SIALANAR Oral solution Ref.[27652] Active ingredients: Glycopyrronium

Sialanar should be prescribed by physicians experienced in the treatment of paediatric patients with neurological disorders.

Posology

Due to the lack of long term safety data, Sialanar is recommended for short-term intermittent use (see section 4.4).

Paediatric population – children and adolescents aged 3 years and older

The dosing schedule for glycopyrronium is based on the weight of the child, starting with approximately 12.8 micrograms/kg per dose (equivalent to 16 micrograms/kg per dose glycopyrronium bromide), three times per day and increasing by the doses shown in Table 1 below, every 7 days. 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 64 micrograms/kg body weight glycopyrronium or 6 ml (1.9 mg glycopyrronium, equivalent to 2.4 mg glycopyrronium bromide) 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.

Undesirable effects may be minimised by using the lowest effective dose necessary to control symptoms. It is important that the carer checks the dose volume in the syringe before administration. The maximum volume of the highest dose is 6 ml. In the event of a known anticholinergic adverse reaction occurring when the dose is increased, the dose should be reduced to the previous lower dose and the event monitored (see section 4.4). If the event does not resolve treatment should be discontinued. In the event of constipation, urinary retention or pneumonia (see section 4.8), treatment should be stopped and the prescribing physician contacted.

Younger children may be more susceptible to adverse reactions and this should be borne in mind when any dose adjustments are carried out.

Following the dose titration period, the child’s sialorrhoea should be monitored, in conjunction with the carer at no longer than 3 monthly intervals, to assess changes in efficacy and/or tolerability over time, and the dose adjusted accordingly. The Table 1 shows the dose in ml of solution to be given for each weight range at each dosing increase.

Table 1. Dosing table for children and adolescents with normal renal function:

¹ refers to μg/kg glycopyrronium
^* Maximum individual dose in this weight range

Special populations

Paediatric population (children aged <3 years)

The safety and efficacy of glycopyrronium bromide in children aged from birth to <3 years has not been established. No data are available.

Adult population

Sialanar is indicated for the paediatric population only. There is limited clinical trial evidence on the use of glycopyrronium in the adult population with pathological drooling.

Elderly

Sialanar 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 Sialanar should not be used in patients over the age of 65 years.

Hepatic impairment

Clinical studies have not been conducted in patients with hepatic impairment. Glycopyrronium is cleared predominantly from the systemic circulation by renal excretion and hepatic impairment is not thought to result in a clinically relevant increase in systemic exposure of glycopyrronium.

Renal impairment

Doses should be reduced by 30% in patients with mild to moderate renal impairment (eGFR <90 - ≥30 ml/min/1.73m²) (see Table 2). This medicinal product is contraindicated in patients with severe renal impairment (eGFR <30 ml/min/1.73m²), including those with end-stage renal disease requiring dialysis (see section 4.3).

Table 2. Dosing table for children and adolescents with mild to moderate renal impairment:

¹ refers to μg/kg glycopyrronium
^* Maximum individual dose in this weight range

Method of administration

For oral use only.

Co-administration with food results in a marked decrease in systemic medicinal product exposure (see section 5.2). Dosing should be at least one hour before or at least two hours after meals or at consistent times with respect to food intake. High fat food should be avoided. Where the child’s specific needs determine that co-administration with food is required, dosing of the medicinal product should be consistently performed during food intake.

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 Tables 1 and 2 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 the child is given the medicinal product through a feeding tube, flush the tube with 10 ml of water after you have given the medicinal product.

The oral syringe should be gently washed with warm water and allowed to dry after each use (i.e. three times per day). Do not use a dishwasher.

Symptoms

Overdose of glycopyrronium can result in anticholinergic syndrome, produced by the inhibition of cholinergic neurotransmission at muscarinic receptor sites. Clinical manifestations are caused by CNS effects, peripheral nervous system effects, or both. Common manifestations include flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status and fever. Additional manifestations include sinus tachycardia, decreased bowel sounds, functional ileus, urinary retention, hypertension, tremulousness and myoclonic jerking.

Management

Patients presenting with anticholinergic toxicity should be transported to the nearest emergency facility with advanced life support capabilities. Pre-hospital gastrointestinal decontamination with activated charcoal is not recommended because of the potential for somnolence and seizures and the resulting risk of pulmonary aspiration. At hospital, activated charcoal can be administered if the patient’s airways can be adequately protected. Physostigmine salicylate is recommended when tachydysrhythmia with subsequent hemodynamic compromise, intractable seizure, severe agitation or psychosis is present.

Patients and/or parents/caregivers should be counselled to ensure an acurate dose is given each time, in order to prevent the harmful consequences of anticholinergic reactions of glycopyrronium seen with dosing errors or overdose.

3 years.

2 months after first opening.

Do not store above 25°C.

Amber coloured glass bottle with a high density polyethylene tamper evident child resistant closure with expanded low density polyethylene liner. The bottle contains 60 ml or 250 ml of oral solution.

Pack size of one bottle, one 8 ml low density polyethylene oral syringe (0.1 ml graduations) and one syringe adaptor.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.