Source: Health Products Regulatory Authority (IE) Revision Year: 2021 Publisher: Clinigen Healthcare B.V., Schiphol Boulevard 359, WTC Schiphol Airport, D Tower 11th floor, 1118BJ Schiphol, Netherlands
Rybrila is indicated for the symptomatic treatment of severe sialorrhoea (chronic pathological drooling) in children and adolescents aged 3 years and older with chronic neurological disorders.
Rybrila should be prescribed by physicians experienced in the treatment of paediatric patients with neurological disorders.
Rybrila is recommended for short-term intermittent use (see section 4.4 and 5.1).
The dosage must be measured and administered with the graduated oral syringe included in the pack. The dosing schedule for Rybrila is based on the weight of the child with the initial dosing of 16 micrograms/kg per dose (equivalent to 20 micrograms/kg per dose glycopyrronium bromide) to be given orally three times daily and titrate in increments of 16 micrograms/kg every 5-7 days based on therapeutic response and adverse reactions (see section 4.4 Anticholinergic effects). Dose titration should be continued until efficacy is balanced with undesirable effects and amended up or down as appropriate, to a maximum individual dose of 80 micrograms/kg body weight glycopyrronium or 15 ml three times a day, whichever is less. Dose titrations should be conducted in discussion with the carer to assess both efficacy and undesirable effects until an acceptable maintenance dose is achieved. For greater detail, see Table 1.
During the four-week titration period, dosing can be increased with the recommended dose titration schedule while ensuring that the anticholinergic adverse events are tolerable. Prior to each increase in dose, review the tolerability of the current dose level with the patient’s caregiver. In the event of a known anticholinergic adverse event (AE) occurring when the dose is increased, the dose should be reduced to the previous lower dose and the event monitored. If the AE does not resolve treatment should be discontinued.
Younger children may be more susceptible to adverse events and this should be kept in mind when dose adjustments are carried out.
Table 1. Dosing table for children and adolescents aged 3 years and older:
| Weight | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 |
|---|---|---|---|---|---|
| kg | (~16 µg/kg)* | (~32 µg/kg)* | (~48µg/kg)* | (~64 µg/kg)* | (~80 µg/kg)* |
| 13-17 | 1.5 ml | 3 ml | 4.5 ml | 6 ml | 7.5 ml |
| 18-22 | 2 ml | 4 ml | 6 ml | 8 ml | 10 ml |
| 23-27 | 2.5 ml | 5 ml | 7.5 ml | 10 ml | 12.5 ml |
| 28-32 | 3 ml | 6 ml | 9 ml | 12 ml | 15 ml |
| 33-37 | 3.5 ml | 7 ml | 10.5 ml | 14 ml | 15 ml |
| 38-42 | 4 ml | 8 ml | 12 ml | 15 ml | 15 ml |
| 43-47 | 4.5 ml | 9 ml | 13.5 ml | 15 ml | 15 ml |
| ≥48 | 5 ml | 10 ml | 15 ml | 15 ml | 15 ml |
* refers to µg/kg Glycopyrronium
Rybrila is not recommended for use in children younger than 3 years.
There is limited clinical evidence on the use of glycopyrronium in the adult population with pathological drooling.
Rybrila is indicated for the paediatric population only. The elderly have a longer elimination half-life and reduced medicinal product clearance as well as limited data to support efficacy in short-term use. As such Rybrila should not be used in patients over the age of 65 years.
Clinical studies have not been evaluated in patients with hepatic impairment. glycopyrronium is eliminated largely from the renal excretion and hepatic impairment is not thought to result in an increase in a systemic exposure of glycopyrronium.
Elimination of glycopyrronium is severely impaired in patients with mild to moderate renal impairment therefore doses should be reduced by 30% (see Table 2). This medicine is contraindicated in severe renal impairment (see section 4.3).
Table 2. Dosing table for children and adolescents with mild to moderate renal impairment:
| Weight | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 |
|---|---|---|---|---|---|
| kg | (~11.2 µg/kg)* | (~22.4 µg/kg)* | (~33.6µg/kg)* | (~44.8 µg/kg)* | (~56 µg/kg)* |
| 13-17 | 1.1 ml | 2.1 ml | 3.2 ml | 4.2 ml | 5.3 ml1 |
| 18-22 | 1.4 ml | 2.8 ml | 4.2 ml | 5.6 ml | 7.0 ml1 |
| 23-27 | 1.8 ml | 3.5 ml | 5.3 ml | 7.0 ml | 8.8 ml1 |
| 28-32 | 2.1 ml | 4.2 ml | 6.3 ml | 8.4 ml | 10.5 ml1 |
| 33-37 | 2.5 ml | 4.9 ml | 7.4 ml | 9.8 ml | 10.5 ml1 |
| 38-42 | 2.8 ml | 5.6 ml | 8.4 ml | 10.5 ml1 | 10.5 ml |
| 43-47 | 3.2 ml | 6.3 ml | 9.5 ml | 10.5 ml1 | 10.5 ml |
| ≥48 | 3.5 ml | 7.0 ml | 10.5 ml | 10.5 ml | 10.5 ml |
* refers to µg/kg Glycopyrronium
1 Maximum individual dose in this weight range
High fat food should be avoided. The presence of high fat food reduces the oral bioavailability of glycopyrronium if given shortly after a meal. Therefore, it should be given at least one hour before or two hours after meals. If the patient’s specific needs determine that co-administration with food is required, dosing of the medicinal product should be consistently performed during food intake (see section 5.2).
Other glycopyrronium products with different strengths are available. Switching between these products without proper dose adjustments may lead to overdose and, in turn, anticholinergic toxicity (see section 4.8 and 4.9).
For oral use and use with nasogastric and or PEG tubes.
The correct quantity of Rybrila should be measured and administered using the oral syringe included in the pack.
Nasogastric or PEG feeding tubes, if used, should be flushed with 20 ml of water immediately after dosing. See Section 6.6 for instructions for use.
Insert the syringe adaptor into the neck of the bottle. Insert the end of the oral syringe into the syringe adaptor and ensure it is secure. Turn the bottle upside down. Gently pull down the plunger to the correct level (see Table 1 for the correct dose). Turn the bottle upright. Remove the oral syringe. Place the oral syringe inside the child’s mouth and press the plunger slowly to gently release the medicinal product. If Rybrila is given through a feeding tube, flush the tube with 20 ml of water after administering the medicinal product.
Since glycopyrronium 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 combat respiratory depression, administer oxygen; utilise a respiratory stimulant such as Doxapram hydrochloride i.v. and artificial respiration.
2 years.
Once opened, the product may be stored for up to 28 days at a maximum of 25°C. Other in use storage times and conditions are the responsibility of the user.
Store below 25°C.
Store in the original bottle. Keep bottle in the original carton in order to protect from light.
For storage conditions after first opening of the medicinal product, see section 6.3.
150 ml amber type III glass bottle with a tamper evident child resistant HDPE/PP screw cap.
Each 150 ml bottle is provided in a cardboard carton with a 15 ml graduated LDPE oral syringe and a PE syringe adaptor to allow the correct dose to be measured.
Rybrila is also available in multipacks of 2 × 150 ml, 3 × 150 ml, 4 × 150 ml, and 5 × 150 ml.
Not all pack sizes may be marketed.
If Rybrila is given through a feeding tube, flush the tube with 20 ml of water after administering the medicinal product. No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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