SIALANAR

Sialanar should be prescribed by physicians experienced in the treatment of paediatric patients with neurological disorders. 4). 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.

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. 4). If the event does not resolve treatment should be discontinued. 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. 4 6* 6 ≥48 2 4 6* 6 6 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. 73m2) (see Table 2). 3).

Table 2. 2 1 refers to μg/kg glycopyrronium *Maximum individual dose in this weight range Method of administration For oral use only. 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.

e. three times per day). Do not use a dishwasher.

Summary of the safety profile Adverse reactions are common with glycopyrronium due to its known pharmacodynamic anticholinergic effects. The most common adverse reactions are dry mouth (11%), constipation (20%), diarrhoea (18%), vomiting (18%), urinary retention (15%), flushing (11%) and nasal congestion (11%).

Adverse reactions are more common with higher doses and prolonged use. Tabulated list of adverse reactions Adverse reactions reported in the literature for trials using glycopyrronium for sialorrhoea in the paediatric population (including 2 placebo controlled trials, an uncontrolled safety study using glycopyrronium for a 6 month period, and 3 supportive studies with adverse reaction data in the target population) are listed by MedDRA system organ class (Table 3).

Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Table 3. List of adverse reactions Adverse reactions Frequency category Infections and infestations Upper respiratory tract infection Common Pneumonia Common Urinary tract infection Common Psychiatric disorders Irritability Very common Agitation Common Drowsiness Common Restlessness Not known Overactivity Not known Short attention span Not known Frustration Not known Mood variable Not known Temper tantrum Not known Adverse reactions Frequency category Intermittent explosive disorder Not known Sensitivity, shyness, and social withdrawal disorder specific to childhood or adolescence Not known Feeling sad Not known Crying Not known Fear Not known Nervous system disorders Headache Uncommon Insomnia Not known Eye disorders Mydriasis Uncommon Nystagmus Uncommon Angle-closure glaucoma Not known Photophobia Not known Dry eyes Not known Cardiac disorders Flushing Very common Transient bradycardia Not known Respiratory, thoracic and mediastinal disorders Nasal congestion Very common Epistaxis Common Reduced bronchial secretions Very common Sinusitis Not known Gastrointestinal disorders Dry mouth Very common Constipation Very common Diarrhoea Very common Vomiting Very common Halitosis Uncommon Oesophageal candidiasis Uncommon Gastrointestinal motility disorder Uncommon Pseudo-obstruction Uncommon Nausea Not known Skin and subcutaneous tissue disorders Rash Common Dryness of the skin Not known Inhibition of sweating Not known Renal and urinary disorders Urinary retention Very common Urinary urgency Not known General disorders and administration site conditions Pyrexia Common Dehydration Uncommon Thirst in hot weather Uncommon Angioedema Not known Allergic reaction Not known Description of selected adverse reactions Urinary retention Urinary retention is a known adverse reaction associated with anticholinergic medicinal products (15%).

Glycopyrronium treatment should be stopped until the urinary retention resolves. 9%). Glycopyrronium treatment should be stopped until the pneumonia resolves. Constipation Constipation is a known adverse reaction associated with anticholinergic medicinal products (30%).

Glycopyrronium treatment should be stopped until the constipation resolves. Central nervous system Although glycopyrronium has limited ability to cross the blood brain barrier, increased central nervous system effects have been reported in clinical trials (23%).

4). Cardiac disorders Glycopyrronium is known to have an effect on heart rate and blood pressure at doses used during anaesthesia although clinical trials in children with chronic drooling have not shown this effect. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Anticholinergic effects Anticholinergic effects such as urinary retention, constipation and overheating due to inhibition of sweating may be dose dependent and difficult to assess in a disabled child. 2). Lack of long-term safety data Published safety data are not available beyond 24 weeks treatment duration.

Given the limited long-term safety data available and the uncertainties around the potential risk for carcinogenicity, total treatment duration should be kept as short as possible. g. 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 likelihood of benefit and the known adverse effect profile, Sialanar should not be given to children with mild to moderate sialorrhoea. 8). The carer should be advised to measure the pulse rate if the child seems unwell and report very fast or very slow heart rate.

Gastro-intestinal disorders Antimuscarinics such as glycopyrronium should be used with caution in patients with gastro- oesophageal reflux disease, pre-existing constipation and diarrhoea. Dental disorders 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.

8). Glycopyrronium should be discontinued if pneumonia is present. 8). 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.

g. intraventricular shunt, brain tumour, encephalitis. Children below the age of 3 years Sialanar is not recommended in children below the age of 3 years since there is very limited data on the efficacy and safety of glycopyrronium in this age group Excipients with known effect Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per maximum dose, that is to say essentially ‘sodium free’.

3 mg sodium benzoate (E211) in each ml.

1. Pregnancy and breast-feeding. Glaucoma. Urinary retention. 73m2), including those with end-stage renal disease requiring dialysis. History of intestinal obstruction, ulcerative colitis, paralytic ileus, pyloric stenosis and myasthenia gravis.

5).