4
[markedly improved]). The main results achieved at Week 4 and Week 12
are shown below:

*p<0.05; ** p<0.0001;
LS = Least Square
(1) No statistical tests performed due to low frequency by treatment and placebo groups as
there are limited data in patients treated in the shoulder muscles.

Black

Back

System Organ Class
Frequency
Nervous system disorders Common

Uncommon
Eye disorders
Very common

Common


Rare
Skin and subcutaneous
Common
tissue disorders
Rare

Marketing Authorisation Holder and
manufacturer

400 x 410 mm Component code:
Leaflet-09 PS Presentation:
Component:
ICN:
02385P Territory:
Proof No.:
ONE Language:
Artwork Amend Date:
17/05/2016 Print supplier:
Specification ref:

System Organ Class
Frequency Adverse Drug Reaction
Nervous system disorders Common
Headache, dizziness,

facial paresis
Eye disorders
Common
Vision blurred, visual

acuity reduced

Uncommon Diplopia, ptosis
Respiratory, thoracic and Common
Dysphonia, dyspnoea
mediastinal disorders
Rare
Aspiration
Gastrointestinal disorders Very common Dysphagia, dry mouth

Uncommon Nausea
Musculoskeletal and
Very common Muscle weakness
connective tissue disorders Common
Neck pain, musculoskeletal

pain, myalgia, pain in

extremity, musculoskeletal

stiffness

Uncommon Muscle atrophy, jaw

disorder
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 two to four weeks.
Blepharospasm and hemifacial spasm

DETACH HERE AND GIVE INFORMATION TO PATIENT

Like all medicines, Dysport can cause side
effects, although not everybody gets them.
Treatment of children with muscle
Dysport may in rare cases cause side
spasms in the leg:
effects away from its site of injection.
Common: may affect up to 1 in 10
Seek urgent medical help if:
people
• You have any problems swallowing, • Weakness of the leg muscles. This
breathing or with your speech or you
may change the way you walk or
have worsened muscle weakness.
make you fall over more
• You develop difficulty in breathing
• Muscle pain
with or without swelling of the face,
• Urinary incontinence
lips, tongue and /or throat, redness
• Diarrhoea.
of the skin or an itchy lumpy rash
(urticaria). This may mean you are
Reporting of side effects
having an allergic reaction to
If you get any side effects, talk to your
Dysport.
doctor, pharmacist or nurse. This
Some side effects may occur in any
includes any possible side effects not
patient treated with Dysport whilst
listed in this leaflet. You can also report
other side effects may depend on the
side effects directly via the Yellow Card
condition being treated.
Scheme at www.mhra.gov.uk/yellowcard
Make sure you read all the sections
By reporting side effects, you can help
that apply to you.
provide more information on the safety
of this medicine.
Treatment of any condition (all
patients):
5. How to store Dysport
Common: may affect up to 1 in 10
Keep this medicine out of the sight and
people
reach of children.
• Bruising, or pain around the site
Do not use this medicine after the
where the injection was given
expiry date which is stated on the label
after ‘EXP’. The expiry date refers to the
• Generalised weakness
last day of that month.
• Fatigue
Store in a refrigerator (2°C-8°C). Do not
• Flu-like symptoms
freeze.
Uncommon: may affect up to 1 in 100
Chemical and physical in-use stability
people
has been demonstrated for the
• Itching
reconstituted solution for 24 hours in a
Rare: may affect up to 1 in 1,000 people refrigerator (2°C-8°C). After the solution
is made up, unless the method of
• Skin rashes
reconstitution precludes the risk of
• Sudden severe pain and weakness
microbial contamination, the product
in shoulder and/or arm (neuralgic
should be used immediately. If not used
amyotrophy).
immediately, in-use storage times and
Treatment of muscle spasms in the arm conditions prior to use are the
responsibility of the user.
and shoulder:
Do not throw away any medicines via
Common: may affect up to 1 in 10
wastewater or household waste. Ask
people
your pharmacist how to throw away
• Muscle weakness
medicines you no longer use. These
Uncommon: may affect up to 1 in 100
measures will help protect the
people
environment.
• Difficulty in swallowing
6. Contents of the pack and other
• Tiredness.
information

Spasmodic torticollis

Human albumin solution,
Lactose.

6.2 Incompatibilities
None known.

6.3 Shelf life
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.

1046736

If you forget an injection of Dysport
Nothing will happen if an injection is
missed other than some of the spasm
or muscle stiffness may return. Tell your
doctor and he will decide when the
next injection is needed.

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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