Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The safety profile of Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol) is based on data from one phase III clinical study in asthma (205715) and three phase III clinical studies and spontaneous reporting in COPD.

Asthma

The asthma study (205715) included 2,436 adult subjects inadequately controlled on their current treatment of combination therapy (ICS plus a LABA) who received fluticasone furoate/umeclidinium/vilanterol or an active comparator of fluticasone furoate/vilanterol for 24 to 52 week’s duration.

COPD

The most frequently reported adverse reactions are nasopharyngitis (7%), headache (5%) and upper respiratory tract infection (2%).

Where adverse reaction frequencies differed between studies and populations, the higher frequency is reported.

Tabulated list of adverse reactions

Adverse reactions are listed by MedDRA system organ class.
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).



System Organ Class              Adverse reactions                             Frequency 
Infections and infestations     Nasopharyngitis                               Very common Pneumonia*                                    Common
Upper respiratory tract infection
Bronchitis
Pharyngitis
Rhinitis
Sinusitis
Influenza
Candidiasis of mouth and throat
Urinary tract infection
Viral respiratory tract infection
Immune system disorders         Hypersensitivity reactions, including         Rare anaphylaxis, angioedema, urticaria, and rash
Metabolism and nutrition        Hyperglycaemia                                Rare disorders
Psychiatric disorders           Anxiety                                       Rare Nervous system disorders        Headache                                      Common Dysgeusia                                     Uncommon
Tremor                                        Rare
Eye disorders                   Vision blurred (see section 4.4)              Uncommon Glaucoma
Eye pain
Intraocular pressure increased                Rare
Cardiac disorders               Supraventricular tachyarrhythmia              Uncommon Tachycardia
Atrial fibrillation
Palpitations                                  Rare
Respiratory, thoracic &         Cough                                         Common mediastinal disorders           Oropharyngeal pain
Dysphonia
Gastrointestinal disorders      Constipation                                  Common Dry mouth                                     Uncommon
Musculoskeletal and             Arthralgia                                    Common connective tissue disorders     Back pain
Fractures                                     Uncommon
Muscle spasms                                 Rare
Renal and urinary disorders     Urinary retention                             Rare Dysuria

Description of selected adverse reactions

*Pneumonia
COPD
In a total of 1810 patients with advanced COPD (mean post-bronchodilator screening FEV1 45% of predicted, standard deviation (SD) 13%), 65% of whom had experienced a moderate/severe COPD exacerbation in the year prior to study entry (study CTT116853), there was a higher incidence of pneumonia events reported up to 24 weeks in patients receiving Trelegy Ellipta (20 patients, 2%) than in patients receiving budesonide/formoterol (7 patients, <1%). Pneumonia which required hospitalisation occurred in 1% of patients receiving Trelegy Ellipta and <1% of patients receiving budesonide/formoterol up to 24 weeks. One fatal case of pneumonia was reported in a patient who received Trelegy Ellipta. In the subset of 430 patients treated for up to 52 weeks, the incidence of pneumonia events reported in both Trelegy Ellipta

and budesonide/formoterol arms was equal at 2%. The incidence of pneumonia with Trelegy Ellipta is comparable with that observed in the fluticasone furoate/vilanterol (FF/VI) 100/25 arm of FF/VI clinical studies in COPD.

In a 52-week study, with a total of 10355 patients with COPD and a history of moderate or severe exacerbations within the prior 12 months (mean post-bronchodilator screening FEV1 46% of predicted, SD 15%) (study CTT116855), the incidence of pneumonia was 8% (317 patients) for Trelegy Ellipta (n = 4151), 7% (292 subjects) for fluticasone furoate/vilanterol (n = 4134), and 5% (97 subjects) for umeclidinium/vilanterol (n = 2070). Fatal pneumonia occurred in 12 of 4151 patients (3.5 per 1000 patient- years) receiving Trelegy Ellipta, 5 of 4134 patients (1.7 per 1000 patient-years) receiving fluticasone furoate/vilanterol, and 5 of 2070 patients (2.9 per 1000 patient-years) receiving umeclidinium/vilanterol.

Asthma
In patients with asthma (study 205715) treated up to 52 weeks, the incidence of pneumonia was 1% (5 of 406 patients) for fluticasone furoate/umeclidinium/vilanterol 92/55/22 micrograms and <1% (4 of 408 patients) for fluticasone furoate/umeclidinium/vilanterol 184/55/22 micrograms. The incidence of pneumonia was 2% in the fluticasone furoate/vilanterol 92/22 micrograms (7 of 407 patients) and fluticasone furoate/vilanterol 184/22 micrograms (7 of 406 patients) groups. The incidence of pneumonia events requiring hospitalisation was similar in the fluticasone furoate/umeclidinium/vilanterol and fluticasone furoate/vilanterol groups (<1% for all groups). There were no fatal pneumonia events.

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 GSK Israel (il.safety@gsk.com).