Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The safety profile is characterised by corticosteroid, anticholinergic and β2-adrenergic class effects related to the individual components of the combination. The most commonly reported adverse reactions in patients receiving this medicinal product were pneumonia (4.6%), headache (2.7%) and urinary tract infection (2.7%).

Tabulated list of adverse reactions

The tabulated list of adverse reactions is based on the experience with this medicinal product in clinical trials and experience with the individual components.

The frequency of adverse reactions is defined using the following convention: 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) and not known (cannot be estimated from available data).

Table 1: Adverse reactions by frequency and system organ class (SOC)

System Organ Class            Preferred term                                     Frequency Infections and infestations   Oral candidiasis                                   Common Pneumonia
Immune system disorders       Hypersensitivity                                   Uncommon Angioedema                                         Not known
Endocrine disorders           Signs or symptoms of systemic                      Very rare glucocorticosteroid effects, e.g. hypofunction of the adrenal gland
Metabolism and nutrition      Hyperglycaemia                                     Common disorders
Psychiatric disorders         Anxiety                                            Common Insomnia
Depression                                         Uncommon
Agitation
Restlessness
Nervousness
Abnormal behaviour                                 Very rare
Nervous system disorders      Headache                                           Common Dizziness                                          Uncommon
Tremor
Eye disorders                 Vision blurred (see section 4.4)                   Not known Cataract
Glaucoma
Cardiac disorders             Palpitations                                       Common Angina pectoris                                    Uncommon
Tachycardia
Cardiac arrhythmias (atrial fibrillation,
supraventricular tachycardia and extrasystoles)
Respiratory, thoracic and     Dysphonia                                          Common mediastinal disorders         Cough
Throat irritation                                  Uncommon
Bronchospasm
Gastrointestinal disorders    Nausea                                             Common Dry mouth                                          Uncommon
Skin and subcutaneous         Bruising                                           Uncommon tissue disorders
Musculoskeletal and           Muscle spasms                                      Common connective tissue disorders
Renal and urinary             Urinary tract infection                            Common disorders                     Urinary retention                                  Uncommon General disorders and         Chest pain                                         Uncommon administration site conditions

Description of selected adverse reactions

Pneumonia
KRONOS was a 24-week study in a total of 1,896 patients with moderate to very severe COPD (mean post-bronchodilator screening FEV1 50% of predicted, standard deviation [SD] 14%), 26% of whom had experienced a COPD exacerbation in the year prior to study entry. The incidence of confirmed pneumonia events reported up to 24 weeks was 1.9% (12 patients) for Trixeo Aerosphere (n=639), 1.6% (10 patients) for formoterol fumarate dihydrate/glycopyrronium (FOR/GLY) MDI 5/7.2 micrograms (n=625), 1.9% (6 patients) for formoterol fumarate dihydrate/budesonide (FOR/BUD) MDI 5/160 micrograms (n=314) and 1.3% (4 patients) for open-labelled formoterol fumarate dihydrate/budesonide Turbuhaler (FOR/BUD) TBH 6/200 micrograms (n=318). In KRONOS, there were no fatal cases of pneumonia with Trixeo Aerosphere.

ETHOS was a 52-week study in a total of 8,529 patients (in the safety population) with moderate to very severe COPD and a history of moderate or severe exacerbations within the prior 12 months (mean post-bronchodilator screening FEV1 43% of predicted, SD 10%). The incidence of confirmed pneumonia was 4.2% (90 patients) for Trixeo Aerosphere (n=2144), 3.5% (75 patients) for formoterol fumarate dihydrate/glycopyrronium/budesonide (FOR/GLY/BUD) MDI 5/7.2/80 micrograms (n=2124), 2.3% (48 subjects) for FOR/GLY MDI 5/7.2 micrograms (n=2125) and 4.5% (96 subjects) FOR/BUD MDI 5/160 micrograms (n=2136). In ETHOS, there were five fatal cases of pneumonia during the treatment phase of the study (two with FOR/GLY/BUD MDI 5/7.2/80, three with FOR/GLY MDI and none with Trixeo Aerosphere).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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