Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The most commonly reported adverse reactions in the main safety, active-controlled clinical study with TOBI Podhaler versus tobramycin nebuliser solution in cystic fibrosis patients with P.
aeruginosa infection were cough, productive cough, pyrexia, dyspnoea, oropharyngeal pain, dysphonia and haemoptysis.
In the placebo-controlled study with TOBI Podhaler, the adverse reactions for which reported frequency was higher with TOBI Podhaler than with placebo were pharyngolaryngeal pain, dysgeusia and dysphonia.
The vast majority of adverse reactions reported with TOBI Podhaler were mild or moderate, and severity did not appear to differ between cycles or between the entire study and on-treatment periods.
Tabulated summary of adverse reactions
Adverse drug reactions in Table 1 are listed according to system organ classes in MedDRA.
Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): 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: frequency cannot be estimated from the available data.
The frequencies in Table 1 are based on the reporting rates from the active-controlled study.
Table 1 Adverse reactions
Adverse reactions                                    Frequency category Ear and labyrinth disorders
Hearing loss                                         Common
Tinnitus                                             Common
Vascular disorders
Haemoptysis                                   Very common
Epistaxis                                     Common
Respiratory, thoracic and mediastinal disorders
Dyspnoea                                      Very common
Dysphonia                                     Very common
Productive cough                              Very common
Cough                                         Very common
Wheezing                                      Common
Rales                                         Common
Chest discomfort                              Common
Nasal congestion                              Common
Bronchospasm                                  Common
Aphonia                                       Common
Sputum discoloured                            Not known
Gastrointestinal disorders
Oropharyngeal pain                            Very common
Vomiting                                      Common
Diarrhoea                                     Common
Throat irritation                             Common
Nausea                                        Common
Dysgeusia                                     Common
Skin and subcutaneous tissue disorders
Rash                                          Common
Musculoskeletal, connective tissue and bone disorders
Musculoskeletal chest pain                    Common
General disorders and administration site conditions
Pyrexia                                       Very common
Malaise                                       Not known
Description of selected adverse drug reactions
Cough was the most frequently reported adverse reaction in both clinical studies. However, no association was observed in either clinical study between the incidence of bronchospasm and cough events.
In the active-controlled study, audiology testing was performed in selected centres accounting for about a quarter of the study population. Four patients in the TOBI Podhaler treatment group experienced significant decreases in hearing which were transient in three patients and persistent in one case.
In the active-controlled open-label study, patients aged 20 years and older tended to discontinue more frequently with TOBI Podhaler than with the nebuliser solution; discontinuations due to adverse events accounted for about half of the discontinuations with each formulation. In children under 13 years of age, discontinuations were more frequent in the TOBI nebuliser solution arm whereas in patients aged 13 to 19, discontinuation rates with both formulations were similar.
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