Adverse reactions : תופעות לוואי

4.8   Undesirable effects

The presentation of the safety profile is based on the experience with Ultibro Breezhaler and the
individual active substances.

Summary of the safety profile
The safety experience with Ultibro Breezhaler was comprised of exposure of up to 15 months at the
recommended therapeutic dose.

Ultibro Breezhaler showed similar adverse reactions to the individual components. As it contains
indacaterol and glycopyrronium, the type and severity of adverse reactions associated with each of
these components may be expected in the combination.

The safety profile is characterised by typical anticholinergic and beta-adrenergic symptoms related to
the individual components of the combination. Other most common adverse reactions related to the
medicinal product (at least 3% of patients for Ultibro Breezhaler and also greater than placebo) were
cough, nasopharyngitis and headache.

Tabulated summary of adverse reactions
Adverse reactions detected during clinical trials and from post-marketing sources are listed by
MedDRA system organ class (Table 1). Within each system organ class, the adverse reactions are
ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse
reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency
category for each adverse reaction is based on the following convention: very common (≥1/10);
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000, <1/1,000); very rare
(<1/10,000); not known (cannot be estimated from the available data).

Table 1      Adverse reactions

Adverse reactions                                               Frequency category
Infections and infestations
Upper respiratory tract infection                               Very common
Nasopharyngitis                                                 Common
Urinary tract infection                                         Common
Sinusitis                                                       Common
Rhinitis                                                        Common
Immune system disorders
Hypersensitivity                                                Common
Angioedema2                                                     Uncommon
Metabolism and nutrition disorders
Hyperglycaemia and diabetes mellitus                            Common
Psychiatric disorders
Insomnia                                                        Uncommon
Nervous system disorders
Dizziness                                                       Common
Headache                                                        Common
Paraesthesia                                                    Rare
Eye disorders
Glaucoma1                                                       Uncommon
Cardiac disorders
Ischaemic heart disease                                         Uncommon
Atrial fibrillation                                             Uncommon
Tachycardia                                                     Uncommon
Palpitations                                                    Uncommon

ULT API JAN21 V 2.0                                                     REF EU SmPC 18Nov2020
Respiratory, thoracic and mediastinal disorders
Cough                                                         Common
Oropharyngeal pain including throat irritation                Common
Paradoxical bronchospasm                                      Uncommon
Dysphonia2                                                    Uncommon
Epistaxis                                                     Uncommon
Gastrointestinal disorders
Dyspepsia                                                     Common
Dental caries                                                 Common
Gastroenteritis                                               Uncommon
Dry mouth                                                     Uncommon
Skin and subcutaneous tissue disorders
Pruritus/rash                                                 Uncommon
Musculoskeletal and connective tissue disorders
Musculoskeletal pain                                          Uncommon
Muscle spasm                                                  Uncommon
Myalgia                                                       Uncommon
Pain in extremity                                             Uncommon
Renal and urinary disorders
Bladder obstruction and urinary retention                     Common
General disorders and administration site conditions
Pyrexia1                                                      Common
Chest pain                                                    Common
Oedema peripheral                                             Uncommon
Fatigue                                                       Uncommon
1
Adverse reaction observed with Ultibro Breezhaler, but not with the individual components.
2
Reports received from post-marketing experience; frequencies calculated, however, on the basis of
clinical trial data.

Description of selected adverse reactions
Cough was common, but usually of mild intensity.

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/