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
* Potassium chloride solid oral dose products
* Anticholinergic medicines

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.
Mild to moderate sialorrhoea
Due to the low potential benefit and the known adverse effect profile, should not be given to children with mild to moderate sialorrhoea.
Cardiac disorders
Should be used with caution in patients with 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, should be used with caution in patients receiving inhalation anaesthesia.
Gastro-intestinal disorders
Glycopyrronium oral solution should be used with caution in patients with gastro-oesophageal reflux disease, ulcerative colitis, pre-existing constipation and diarrhoea. 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 Glycopyrronium bromide 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.
Dental
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.
Respiratory disorders
Glycopyrronium can cause thickening of secretions, which may increase the risk of
respiratory infection and pneumonia. Glycopyrronium should be discontinued if pneumonia is present.
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.
Renal disorders
Because of prolongation of renal elimination, repeated or large doses should be avoided in patients with uraemia.
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.

No interaction studies have been preformed.
Contraindication of concomitant use
Potassium chloride solid oral dose products: glycopyrronium may potentiate the risk of upper gastrointestinal injury associated with oral solid formulations of potassium chloride due to increased gastrointestinal transit time creating a high localized concentration of potassium ions. An association with upper GI bleeding and smallbowel ulceration, stenosis, perforation, and obstruction has been observed.
Anticholinergic medicines: concomitant use of anticholinergics may increase the risk of anticholinergic side effects. Anticholinergics may delay the gastrointestinal absorption of other anticholinergics administered orally and also increase the risk of anticholinergic side effects.
Concomitant use to be considered with caution including dose adjustment
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). Dosage may need to be decreased in patients receiving two or more antimuscarinic drugs concomitantly.
Corticosteroids: Steroid-induced glaucoma may develop with topical, inhaled, oral or
intravenous, steroid administration. Concomitant use may result in increased intraocular pressure via an open- or a closed-angle mechanism.
Concurrent use with slow-dissolving tablets of digoxin, atenolol or metformin may result in increased serum levels of these medicines.
Skeletal muscle relaxants: Concurrent use of anticholinergics after administration of skeletal muscle relaxants may potentiate systemic anticholinergic effects. Use of anticholinergics after administration of botulinum toxin may potentiate systemic anticholinergic effects.
Opioids: active substances such as pethidine and codeine may result in additive central nervous system and gastrointestinal adverse effects, and increase the risk of severe constipation or paralytic ileus and CNS depression. If concomitant use cannot be avoided, patients should be monitored for potentially excessive or prolonged CNS depression and constipation.
Antispasmodics:  Glycopyrronium may antagonizethe pharmacologiceffects of on gastrointestinal prokinetic active substances such as Domperidone and Metoclopramide.
Topiramate and zonisamide: Glycopyrronium may potentiate the effects of oligohidrosis and hyperthermia associated with the use of topiramate, particularly in paediatric patients.
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)
Inhaled anaesthetics: potential change to normal heart rhythm

Pregnancy: There is limited amount of data (less than 300 pregnancy outcomes) from the use of this medical product in pregnant women. The assessment of reproductive endpoints for glycopyrronium is limited. As a precautionary measure, it is preferable to avoid the use of glycopyrronium bromide during pregnancy.
Lactation: A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

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