Adverse reactions : תופעות לוואי

4.8   Undesirable effects

General
Side effects related to spread of toxin distant from the site of administration have been reported, such as dry mouth, 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.
DYSP-SPC-1121-V1                                       Page 11 of 27
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 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to < 1/1,000); very rare (1<1/10,000); not known (cannot be estimated from the available data).

The following adverse reactions were seen in patients treated across a variety of indications including blepharospasm, hemifacial spasm, torticollis, spasticity associated with either cerebral palsy or stroke/TBI and axillary hyperhidrosis:

System Organ Class                  Frequency      Adverse Drug Reaction Nervous system disorders            Rare           Neuralgic amyotrophy Skin and subcutaneous tissue        Uncommon       Pruritus disorders                           Rare           Rash
General disorders and               Common         Asthenia, fatigue, influenza like illness administration site conditions                     and injection site reactions (e.g. pain, bruising, pruritus, oedema)

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 in adults

System Organ Class                  Frequency        Adverse Drug Reaction Gastrointestinal disorders          Uncommon         Dysphagia*
Musculoskeletal and connective      Common           Muscular weakness, tissue disorders                                     musculoskeletal pain, pain in the extremity
* The frequency for Dysphagia was derived from pooled data from open-label studies.
Dysphagia was not observed in the double-blind studies in the Adult Upper Limb (AUL) indication.

Focal spasticity affecting the lower limbs in adults

System Organ Class                  Frequency          Adverse Drug Reaction Gastrointestinal disorders          Common             Dysphagia
Musculoskeletal and connective      Common             Muscular weakness, myalgia tissue disorders
General disorders and               Common             Asthenia, fatigue, influenza-like administration site conditions                         illness, injection site reactions (pain, bruising, rash, pruritus)
Injury, poisoning and               Common             Fall procedural complications

Dynamic equinus foot deformity due to focal spasticity in ambulant paediatric cerebral palsy patients, two years of age or older

System Organ Class                  Frequency          Adverse Drug Reaction Musculoskeletal and connective      Common             Myalgia, muscular weakness tissue disorders
Renal and urinary disorders         Common             Urinary incontinence General disorders and               Common             Influenza-like illness, injection administration site conditions                         site reaction (e.g. pain, erythema, bruising etc.), gait disturbance,
fatigue
Uncommon           Asthenia
DYSP-SPC-1121-V1                                      Page 12 of 27
Injury, poisoning and             Common              Fall procedural complications

Focal spasticity of upper limbs in paediatric cerebral palsy patients, two years of age or older 
System Organ Class               Frequency                         Adverse Drug Reaction Musculoskeletal and              Common                            Muscular weakness, Pain in connective tissue disorders                                        extremity Uncommon                          Myalgia
General disorders and            Common                            Influenza-like illness, administration site conditions                                     Asthenia, Fatigue, Injection site bruising
Uncommon                          Injection site eczema, Injection site pain, Injection site rash,
Injection site swelling
Skin and subcutaneous tissue     Common                            Rash disorders

Focal spasticity of upper and lower limbs in paediatric cerebral palsy patients, two years of age or older

When treating upper and lower limbs concomitantly with Dysport at a total dose of up to 30 U/kg or 1000 U whichever is lower, there are no safety findings in addition to those expected from treating either upper limb or lower limb muscles alone.

Spasmodic torticollis

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 connective    Very common         Muscle weakness 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

System Organ Class                Frequency           Adverse Drug Reaction Nervous system disorders          Common              Facial paresis
Uncommon            VIIth nerve paralysis
Eye disorders                     Very common         Ptosis
Common              Diplopia, dry eye, lacrimation increased

DYSP-SPC-1121-V1                                     Page 13 of 27
Rare              Ophthalmoplegia
Skin and subcutaneous tissue        Common            Eyelid oedema disorders                           Rare              Entropion

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

Axillary hyperhidrosis

System Organ Class               Frequency                        Adverse Drug Reaction Skin and subcutaneous tissue     Common                           Compensatory sweating disorders

Moderate to severe glabellar lines

System Organ Class               Frequency                       Adverse Drug Reaction Nervous system disorders         Very common                     Headache Common                          Temporary facial paresis (due to temporary paresis of facial muscles proximal to injection sites, predominantly describes brow paresis)
Uncommon                        Dizziness
Eye disorders                    Common                          Asthenopia, Eyelid ptosis, Eyelid oedema, Lacrimation increased, Dry eye, Muscle twitching (twitching of muscles around the eyes)
Uncommon                        Visual impairment, Vision blurred, Diplopia
Rare                            Eye movement disorder
Skin and subcutaneous tissue     Uncommon                        Pruritus, Rash disorders
Rare                            Urticaria
General disorders and            Very common                     Injection site reactions (e.g.
administration site conditions                                   erythema, oedema, irritation, rash, pruritus, paraesthesia, pain,
discomfort, stinging and haematoma)
Immune system disorders          Uncommon                        Hypersensitivity 
Moderate to severe lateral canthal lines

System Organ Class               Frequency                       Adverse Drug Reaction Nervous system disorders         Common                          Headache, Temporary facial paresis (temporary paresis of facial muscles proximal to injection sites)
Eye disorders                    Common                          Eyelid oedema, Eyelid ptosis Uncommon                        Dry eye

DYSP-SPC-1121-V1                                     Page 14 of 27
General disorders and             Common                           Injection site reactions (e.g.
administration site conditions                                     haematoma, pruritus and oedema)

Post-marketing experience
System Organ Class                Frequency                         Adverse Drug Reaction Immune system disorders           Not known                         Hypersensitivity Nervous system disorders          Not known                         Hypoaesthesia Musculoskeletal and               Not known                         Muscle atrophy connective tissue disorders

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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/