Enurev Breezhaler

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



 

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1. NAME OF THE MEDICINAL PRODUCT 
 

Enurev Breezhaler 44 micrograms inhalation powder, hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each capsule contains 63 micrograms of glycopyrronium bromide equivalent to 50 micrograms of 

glycopyrronium. 

 

Each delivered dose (the dose that leaves the mouthpiece of the inhaler) contains 55 micrograms of 

glycopyrronium bromide equivalent to 44 micrograms of glycopyrronium. 

 

Excipient(s) with known effect: 

Each capsule contains 23.6 mg lactose (as monohydrate). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Inhalation powder, hard capsule (inhalation powder). 

 

Transparent orange capsules containing a white powder, with the product code “GPL50” printed in 

black above and the company logo ( ) printed in black below a black bar. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Enurev Breezhaler is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult 

patients with chronic obstructive pulmonary disease (COPD). 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose is the inhalation of the content of one capsule once daily using the Enurev 

Breezhaler inhaler. 

 

Enurev Breezhaler is recommended to be administered, at the same time of the day each day. If a dose 

is missed, the next dose should be taken as soon as possible. Patients should be instructed not to take 

more than one dose in a day. 

 

Special populations 

Elderly population 

Enurev Breezhaler can be used at the recommended dose in elderly patients (75 years of age and 

older) (see section 4.8). 

 

Renal impairment 

Enurev Breezhaler can be used at the recommended dose in patients with mild to moderate renal 

impairment. In patients with severe renal impairment or end-stage renal disease requiring dialysis 

Enurev Breezhaler should be used only if the expected benefit outweighs the potential risk since the 

systemic exposure to glycopyrronium may be increased in this population (see sections 4.4 and 5.2). 

 

  



 

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Hepatic impairment 

No studies have been conducted in patients with hepatic impairment. Glycopyrronium is 

predominantly cleared by renal excretion and therefore no major increase in exposure is expected in 

patients with hepatic impairment. No dose adjustment is required in patients with hepatic impairment. 

 

Paediatric population 

There is no relevant use of Enurev Breezhaler in the paediatric population (under 18 years) in the 

indication COPD. 

 

Method of administration 

For inhalation use only. 

 

The capsules must be administered only using the Enurev Breezhaler inhaler (see section 6.6). 

 

The capsules must only be removed from the blister immediately before use. 

 

The capsules must not be swallowed. 

 

Patients should be instructed on how to administer the medicinal product correctly. Patients who do 

not experience improvement in breathing should be asked if they are swallowing the medicinal 

product rather than inhaling it. 

 

For instructions on use of the medicinal product before administration, see section 6.6. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 

 

Not for acute use 

Enurev Breezhaler is a once-daily, long-term maintenance treatment and is not indicated for the initial 

treatment of acute episodes of bronchospasm, i.e. as a rescue therapy. 

 

Hypersensitivity 

Immediate hypersensitivity reactions have been reported after administration of Enurev Breezhaler. If 

signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing 

or swallowing, swelling of the tongue, lips, and face), urticaria or skin rash, treatment should be 

discontinued immediately and alternative therapy instituted. 

 

Paradoxical bronchospasm 

In clinical studies with Enurev Breezhaler, paradoxical bronchospasm was not observed. However, 

paradoxical bronchospasm has been observed with other inhalation therapy and can be 

life-threatening. If this occurs, treatment should be discontinued immediately and alternative therapy 

instituted. 

 

Anticholinergic effect 

Enurev Breezhaler should be used with caution in patients with narrow-angle glaucoma or urinary 

retention. 

 

Patients should be informed about the signs and symptoms of acute narrow-angle glaucoma and 

should be informed to stop using Enurev Breezhaler and to contact their doctor immediately should 

any of these signs or symptoms develop. 

 

  



 

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Patients with severe renal impairment 

A moderate mean increase in total systemic exposure (AUClast) of up to 1.4-fold was seen in subjects 

with mild and moderate renal impairment and up to 2.2-fold in subjects with severe renal impairment 

and end-stage renal disease. In patients with severe renal impairment (estimated glomerular filtration 

rate below 30 ml/min/1.73 m2), including those with end-stage renal disease requiring dialysis, Enurev 

Breezhaler should be used only if the expected benefit outweighs the potential risk (see section 5.2). 

These patients should be monitored closely for potential adverse reactions. 

 

Patients with a history of cardiovascular disease 

Patients with unstable ischaemic heart disease, left ventricular failure, history of myocardial infarction, 

arrhythmia (excluding chronic stable atrial fibrillation), a history of long QT syndrome or whose QTc 

(Fridericia method) was prolonged (>450 ms for males or >470 ms for females) were excluded from 

the clinical trials, and therefore the experience in these patient groups is limited. Enurev Breezhaler 

should be used with caution in these patient groups. 

 

Excipients 

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-

galactose malabsorption should not take this medicinal product. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

The co-administration of Enurev Breezhaler with other anticholinergic-containing medicinal products 

has not been studied and is therefore not recommended. 

 

Although no formal drug interaction studies have been performed, Enurev Breezhaler has been used 

concomitantly with other medicinal products commonly used in the treatment of COPD without 

clinical evidence of drug interactions. These include sympathomimetic bronchodilators, 

methylxanthines, and oral and inhaled steroids. 

 

In a clinical study in healthy volunteers, cimetidine, an inhibitor of organic cation transport which is 

thought to contribute to the renal excretion of glycopyrronium, increased total exposure (AUC) to 

glycopyrronium by 22% and decreased renal clearance by 23%. Based on the magnitude of these 

changes, no clinically relevant drug interaction is expected when glycopyrronium is co-administered 

with cimetidine or other inhibitors of organic cation transport. 

 

Concomitant administration of glycopyrronium and orally inhaled indacaterol, a beta2-adrenergic 

agonist, under steady-state conditions of both active substances did not affect the pharmacokinetics of 

either medicinal product. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

There are no data from the use of Enurev Breezhaler in pregnant women. Animal studies do not 

indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 

Glycopyrronium should only be used during pregnancy if the expected benefit to the patient justifies 

the potential risk to the foetus. 

 

Breast-feeding 

It is unknown whether glycopyrronium bromide is excreted in human milk. However, glycopyrronium 

bromide (including its metabolites) was excreted in the milk of lactating rats (see section 5.3). The use 

of glycopyrronium by breast-feeding women should only be considered if the expected benefit to the 

woman is greater than any possible risk to the infant (see section 5.3). 

 

Fertility 

Reproduction studies and other data in animals do not indicate a concern regarding fertility in either 

males or females (see section 5.3). 

  



 

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4.7 Effects on ability to drive and use machines 

 

Glycopyrronium has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

The most common anticholinergic adverse reaction was dry mouth (2.4%). The majority of the reports 

of dry mouth were suspected to be related to the medicinal product and were mild, with none being 

severe. 

 

The safety profile is further characterised by other symptoms related to the anticholinergic effects, 

including signs of urinary retention, which were uncommon. Gastrointestinal effects including 

gastroenteritis and dyspepsia were also observed. Adverse reactions related to local tolerability 

included throat irritation, nasopharyngitis, rhinitis and sinusitis. 

 

Tabulated summary of adverse reactions 

Adverse reactions reported during the first six months of two pooled pivotal Phase III trials of 6 and 

12 months duration are listed by MedDRA system organ class (Table 1). 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 1 Adverse reactions 
 

Adverse reactions Frequency category 

Infections and infestations  

Nasopharyngitis1) Common 

Rhinitis Uncommon 

Cystitis Uncommon 

  

Immune system disorders  

Hypersensitivity Uncommon 

Angioedema2)  Uncommon 

  

Metabolism and nutrition disorders  

Hyperglycaemia Uncommon 

  

Psychiatric disorders  

Insomnia Common 

  

Nervous system disorders  

Headache3) Common 

Hypoaesthesia Uncommon 

  

Cardiac disorders  

Atrial fibrillation Uncommon 

Palpitations Uncommon 

  



 

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Respiratory, thoracic and mediastinal disorders  

Sinus congestion Uncommon 

Productive cough Uncommon 

Throat irritation Uncommon 

Epistaxis Uncommon 

Dysphonia2) Uncommon 

Paradoxical bronchospasm2) Not known 

  

Gastrointestinal disorders  

Dry mouth Common 

Gastroenteritis Common 

Nausea2) Uncommon 

Vomiting1) 2) Uncommon 

Dyspepsia Uncommon 

Dental caries Uncommon 

  

Skin and subcutaneous tissue disorders  

Rash Uncommon 

Pruritus2) Uncommon 

  

Musculoskeletal and connective tissue disorders  

Musculoskeletal pain1) 2) Common 

Pain in extremity Uncommon 

Musculoskeletal chest pain Uncommon 

  

Renal and urinary disorders  

Urinary tract infection3) Common 

Dysuria Uncommon 

Urinary retention Uncommon 

  

General disorders and administration site conditions  

Fatigue Uncommon 

Asthenia Uncommon 

1) More frequent for glycopyrronium than placebo in the 12 months database only. 

2) Reports have been received from post-approval marketing experience in association with the use of 

Enurev Breezhaler. These were reported voluntarily from a population of uncertain size, and it is 

therefore not always possible to reliably estimate the frequency or establish a causal relationship to 

drug exposure. Therefore the frequency was calculated from clinical trial experience. 

3) Seen more frequently for glycopyrronium than placebo in elderly >75 years only. 

 

Description of selected adverse reactions 

In the pooled 6-month database the frequency of dry mouth was 2.2% versus 1.1%, of insomnia 1.0% 

versus 0.8%, and of gastroenteritis 1.4% versus 0.9%, for Enurev Breezhaler and placebo respectively. 

 

Dry mouth was reported mainly during the first 4 weeks of treatment with a median duration of four 

weeks in the majority of patients. However in 40% of cases symptoms continued for the entire 6-

month period. No new cases of dry mouth were reported in months 7-12. 

 

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. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

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4.9 Overdose 
 

High doses of glycopyrronium may lead to anticholinergic signs and symptoms for which 

symptomatic treatment may be indicated. 

 

Acute intoxication by inadvertent oral ingestion of Enurev Breezhaler capsules is unlikely due to the 

low oral bioavailability (about 5%). 

 

Peak plasma levels and total systemic exposure following intravenous administration of 

150 micrograms glycopyrronium bromide (equivalent to 120 micrograms glycopyrronium) in healthy 

volunteers were respectively about 50-fold and 6-fold higher than the peak and total exposure at 

steady-state achieved with the recommended dose (44 micrograms once daily) of Enurev Breezhaler 

and were well tolerated. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Drugs for obstructive airway diseases, anticholinergics, ATC code: 

R03BB06 

 

Mechanism of action 

Glycopyrronium is an inhaled long-acting muscarinic receptor antagonist (anticholinergic) for 

once-daily maintenance bronchodilator treatment of COPD. Parasympathetic nerves are the major 

bronchoconstrictive neural pathway in airways, and cholinergic tone is the key reversible component 

of airflow obstruction in COPD. Glycopyrronium works by blocking the bronchoconstrictor action of 

acetylcholine on airway smooth muscle cells, thereby dilating the airways. 

 

Glycopyrronium bromide is a high affinity muscarinic receptor antagonist. A greater than 4-fold 

selectivity for the human M3 receptors over the human M2 receptor has been demonstrated using 

radioligand binding studies. It has a rapid onset of action as evidenced by observed receptor 

association/dissociation kinetic parameters and the onset of action after inhalation in clinical studies. 

 

The long duration of action can be partly attributed to sustained concentrations of active substance in 

the lung as reflected by the prolonged terminal elimination half-life of glycopyrronium after inhalation 

via the Enurev Breezhaler inhaler in contrast to the half life after intravenous administration (see 

section 5.2). 

 

Pharmacodynamic effects 

The clinical Phase III development programme included two phase III studies: a 6-month 

placebo-controlled study and a 12-month placebo and active-controlled (open label tiotropium 

18 micrograms once daily) study, both in patients with clinical diagnosis of moderate to severe COPD. 

 

  



 

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Effects on lung function 

Enurev Breezhaler 44 micrograms once daily provided consistently statistically significant 

improvement in lung function (forced expiratory volume in one second, FEV1, forced vital capacity, 

FVC, and inspiratory capacity, IC) in a number of clinical studies. In phase III studies, bronchodilator 

effects were seen within 5 minutes after the first dose and were maintained over the 24-hour dosing 

interval from the first dose. There was no attenuation of the bronchodilator effect over time in the 6- 

and 12-month studies. The magnitude of the effect was dependent on the degree of reversibility of 

airflow limitation at baseline (tested by administration of a short-acting muscarinic antagonist 

bronchodilator): Patients with the lowest degree of reversibility at baseline (<5%) generally exhibited 

a lower bronchodilator response than patients with a higher degree of reversibility at baseline (≥5%). 

At 12 weeks (primary endpoint), Enurev Breezhaler increased trough FEV1 by 72 ml in patients with 

the lowest degree of reversibility (<5%) and by 113 ml in those patients with a higher degree of 

reversibility at baseline (≥5%) compared to placebo (both p<0.05). 

 

In the 6-month study, Enurev Breezhaler increased FEV1 after the first dose with an improvement of 

93 ml within 5 minutes and 144 ml within 15 minutes of dosing, compared to placebo (both p<0.001). 

In the 12-month study, the improvements were 87 ml at 5 minutes and 143 ml at 15 minutes (both 

p<0.001). In the 12-month study, Enurev Breezhaler produced statistically significant improvements in 

FEV1 compared to tiotropium in the first 4 hours after dosing on day 1 and at week 26, and 

numerically greater values for FEV1 in the first 4 hours after dosing than tiotropium at week 12 and 

week 52. 

 

The values for FEV1 at the end of the dosing interval (24 h post dose) were similar between the first 

dose and those seen after 1 year of dosing. At 12 weeks (primary endpoint), Enurev Breezhaler 

increased trough FEV1 by 108 ml in the 6-month study and by 97 ml in the 12-month study compared 

to placebo (both p<0.001). In the 12-month study, the improvement versus placebo for tiotropium was 

83 ml (p<0.001). 

 

Symptomatic outcomes 

Enurev Breezhaler administered at 44 micrograms once daily statistically significantly reduced 

breathlessness as evaluated by the Transitional Dyspnoea Index (TDI). In a pooled analysis of the 6- 

and 12-month pivotal studies a statistically significantly higher percentage of patients receiving 

Enurev Breezhaler responded with a 1 point or greater improvement in the TDI focal score at week 26 

compared to placebo (58.4% and 46.4% respectively, p<0.001). These findings were similar to those 

seen in patients receiving tiotropium, 53.4% of whom responded with 1 point or greater improvement 

(p=0.009 compared to placebo). 

 

Enurev Breezhaler once daily has also shown a statistically significant effect on health-related quality 

of life measured using the St. George’s Respiratory Questionnaire (SGRQ). A pooled analysis of the 

6- and 12-month pivotal studies found a statistically significantly higher percentage of patients 

receiving Enurev Breezhaler responded with a 4 point or greater improvement in SGRQ compared to 

placebo at week 26 (57.8% and 47.6% respectively, p<0.001). For patients receiving tiotropium, 

61.0% responded with a 4 point or greater improvement in SGRQ (p=0.004 compared to placebo). 

 

COPD exacerbations reduction 

COPD exacerbation data was collected in the 6- and 12–month pivotal studies. In both studies, the 

percentage of patients experiencing a moderate or severe exacerbation (defined as requiring treatment 

with systemic corticosteroids and/or antibiotics or hospitalisation) was reduced. In the 6-month study, 

the percentage of patients experiencing a moderate or severe exacerbation was 17.5% for Enurev 

Breezhaler and 24.2% for placebo (Hazard ratio: 0.69, p=0.023), and in the 12-month study it was 

32.8% for Enurev Breezhaler and 40.2% for placebo (Hazard ratio: 0.66, p=0.001). In a pooled 

analysis of the first 6 months of treatment in the 6- and 12-month studies, compared to placebo Enurev 

Breezhaler statistically significantly prolonged time to first moderate or severe exacerbation and 

reduced the rate of moderate or severe COPD exacerbations (0.53 exacerbations/year versus 

0.77exacerbations /year, p<0.001). The pooled analysis also showed fewer patients treated with 

Enurev Breezhaler than with placebo experienced an exacerbation requiring hospitalisation (1.7% 

versus 4.2%, p=0.003). 



 

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Other effects 

Enurev Breezhaler once daily statistically significantly reduced the use of rescue medication 

(salbutamol) by 0.46 puffs per day (p=0.005) over 26 weeks and by 0.37 puffs per day (p=0.039) over 

52 weeks, compared to placebo for the 6- and 12-month studies, respectively. 

 

In a 3-week study where exercise tolerance was tested via cycle ergometer at submaximal (80%) 

workload (submaximal exercise tolerance test), Enurev Breezhaler, dosed in the morning, reduced 

dynamic hyperinflation and improved the length of time exercise could be maintained from the first 

dose onwards. On the first day of treatment inspiratory capacity under exercise was improved by 

230 ml and exercise endurance time was improved by 43 seconds (an increase of 10%) compared to 

placebo. After three weeks of treatment the improvement in inspiratory capacity with Enurev 

Breezhaler was similar to the first day (200 ml), exercise endurance time however had increased by 

89 seconds (an increase of 21%) compared to placebo. Enurev Breezhaler was found to decrease 

dyspnoea and leg discomfort when exercising as measured using Borg scales. Enurev Breezhaler also 

reduced dyspnoea at rest measured using the Transitional Dyspnoea Index. 

 

Secondary pharmacodynamic effects 

No change in mean heart rate or QTc interval was observed with Enurev Breezhaler in doses up to 

176 micrograms in COPD patients. In a thorough QT study in 73 healthy volunteers, a single inhaled 

dose of glycopyrronium 352 micrograms (8 times the therapeutic dose) did not prolong the QTc 

interval and slightly reduced heart rate (maximal effect -5.9 bpm; average effect over 

24 hours -2.8 bpm) when compared to placebo. The effect on heart rate and QTc interval of 

150 micrograms glycopyrronium bromide (equivalent to 120 micrograms glycopyrronium) 

administered intravenously was investigated in young healthy subjects. Peak exposures (Cmax) about 

50-fold higher than after inhalation of glycopyrronium 44 micrograms at steady state were achieved 

and did not result in tachycardia or QTc prolongation. A slight reduction in heart rate (mean difference 

over 24 h -2 bpm when compared to placebo), which is a known effect of low exposures to 

anticholinergic compounds in young healthy subjects, was observed. 

 

Paediatric population 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Enurev Breezhaler in all subsets of the paediatric population in COPD (see section 4.2 for information 

on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Following oral inhalation using the Enurev Breezhaler inhaler, glycopyrronium was rapidly absorbed 

and reached peak plasma levels at 5 minutes post dose. 

 

The absolute bioavailability of glycopyrromium inhaled via Enurev Breezhaler was estimated to be 

about 45% of the delivered dose. About 90% of systemic exposure following inhalation is due to lung 

absorption and 10% is due to gastrointestinal absorption. 

 

In patients with COPD, pharmacokinetic steady-state of glycopyrronium was reached within one week 

of the start of treatment. The steady-state mean peak and trough plasma concentrations of 

glycopyrronium for a 44 micrograms once-daily dosing regimen were 166 picograms/ml and 

8 picograms/ml, respectively. Steady-state exposure to glycopyrronium (AUC over the 24-hour dosing 

interval) was about 1.4- to 1.7-fold higher than after the first dose. 

 

Distribution 

After intravenous dosing, the steady-state volume of distribution of glycopyrronium was 83 litres and 

the volume of distribution in the terminal phase was 376 litres. The apparent volume of distribution in 

the terminal phase following inhalation was almost 20-fold larger, which reflects the much slower 

elimination after inhalation. The in vitro human plasma protein binding of glycopyrronium was 38% 

to 41% at concentrations of 1 to 10 nanograms/ml. 



 

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Biotransformation 

In vitro metabolism studies showed consistent metabolic pathways for glycopyrronium bromide 

between animals and humans. Hydroxylation resulting in a variety of mono-and bis-hydroxylated 

metabolites and direct hydrolysis resulting in the formation of a carboxylic acid derivative (M9) were 

seen. In vivo, M9 is formed from the swallowed dose fraction of inhaled glycopyrronium bromide. 

Glucuronide and/or sulfate conjugates of glycopyrronium were found in urine of humans after 

repeated inhalation, accounting for about 3% of the dose. 

 

Multiple CYP isoenzymes contribute to the oxidative biotransformation of glycopyrronium. Inhibition 

or induction of the metabolism of glycopyrronium is unlikely to result in a relevant change of systemic 

exposure to the active substance. 

 

In vitro inhibition studies demonstrated that glycopyrronium bromide has no relevant capacity to 

inhibit CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4/5, the 

efflux transporters MDR1, MRP2 or MXR, and the uptake transporters OCT1 or OCT2. In vitro 

enzyme induction studies did not indicate a clinically relevant induction by glycopyrronium bromide 

for cytochrome P450 isoenzymes, or for UGT1A1 and the transporters MDR1 and MRP2. 

 

Elimination 

After intravenous administration of [3H]-labelled glycopyrronium bromide to humans, the mean 

urinary excretion of radioactivity in 48 hours amounted to 85% of the dose. A further 5% of the dose 

was found in the bile. 

 

Renal elimination of parent drug accounts for about 60 to 70% of total clearance of systemically 

available glycopyrronium whereas non-renal clearance processes account for about 30 to 40%. Biliary 

clearance contributes to the non-renal clearance, but the majority of non-renal clearance is thought to 

be due to metabolism. 

 

Mean renal clearance of glycopyrronium following inhalation was in the range of 17.4 and 

24.4 litres/h. Active tubular secretion contributes to the renal elimination of glycopyrronium. Up to 

23% of the delivered dose was found in urine as parent drug. 

 

Glycopyrronium plasma concentrations declined in a multi-phasic manner. The mean terminal 

elimination half-life was much longer after inhalation (33 to 57 hours) than after intravenous 

(6.2 hours) and oral (2.8 hours) administration. The elimination pattern suggests sustained lung 

absorption and/or transfer of glycopyrronium into the systemic circulation at and beyond 24 hours 

after inhalation. 

 

Linearity/non-linearity 

In COPD patients both systemic exposure and total urinary excretion of glycopyrronium at 

pharmacokinetic steady state increased about dose-proportionally over the dose range of 44 to 

176 micrograms. 

 

Special populations 

A population pharmacokinetic analysis of data in COPD patients identified body weight and age as 

factors contributing to inter-patient variability in systemic exposure. Enurev Breezhaler 

44 micrograms once daily can be safely used in all age and body weight groups. 

 

Gender, smoking status and baseline FEV1 had no apparent effect on systemic exposure. 

 

There were no major differences in total systemic exposure (AUC) between Japanese and Caucasian 

subjects following inhalation of glycopyrronium bromide. Insufficient pharmacokinetic data is 

available for other ethnicities or races. 

 

Patients with hepatic impairment 

Clinical studies have not been conducted in patients with hepatic impairment. Glycopyrronium is 



 

11 

cleared predominantly from the systemic circulation by renal excretion. Impairment of the hepatic 

metabolism of glycopyrronium is not thought to result in a clinically relevant increase of systemic 

exposure. 

 

Patients with renal impairment 

Renal impairment has an impact on the systemic exposure to glycopyrronium bromide. A moderate 

mean increase in total systemic exposure (AUClast) of up to 1.4-fold was seen in subjects with mild and 

moderate renal impairment and up to 2.2-fold in subjects with severe renal impairment and end-stage 

renal disease. In COPD patients with mild and moderate renal impairment (estimated glomerular 

filtration rate, eGFR ≥30 ml/min/1.73 m2) Enurev Breezhaler can be used at the recommended dose. In 

patients with severe renal impairment (eGFR <30 ml/min/1.73 m2), including those with end-stage 

renal disease requiring dialysis, Enurev Breezhaler should only be used if the expected benefit 

outweighs the potential risk (see section 4.4). 

 

5.3 Preclinical safety data 
 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction 

and development. 

 

Effects attributable to the muscarinic receptor antagonist properties of glycopyrronium bromide 

included mild to moderate increases in heart rate in dogs, lens opacities in rats and, reversible changes 

associated with reduced glandular secretions in rats and dogs. Mild irritancy or adaptive changes in the 

respiratory tract were seen in rats. All these findings occurred at exposures sufficiently in excess of 

those anticipated in humans. 

 

Glycopyrronium was not teratogenic in rats or rabbits following inhalation administration. Fertility 

and pre- and post-natal development were not affected in rats. Glycopyrronium bromide and its 

metabolites did not significantly cross the placental barrier of pregnant mice, rabbits and dogs. 

Glycopyrronium bromide (including its metabolites) was excreted into the milk of lactating rats and 

reached up to 10-fold higher concentrations in the milk than in the blood of the dam. 

 

Genotoxicity studies did not reveal any mutagenic or clastogenic potential for glycopyrronium 

bromide. Carcinogenicity studies in transgenic mice using oral administration and in rats using 

inhalation administration revealed no evidence of carcinogenicity at systemic exposures (AUC) of 

approximately 53-fold higher in mice and 75-fold higher in rats than the maximum recommended dose 

of 44 micrograms once daily for humans. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Capsule content 

Lactose monohydrate 

Magnesium stearate 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

2 years 

 

Each inhaler should be disposed of after all capsules have been used. 

  



 

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6.4 Special precautions for storage 

 

Do not store above 25°C. 

 

The capsules must always be stored in the original blister in order to protect from moisture. The 

capsules must only be removed immediately before use. 

 

6.5 Nature and contents of container 

 

Enurev Breezhaler is a single-dose inhaler. Inhaler body and cap are made from acrylonitrile butadiene 

styrene, push buttons are made from methyl metacrylate acrylonitrile butadiene styrene. Needles and 

springs are made from stainless steel. Each blister strip contains either 6 or 10 hard capsules. 

 

PA/Alu/PVC – Alu perforated unit-dose blister 

 

Packs containing 6x1, 10x1, 12x1 or 30x1 hard capsules, together with one inhaler. 

 

Multipacks containing 90 (3 packs of 30x1) hard capsules and 3 inhalers. 

Multipacks containing 96 (4 packs of 24x1) hard capsules and 4 inhalers. 

Multipacks containing 150 (15 packs of 10x1) hard capsules and 15 inhalers. 

Multipacks containing 150 (25 packs of 6x1) hard capsules and 25 inhalers. 

 

Not all pack sizes may be marketed. 

 

  



 

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6.6 Special precautions for disposal and other handling 
 

The inhaler provided with each new prescription should be used. Each inhaler should be disposed of 

after all capsules have been used. 

 

Instructions for handling and use 

 

Please read the full Instructions for Use before using the Enurev Breezhaler. 

 

 

 

 

 

 

Insert Pierce and release Inhale deeply Check capsule is 

empty 

 
  

 

 
   

 
   

 

 

 

 

 

 

 

 

 

 

 
Step 1a: 

Pull off cap 

Step 2a: 

Pierce capsule once 

Hold the inhaler upright. 

Pierce capsule by firmly 

pressing both side 

buttons at the same time. 

Step 3a: 

Breathe out fully 

Do not blow into the 

inhaler. 

Check capsule is empty 

Open the inhaler to see if 

any powder is left in the 

capsule. 

 

You should hear a noise 

as the capsule is pierced. 

Only pierce the capsule 

once. 

 

If there is powder left in 

the capsule: 

Close the inhaler. 

Repeat steps 3a to 3c. 

Step 1b: 

Open inhaler 

 
Step 2b: 

Release side buttons 

Step 3b: 

Inhale medicine deeply 

Hold the inhaler as shown 

in the picture. 

Place the mouthpiece in 

your mouth and close your 

lips firmly around it. 

Do not press the side 

buttons. 

 
Powder Empty 

remaining 

1 2 3 
Chec

k 



 

14 

 

 

 Breathe in quickly and as 

deeply as you can. 

During inhalation you will 

hear a whirring noise. 

You may taste the 

medicine as you inhale. 

   

Step 1c: 

Remove capsule 

Separate one of the 

blisters from the blister 

card. 

Peel open the blister and 

remove the capsule. 

Do not push the capsule 

through the foil. 

Do not swallow the 

capsule. 

 

 
Step 3c: 

Hold breath 

Hold your breath for up to 

5 seconds. 

Remove empty capsule 

Put the empty capsule in 

your household waste. 

 

Close the inhaler and 

replace the cap. 

 
Step 1d: 

Insert capsule 

Never place a capsule 

directly into the 

mouthpiece. 

 

  Important Information 

 Enurev Breezhaler 
capsules must always be 

stored in the blister card 

and only removed 

immediately before use. 

 Do not push the capsule 
through the foil to 

remove it from the 

blister. 

 Do not swallow the 
capsule. 

 Do not use the Enurev 
Breezhaler capsules 

with any other inhaler. 

 Do not use the Enurev 
Breezhaler inhaler to 

take any other capsule 

medicine. 

 Never place the capsule 
into your mouth or the 

mouthpiece of the 

inhaler. 

 Do not press the side 
buttons more than once. 

 Do not blow into the 
mouthpiece. 

 Do not press the side 
buttons while inhaling 

through the mouthpiece. 

 Do not handle capsules 
with wet hands. 

 Never wash your inhaler 
with water. 

 
Step 1e: 

Close inhaler 

 



 

15 

Your Seebri Breezhaler Inhaler pack contains: 

 One Seebri Breezhaler inhaler 

 One or more blister cards, each containing either 
6 or 10 Seebri Breezhaler capsules to be used in 

the inhaler 

 

 
 

 

 

Frequently Asked 

Questions 

 

Why didn’t the inhaler 

make a noise when I 

inhaled? 

The capsule may be stuck 

in the capsule chamber. If 

this happens, carefully 

loosen the capsule by 

tapping the base of the 

inhaler. Inhale the 

medicine again by 

repeating steps 3a to 3c. 

 

What should I do if there 

is powder left inside the 

capsule? 

You have not received 

enough of your medicine. 

Close the inhaler and 

repeat steps 3a to 3c. 

 

I coughed after inhaling 

– does this matter? 

This may happen. As long 

as the capsule is empty 

you have received enough 

of your medicine. 

 

I felt small pieces of the 

capsule on my tongue – 

does this matter? 

This can happen. It is not 

harmful. The chances of 

the capsule breaking into 

small pieces will be 

increased if the capsule is 

pierced more than once. 

Cleaning the inhaler 

Wipe the mouthpiece 

inside and outside with a 

clean, dry, lint-free cloth to 

remove any powder 

residue. Keep the inhaler 

dry. Never wash your 

inhaler with water. 

Disposing of the inhaler 

after use 

Each inhaler should be 

disposed of after all 

capsules have been used. 

Ask your pharmacist how 

to dispose of medicines 

and inhalers that are no 

longer required. 

 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

  

Blister Card 

Blister 

Inhaler base Inhaler 

Base 

Cap 

Side 

buttons 

Capsule 

chamber 
Mouthpiece 

Screen 



 

16 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/789/001-008 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 28 September 2012 

Date of latest renewal: 13 July 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

 

  

http://www.ema.europa.eu/


 

17 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 



 

18 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 
 

The MAH shall perform the pharmacovigilance activities and interventions detailed in the agreed 

RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent updates of 

the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency. 

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a signifcant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

  



 

19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



 

20 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



 

21 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Enurev Breezhaler 44 micrograms inhalation powder, hard capsules 

glycopyrronium (as glycopyrronium bromide) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 50 micrograms glycopyrronium. The amount of glycopyrronium delivered is 

44 micrograms. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: lactose and magnesium stearate. 

See package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Inhalation powder, hard capsule 

 

6 x 1 capsules + 1 inhaler 

10 x 1 capsules + 1 inhaler 

12 x 1 capsules + 1 inhaler 

30 x 1 capsules + 1 inhaler 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For use only with the inhaler provided in the pack. 

Do not swallow capsules. 

Read the package leaflet before use. 

Inhalation use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

  



 

22 

 

8. EXPIRY DATE 

 

EXP 

The inhaler in each pack should be disposed of after all capsules in that pack have been used. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store the capsules in the original blister in order to protect from moisture. Do not remove from the 

blister until immediately before use. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/789/001 6 capsules + 1 inhaler 

EU/1/12/789/007 10 capsules + 1 inhaler 

EU/1/12/789/002 12 capsules + 1 inhaler 

EU/1/12/789/003 30 capsules + 1 inhaler 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Enurev Breezhaler 

 

  



 

23 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 
  



 

24 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Enurev Breezhaler 44 micrograms inhalation powder, hard capsules 

glycopyrronium (as glycopyrronium bromide) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 50 micrograms glycopyrronium. The amount of glycopyrronium delivered is 

44 micrograms. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: lactose and magnesium stearate. 

See package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Inhalation powder, hard capsule 

 

Multipack: 90 (3 packs of 30 x 1) capsules + 3 inhalers. 

Multipack: 96 (4 packs of 24 x 1) capsules + 4 inhalers. 

Multipack: 150 (15 packs of 10 x 1) capsules + 15 inhalers. 

Multipack: 150 (25 packs of 6 x 1) capsules + 25 inhalers. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For use only with the inhaler provided in the pack. 

Do not swallow capsules. 

Read the package leaflet before use. 

Inhalation use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

  



 

25 

 

8. EXPIRY DATE 

 

EXP 

The inhaler in each pack should be disposed of after all capsules in that pack have been used. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store the capsules in the original blister in order to protect from moisture. Do not remove from the 

blister until immediately before use. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/789/004 Multipack comprising 3 packs (30 capsules + 1 inhaler) 

EU/1/12/789/005 Multipack comprising 4 packs (24 capsules + 1 inhaler) 

EU/1/12/789/008 Multipack comprising 15 packs (10 capsules + 1 inhaler) 

EU/1/12/789/006 Multipack comprising 25 packs (6 capsules + 1 inhaler) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Enurev Breezhaler 

 

  



 

26 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 
  



 

27 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Enurev Breezhaler 44 micrograms inhalation powder, hard capsules 

glycopyrronium (as glycopyrronium bromide) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 50 micrograms glycopyrronium. The amount of glycopyrronium delivered is 

44 micrograms micrograms. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: lactose and magnesium stearate. 

See package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Inhalation powder, hard capsule 

 

30 x 1 capsules + 1 inhaler. Component of a multipack. Not to be sold separately. 

24 x 1 capsules + 1 inhaler. Component of a multipack. Not to be sold separately. 

10 x 1 capsules + 1 inhaler. Component of a multipack. Not to be sold separately. 

6 x 1 capsules + 1 inhaler. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For use only with the inhaler provided in the pack. 

Do not swallow capsules. 

Read the package leaflet before use. 

Inhalation use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

  



 

28 

 

8. EXPIRY DATE 

 

EXP 

The inhaler in each pack should be disposed of after all capsules in that pack have been used. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Store the capsules in the original blister in order to protect from moisture. Do not remove from the 

blister until immediately before use. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/789/004 Multipack comprising 3 packs (30 capsules + 1 inhaler) 

EU/1/12/789/005 Multipack comprising 4 packs (24 capsules + 1 inhaler) 

EU/1/12/789/008 Multipack comprising 15 packs (10 capsules + 1 inhaler) 

EU/1/12/789/006 Multipack comprising 25 packs (6 capsules + 1 inhaler) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Enurev Breezhaler 

 

  



 

29 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 
  



 

30 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INNER LID OF OUTER CARTON OF UNIT PACK AND OF INTERMEDIATE CARTON OF 

MULTIPACK 

 

 

1. OTHER 

 

1  Insert 

2  Pierce and release 

3  Inhale deeply 

Check  Check capsule is empty 

 

Read the leaflet before use. 

  



 

31 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Enurev Breezhaler 44 mcg inhalation powder 

glycopyrronium 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Inhalation use only 

  



 

32 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

33 

Package leaflet: Information for the user 
 

Enurev Breezhaler 44 micrograms inhalation powder, hard capsules 

glycopyrronium 

(as glycopyrronium bromide) 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 
 

1. What Enurev Breezhaler is and what it is used for 

2. What you need to know before you use Enurev Breezhaler 

3. How to use Enurev Breezhaler 

4. Possible side effects 

5. How to store Enurev Breezhaler 

6. Contents of the pack and other information 

 

 

1. What Enurev Breezhaler is and what it is used for 

 

What Enurev Breezhaler is 

This medicine contains an active substance called glycopyrronium bromide. This belongs to a group of 

medicines called bronchodilators. 

 

What Enurev Breezhaler is used for 

This medicine is used to make breathing easier for adult patients who have breathing difficulties due to 

a lung disease called chronic obstructive pulmonary disease (COPD). 

 

In COPD the muscles around the airways tighten. This makes breathing difficult. This medicine blocks 

the tightening of these muscles in the lungs, making it easier for air to get in and out of the lungs. 

 

If you use this medicine once a day, it will help to reduce the effects of COPD on your everyday life. 

 

 

2. What you need to know before you use Enurev Breezhaler 
 

Do not use Enurev Breezhaler 
- if you are allergic to glycopyrronium bromide or any of the other ingredients of this medicine 

(listed in section 6). 

 

Warnings and precautions 
Talk to your doctor before using Enurev Breezhaler, if any of the following applies to you: 

- you have kidney problems. 
- you have an eye problem called narrow-angle glaucoma. 
- you have difficulty passing urine. 
 

  



 

34 

During treatment with Enurev Breezhaler, stop taking this medicine and tell your doctor 

immediately: 

- if you experience tightness of the chest, coughing, wheezing or breathlessness immediately after 
using Enurev Breezhaler (signs of bronchospasm). 

- if you experience difficulties in breathing or swallowing, swelling of the tongue, lips or face, 
skin rash, itching and hives (signs of allergic reaction). 

- if you experience eye pain or discomfort, temporary blurring of vision, visual halos or coloured 
images in association with red eyes. These may be signs of an acute attack of narrow-angle 

glaucoma. 

 

Enurev Breezhaler is used as a maintenance treatment for your COPD. Do not use this medicine to 

treat a sudden attack of breathlessness or wheezing. 

 

Children and adolescents 
Do not give this medicine to children or adolescents below the age of 18 years. 

 

Other medicines and Enurev Breezhaler 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. This includes medicines similar to Enurev Breezhaler used for your lung disease, such as 

ipratropium, oxitropium or tiotropium (so called anticholinergics). 

 

No specific side effects have been reported when Enurev Breezhaler has been used together with other 

medicines used to treat COPD such as reliever inhalers (e.g. salbutamol), methylxanthines (e.g. 

theophylline) and/or oral and inhaled steroids (e.g. prednisolone). 

 

Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 

There are no data from the use of this medicine in pregnant women and it is not known whether the 

active substance of this medicine passes into human milk. 

 

Driving and using machines 

It is unlikely that this medicine will affect your ability to drive and use machines. 

 

Enurev Breezhaler contains lactose 

This medicine contains lactose. If you have been told by your doctor that you have an intolerance to 

some sugars, contact your doctor before taking this medicine. 

 

 

3. How to use Enurev Breezhaler 
 

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 

or pharmacist if you are not sure. 

 

How much Enurev Breezhaler to use 

The usual dose is to inhale the content of one capsule each day. 

You only need to inhale once a day because the effect of this medicine lasts for 24 hours. 

Do not use more than your doctor tells you to use. 

 

Elderly people 

You can use this medicine if you are aged 75 years and over at the same dose as for other adults. 

 

When to inhale Enurev Breezhaler 

Use this medicine at the same time each day. This will also help you to remember to use it. 

 

You can inhale this medicine anytime before or after food or drink. 



 

35 

 

How to inhale Enurev Breezhaler 
- In this pack, you will find an inhaler and capsules (in blisters) that contain the medicine as 

inhalation powder. Only use the capsules with the inhaler provided in this pack (Enurev 

Breezhaler inhaler). The capsules should remain in the blister until you need to use them. 

- Do not push the capsule through the foil. 
- When you start a new pack, use the new Enurev Breezhaler inhaler that is supplied in the pack. 
- Dispose of each inhaler after after all capsules in that pack have been used. 
- Do not swallow the capsules. 
- Please read the instructions at the end of this leaflet for more information on how to use the 

inhaler. 

 

If you use more Enurev Breezhaler than you should 

If you have inhaled too much of this medicine or if someone else accidentally uses your capsules, you 

must immediately either tell your doctor or go to the nearest emergency unit. Show the pack of Enurev 

Breezhaler. Medical attention may be needed. 

 

If you forget to use Enurev Breezhaler 

If you forget to inhale a dose, take one as soon as possible. However, do not take two doses on the 

same day. Then take the next dose as usual. 

 

How long to continue your treatment with Enurev Breezhaler 

- Keep using this medicine for as long as your doctor tells you. 
- COPD is a long-term disease and you should use this medicine every day and not only when 

you have breathing problems or other symptoms of COPD. 

If you have questions about how long to continue your treatment with this medicine, talk to your 

doctor or pharmacist. 

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Some side effects may be serious but are uncommon 

(may affect up to 1 in 100 people) 

 Irregular heart beat 

 High level of blood sugar (hyperglycaemia: typical symptoms include excessive thirst or hunger 
and frequent urination) 

 Rash, itching, hives, difficulty breathing or swallowing, dizziness (possible signs of allergic 
reaction) 

 Swelling mainly of the tongue, lips, face or throat (possible signs of angioedema) 
If you get any of these side effects, tell your doctor immediately. 

 

Some side effects may be serious, but the frequency of these side effects is not known 

(frequency cannot be estimated from the available data) 

 Difficulty breathing with wheezing or coughing (signs of paradoxical bronchospasm) 

 

Some side effects are common 

(may affect up to 1 in 10 people) 

 Dry mouth 

 Difficulty sleeping 

 Runny or stuffy nose, sneezing, sore throat 

 Diarrhoea or stomach ache 

 Musculoskeletal pain 



 

36 

 

Some side effects are uncommon 

(may affect up to 1 in 100 people) 

 Difficulty and pain when passing urine 

 Painful and frequent urination 

 Palpitations 

 Rash 

 Numbness 

 Cough with sputum 

 Dental caries 

 Feeling of pressure or pain in the cheeks and forehead 

 Nose bleeds 

 Pain in arms or legs 

 Pain in muscles, bones or joints of the chest 

 Stomach discomfort after meals 

 Throat irritation 

 Tiredness 

 Weakness 

 Itching 

 Voice alteration (hoarseness) 

 Nausea 

 Vomiting 
 

Some elderly patients above 75 years of age experienced headache (frequency common) and urinary 

tract infection (frequency common). 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

 

 

5. How to store Enurev Breezhaler 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the carton and blister after “EXP”. 

The expiry date refers to the last day of that month. 

 

Do not store above 25°C. 

 

Store the capsules in the original blister in order to protect from moisture. Do not remove from the 

blister until immediately before use. 

 

The inhaler in each pack should be disposed of after all capsules in that pack have been used. 

 

Do not use this medicine if you notice that the pack is damaged or shows signs of tampering. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

37 

6. Contents of the pack and other information 

 

What Enurev Breezhaler contains 

- The active substance is glycopyrronium bromide. Each capsule contains 63 micrograms of 
glycopyrronium bromide (equivalent to 50 micrograms glycopyrronium). The delivered dose 

(the dose that leaves the mouthpiece of the inhaler) is equivalent to 44 micrograms of 

glycopyrronium. 

- The other ingredients of the inhalation powder are lactose monohydrate and magnesium 
stearate. 

 

What Enurev Breezhaler looks like and contents of the pack 

Enurev Breeyhaler 44 micrograms inhalation powder, hard capsules are transparent and orange and 

contain a white powder. They have the product code “GPL50” printed in black above and a company 

logo ( ) printed in black below a black bar. 

 

Each pack contains a device called an inhaler, together with capsules in blisters. Each blister strip 

contains either 6 or 10 hard capsules. 

 

The following pack sizes are available: 

Packs containing 6x1, 10x1, 12x1 or 30x1 hard capsules, together with one inhaler. 

 

Multipacks containing 90 (3 packs of 30x1) hard capsules and 3 inhalers. 

Multipacks containing 96 (4 packs of 24x1) hard capsules and 4 inhalers. 

Multipacks containing 150 (15 packs of 10x1) hard capsules and 15 inhalers. 

Multipacks containing 150 (25 packs of 6x1) hard capsules and 25 inhalers. 
 

Not all pack sizes may be available in your country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

  



 

38 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Ferrer Internacional, S.A. 

Tel: +34 93 600 37 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

  



 

39 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

 

This leaflet was last revised in 

 

 

Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

 



 

40 

Instructions for use of Enurev Breezhaler inhaler 

 

 

Please read the full Instructions for Use before using the Enurev Breezhaler. 

 

 

 
 

 

Insert Pierce and release Inhale deeply Check capsule is empty 

 
  

 

 
   

 
   

 

 

 

 

 

 

 
Step 1a: 

Pull off cap 

Step 2a: 

Pierce capsule once 

Hold the inhaler upright. 

Pierce capsule by firmly 

pressing both side 

buttons at the same time. 

Step 3a: 

Breathe out fully 

Do not blow into the 

inhaler. 

Check capsule is empty 

Open the inhaler to see if 

any powder is left in the 

capsule. 

 

You should hear a noise 

as the capsule is pierced. 

Only pierce the capsule 

once. 

 

If there is powder left in 

the capsule: 

Close the inhaler. 

Repeat steps 3a to 3c. 

Step 1b: 

Open inhaler 

 
Step 2b: 

Release side buttons 

Step 3b: 

Inhale medicine deeply 

Hold the inhaler as 

shown in the picture. 

Place the mouthpiece in 

your mouth and close 

your lips firmly around 

it. 

Do not press the side 

buttons. 

 
Powder Empty 

remaining 

1 
 

2 
 

3 
 

Check 
 



 

41 

 

 

 Breathe in quickly and as 

deeply as you can. 

During inhalation you 

will hear a whirring 

noise. 

You may taste the 

medicine as you inhale. 

 

Step 1c: 

Remove capsule 

Separate one of the 

blisters from the blister 

card. 

Peel open the blister and 

remove the capsule. 

Do not push the capsule 

through the foil. 

Do not swallow the 

capsule. 

 

 
Step 3c: 

Hold breath 

Hold your breath for up 

to 5 seconds. 

Remove empty capsule 

Put the empty capsule in 

your household waste. 

 

Close the inhaler and 

replace the cap. 

 
Step 1d: 

Insert capsule 

Never place a capsule 

directly into the 

mouthpiece. 

 

  Important Information 

 Enurev Breezhaler 
capsules must always be 

stored in the blister card 

and only removed 

immediately before use. 

 Do not push the capsule 
through the foil to 

remove it from the 

blister. 

 Do not swallow the 
capsule. 

 Do not use the Enurev 
Breezhaler capsules 

with any other inhaler. 

 Do not use the Enurev 
Breezhaler inhaler to 

take any other capsule 

medicine. 

 Never place the capsule 
into your mouth or the 

mouthpiece of the 

inhaler. 

 Do not press the side 
buttons more than once. 

 Do not blow into the 
mouthpiece. 

 Do not press the side 
buttons while inhaling 

through the mouthpiece. 

 Do not handle capsules 
with wet hands. 

 Never wash your inhaler 
with water. 

 
Step 1e: 

Close inhaler 

 



 

42 

Your Seebri Breezhaler Inhaler pack contains: 

 One Seebri Breezhaler inhaler 

 One or more blister cards, each containing either 
6 or 10 Seebri Breezhaler capsules to be used in 

the inhaler 

 

 
 

 

 

Frequently Asked 

Questions 

 

Why didn’t the inhaler 

make a noise when I 

inhaled? 

The capsule may be stuck 

in the capsule chamber. If 

this happens, carefully 

loosen the capsule by 

tapping the base of the 

inhaler. Inhale the 

medicine again by 

repeating steps 3a to 3c. 

 

What should I do if there 

is powder left inside the 

capsule? 

You have not received 

enough of your medicine. 

Close the inhaler and 

repeat steps 3a to 3c. 

 

I coughed after inhaling 

– does this matter? 

This may happen. As long 

as the capsule is empty 

you have received enough 

of your medicine. 

 

I felt small pieces of the 

capsule on my tongue – 

does this matter? 

This can happen. It is not 

harmful. The chances of 

the capsule breaking into 

small pieces will be 

increased if the capsule is 

pierced more than once. 

Cleaning the inhaler 

Wipe the mouthpiece 

inside and outside with a 

clean, dry, lint-free cloth to 

remove any powder 

residue. Keep the inhaler 

dry. Never wash your 

inhaler with water. 

Disposing of the inhaler 

after use 

Each inhaler should be 

disposed of after all 

capsules have been used. 

Ask your pharmacist how 

to dispose of medicines 

and inhalers that are no 

longer required. 

 

 

Blister Card 

Blister 

Inhaler base Inhaler 

Base 

Cap 

Side 

buttons 

Capsule 

chamber 
Mouthpiece 

Screen 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET