Sialanar

HOS-216783 · has-adverse-reaction-information · PDF-Seite 8

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 8  Adverse reactions Frequency cate

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HOS-216789 · has-adverse-reaction-information · PDF-Seite 22

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 2). 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 2. 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 Intermitten

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HOS-216785 · has-contraindication-information · PDF-Seite 18

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Pregnancy and breast-feeding. Glaucoma. Urinary retention. Severe renal impairment (eGFR < 30 ml/min/1.73 m2), including those with end-stage renal disease requiring dialysis. 18 History of intestinal obstruction, ulcerative colitis, paralytic ileus, pyloric stenosis and myasthenia gravis. Concomitant treatment with potassium chloride solid oral dose and anticholinergics (see section 4.5).

HOS-216779 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Pregnancy and breast-feeding. Glaucoma. Urinary retention. Severe renal impairment (eGFR <30 ml/min/1.73m2), including those with end-stage renal disease requiring dialysis. History of intestinal obstruction, ulcerative colitis, paralytic ileus, pyloric stenosis and myasthenia gravis. Concomitant treatment with potassium chloride solid oral dose and anticholinergics (see section 4.5). 4

HOS-216784 · has-indication-information · PDF-Seite 16

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

HOS-216778 · has-indication-information · PDF-Seite 2

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

HOS-216781 · has-interaction-information · PDF-Seite 6

No interaction studies have been performed. Paediatric population There are limited data available relating to interactions with other medicinal products in the paediatric age group. The following medicinal product interaction information is relevant to glycopyrronium. Contraindications of concomitant use (see section 4.3) Potassium chloride solid oral dose 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 gastrointestinal bleeding and small bowel ulceration, stenosis, perforation, and obstruction has been observed. Anticholinergics 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. 6 Concomitant use to be considered with caution Antispasmodics Glycopyrronium may antagonize the pharmacologic effects of gastrointestinal prokinetic active substances such as domperidone and metoclopramide. Topiramate Glycopyrronium may potentiate the effects of oligohidrosis and hyperthermia associated with the use of topiramate, particularly in pediatric patients. Sedating antihistamines Sedating antihistamines may have additive anticholinergic effects. A reduction in anticholinergic and/or antihistamine dose may be necessary. Neuroleptics/antipsychotics The effects of active substances such as phenothiazines, clozapine and haloperidol may be potentiated. A reduction in anticholinergic and/or neuroleptic/antipsychotic dose may be necessary. Skeletal muscle relaxants Use of anticholinergics after administration of botulinum toxin may potentiate systemic anticholinergic effects. Tricyclic antidepressants and MAOIs Tricyclic antidepressants and MAOIs may have additive anticholinergic effects. A reduction in anticholinergic and/or tricyclic antidepressants and MAOIs dose may be necessary. 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 excessiv

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HOS-216787 · has-interaction-information · PDF-Seite 20

No interaction studies have been performed. Paediatric population There are limited data available relating to interactions with other medicinal products in the paediatric age group. The following medicinal product interaction information is relevant to glycopyrronium. Contraindications of concomitant use (see section 4.3) Potassium chloride solid oral dose 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 gastrointestinal bleeding and small bowel ulceration, stenosis, perforation, and obstruction has been observed. Anticholinergics 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 Antispasmodics Glycopyrronium may antagonize the pharmacologic effects of gastrointestinal prokinetic active substances such as domperidone and metoclopramide. Topiramate Glycopyrronium may potentiate the effects of oligohidrosis and hyperthermia associated with the use of topiramate, particularly in paediatric patients. 20 Sedating antihistamines Sedating antihistamines may have additive anticholinergic effects. A reduction in anticholinergic and/or antihistamine dose may be necessary. Neuroleptics/antipsychotics The effects of active substances such as phenothiazines, clozapine and haloperidol may be potentiated. A reduction in anticholinergic and/or neuroleptic/antipsychotic dose may be necessary. Skeletal muscle relaxants Use of anticholinergics after administration of botulinum toxin may potentiate systemic anticholinergic effects. Tricyclic antidepressants and MAOIs Tricyclic antidepressants and MAOIs may have additive anticholinergic effects. A reduction in anticholinergic and/or tricyclic antidepressants and MAOIs dose may be necessary. 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 excessiv

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HOS-216782 · has-pregnancy-information · PDF-Seite 7

Women of child-bearing potential Effective contraception should be considered prior to treating women of childbearing age, where appropriate. Pregnancy There are no data on the use of Sialanar in pregnant women. The assessment of reproductive endpoints for glycopyrronium is limited (see section 5.3). Glycopyrronium is contraindicated during pregnancy (see section 4.3). 7 Breast-feeding Safety in breast-feeding has not been established. Use while breast-feeding is contraindicated (see section 4.3). Fertility There are no data on the effects of Sialanar on male or female fertility. Reproductive performance in rats given glycopyrronium shows a decrease in the rate of conception and in survival rate at weaning. There are insufficient data in the public domain to adequately assess effects on the reproductive system in young adults (see section 5.3).

HOS-216788 · has-pregnancy-information · PDF-Seite 21

Women of child-bearing potential Effective contraception should be considered prior to treating women of childbearing age, where appropriate. Pregnancy There are no data on the use of Sialanar in pregnant women. The assessment of reproductive endpoints for glycopyrronium is limited (see section 5.3). Glycopyrronium is contraindicated during pregnancy (see section 4.3). Breast-feeding Safety in breast-feeding has not been established. Use while breast-feeding is contraindicated (see section 4.3). Fertility There are no data on the effects of Sialanar on male or female fertility. Reproductive performance in rats given glycopyrronium shows a decrease in the rate of conception and in survival rate at weaning. There are insufficient data in the public domain to adequately assess effects on the reproductive system in young adults (see section 5.3). 21

HOS-216786 · has-warning-information · PDF-Seite 19

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. Monitoring by physicians and caregivers is required with adherence to the management instructions below: The carer should stop treatment and seek advice from the prescriber in the event of: • constipation • urinary retention • pneumonia • allergic reaction • pyrexia • very hot weather • changes in behaviour After evaluating the event, the prescriber will decide if treatment should remain stopped or if this should continue at a lower dose (see section 4.2). 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. If continuous treatment is needed (e.g. in a palliative setting) or the treatment is repeated intermittently (e.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. Cardiac disorders Glycopyrronium should be used with caution in patients with acute myocardial infarction, hypertension, coronary artery disease, cardiac arrhythmias and conditions characterised by tachycardia (including thyrotoxicosis, cardiac insufficiency, cardiac surgery) due to the potential increase in heart rate, blood pressure and rhythm disorders produced by its administration (see section 4.8). 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. 19 Respiratory disorders Glycopyrronium can cause thi

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HOS-216780 · has-warning-information · PDF-Seite 5

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. Monitoring by physicians and caregivers is required with adherence to the management instructions below: The carer should stop treatment and seek advice from the prescriber in the event of: • constipation • urinary retention • pneumonia • allergic reaction • pyrexia • very hot weather • changes in behaviour After evaluating the event, the prescriber will decide if treatment should remain stopped or if this should continue at a lower dose (see section 4.2). 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. If continuous treatment is needed (e.g. in a palliative setting) or the treatment is repeated intermittently (e.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. Cardiac disorders Glycopyrronium should be used with caution in patients with acute myocardial infarction, hypertension, coronary artery disease, cardiac arrhythmias and conditions characterised by tachycardia (including thyrotoxicosis, cardiac insufficiency, cardiac surgery) due to the potential increase in heart rate, blood pressure and rhythm disorders produced by its administration (see section 4.8). 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. 5 Respiratory disorders Glycopyrronium can cause

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