Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Many of the listed undesirable effects can be assigned to the anticholinergic properties of tiotropium bromide.

Tabulated summary of adverse reactions
The frequencies assigned to the undesirable effects listed below are based on crude incidence rates of adverse drug reactions (i.e. events attributed to tiotropium) observed in the tiotropium group pooled from 7 placebo-controlled clinical trials in COPD (3,282 patients) and 12 placebo-controlled clinical trials in adult and paediatric patients with asthma (1,930 patients) with treatment periods ranging from four weeks to one year.

Frequency 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), not known (cannot be estimated from the available data) 
COPD:

System Organ Class / MedDRA Preferred Term               Frequency
COPD
Metabolism and nutrition disorders
Dehydration                                              Not known

Nervous system disorders
Dizziness                                                Uncommon
Headache                                                 Uncommon
Insomnia                                                 Rare

Spiriva Respimat                                          Prescribing information Solution for inhalation                                   July 2019
System Organ Class / MedDRA Preferred Term                  Frequency COPD

Eye disorders
Glaucoma                                                    Rare
Intraocular pressure increased                              Rare
Vision blurred                                              Rare

Cardiac disorders
Atrial fibrillation                                         Rare
Palpitations                                                Rare
Supraventricular tachycardia                                Rare
Tachycardia                                                 Rare
Respiratory, thoracic and mediastinal disorders
Cough                                                       Uncommon
Pharyngitis                                                 Uncommon
Dysphonia                                                   Uncommon
Epistaxis                                                   Rare
Bronchospasm                                                Rare
Laryngitis                                                  Rare
Sinusitis                                                   Not known 
Gastrointestinal disorders
Dry Mouth                                                   Common
Constipation                                                Uncommon
Oropharyngeal candidiasis                                   Uncommon
Dysphagia                                                   Rare
Gastrooesophageal reflux disease                            Rare
Dental caries                                               Rare
Gingivitis                                                  Rare
Glossitis                                                   Rare
Stomatitis                                                  Not known Intestinal obstruction, including ileus paralytic           Not known Nausea                                                      Not known 
Skin and subcutaneous tissue disorders, immune system disorders
Rash                                                        Uncommon
Pruritus                                                    Uncommon
Angioneurotic oedema                                        Rare
Urticaria                                                   Rare
Skin infection/skin ulcer                                   Rare
Dry skin                                                    Rare
Hypersensitivity (including immediate reactions)            Not known Anaphylactic reaction                                       Not known 
Musculoskeletal and connective tissue disorders
Joint swelling                                              Not known 
Renal and urinary disorders
Urinary retention                                           Uncommon
Dysuria                                                     Uncommon
Urinary tract infection                                     Rare
Spiriva Respimat                                          Prescribing information Solution for inhalation                                   July 2019

Asthma:

System Organ Class / MedDRA Preferred Term                  Frequency Asthma

Metabolism and nutrition disorders
Dehydration                                                 Not known 
Nervous system disorders
Dizziness                                                   Uncommon
Headache                                                    Uncommon
Insomnia                                                    Uncommon

Eye disorders
Glaucoma                                                    Not known Intraocular pressure increased                              Not known Vision blurred                                              Not known 
Cardiac disorders
Atrial fibrillation                                         Not known Palpitations                                                Uncommon
Supraventricular tachycardia                                Not known Tachycardia                                                 Not known 
Respiratory, thoracic and mediastinal disorders
Cough                                                       Uncommon
Pharyngitis                                                 Uncommon
Dysphonia                                                   Uncommon
Epistaxis                                                   Rare
Bronchospasm                                                Uncommon
Laryngitis                                                  Not known Sinusitis                                                   Not known 
Gastrointestinal disorders
Dry Mouth                                                   Uncommon
Constipation                                                Rare
Oropharyngeal candidiasis                                   Uncommon
Dysphagia                                                   Not known Gastrooesophageal reflux disease                            Not known Dental caries                                               Not known Gingivitis                                                  Rare
Glossitis                                                   Not known Stomatitis                                                  Rare
Intestinal obstruction, including ileus paralytic           Not known Nausea                                                      Not known 
Skin and subcutaneous tissue disorders, immune system disorders
Rash                                                        Uncommon
Pruritus                                                    Rare
Angioneurotic oedema                                        Rare
Urticaria                                                   Rare
Skin infection/skin ulcer                                   Not known 
Spiriva Respimat                                        Prescribing information Solution for inhalation                                 July 2019
System Organ Class / MedDRA Preferred Term                Frequency
Asthma
Dry skin                                                  Not known
Hypersensitivity (including immediate reactions)          Rare
Anaphylactic reaction                                     Not known

Musculoskeletal and connective tissue disorders
Joint swelling                                            Not known

Renal and urinary disorders
Urinary retention                                         Not known
Dysuria                                                   Not known
Urinary tract infection                                   Rare


Description of selected adverse reactions
In controlled clinical studies in COPD, the commonly observed undesirable effects were anticholinergic undesirable effects such as dry mouth which occurred in approximately 2.9 % of patients. In asthma the incidence of dry mouth was 0.83%.

In 7 clinical trials in COPD, dry mouth led to discontinuation in 3 of 3,282 tiotropium treated patients (0.1 %). No discontinuations due to dry mouth were reported in 12 clinical trials in asthma (1,930 patients).

Serious undesirable effects consistent with anticholinergic effects include glaucoma, constipation, intestinal obstruction including ileus paralytic and urinary retention.

Paediatric population
The safety database includes 560 paediatric patients (296 patients aged 1 to 11 and 264 patients aged 12 to 17) from 5 placebo-controlled clinical trials with treatment periods ranging between 12 weeks to one year. The frequency, type and severity of adverse reactions in the paediatric popuation are similar as in adults.

Other special population
An increase in anticholinergic effects may occur with increasing age.

Reporting of suspected adverse reactions
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form
(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.h ealth.gov.il )