Special Warning : אזהרת שימוש

4.4       Special warnings and precautions for use

Rybrila oral solution should be used with caution in gastro-oesophageal reflux disease, ulcerative colitis, pre-existing constipation, acute myocardial infarction, hypertension, conditions characterised by tachycardia (including hyperthyroidism, cardiac insufficiency, cardiac surgery) because of the increase in heart rate produced by its administration, coronary artery disease and cardiac arrhythmias.

Due to the potential change to normal heart rhythm, Rybrila should be used with caution in patients receiving inhalation anaesthesia.

Diarrhoea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance treatment with this drug would be inappropriate and possibly harmful.

As Rybrila inhibits sweating, patients with increased temperature should be observed closely.
In the presence of a high environmental temperature, heat prostration (fever and heat stroke due to decreased sweating) can occur with use of Rybrila oral solution.

Because of prolongation of renal elimination, repeated or large doses of Rybrila should be avoided in patients with uraemia.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.
This is due to the presence of sorbitol (E420) in this medicine.

Rybrila contains sodium propyl parahydroxybenzoate (E217) and sodium methyl parahydroxybenzoate (E219). These may cause allergic reactions (possibly delayed).

This medicinal product contains less than 1 mmol sodium (23 mg) per maximum dose, i.e.
essentially is ‘sodium free ’.

Rybrila is not recommended for use in children younger than 3 years of age.
Anticholinergic effects
Anticholinergic effects such as urinary retention, constipation and overheating due to inhibition of sweating are dose dependent. Monitoring by physicians and caregivers is required with adherence to the management instructions below:

Management of important anticholinergic side effects

The carer should stop treatment and seek advice from the prescriber in the event of: 
• constipation
• urinary retention
• pneumonia
• allergic reaction
• pyrexia
• very hot weather
• changes in behaviour 
After evaluating the event, the prescriber will decide if treatment should remain stopped or if this should continue at a lower dose.

Lack of long-term safety data
Safety data are not available beyond 24 weeks treatment duration. Given the limited long- term safety data available and the uncertainties around the long term use of the product, the treatment duration should be kept as short as possible. If continuous treatment is needed (e.g.
in a palliative setting) or the treatment is repeated intermittently (e.g. in the non palliative setting treating chronic disease) benefits and risks should be carefully considered on a case by case basis and treatment should be closely monitored.

Mild to moderate sialorrhoea
Due to the low potential benefit and the known adverse effect profile, Rybrila should not be given to children with mild to moderate sialorrhoea
.

Since reduced salivation can increase the risk of oral cavities and periodontal diseases, it is important that patients receive adequate daily dental hygiene and regular dental health checks.

CNS adverse events
Increased central nervous system effects have been reported in clinical trials including: irritability; drowsiness; restlessness; overactivity; short attention span; frustration; mood changes; temper outbursts or explosive behaviour; excessive sensitivity; seriousness or sadness; frequent crying episodes; fearfulness. Behavioural changes should be monitored.
As a consequence of its quaternary charge glycopyrronium has limited ability to penetrate the blood brain barrier, although the extent of penetration is unknown. Caution should be exercised in children with compromised blood brain barrier eg. Intraventicular shunt, brain tumour, encephalitis.

Growth and development
The effects of glycopyrronium on the reproductive system have not been investigated.
Whilst clinical studies do not report any short or long-term effect of glycopyrronium on neurodevelopment or growth, no studies have been conducted to specifically address these issues.

Effects on Driving

4.7         Effects on ability to drive and use machines
Rybrila oral solution may influence the ability to drive and use machines because it may produce drowsiness or blurred vision. In this event, the patient should be warned not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, or performing hazardous work while taking this drug.