Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The most common anticholinergic adverse reaction was dry mouth (2.4%). The majority of the reports of dry mouth were suspected to be related to the medicinal product and were mild, with none being severe.

The safety profile is further characterised by other symptoms related to the anticholinergic effects, including signs of urinary retention, which were uncommon. Gastrointestinal effects including gastroenteritis and dyspepsia were also observed. Adverse reactions related to local tolerability included throat irritation, nasopharyngitis, rhinitis and sinusitis.

Tabulated summary of adverse reactions
Adverse reactions reported during the first six months of two pooled pivotal Phase III trials of 6 and 12 months duration 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 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

SEE API FEB22 V2                                                                  REF EU SmPC Nov2021 Table 1     Adverse reactions

Adverse reactions                                            Frequency category Infections and infestations
Nasopharyngitis1)                                            Common
Rhinitis                                                     Uncommon Cystitis                                                     Uncommon 
Immune system disorders
Hypersensitivity                                             Uncommon Angioedema2)                                                 Uncommon 
Metabolism and nutrition disorders
Hyperglycaemia                                               Uncommon 
Psychiatric disorders
Insomnia                                                     Common

Nervous system disorders
Headache3)                                                   Common
Hypoaesthesia                                                Uncommon 
Cardiac disorders
Atrial fibrillation                                          Uncommon Palpitations                                                 Uncommon 
Respiratory, thoracic and mediastinal disorders
Sinus congestion                                             Uncommon Productive cough                                             Uncommon Throat irritation                                            Uncommon Epistaxis                                                    Uncommon Dysphonia2)                                                  Uncommon Paradoxical bronchospasm2)                                   Not known 
Gastrointestinal disorders
Dry mouth                                                    Common
Gastroenteritis                                              Common
Nausea2)                                                     Uncommon Vomiting1) 2)                                                Uncommon Dyspepsia                                                    Uncommon Dental caries                                                Uncommon 
Skin and subcutaneous tissue disorders
Rash                                                         Uncommon SEE API FEB22 V2                                                           REF EU SmPC Nov2021 Pruritus2)                                                      Uncommon 
Musculoskeletal and connective tissue disorders
Musculoskeletal pain1) 2)                                       Common Pain in extremity                                               Uncommon Musculoskeletal chest pain                                      Uncommon 
Renal and urinary disorders
Urinary tract infection3)                                       Common Dysuria                                                         Uncommon Urinary retention                                               Uncommon 
General disorders and administration site conditions
Fatigue                                                         Uncommon Asthenia                                                        Uncommon 
1) More frequent for glycopyrronium than placebo in the 12 months database only.
2) Reports have been received from post-approval marketing experience in association with the use of
Seebri Breezhaler. These were reported voluntarily from a population of uncertain size, and it is therefore not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure. Therefore the frequency was calculated from clinical trial experience.
3) Seen more frequently for glycopyrronium than placebo in elderly >75 years only.


Description of selected adverse reactions
In the pooled 6-month database the frequency of dry mouth was 2.2% versus 1.1%, of insomnia 1.0% versus 0.8%, and of gastroenteritis 1.4% versus 0.9%, for Seebri Breezhaler and placebo respectively.

Dry mouth was reported mainly during the first 4 weeks of treatment with a median duration of four weeks in the majority of patients. However in 40% of cases symptoms continued for the entire 6- month period. No new cases of dry mouth were reported in months 7-12.

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/.