Adverse reactions : תופעות לוואי

4.8 Undesirable effects
In controlled clinical trials (4) and uncontrolled clinical trials (1) with Bramitob (565 patients treated), the most common reactions were those concerning the respiratory tract (cough and dysphonia).
The adverse reactions reported in the clinical trials (see below) are classified as: common (≥1/100 and <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 and <1/1,000); very rare (<1/10,000).
System Organ Class                Adverse Reaction                                Frequency Infections & Infestations         Fungal infection, oral candidiasis              Uncommon System Organ Class               Adverse Reaction                              Frequency Nervous system disorders         Headache                                      Uncommon Ear and labyrinth disorders      Vertigo, hypoacusis, deafness                 Uncommon neurosensory (see section 4.4)
Respiratory, thoracic and        Cough ,dysphonia                              Common mediastinal disorders            Forced expiratory volume decreased,           Uncommon dyspnoea, rales, haemoptysis,
oropharyngeal pain, productive cough
Gastrointestinal disorders       Salivary hypersecretion, glossitis,           Uncommon abdominal pain upper, nausea
Skin and subcutaneous tissue     Rash                                          Uncommon disorders
General disorders and            Asthenia, chest discomfort, mucosal           Uncommon administration site conditions   dryness
Investigations                   Transaminases increased                       Uncommon 
In controlled clinical trials with other nebulised tobramycin containing medicines, dysphonia and tinnitus were the only undesirable effects reported in significantly more patients treated with tobramycin; (13% tobramycin vs. 7% control) and (3% tobramycin vs. 0% control) respectively.
These episodes of tinnitus were transient and resolved without discontinuation of tobramycin therapy, and were not associated with permanent loss of hearing on audiogram testing. The risk of tinnitus did not increase with repeated cycles of exposure to tobramycin.

Additional undesirable effects, some of which are common sequelae of the underlying disease, but where a causal relationship to tobramycin could not be excluded were: sputum discoloured, respiratory tract infection, myalgia, nasal polyps and otitis media.


In addition, cumulative post-marketing data with products containing nebulised tobramycin referred the following adverse reactions (same frequency classification reported above): System Organ Class               Adverse Reaction                              Frequency Infections & Infestations        Laryngitis                                    Rare Fungal infection, oral candidiasis            Very rare
Blood and lymphatic system       Lymphadenopathy                               Very rare disorders
Immune system disorders          Hypersensitivity                              Very rare Metabolism and nutrition         Anorexia                                      Rare disorders

Nervous system disorders         Dizziness, headache, aphonia                  Rare Somnolence                                    Very rare
Ear and labyrinth disorders      Tinnitus, hearing loss (see section 4.4)      Rare Ear disorders, ear pain                       Very rare
Respiratory, thoracic and        Cough, pharyngitis, dysphonia, dyspnoea       Uncommon mediastinal disorders            Bronchospasm, chest discomfort, lung          Rare disorder, haemoptysis, epistaxis, rhinitis,
asthma, productive cough
Hyperventilation, hypoxia, sinusitis          Very rare
Gastrointestinal disorders       Dysgeusia, mouth ulceration,vomiting,         Rare nausea
System Organ Class                Adverse Reaction                              Frequency Diarrhoea, abdominal pain                     Very rare
Skin and subcutaneous tissue      Rash                                          Rare disorders                         Urticaria, pruritus                           Very rare Musculo-skeletal, connective      Back pain                                     Very rare tissue and bone disorders
General disorders and             Asthenia, pyrexia, chest pain, pain, nausea   Rare administration site conditions    Malaise                                       Very rare Investigations                    Pulmonary function test decreased             Rare 
In open label studies and post-marketing experience, some patients with a history of prolonged previous or concomitant use of intravenous aminoglycosides have experienced hearing loss (see    4.4).
Parenteral aminoglycosides have been associated with hypersensitivity, ototoxicity and nephrotoxicity (see sections 4.3 “Contraindications” and 4.4 “Special warnings and precautions for use”).

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
Additionally, you should also report to Kamada LTD to email address: pharmacovigilance@kamada.com