Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Usually, undesirable effects are observed within the first week after treatment and are temporary in nature. Undesirable effects may be related to the active substance, the injection procedure, or both.

Undesirable effects independent from indication

Application related undesirable effects
Localised pain, inflammation, paraesthesia, hypoaesthesia, tenderness, swelling, oedema, erythema, itching, localised infection, haematoma, bleeding and/or bruising may be associated with the injection.
Needle related pain and/or anxiety may result in vasovagal responses, including transient symptomatic hypotension, nausea, tinnitus, and syncope.

Undesirable effects of the substance class botulinum toxin type A
Localised muscle weakness is one expected pharmacological effect of botulinum toxin type A.
Blepharoptosis, which can be caused by injection technique, is associated with the pharmacological effect of XEOMIN.

Toxin spread
When treating other indication with botulinum toxins, undesirable effects related to spread of toxin distant from the site of administration have been reported very rarely to produce symptoms consistent with botulinum toxin type A effects (excessive muscle weakness, dysphagia, and aspiration pneumonia with a fatal outcome in some cases) (see section 4.4). Undesirable effects such as these cannot be completely ruled out with the use of XEOMIN.

Hypersensitivity reactions
Serious and/or immediate hypersensitivity reactions including anaphylaxis, serum sickness, urticaria, soft tissue oedema, and dyspnoea have been rarely reported. Some of these reactions have been reported following the use of conventional botulinum toxin type A complex either alone or in combination with other agents known to cause similar reactions.

Undesirable effects from clinical experience

The following adverse reactions have been reported with XEOMIN. he frequency categories are 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 (< 1/10,000); not known (cannot be estimated from the available data).



Blepharospasm
System Organ Class                         Adverse Reaction                             Frequency Nervous system disorders                   Headache, facial paresis                     Uncommon Eye disorders                              Eyelid ptosis                                Very common
Dry eyes, vision blurred, visual             Common impairment
Diplopia, lacrimation increased              Uncommon
Gastrointestinal disorders                 Dry mouth                                    Common Dysphagia                                    Uncommon
Skin and subcutaneous tissue disorders     Rash                                         Uncommon Musculoskeletal and connective tissue      Muscular weakness                            Uncommon disorders
General disorders and administration       Injection site pain                          Common site conditions                            Fatigue                                      Uncommon 
Spasmodic torticollis
System Organ Class                         Adverse Reaction                              Frequency Infections and infestations                Upper respiratory tract infection             Common Nervous system disorders                   Headache, presyncope, dizziness               Common Speech disorder                               Uncommon
Respiratory, thoracic and mediastinal      Dysphonia, dyspnoea                           Uncommon disorders
Gastrointestinal disorders                 Dysphagia                                     Very common
Dry mouth, nausea                             Common
Skin and subcutaneous tissue disorders     Hyperhidrosis                                 Common Rash                                          Uncommon
Musculoskeletal and connective tissue      Neck pain, muscular weakness, myalgia,        Common disorders                                  muscle spasms, musculoskeletal stiffness General disorders and administration       Injection site pain, asthenia                 Common site conditions

The management of spasmodic torticollis may cause dysphagia with varying degrees of severity with the potential for aspiration which may require medical intervention. Dysphagia may persist for two to three weeks after injection, but has been reported in one case to last five months.



Post-stroke Spasticity of the upper limb
System Organ Class                         Adverse Reaction                               Frequency Nervous system disorders                   Headache, hypoaesthesia                        Uncommon Gastrointestinal disorders                 Dry mouth                                      Common Dysphagia, nausea                              Uncommon
Musculoskeletal and connective tissue      Muscular weakness, pain in extremity,          Uncommon disorders                                  myalgia
General disorders and administration       Asthenia                                       Uncommon site conditions                            Injection site pain                            Not known 
Moderate to severe Vertical Lines between the Eyebrows seen at frown (Glabellar Frown Lines) The following adverse reactions were reported with XEOMIN:

System Organ Class                          Adverse Reaction                              Frequency Infections and infestations                 Bronchitis, Nasopharyngitis, Influenza like   Uncommon illness
Psychiatric disorders                       Insomnia                                      Uncommon Nervous system disorders                    Headache                                      Common Eye disorders                               Eyelid oedema, eyelid ptosis, blurred         Uncommon vision
Skin and subcutaneous tissue disorders      Pruritus, Skin nodule, Brow ptosis            Uncommon Musculoskeletal and connective tissue       Mephisto sign (lateral elevation of           Common disorders                                   eyebrows)
Muscle twitching, M uscle spasm,              Uncommon
F acialasymmetry (brow asymmetry)
General disorders and administration site   Injection site haematoma, injection site      Uncommon conditions                                  pain, (local) Tenderness, Fatigue, Discomfort (heavy feeling of eyelid/ eyebrow)
Vascular disorders                          Haematoma                                     Uncommon 
Post-Marketing Experience
The following adverse reactions were reported with unknown frequency for the use of XEOMIN since market launch independent from indication:

System Organ Class                         Adverse Reaction
Immune system disorders                    Hypersensitivity reactions like swelling, oedema (also distant from injection site), erythema, pruritus, rash
(localised and generalised) and breathlessness
Musculoskeletal and connective tissue      Muscle atrophy disorders
General disorders and administration       Flu-like symptoms site conditions



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 via either a link of "Side Effects Reporting form" located at the Ministry of Health internet site home page, (http://www.health.gov.il) which refer the user to an online adverse reaction reporting form, or by entering the following link: https://sideeffects.health.gov.il.