Adverse reactions : תופעות לוואי

4.8         Undesirable effects

Rybrila may produce the following effects, which are extensions of its fundamental pharmacological actions: dry mouth, diminished gastrointestinal motility, difficulty in micturition, increased body temperature and inhibition of sweating.

Side-effects of antimuscarinics include difficulty swallowing, difficulty talking, thirst, constipation, transient bradycardia (followed by tachycardia, palpitation and arrhythmias), reduced bronchial secretions, urinary urgency and retention, dilatation of the pupils with loss of accommodation, photophobia, flushing, and dryness of the skin.

Other side-effects that occur less frequently include confusion (particularly in the elderly), nausea, vomiting, drowsiness, dizziness and angle-closure glaucoma.

Summary of the safety profile
The highest incidence of adverse reactions associated with Rybrila therapy is related to its anticholinergic properties1 i.e. dry mouth (13%), constipation (16%), diarrhoea (9.4%), nasal congestion (8.4%), vomiting (11.4%), urinary retention (5.4%) etc.
Pulmonary undesirable effects including upper respiratory infection and pneumonia have been reported. The incidence rate cannot be calculated from the available data (See Section 4.4).
There is no data on the long-term use of the product. (see section 4.4).

Tabulated list of adverse reactions

Adverse reactions associated with Rybrila obtained from published studies1 are tabulated below according to the following convention: Very common (>1/10); Common (>1/100, <1/10); Uncommon (>1/1,000, <1/100); Unknown (cannot be estimated from the available data)

System Organ Class/ Adverse reaction                          Frequency Immune system disorder
Allergic reaction                                             Uncommon 
Nervous system disorder
Headache                                                      Unknown Somnolence                                             Unknown
Drowsiness                                             Unknown
Seizure (worsening)                                    Uncommon
Dizziness                                              Unknown
Insomnia                                               Uncommon
Gastrointestinal disorder
Dry mouth                                              Very common
Constipation                                           Very common
Diarrhoea                                              Very common
Vomiting                                               Very common
Pseudo-obstruction                                     Uncommon
Gastrointestinal mobility disorder                     Uncommon
Eosophageal candidiasis                                Uncommon
Breath odour                                           Uncommon
Nausea                                                 Unknown
Infections and infestations
Upper respiratory infection                            Unknown
Pneumonia                                              Common
Otitis media                                           Unknown
Streptoccocal pharyngitis                              Unknown
Urinary tract infection                                Unknown
Psychiatric disorder
Behavioural changes2                                   Very common
Eye disorder
Nystagmus                                              Uncommon
Mydriasis                                              Unknown
Blurred vision                                         Unknown
Angle-closure glaucoma                                 Unknown
Photophobia                                            Unknown
Dry Eyes                                               Unknown
Cardiac disorder
Flushing                                               Very common
Angioedema                                             Unknown
Transient bradycardia                                  Unknown
Respiratory, thoracic and mediastinal disorders
Nasal congestion                                       Very common
Reduced bronchial secretions                           Very common
Epistaxis                                              Unknown
Sinusitis                                              Unknown
Skin and subcutaneous tissue disorder
Rash                                                   Unknown
Hives                                                  Uncommon
Skin dryness                                           Unknown
Sweat inhibition                                       Unknown
Renal and urinary disorders
Urinary retention                                      Common
Urinary urgency                                        Uncommon
General disorders and administration site conditions
Pyrexia                                                Common
Dehydration                                            Uncommon
Thirst                                                 Uncommon
1Frequency categories are assigned from the pooled data from the following published studies: double blinded placebo controlled trials Mier et al. and Zeller et al. 2012a, one retrospective review Bachrach et al., and three one open –label studies Zeller et al 2012b, Stern and Blasco et al. with a total of 297 patients exposed to glycopyrromium.

2
Behavioural changes include agitation, drowsiness, restlessness, overactivity, short attention span, frustration, irritability, mood changes, temper outbursts, explosive behaviour, excessive sensitivity, seriousness, sadness, frequent crying, fearfulness.

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/