Rybrila

/ CTS

Short-term, intermittent use is recommended.
The dosage must be measured and administered with the graduated syringe included in the pack.
The dosing schedule is based on the weight of the child with the initial dosing of 0.02 mg/kg to be given orally three times daily and titrate in increments of 0.02 mg/kg every 5-7 days based on therapeutic response and adverse reactions. The maximum recommended dosage is 0.1 mg/kg three times daily not to exceed 1.5-3 mg per dose based upon weight.
See prescribing information for full details.

Symptomatic treatment of severe sialorrhoea (chronic pathological drooling) in children and adolescents aged 3 years and older with chronic neurological disorders.

* Hypersensitivity to the active substance or to any of the excipients
* Angle-closure glaucoma
* Myasthenia gravis (large doses of quaternary ammonium compounds have been shown to antagonise end plate nicotinic receptors)
* Pyloric stenosis
* Paralytic ileus
* Prostatic enlargement
* Urinary retention
* Severe renal impairment (eGFR <30 ml/min/1.73m2, including those with end-stage renal disease requiring dialysis
* Intestinal obstruction
* Pregnancy and breast-feeding.
* Potassium chloride solid oral dose products
* Anticholinergic medicines

* 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, Glycopyrronium bromide 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.
* Because of prolongation of renal elimination, repeated or large doses should be avoided in patients with uraemia.
* Patients with rare hereditary problems of fructose intolerance should not take this medicine.
* Not recommended for use in children younger than 3 years of age
*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
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.
Lack of long-term safety data
Safety data are not available beyond 24 weeks treatment duration.
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.
See prescribing information for full details.

Very common: Dry mouth, Constipation, Diarrhoea, Vomiting, Behavioural changes, Flushing, Nasal congestion, Reduced bronchial secretions.
Common: Pneumonia, Urinary retention, Pyrexia.
See prescribing information for full details.

Class interactions
Many drugs have antimuscarinic effects; concomitant use of two or more of such drugs can increase side-effects such as dry mouth, urine retention and constipation. Concomitant use can also lead to confusion in the elderly. The Glycopyrronium bromide dosage may need to be decreased in patients receiving two or more antimuscarinic drugs concomitantly.
Increased antimuscarinic side-effects: amantadine; tricyclic antidepressants; antihistamines; clozapine; disopyramide; MAOIs; nefopam; memantine; phenothiazines (increased antimuscarinic side effects of phenothiazines but reduced plasma concentrations).
Possibly increased antimuscarinic side-effects: tricyclic (related) antidepressants
Anticholinergic agents may delay absorption of other medication given concomitantly.
Concurrent administration of anticholinergics and corticosteroids may result in increased intraocular pressure.
Concurrent use with slow-dissolving tablets of digoxin, atenolol or metformin may result in increased serum levels of these medicines.
Concurrent use with parasympathomimetics may antagonise the effect.
Specific interactions
Domperidone/Metoclopramide: antagonism of effect on gastro-intestinal activity
Levodopa: absorption of levodopa possibly reduced
Haloperidol: effects of haloperidol possibly reduced
Nitrates: possibly reduced effect of sublingual nitrates (failure to dissolve under the tongue owing to dry mouth)
Topiramate and zonisamide: enhanced effect (reduction of sweating)
Inhaled anaesthetics: potential change to normal heart rhythm

Pregnancy: There are no data on the use of Glycopyrronium bromide oral solution in pregnant women. The assessment of reproductive endpoints for glycopyrronium is limited. Glycopyrronium is contraindicated in pregnancy.
Lactation: Safety in breast-feeding has not been established. Use whilst breast feeding is contraindicated 

Since Glycopyrronium bromide is a quaternary ammonium agent, symptoms of overdosage are peripheral rather than central in nature. Theoretically, with overdosage, a curare-like action may occur, i.e. neuro-muscular blockade leading to muscular weakness and possible paralysis. Furthermore, the likelihood of experiencing anticholinergic side effects is increased.
Treatment of overdose is symptomatic and supportive.
* To guard against further absorption of the drug, use gastric lavage, cathartics and/or enemas.
* To combat peripheral anticholinergic effects (residual mydriasis, dry mouth, etc.), utilise a quaternary ammonium anticholinesterase, such as neostigmine. Proportionately smaller doses should be used in children.
* To combat hypotension, use pressor amines (norepinephrine, metaraminol) i.v. and supportive care.
* To combat respiratory depression, administer oxygen; utilise a respiratory stimulant such as Doxapram hydrochloride i.v. and artificial respiration.

Once opened, the product may be stored for up to 28 days at a maximum of 25°C