Trydonis

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Trydonis 87 micrograms/5 micrograms/9 micrograms pressurised inhalation, solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each delivered dose (the dose leaving the mouthpiece) contains 87 micrograms of beclometasone 
dipropionate, 5 micrograms of formoterol fumarate dihydrate and 9 micrograms of glycopyrronium (as 
11 micrograms glycopyrronium bromide). 
 
Each metered dose (the dose leaving the valve) contains 100 micrograms of beclometasone 
dipropionate, 6 micrograms of formoterol fumarate dihydrate and 10 micrograms of glycopyrronium 
(as 12.5 micrograms glycopyrronium bromide). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Pressurised inhalation, solution (pressurised inhalation). 
 
Colourless to yellowish liquid solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary 
disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid and a 
long-acting beta2-agonist or a combination of a long-acting beta2-agonist and a long-acting 
muscarinic antagonist (for effects on symptoms control and prevention of exacerbations see 
section 5.1). 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults 
The recommended dose is two inhalations of Trydonis twice daily. 
The maximum dose is two inhalations of Trydonis twice daily. 
 
Special populations 
 
Elderly  
No dosage adjustment is required in elderly patients (65 years of age and older). 
 
Renal impairment 
Trydonis can be used at the recommended dose in patients with mild to moderate renal impairment. 
Use of Trydonis in patients with severe renal impairment or end-stage renal disease requiring dialysis, 
especially if associated with significant body weight reduction, should be considered only if the 
expected benefit outweighs the potential risk (see section 4.4 and section 5.2). 
 
Hepatic impairment 
There are no relevant data on the use of Trydonis in patients with severe hepatic impairment and the 
medicinal product should be used with caution in these patients (see section 4.4 and section 5.2). 



 

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Paediatric population 
There is no relevant use of Trydonis in the paediatric population (under 18 years of age) for the 
indication of COPD. 
 
Method of administration 
 
For inhalation use. 
 
To ensure proper administration of the medicinal product, the patient should be shown how to use the 
inhaler correctly by a physician or other healthcare professional, who should also regularly check the 
adequacy of the patient’s inhalation technique. The patient should be advised to read the Package 
Leaflet carefully and follow the instructions for use as given in the leaflet. 
 
After inhaling, patients should rinse their mouth or gargle with water without swallowing it or brush 
their teeth (see section 4.4 and 6.6). 
 
Trydonis is provided with a dose counter or dose indicator on the back of the inhaler, which shows 
how many actuations are left. For the 60 and 120 actuation pressurised containers each time the patient 
presses the container a puff of the solution is released and the counter counts down by one.  
For the 180 actuation pressurised container, each time the patient presses the pressurised container a 
puff of the solution is released and the counter rotates by a small amount; the number of puffs 
remaining is displayed in intervals of 20. 
Patients should be advised not to drop the inhaler as this may cause the counter to count down. 
 
For instructions for use, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Not for acute use 
 
Trydonis is not indicated for the treatment of acute episodes of bronchospasm, or to treat an acute 
COPD exacerbation (i.e. as a rescue therapy). 
 
Hypersensitivity 
 
Immediate hypersensitivity reactions have been reported after administration of Trydonis. 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, Trydonis should be 
discontinued immediately and alternative therapy instituted. 
 
Paradoxical bronchospasm 
 
Paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath 
after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator (reliever). 
Trydonis should be discontinued immediately, the patient assessed and alternative therapy instituted if 
necessary. 
 
Deterioration of disease 
 
It is recommended that treatment with Trydonis should not be stopped abruptly. If patients find the 
treatment ineffective, they should continue treatment but medical attention must be sought. Increasing 
use of reliever bronchodilators indicates a worsening of the underlying condition and warrants a 



 

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reassessment of the therapy. Sudden and progressive deterioration in the symptoms of COPD is 
potentially life-threatening and the patient should undergo urgent medical assessment. 
 
Cardiovascular effects 
 
Trydonis should be used with caution in patients with cardiac arrhythmias, especially third degree 
atrioventricular block and tachyarrhythmias (accelerated and/or irregular heart beat), idiopathic 
subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, severe heart disease 
(particularly acute myocardial infarction, ischaemic heart disease, congestive heart failure), occlusive 
vascular diseases (particularly arteriosclerosis), arterial hypertension and aneurysm. 
Caution should also be exercised when treating patients with known or suspected prolongation of the 
QTc interval (QTc > 450 milliseconds for males, or > 470 milliseconds for females), either congenital 
or induced by medicinal products as these patients were excluded from clinical trials with Trydonis. 
 
If anaesthesia with halogenated anaesthetics is planned, it should be ensured that Trydonis is not 
administered for at least 12 hours before the start of anaesthesia as there is a risk of cardiac 
arrhythmias. 
 
Caution is also required when Trydonis is used by patients with thyrotoxicosis, diabetes mellitus, 
pheochromocytoma and untreated hypokalaemia. 
 
Pneumonia in patients with COPD 
 
An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been 
observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an 
increased risk of pneumonia with increasing steroid dose but this has not been demonstrated 
conclusively across all studies. 
 
There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia 
risk among inhaled corticosteroid products. 
 
Physicians should remain vigilant for the possible development of pneumonia in patients with COPD 
as the clinical features of such infections overlap with the symptoms of COPD exacerbations. 
 
Risk factors for pneumonia in patients with COPD include current smoking, older age, low body mass 
index (BMI) and severe COPD. 
 
Systemic corticosteroid effects 
 
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for 
long periods. The daily dose of Trydonis corresponds to a medium dose of inhaled corticosteroid; 
furthermore, these effects are much less likely to occur than with oral corticosteroids. Possible 
systemic effects include: Cushing's syndrome, Cushingoid features, adrenal suppression, growth 
retardation, decrease in bone mineral density, cataract, glaucoma and, more rarely, a range of 
psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, 
depression or aggression (particularly in children). Therefore, it is important that the patient is 
reviewed regularly. 
 
Trydonis should be administered with caution in patients with active or quiescent pulmonary 
tuberculosis, fungal and viral infections in the airways. 
 
Hypokalaemia 
 
Potentially serious hypokalaemia may result from beta2-agonist therapy. This has the potential to 
produce adverse cardiovascular effects. Particular caution is advised in severe COPD as this effect 
may be potentiated by hypoxia. Hypokalaemia may also be potentiated by concomitant treatment with 



 

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other medicinal products which can induce hypokalaemia, such as xanthine derivatives, steroids and 
diuretics (see section 4.5). 
Caution is also recommended when a number of reliever bronchodilators are used. It is recommended 
that serum potassium levels are monitored in such situations. 
 
Hyperglycaemia 
 
The inhalation of formoterol may cause a rise in blood glucose levels. Therefore, blood glucose should 
be monitored during treatment following established guidelines in patients with diabetes. 
 
Anticholinergic effect 
 
Glycopyrronium should be used with caution in patients with narrow-angle glaucoma, prostatic 
hyperplasia or urinary retention. Patients should be informed about the signs and symptoms of acute 
narrow-angle glaucoma and should be informed to stop using Trydonis and to contact their doctor 
immediately should any of these signs or symptoms develop. 
Additionally, due to the anticholinergic effect of glycopyrronium, the long-term co-administration of 
Trydonis with other anticholinergic-containing medicinal products is not recommended (see 
section 4.5). 
 
Patients with severe renal impairment 
 
In patients with severe renal impairment, including those with end-stage renal disease requiring 
dialysis, especially if associated with a significant body weight reduction, Trydonis should be used 
only if the expected benefit outweighs the potential risk (see section 5.2). These patients should be 
monitored for potential adverse reactions. 
 
Patients with severe hepatic impairment 
 
In patients with severe hepatic impairment, Trydonis should be used only if the expected benefit 
outweighs the potential risk (see section 5.2). These patients should be monitored for potential adverse 
reactions. 
 
Use with a spacer 
 
Single dose pharmacokinetic data (see section 5.2) have demonstrated that in comparison to routine 
use without a spacer device, the use of Trydonis with the AeroChamber Plus spacer device increased 
the total systemic exposure (AUC0-t) to glycopyrronium. However, available safety data from long-
term clinical studies have not raised any significant safety concerns (see section 5.1). 
 
Prevention of oropharyngeal infections 
 
In order to reduce the risk of oropharyngeal candida infection, patients should be advised to rinse their 
mouth or gargle with water without swallowing it or brush their teeth after inhaling the prescribed 
dose. 
 
Visual disturbance 
 
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents 
with symptoms such as blurred vision or other visual disturbances, the patient should be considered for 
referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma 
or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use 
of systemic and topical corticosteroids. 
 



 

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4.5 Interaction with other medicinal products and other forms of interaction 
 
Pharmacokinetic interactions 
 
Since glycopyrronium is eliminated mainly by the renal route, drug interaction could potentially occur 
with medicinal products affecting renal excretion mechanisms (see section 5.2). The effect of organic 
cation transport inhibition (using cimetidine as a probe inhibitor of OCT2 and MATE1 transporters) in 
the kidneys on inhaled glycopyrronium disposition showed a limited increase in its total systemic 
exposure (AUC0-t) by 16% and a slight decrease in renal clearance by 20% due to co administration of 
cimetidine. 
 
Beclometasone is less dependent on CYP3A metabolism than some other corticosteroids, and in 
general interactions are unlikely; however, the possibility of systemic effects with concomitant use of 
strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded, and therefore caution and 
appropriate monitoring is advised with the use of such medicinal products. 
 
Pharmacodynamic interactions 
 
Related to formoterol 
Non-cardioselective beta-blockers (including eye drops) should be avoided in patients taking inhaled 
formoterol. If they are administered for compelling reasons, the effect of formoterol will be reduced or 
abolished.  
 
Concomitant use of other beta-adrenergic medicinal products can have potentially additive effects; 
therefore, caution is required when other beta-adrenergic medicinal products are prescribed 
concomitantly with formoterol. 
 
Concomitant treatment with quinidine, disopyramide, procainamide, antihistamines, monoamine 
oxidase inhibitors, tricyclic antidepressants and phenothiazines can prolong the QT interval and 
increase the risk of ventricular arrhythmias. In addition, L-dopa, L-thyroxine, oxytocin and alcohol 
can impair cardiac tolerance towards beta2-sympathomimetics. 
 
Concomitant treatment with monoamine oxidase inhibitors, including medicinal products with similar 
properties such as furazolidone and procarbazine, may precipitate hypertensive reactions. 
 
There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with 
halogenated hydrocarbons. 
 
Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate a possible 
hypokalaemic effect of beta2-agonists (see section 4.4). Hypokalaemia may increase the disposition 
towards arrhythmias in patients who are treated with digitalis glycosides. 
 
Related to glycopyrronium 
The long-term co-administration of Trydonis with other anticholinergic-containing medicinal products 
has not been studied and is therefore not recommended (see section 4.4). 
 
Excipients 
 
Trydonis contains a small amount of ethanol. There is a theoretical potential for interaction in 
particularly sensitive patients taking disulfiram or metronidazole. 
 
4.6 Fertility, pregnancy and lactation 
 
There is no experience with or evidence of safety issues on the use of the propellant norflurane 
(HFA134a) during human pregnancy or lactation. However, studies on the effect of HFA134a on the 
reproductive function and embryofoetal development in animals revealed no clinically relevant 
adverse effects. 



 

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Pregnancy 
 
There are no or limited amount of data from the use of Trydonis in pregnant women. 
Studies in animals have shown reproductive toxicity (see section 5.3). Glucocorticoid agents are 
known to cause effects in the early gestation phase, while beta2-sympathomimetic agents like 
formoterol have tocolytic effects. Therefore, as a precautionary measure, it is preferable to avoid the 
use of Trydonis during pregnancy and during labour. 
 
Trydonis should only be used during pregnancy if the expected benefit to the patient outweighs the 
potential risk to the foetus. Infants and neonates born to mothers receiving substantial doses of 
Trydonis should be observed for adrenal suppression. 
 
Breast-feeding 
 
There are no relevant clinical data on the use of Trydonis during breast-feeding in humans.  
 
Glucocorticoids are excreted in human milk. It is reasonable to assume that beclometasone 
dipropionate and its metabolites are also excreted into breast-milk. 
It is unknown whether formoterol or glycopyrronium (including their metabolites) pass into human 
breast-milk but they have been detected in the milk of lactating animals. Anticholinergic agents like 
glycopyrronium could suppress lactation. 
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from 
Trydonis therapy taking into account the benefit of breast-feeding for the child and the benefit of 
therapy for the mothers. 
 
Fertility 
 
No specific studies have been performed with Trydonis with regard to the safety in human fertility. 
Animal studies have shown impairment of fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Trydonis has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported adverse reactions with Trydonis were oral candidiasis (which occurred 
in 0.8% of the exposed subjects), which is normally associated with inhaled corticosteroids; muscle 
spasms (0.4%), which can be attributed to the long-acting beta2-agonist component; dry mouth 
(0.4%), which is a typical anticholinergic effect. 
 
Tabulated summary of adverse reactions 
 
The clinical development programme of Trydonis was conducted in patients with moderate, severe or 
very severe COPD. A total of 3,346 patients were treated with beclometasone dipropionate/formoterol 
fumarate dihydrate/glycopyrronium 87 micrograms/5 micrograms/9 micrograms at the target dose 
regimen (two inhalations twice daily) in multiple dose studies. 
The frequency of adverse reactions is defined using 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) and not known (cannot be estimated from available data). 
 



 

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MedDRA system organ 
class Adverse reaction Frequency 

Infections and Infestations 

Pneumonia (in COPD patients), pharyngitis, oral 
candidiasis, urinary tract infection1, nasopharyngitis1 Common 

Influenza1, oral fungal infection, oropharyngeal 
candidiasis, oesophageal candidiasis1, sinusitis1, 
rhinitis1, gastroenteritis1, vulvovaginal candidiasis1 

Uncommon 

Lower respiratory tract infection (fungal) Rare 
Blood and lymphatic 
system disorders 

Granulocytopenia1 Uncommon 
Thrombocytopenia1 Very rare 

Immune system disorders 
Dermatitis allergic1 Uncommon 
Hypersensitivity reactions, including erythema, lips, 
face, eye and pharyngeal oedema Rare 

Endocrine disorders Adrenal suppression1 Very rare 
Metabolism and nutrition 
disorders 

Hypokalaemia, hyperglycaemia Uncommon 
Decreased appetite Rare 

Psychiatric disorders 

Restlessness1 Uncommon 
Psychomotor hyperactivity1, sleep disorders1, anxiety, 
depression1, aggression1, behavioural changes 
(predominantly in children) 1 

Frequency not 
known 

Insomnia Rare 

Nervous system disorders 
Headache Common 
Tremor, dizziness, dysgeusia1, hypoaesthesia1 Uncommon 
Hypersomnia Rare 

Eye disorders Vision, blurred
1 (see also section 4.4) Frequency not known 

Glaucoma1, cataract1 Very rare 
Ear and labyrinth disorders Otosalpingitis1 Uncommon 

Cardiac disorders 

Atrial fibrillation, electrocardiogram QT prolonged, 
tachycardia, tachyarrhythmia1, palpitations Uncommon 

Angina pectoris (stable1 and unstable), ventricular 
extrasystoles1, nodal rhythm, sinus bradycardia Rare 

Vascular disorders Hyperaemia
1, flushing1, hypertension Uncommon 

Extravasation blood  Rare 

Respiratory, thoracic and 
mediastinal disorders 

Dysphonia Common 
Cough, productive cough1, throat irritation, epistaxis1 Uncommon 
Bronchospasm paradoxical1, oropharyngeal pain, 
pharyngeal erythema, pharyngeal inflammation, dry 
throat 

Rare 

Dyspnoea1 Very rare 

Gastrointestinal disorders 
Diarrhoea1, dry mouth, dysphagia1, nausea, dyspepsia1, 
burning sensation of the lips1, dental caries1, 
(aphthous) stomatitis 

Uncommon 

Skin and subcutaneous 
tissue disorders 

Rash1, urticaria1, pruritus, hyperhidrosis1 Uncommon 
Angioedema1 Rare 

Musculoskeletal and 
connective tissue disorders 

Muscle spasms, myalgia, pain in extremity1, 
musculoskeletal chest pain1 Uncommon 

Growth retardation1 Very rare 
Renal and urinary 
disorders Dysuria, urinary retention, nephritis

1 Rare 

General disorders and 
administration site 
conditions 

Fatigue1  Uncommon 
Asthenia Rare 
Oedema peripheral1 Very rare 



 

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MedDRA system organ 
class Adverse reaction Frequency 

Investigations 

C-reactive protein increased1, platelet count 
increased1, free fatty acids increased1, blood insulin 
increased1, blood ketone body increased1, cortisol 
decreased1 

Uncommon 

Blood pressure increased1, blood pressure decreased1 Rare 
Bone density decreased1 Very rare 

1 Adverse reactions reported in the SmPC of at least one of the individual components, but not observed as adverse reactions 
in the clinical development of Trydonis  
 
Among the observed adverse reactions the following are typically associated with: 
 
Beclometasone dipropionate: pneumonia, oral fungal infections, lower respiratory tract infection 
fungal, dysphonia, throat irritation, hyperglycaemia, psychiatric disorders, cortisol decreased, blurred 
vision. 
 
Formoterol: hypokalaemia, hyperglycaemia, tremor, palpitations, muscle spasms, electrocardiogram 
QT prolonged, blood pressure increased, blood pressure decreased, atrial fibrillation, tachycardia, 
tachyarrhythmia, angina pectoris (stable and unstable), ventricular extrasystoles, nodal rhythm. 
 
Glycopyrronium: glaucoma, atrial fibrillation, tachycardia, palpitations, dry mouth, dental caries, 
dysuria, urinary retention, urinary tract infection.  
 
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. 
 
4.9 Overdose 
 
An overdose of Trydonis may produce signs and symptoms due to the individual component’s actions, 
including those seen with overdose of other beta2-agonists or anticholinergics and consistent with the 
known inhaled corticosteroid class effects (see section 4.4). If overdose occurs, the patient’s symptoms 
should be treated supportively with appropriate monitoring as necessary. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs for obstructive airway diseases, adrenergics in combination with 
anticholinergics incl. triple combinations with corticosteroids. ATC code: R03AL09. 
 
Mechanism of action and pharmacodynamic effects 
 
Trydonis contains beclometasone dipropionate, formoterol and glycopyrronium in a solution 
formulation resulting in an aerosol with extrafine particles with an average mass median aerodynamic 
diameter (MMAD) of around 1.1 micrometres and co-deposition of the three components. The aerosol 
particles of Trydonis are on average much smaller than the particles delivered in non-extrafine 
formulations. For beclometasone dipropionate, this results in a more potent effect than formulations 
with a non-extrafine particle size distribution (100 micrograms of beclometasone dipropionate 
extrafine in Trydonis are equivalent to 250 micrograms of beclometasone dipropionate in a 
non-extrafine formulation). 
 



 

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Beclometasone dipropionate 
Beclometasone dipropionate given by inhalation at recommended doses has a glucocorticoid anti-
inflammatory action within the lungs. Glucocorticoids are widely used for the suppression of 
inflammation in chronic inflammatory diseases of the airways such as COPD. Their action is mediated 
by the binding to glucocorticoid receptors in the cytoplasm resulting in the increased transcription of 
genes coding for antiinflammatory proteins. 
 
Formoterol 
Formoterol is a selective beta2-adrenergic agonist that produces relaxation of bronchial smooth muscle 
in patients with reversible airways obstruction. The bronchodilating effect sets in rapidly, within 
1-3 minutes after inhalation, and has a duration of 12 hours after a single dose. 
 
Glycopyrronium 
Glycopyrronium is a high-affinity, long-acting muscarinic receptor antagonist (anticholinergic) used 
for inhalation as bronchodilator treatment of 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 with a greater than 
4-fold selectivity for the human M3 receptors over the human M2 receptor as it has been 
demonstrated. 
 
Clinical efficacy and safety 
 
The Phase III clinical development programme in COPD included two 52-week active-controlled 
studies. Study TRILOGY compared Trydonis with a fixed combination of beclometasone dipropionate 
and formoterol 100/6 micrograms two inhalations twice daily (1,368 randomised patients). Study 
TRINITY compared Trydonis with tiotropium 18 micrograms inhalation powder, hard capsule, one 
inhalation once daily; in addition, effects were compared with an extemporary triple combination 
made of a fixed combination of beclometasone dipropionate and formoterol 100/6 micrograms two 
inhalations twice daily plus tiotropium 18 micrograms inhalation powder, hard capsule, one inhalation 
once daily (2,691 randomised patients). Both studies were conducted in patients with a clinical 
diagnosis of COPD with severe to very severe airflow limitation (FEV1 less than 50% predicted), with 
symptoms assessed as a COPD Assessment Test (CAT) score of 10 or above, and with at least one 
COPD exacerbation in the previous year. The two studies included approximately 20% of patients 
who used the AeroChamber Plus spacer. 
In addition, two Phase IIIb studies were conducted to support the clinical efficacy and safety of 
Trydonis. TRISTAR was a 26-week active-controlled open label study comparing Trydonis with an 
extemporary combination made of a fixed combination of fluticasone/vilanterol 92/22 micrograms 
inhalation powder, one inhalation once daily plus tiotropium 18 micrograms inhalation powder, hard 
capsule, one inhalation once daily (1,157 randomised patients). TRIBUTE was a 52-week active-
controlled study comparing Trydonis with a fixed combination of indacaterol/glycopyrronium 85/43 
micrograms inhalation powder, hard capsule, one inhalation once daily (1,532 randomised patients). 
Both studies were conducted in a similar population of COPD patients as studies TRILOGY and 
TRINITY.  
 
Reduction of COPD exacerbations 
Compared with a fixed combination of beclometasone dipropionate and formoterol, Trydonis reduced 
the rate of moderate/severe exacerbations over 52 weeks by 23% (rate: 0.41 versus 0.53 events per 
patient/year; p = 0.005). Compared with tiotropium, Trydonis reduced the rate of moderate/severe 
exacerbations over 52 weeks by 20% (rate: 0.46 versus 0.57 events per patient/year; p = 0.003). 
Compared with a fixed combination of indacaterol and glycopyrronium, Trydonis reduced the rate of 
moderate/severe exacerbations over 52 weeks by 15% (rate: 0.50 versus 0.59 events per patient/year; 
p = 0.043). Compared with tiotropium, Trydonis also reduced the rate of severe exacerbations (i.e. 
excluding moderate exacerbations) by 32% (rate: 0.067 versus 0.098 events per patient/year; 
p = 0.017). No differences were observed when comparing Trydonis with the extemporary triple 
combination made of beclometasone dipropionate and formoterol fixed combination plus tiotropium 
(moderate/severe exacerbation rate: 0.46 versus 0.45 events per patient/year). 



 

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In addition, compared with both a fixed combination of beclometasone dipropionate and formoterol 
and with tiotropium, Trydonis significantly prolonged the time to first exacerbation (hazard ratio 0.80 
and 0.84 respectively; p = 0.020 and 0.015 respectively), with no differences between Trydonis and 
the extemporary triple combination made of beclometasone dipropionate and formoterol fixed 
combination plus tiotropium (hazard ratio 1.06). 
 
Effects on lung function 
 
Pre-dose FEV1 
Compared with a fixed combination of beclometasone dipropionate and formoterol, Trydonis 
improved pre-dose FEV1 by 81 mL after 26 weeks of treatment and by 63 mL after 52 weeks of 
treatment. Compared with tiotropium, Trydonis improved pre-dose FEV1 by 51 mL after 26 weeks of 
treatment and by 61 mL after 52 weeks of treatment. These improvements were statistically significant 
(p < 0.001). Compared with a fixed combination of indacaterol and glycopyrronium, Trydonis 
improved average pre-dose FEV1 over the 52-week treatment period by 22 mL (p=0.018). Similar 
improvements, although not statistically significant, were observed at weeks 26 and 52.  
No differences were observed when comparing Trydonis and the extemporary triple combination 
made of a fixed combination of beclometasone dipropionate and formoterol plus tiotropium 
(difference of 3 mL in pre-dose FEV1 after 52 weeks of treatment). 
 
2-hour post-dose FEV1 
Compared with a fixed combination of beclometasone dipropionate and formoterol, Trydonis 
significantly improved 2-hour post dose FEV1 by 117 mL after 26 weeks of treatment and by 103 mL 
after 52 weeks of treatment (p < 0.001). This endpoint was only measured in study TRILOGY. 
 
Inspiratory Capacity (IC) 
Compared with tiotropium, Trydonis significantly improved IC by 39 mL (p = 0.025) and 60 mL 
(p = 0.001) after 26 and 52 weeks of treatment respectively. Similar effects were seen when comparing 
Trydonis with the extemporary triple combination. This endpoint was only measured in study 
TRINITY. 
 
Symptomatic outcomes 
Trydonis significantly improved dyspnoea (measured as the Transition Dyspnoea Index – TDI - focal 
score) after 26 weeks of treatment compared with baseline (by 1.71 units; p < 0.001), but the adjusted 
mean difference versus a fixed combination of beclometasone dipropionate and formoterol was not 
statistically significant (0.21 units; p = 0.160). A responder analysis showed that a significantly greater 
percentage of patients had a clinically significant improvement (focal score greater than or equal to 1) 
after 26 weeks with Trydonis than with a fixed combination of beclometasone dipropionate and 
formoterol (57.4% versus 51.8%; p = 0.027). TDI was only measured in study TRILOGY. 
Trydonis was also statistically significantly superior to a fixed combination of beclometasone 
dipropionate and formoterol, to tiotropium and to a fixed combination of indacaterol and 
glycopyrronium in terms of improvement in quality of life (measured by the Saint George Respiratory 
Questionnaire – SGRQ - total score). No differences were observed when comparing Trydonis and the 
extemporary triple combination made of fluticasone and vilanterol fixed combination plus tiotropium.  
A responder analysis showed that a significantly greater percentage of patients had a clinically 
significant improvement (reduction versus baseline of greater than or equal to 4) after 26 and 52 weeks 
with Trydonis than with a fixed combination of beclometasone dipropionate and formoterol and with 
tiotropium. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Trydonis in all subsets of the paediatric population in COPD (see section 4.2 for information on 
paediatric use). 
 



 

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5.2 Pharmacokinetic properties 
 
Related to Trydonis 
 
The systemic exposure to beclometasone dipropionate, formoterol and glycopyrronium has been 
investigated in a pharmacokinetic study conducted in healthy subjects. The study compared data 
obtained after treatment with a single dose of Trydonis (4 inhalations of 100/6/25 micrograms, a 
non-marketed formulation containing twice the approved strength of glycopyrronium) or a single dose 
of the extemporary combination of beclometasone dipropionate/formoterol (4 inhalations of 
100/6 micrograms) plus glycopyrronium (4 inhalations of 25 micrograms). The maximum plasma 
concentration and systemic exposure of beclometasone dipropionate main active metabolite 
(beclometasone 17-monopropionate) and formoterol were similar after administration of the fixed or 
extemporary combination. For glycopyrronium, the maximum plasma concentration was similar after 
administration of the fixed or extemporary combination, while the systemic exposure was slightly 
higher after administration of Trydonis than with the extemporary combination. This study also 
investigated the potential pharmacokinetic interaction between the active components of Trydonis by 
comparing the pharmacokinetic data obtained after a single dose of the extemporary combination or 
after a single dose of the single components beclometasone dipropionate/formoterol or 
glycopyrronium. There was no clear evidence of pharmacokinetic interaction, however the 
extemporary combination showed formoterol and glycopyrronium levels transiently slightly higher 
immediately after dosing compared with the single components. It is noted that single component 
glycopyrronium, formulated as pressurised metered dose inhaler, which was used in the PK studies, is 
not available on the market.  
 
A comparison across studies showed that the pharmacokinetics of beclometasone 17-monopropionate, 
formoterol and glycopyrronium is similar in COPD patients and in healthy subjects. 
 
Effect of a spacer 
The use of Trydonis with the AeroChamber Plus spacer in COPD patients increased the lung delivery 
of beclometasone 17-monopropionate, formoterol and glycopyrronium (maximum plasma 
concentration increased by 15%, 58% and 60% respectively). The total systemic exposure (as 
measured by AUC0-t) was slightly reduced for beclometasone 17-monopropionate (by 37%) and 
formoterol (by 24%), while it was increased for glycopyrronium (by 45%). See also section 4.4. 
 
Effect of renal impairment 
Systemic exposure (AUC0-t) to beclometasone dipropionate, to its metabolite beclometasone 
17-monopropionate and to formoterol was not affected by mild to severe renal impairment. For 
glycopyrronium, there was no impact in subjects with mild and moderate renal impairment. However, 
an increase in total systemic exposure of up to 2.5-fold was observed in subjects with severe renal 
impairment (glomerular filtration rate below 30 mL/min/1.73 m2), as a consequence of a significant 
reduction of the amount excreted in urine (approximately 90% reduction of glycopyrronium renal 
clearance). Simulations performed with a pharmacokinetic model showed that even when covariates 
had extreme values (body weight less than 40 kg and concomitant glomerular filtration rate below 
27 mL/min/1.73 m²), exposure to Trydonis active substances remains in approximately a 2.5-fold 
range compared to the exposure in a typical patient with median covariate values. 
 
Related to beclometasone dipropionate 
 
Beclometasone dipropionate is a pro-drug with weak glucocorticoid receptor binding affinity that is 
hydrolysed via esterase enzymes to an active metabolite beclometasone 17-monopropionate which has 
a more potent topical anti-inflammatory activity compared with the pro-drug beclometasone 
dipropionate. 
 
Absorption, distribution and biotransformation 
Inhaled beclometasone dipropionate is rapidly absorbed through the lungs; prior to absorption there is 
extensive conversion to beclometasone 17-monopropionate via esterase enzymes that are found in 
most tissues. The systemic availability of the active metabolite arises from lung (36%) and from 



 

13 

gastrointestinal absorption of the swallowed dose. The bioavailability of swallowed beclometasone 
dipropionate is negligible; however, pre-systemic conversion to beclometasone 17-monopropionate 
results in 41% of the dose being absorbed as the active metabolite. There is an approximately linear 
increase in systemic exposure with increasing inhaled dose. The absolute bioavailability following 
inhalation is approximately 2% and 62% of the nominal dose for unchanged beclometasone 
dipropionate and beclometasone 17-monopropionate respectively. Following intravenous dosing, the 
disposition of beclometasone dipropionate and its active metabolite is characterised by high plasma 
clearance (150 and 120 L/h respectively), with a small volume of distribution at steady state for 
beclometasone dipropionate (20 L) and larger tissue distribution for its active metabolite (424 L). 
Plasma protein binding is moderately high. 
 
Elimination 
Faecal excretion is the major route of beclometasone dipropionate elimination mainly as polar 
metabolites. The renal excretion of beclometasone dipropionate and its metabolites is negligible. The 
terminal elimination half-lives are 0.5 hours and 2.7 hours for beclometasone dipropionate and 
beclometasone 17-monopropionate respectively. 
 
Patients with hepatic impairment 
The pharmacokinetics of beclometasone dipropionate in patients with hepatic impairment has not been 
studied, however, as beclometasone dipropionate undergoes a very rapid metabolism via esterase 
enzymes present in intestinal fluid, serum, lungs and liver to form the more polar products 
beclometasone 21-monopropionate, beclometasone 17-monopropionate and beclometasone, hepatic 
impairment is not expected to modify the pharmacokinetics and safety profile of beclometasone 
dipropionate. 
 
Related to formoterol 
 
Absorption and distribution 
Following inhalation, formoterol is absorbed from both the lung and the gastrointestinal tract. The 
fraction of an inhaled dose that is swallowed after administration with a metered dose inhaler may 
range between 60% and 90%. At least 65% of the fraction that is swallowed is absorbed from the 
gastrointestinal tract. Peak plasma concentrations of the unchanged active substance occur within 0.5 
to 1 hours after oral administration. Plasma protein binding of formoterol is 61-64% with 34% bound 
to albumin. There was no saturation of binding in the concentration range attained with therapeutic 
doses. The elimination half-life determined after oral administration is 2-3 hours. Absorption of 
formoterol is linear following inhalation of 12 to 96 micrograms of formoterol. 
 
Biotransformation 
Formoterol is widely metabolised and the prominent pathway involves direct conjugation at the 
phenolic hydroxyl group. Glucuronide acid conjugate is inactive. The second major pathway involves 
O-demethylation followed by conjugation at the phenolic 2'-hydroxyl group. Cytochrome P450 
isoenzymes CYP2D6, CYP2C19 and CYP2C9 are involved in the O-demethylation of formoterol. 
Liver appears to be the primary site of metabolism. Formoterol does not inhibit CYP450 enzymes at 
therapeutically relevant concentrations. 
 
Elimination 
The cumulative urinary excretion of formoterol after single inhalation from a dry powder inhaler 
increased linearly in the 12-96 micrograms dose range. On average, 8% and 25% of the dose was 
excreted as unchanged and total formoterol, respectively. Based on plasma concentrations measured 
following inhalation of a single 120 micrograms dose by 12 healthy subjects, the mean terminal 
elimination half-life was determined to be 10 hours. The (R,R)- and (S,S)-enantiomers represented 
about 40% and 60% of unchanged active substance excreted in the urine, respectively. The relative 
proportion of the two enantiomers remained constant over the dose range studied and there was no 
evidence of relative accumulation of one enantiomer over the other after repeated dosing. After oral 
administration (40 to 80 micrograms), 6% to 10% of the dose was recovered in urine as unchanged 
active substance in healthy subjects; up to 8% of the dose was recovered as the glucuronide. A total 



 

14 

67% of an oral dose of formoterol is excreted in urine (mainly as metabolites) and the remainder in the 
faeces. The renal clearance of formoterol is 150 mL/min. 
 
Patients with hepatic impairment 
The pharmacokinetics of formoterol has not been studied in patients with hepatic impairment; 
however, as formoterol is primarily eliminated via hepatic metabolism, an increased exposure can be 
expected in patients with severe hepatic impairment. 
 
Related to glycopyrronium  
 
Absorption and distribution 
Glycopyrronium has a quaternary ammonium structure which limits its passage across biological 
membranes and produces slow, variable and incomplete gastrointestinal absorption. Following 
glycopyrronium inhalation, the lung bioavailability was 10.5% (with activated charcoal ingestion) 
while the absolute bioavailability was 12.8% (without activated charcoal ingestion) confirming the 
limited gastrointestinal absorption and indicating that more than 80% of glycopyrronium systemic 
exposure was from lung absorption. After repeated inhalation of twice daily doses ranging from 12.5 
to 50 micrograms via pressurised metered dose inhaler in COPD patients, glycopyrronium showed 
linear pharmacokinetics with little systemic accumulation at steady state (median accumulation ratio 
2.2-2.5).  
The apparent volume of distribution (Vz) of inhaled glycopyrronium was increased compared to 
intravenous (i.v.) infusion (6420 L versus 323 L), reflecting the slower elimination after inhalation.  
 
Biotransformation 
The metabolic pattern of glycopyrronium in vitro (humans, dogs, rats, mice and rabbits liver 
microsomes and hepatocytes) was similar among species and the main metabolic reaction was the 
hydroxylation on the phenyl or ciclopentyl rings. CYP2D6 was found to be the only enzyme 
responsible for glycopyrronium metabolism. 
 
Elimination 
The mean elimination half-life of glycopyrronium in healthy volunteers was approximately 6 hours 
after i.v. injection while after inhalation in COPD patients it ranged from 5 to 12 hours at steady state. 
After a glycopyrronium single i.v. injection, 40% of the dose was excreted in the urine within 
24 hours. In COPD patients receiving repeated twice daily administration of inhaled glycopyrronium, 
the fraction of the dose excreted in urine ranged from 13.0% to 14.5% at steady state. Mean renal 
clearance was similar across the range of doses tested and after single and repeated inhalation (range 
281-396 mL/min). 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeat dose toxicity and toxicity to reproduction and development. 
 
Safety pharmacology  
In an inhalation study in telemetered dogs, the cardiovascular system was a major target system for 
acute effects of Trydonis (increase in heart rate, decrease in blood pressure, ECG changes at higher 
doses), effects probably mainly related to the beta2-adrenergic activity of formoterol and the 
anti-muscarinic activity of glycopyrronium. There was no evidence for overadditive effects of the 
triple combination when compared with the single components. 
 
Repeat dose toxicity 
In repeat dose inhalation studies with Trydonis in rats and dogs of up to 13 weeks duration, the main 
observed alterations were related to effects on the immune system (probably due to systemic 
corticosteroid effects of beclometasone dipropionate and its active metabolite beclometasone-
17-monopropionate) and on the cardiovascular system (probably related to the beta2-adrenergic 
activity of formoterol and the anti-muscarinic activity of glycopyrronium). The toxicological profile of 



 

15 

the triple combination reflected that of the single active components without a relevant increase in 
toxicity and without unexpected findings. 
 
Reproductive and development toxicity 
Beclometasone dipropionate/beclometasone-17-monopropionate was considered responsible for 
reproductive toxicity effects in rats such as reduction of the conception rate, fertility index, early 
embryonic development parameters (implantation loss), delay in ossification and increased incidence 
of visceral variations; while tocolytic and anti-muscarinic effects, attributed to the beta2-adrenergic 
activity of formoterol and the anti-muscarinic activity of glycopyrronium, affected pregnant rats in the 
late phase of gestation and/or early phase of lactation, leading to loss of pups. 
 
Genotoxicity 
Genotoxicity of Trydonis has not been evaluated, however, the single active components were devoid 
of genotoxic activity in the conventional test systems. 
 
Carcinogenicity 
Carcinogenicity studies have not been performed with Trydonis. However, in a 104-week rat 
inhalation carcinogenicity study and an oral 26-week carcinogenicity study in transgenic Tg.rasH2 
mice, glycopyrronium bromide showed no carcinogenic potential and published data concerning long-
term studies conducted with beclometasone dipropionate and formoterol fumarate in rats do not 
indicate a clinically relevant carcinogenic potential. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Ethanol anhydrous 
Hydrochloric acid 
Norflurane (propellant) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
60 actuation pressurised container: 21 months. 
 
Chemical and physical in-use stability has been demonstrated for 2 months at 25°C. 
After dispensing, the medicinal product may be stored for a maximum of 2 months at a temperature up 
to 25°C. Other in-use storage times and conditions are under the responsibility of the user. 
 
120 and 180 actuation pressurised container: 22 months. 
 
Chemical and physical in-use stability has been demonstrated for 4 months at 25°C. 
After dispensing, the medicinal product may be stored for a maximum of 4 months at a temperature up 
to 25°C. Other in-use storage times and conditions are under the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Prior to dispensing: 
Store in a refrigerator (2°C-8°C). 
 
Do not freeze.  
Do not expose to temperatures higher than 50°C. 
Do not pierce the pressurised container. 



 

16 

 
For in-use storage conditions, see section 6.3. 
 
6.5 Nature and contents of container 
 
Pressurised container (coated aluminium), with a metering valve. The pressurised container is inserted 
in a polypropylene inhaler which incorporates a mouthpiece and a dose counter (60 actuations or 
120 actuations per pressurised container) or dose indicator (180 actuations per pressurised container) 
and is provided with a polypropylene mouthpiece cap. 
 
Pack sizes of 1 container of 60, 120 or 180 actuations and multipacks of 2 or 3 containers of 
120 actuations each. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
For pharmacists: 
 
Enter the date of dispensing to the patient on the pack. 
 
 
Instructions for use 
 
Priming the inhaler 
Before using the inhaler for the first time, the patient should release one actuation into the air in order 
to ensure that the inhaler is working properly (priming). Before priming the 60, 120 or 180 actuation 
pressurised containers, the counter/indicator should read 61, 121 or 180, respectively. After priming, 
the counter/indicator should read 60, 120 or 180.  
 
Use of the inhaler 
Patients should stand or sit in an upright position when inhaling from their inhaler. The steps below 
should be followed. IMPORTANT: steps 2 to 5 should not be performed too quickly: 
1. Patients should remove the protective cap from the mouthpiece and check that the mouthpiece is 

clean and free from dust and dirt or any other foreign objects. 
2. Patients should breathe out slowly and as deeply as comfortable, in order to empty their lungs. 
3. Patients should hold the inhaler vertically with its body upwards and place the mouthpiece 

between their teeth without biting. Their lips should then be placed around the mouthpiece, with 
the tongue flat under it.  

4. At the same time, patients should breathe in slowly and deeply through the mouth until the 
lungs are full of air (this should take approximately 4 – 5 seconds). Immediately after starting to 
breathe in, patients should firmly press down on the top of the pressurised container to release 
one puff. 

5. Patients should then hold their breath for as long as comfortably possible, then remove the 
inhaler from the mouth and breathe out slowly. Patients should not breathe out into the inhaler. 

6. Patients should then check the dose counter or dose indicator to ensure it has moved 
accordingly. 

 
To inhale the second puff, patients should keep the inhaler in a vertical position for approximately 
30 seconds and repeat steps 2 to 6. 
 
If mist appears after the inhalation, either from the inhaler or from the sides of the mouth, the 
procedure should be repeated from step 2. 
 



 

17 

After use, patients should close the inhaler with the protective mouthpiece cover and check the dose 
counter or dose indicator. 
 
After inhaling, patients should rinse their mouth or gargle with water without swallowing it or brush 
their teeth (see sections 4.2 and 4.4). 
 
When to get a new inhaler 
Patients should be advised to get a new inhaler when the dose counter or indicator shows the number 
20. They should stop using the inhaler when the counter or indicator shows 0 as any puffs left in the 
device may not be enough to release a full actuation. 
 
Additional instructions for specific groups of patients 
For patients with weak hands it may be easier to hold the inhaler with both hands. Therefore, the index 
fingers should be placed on the top of the pressurised container and both thumbs on the base of the 
inhaler.  
 
Patients who find it difficult to synchronise aerosol actuation with inspiration of breath may use the 
AeroChamber Plus spacer device, properly cleaned as described in the relevant leaflet. They should be 
advised by their doctor or pharmacist about the proper use and care of their inhaler and spacer and 
their technique checked to ensure optimum delivery of the inhaled active substance to the lungs. This 
may be obtained by the patients using the AeroChamber Plus by one continuous slow and deep breath 
through the spacer, without any delay between actuation and inhalation. Alternatively, patients may 
simply breathe in and out (through the mouth) after the actuation, as instructed in the spacer leaflet, to 
obtain the active substance. See section 4.4 and section 5.2. 
 
Cleaning 
For the regular cleaning of the inhaler, patients should remove weekly the cap from the mouthpiece 
and wipe the outside and inside of the mouthpiece with a dry cloth. They should not remove the 
pressurised container from the actuator and should not use water or other liquids to clean the 
mouthpiece. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Chiesi Farmaceutici S.p.A. 
Via Palermo 26/A 
43122 Parma 
Italy 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1274/001 
EU/1/18/1274/002 
EU/1/18/1274/003 
EU/1/18/1274/004 
EU/1/18/1274/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 April 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{DD month YYYY} 



 

18 

 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu, and on the website of {name of MS Agency (link)}. 
 



 

19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS 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 

 



 

20 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Chiesi Farmaceutici S.p.A. 
Via San Leonardo 96 
43122 Parma 
Italy 
 
Chiesi SAS 
2 rue des Docteurs Alberto et Paolo Chiesi 
41260 La Chaussée Saint Victor 
France 
 
Chiesi Pharmaceuticals GmbH 
Gonzagagasse 16/16 
1010 Wien 
Austria 
 
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. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
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 required 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 significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



 

21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 

22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



 

23 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (SINGLE PACKS AND MULTIPACK ONLY: contains Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Trydonis 87/5/9 micrograms pressurised inhalation, solution 
 
beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each delivered dose contains 87 micrograms of beclometasone dipropionate, 5 micrograms of 
formoterol fumarate dihydrate and 9 micrograms of glycopyrronium. 
 
Each metered dose (the dose leaving the valve) contains 100 micrograms of beclometasone 
dipropionate, 6 micrograms of formoterol fumarate dihydrate and 10 micrograms of glycopyrronium. 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: anhydrous ethanol, hydrochloric acid; propellant: norflurane. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Pressurised inhalation, solution. 
 
1 pressurised container of 60 actuations. 
1 pressurised container of 120 actuations.  
Multipack: 240 actuations (2 pressurised containers of 120 actuations each). 
Multipack: 360 actuations (3 pressurised containers of 120 actuations each).  
1 pressurised container of 180 actuations. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
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 
 
 



 

24 

8. EXPIRY DATE  
 
EXP 
 
60 actuation pressurised container: 
After dispensing: 
Store at 25°C for a maximum of 2 months. 
 
120 and 180 actuation pressurised container: 
After dispensing: 
Store at 25°C for a maximum of 4 months. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Prior to dispensing: 
Store in a refrigerator.  
 
Do not freeze.  
Do not expose to temperatures higher than 50°C.  
Do not pierce the pressurised container. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Multipack outer carton 
Also enter the date of dispensing on each individual pack. 
 
Dispensing date  
 
dd/mm/yyyy 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Chiesi Farmaceutici S.p.A. 
Via Palermo 26/A 
43122 Parma 
Italy 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1274/001 
EU/1/18/1274/002 
EU/1/18/1274/003 
EU/1/18/1274/004 
EU/1/18/1274/005 
 
 
13. BATCH NUMBER 
 
Lot 
 



 

25 

 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Trydonis 87/5/9 mcg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number} 
 



 

26 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INTERMEDIATE OUTER CARTON (MULTIPACK ONLY: no Blue Box is included) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trydonis 87/5/9 micrograms pressurised inhalation, solution 
 
beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each delivered dose contains 87 micrograms of beclometasone dipropionate, 5 micrograms of 
formoterol fumarate dihydrate and 9 micrograms of glycopyrronium. 
 
Each metered dose (the dose leaving the valve) contains 100 micrograms of beclometasone 
dipropionate, 6 micrograms of formoterol fumarate dihydrate and 10 micrograms of glycopyrronium. 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: anhydrous ethanol, hydrochloric acid; propellant: norflurane. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Pressurised inhalation, solution. 
 
1 pressurised container of 120 actuations. 
 
Component of a multipack, cannot be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
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 
 
 
8. EXPIRY DATE  
 
EXP 
 



 

27 

After dispensing: 
Store at 25°C for a maximum of 4 months. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Prior to dispensing: 
Store in a refrigerator.  
 
Do not freeze.  
Do not expose to temperatures higher than 50°C.  
Do not pierce the pressurised container. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Dispensing date  
 
dd/mm/yyyy 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Chiesi Farmaceutici S.p.A. 
Via Palermo 26/A 
43122 Parma 
Italy 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1274/004 
EU/1/18/1274/005 
 
 
13. BATCH NUMBER  
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Trydonis 87/5/9 mcg 
 
 



 

28 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 



 

29 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
ALUMINIUM CONTAINER 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Trydonis 87/5/9 micrograms 
pressurised inhalation  
 
beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium 
 
Inhalation use 
 
 
2. METHOD OF ADMINISTRATION  
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
60 actuations 
120 actuations 
180 actuations 
 
 
6. OTHER 
 
 



 

30 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PLASTIC ACTUATOR 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Trydonis 87/5/9 mcg 
 
 
2. METHOD OF ADMINISTRATION  
 
 
 
3. EXPIRY DATE  
 
 
 
4. BATCH NUMBER  
 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
 
 
6. OTHER 
 



 

31 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 

32 

Package leaflet: Information for the user 
 

Trydonis 87 micrograms/5 micrograms/9 micrograms pressurised inhalation, solution 
beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium 

 
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 or pharmacist. 
- 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 or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 

 
What is in this leaflet 
1. What Trydonis is and what it is used for 
2. What you need to know before you use Trydonis 
3. How to use Trydonis 
4. Possible side effects 
5. How to store Trydonis 
6. Contents of the pack and other information 
 
 
1. What Trydonis is and what it is used for 
 
Trydonis is a medicine to help breathing that contains the three active substances: 
• beclometasone dipropionate,  
• formoterol fumarate dihydrate and  
• glycopyrronium.  
 
Beclometasone dipropionate belongs to a group of medicines called corticosteroids which act to 
reduce the swelling and irritation in your lungs. 
 
Formoterol and glycopyrronium are medicines called long-acting bronchodilators. They act in 
different ways to relax the muscles in your airways, helping to open the airways wider and allowing 
you to breathe more easily. 
 
Regular treatment with these three active substances helps to relieve and prevent symptoms such as 
shortness of breath, wheezing and cough in adult patients with chronic obstructive pulmonary disease 
(COPD). Trydonis can reduce exacerbations (flare-ups) of COPD symptoms. COPD is a serious long-
term disease in which the airways become blocked and air sacs inside the lungs become damaged, 
leading to difficulty breathing. 
 
 
2. What you need to know before you use Trydonis 
 
Do not use Trydonis: 
 
If you are allergic to beclometasone dipropionate, formoterol fumarate dihydrate and glycopyrronium 
or to any of the other ingredients of this medicine (listed in section 6). 
 
Warnings and precautions: 
 
Trydonis is used as a maintenance treatment for your COPD. Do not use this medicine to treat a 
sudden attack of breathlessness or wheezing. 
 



 

33 

If your breathing gets worse: 
 
If you develop worsening shortness of breath or wheezing (breathing with a whistling sound), straight 
after inhaling your medicine, stop using Trydonis inhaler and use your quick-acting “reliever” inhaler 
straightaway. You should contact your doctor straightaway. Your doctor will assess your symptoms 
and if necessary may start you on a different treatment.  
See also section 4, “Possible side effects”. 
 
If your COPD gets worse: 
 
If your symptoms get worse or are difficult to control (e.g. if you are using a separate “reliever” 
inhaler more frequently) or if your “reliever” inhaler does not improve your symptoms, see your 
doctor immediately. Your COPD may be getting worse and your doctor may need to prescribe 
different treatment. 
 
Talk to your doctor or pharmacist before using Trydonis: 
 
• if you have any heart problems, such as angina (heart pain, pain in the chest), a recent heart 

attack (myocardial infarction), heart failure, narrowing of the arteries around your heart 
(coronary heart disease), disease of your heart valves or any other abnormalities of your heart or 
if you have a condition known as hypertrophic obstructive cardiomyopathy (also known as 
HOCM, a condition where the heart muscle is abnormal). 

 
• if you have disorders of your heart rhythm such as irregular heart rate, a fast pulse rate or 

palpitations or if you have been told that your heart trace (ECG) is abnormal. 
 
• if you have narrowing of the arteries (also known as arteriosclerosis), if you have high blood 

pressure or if you have an aneurysm (abnormal bulging of the blood vessel wall). 
 
• if you have an overactive thyroid gland. 
 
• if you have low blood levels of potassium (hypokalaemia). The combination of Trydonis with 

some other COPD medicines or medicines such as diuretics (medicines that make the body lose 
water, to treat heart disease or high blood pressure), can cause a sharp fall in your blood level of 
potassium. Therefore, your doctor may wish to measure the potassium levels in your blood from 
time to time. 

 
• if you have any disease of your liver or kidneys. 
 
• if you have diabetes. High doses of formoterol may increase your blood glucose and therefore 

you may need to have extra blood tests to check your blood sugar when you start using this 
medicine, and from time to time during treatment. 

 
• if you have a tumour of the adrenal gland (known as a phaeochromocytoma). 
 
• if you are due to have an anaesthetic. Depending on the type of anaesthetic, it may be necessary 

to stop using Trydonis at least 12 hours before the anaesthesia. 
 
• if you are being, or have ever been, treated for tuberculosis (TB) or if you have a chest 

infection. 
 
• if you have an eye problem called narrow-angle glaucoma. 
 
• if you have difficulty passing urine.  
 
• if you have an infection of the mouth or throat. 



 

34 

 
If any of the above applies to you, tell your doctor before you use Trydonis.  
If you have or have had any medical problems or any allergies or if you are not sure if you can use 
Trydonis, talk to your doctor or pharmacist before using the inhaler.  
 
If you are already using Trydonis  
If you are using Trydonis or high doses of other inhaled corticosteroids over long periods and you 
come into a situation of stress (e.g. being taken to hospital after an accident, having a serious injury or 
before an operation) you may need more of this medicine. In such a situation, your doctor may need to 
increase your dose of corticosteroids to cope with the stress and may prescribe them as tablets or 
injections. 
Contact your doctor if you experience blurred vision or other visual disturbances. 
 
Children and adolescents 
Do not give this medicine to children and adolescents below the age of 18 years. 
 
Other medicines and Trydonis 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This includes medicines similar to Trydonis used for your lung disease.  
 
Some medicines may increase the effects of Trydonis and your doctor may wish to monitor you 
carefully if you are taking these medicines (including some medicines for HIV: ritonavir, cobicistat). 
 
Do not use this medicine with a beta-blocker medicine (used for treating certain heart problems 
such as angina or for reducing blood pressure) unless your doctor has chosen a beta-blocker that does 
not affect your breathing. Beta-blockers (including beta-blocker eye-drops) may reduce the effects of 
formoterol or make it not work at all. On the other hand, using other beta2-agonist medicines (which 
work in the same way as formoterol) may increase the effects of formoterol. 
 
Using Trydonis together with:  
 
• medicines for treating  

- abnormal heart rhythms (quinidine, disopyramide, procainamide),  
- allergic reactions (antihistamines),  
- symptoms of depression or mental disorders such as monoamine oxidase inhibitors (for 

example phenelzine and isocarboxazid), tricyclic antidepressants (for example amitriptyline 
and imipramine), phenothiazines  

can cause some changes in the electrocardiogram (ECG, heart trace). They may also increase 
the risk of disturbances of heart rhythm (ventricular arrhythmias). 

 
• medicines for treating Parkinson’s disease (levodopa), to treat an underactive thyroid gland 

(levothyroxine), medicines containing oxytocin (which causes uterine contraction) and alcohol 
can increase the chances of formoterol side effects on the heart. 

 
• monoamine oxidase inhibitors (MAOIs), including medicines with similar properties like 

furazolidone and procarbazine, used to treat mental disorders, can cause a rise in blood pressure. 
 
• medicines for treating heart disease (digoxin) can cause a fall in your blood potassium level. 

This may increase the likelihood of abnormal heart rhythms. 
 
• other medicines used to treat COPD (theophylline, aminophylline or corticosteroids) and 

diuretics may also cause a fall in your potassium level.  
 
• some anaesthetics can increase the risk of abnormal heart rhythms. 
 



 

35 

• Disulfiram, a medicine used in the treatment of people with alcoholism (drinking problems) or 
metronidazole, an antibiotic to treat infection in your body can cause side effects (e.g. feeling 
sick, being sick, stomach pain) due to the small amount of alcohol in Trydonis. 

 
Pregnancy and breast-feeding  
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 using this medicine.  
 
You should only use Trydonis during pregnancy if you are advised to do so by your doctor. It is 
preferable to avoid the use of Trydonis during labour due to the inhibitory effects of formoterol on 
uterine contractions. 
You should not use Trydonis during breast-feeding. You and your doctor must make a decision 
whether to discontinue breast-feeding or to discontinue/abstain from Trydonis therapy taking into 
account the benefit of breast-feeding for your child and the benefit of therapy for you. 
 
Driving and using machines 
Trydonis is unlikely to affect your ability to drive and use machines. 
 
 
3. How to use Trydonis 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
 
Adults 
The recommended dose is two puffs in the morning and two puffs in the evening.  
 
If you feel that the medicine is not very effective, talk to your doctor. 
If you have been using a different inhaler containing beclometasone dipropionate previously, ask your 
doctor for advice, as the effective dose of beclometasone dipropionate in Trydonis for the treatment of 
COPD may be lower than that of some other inhalers.  
 
Route of administration 
Trydonis is for inhalation use. 
You should inhale the medicine through your mouth and this takes the medicine directly into your 
lungs. 
 
This medicine is contained in a pressurised container in a plastic inhaler with a mouthpiece.  
 
Trydonis is available in three container sizes:  
• a container providing 60 puffs 
• a container providing 120 puffs 
• a container providing 180 puffs. 
 
If you have been prescribed a container providing 60 puffs or 120 puffs 
There is a counter on the back of the inhaler, which tells you how many doses are left. Each time you 
press the pressurised container, a puff of medicine is released and the counter will count down by one. 
Take care not to drop the inhaler as this may cause the counter to count down. 
 
If you have been prescribed a container providing 180 puffs 
There is an indicator on the back of the inhaler, which tells you how many doses are left. Each time 
you press the pressurised container, a puff of medicine is released and the dose indicator rotates by a 
small amount. The number of puffs remaining is displayed in intervals of 20. Take care not to drop the 
inhaler as this may cause the dose indicator to count down. 
 



 

36 

Testing your inhaler 
Before using the inhaler for the first time, you should test your inhaler to make sure that it is working 
properly, as follows.  
1. Depending on the container size prescribed to you, check that the dose counter reads 61 or 121 

and that the dose indicator reads 180 
2. Remove the protective cap from the mouthpiece 
3. Hold your inhaler upright with the mouthpiece at the bottom  
4. Direct the mouthpiece away from yourself and firmly press the pressurised container to release 

one puff 
5. Check the dose counter or dose indicator. If you are testing your inhaler for the first time, the 

counter should read:  
 

60 
- when using the container 

providing 60 puffs 

120 
- when using the container 

providing 120 puffs 

180 
- when using the container 

providing 180 puffs 

   
 
How to use your inhaler 
Stand or sit up when inhaling.  
IMPORTANT: Do not perform steps 2 to 5 too quickly.  

 
1. Remove the protective cap from the mouthpiece and check that the mouthpiece is clean and free 

from dust and dirt. 
2. Breathe out as slowly and deeply as possible, in order to empty your lungs. 
3. Hold the inhaler upright with the mouthpiece at the bottom and place the mouthpiece between 

your teeth without biting it. Then place your lips around the mouthpiece, with the tongue flat 
under it. 

4. Breathe in slowly and deeply through your mouth to fill your lungs with air (this should take 
about 4–5 seconds). Just after starting to breathe in, press down firmly on the top of the 
pressurised container to release one puff.  

5. Hold your breath for as long as possible and, finally, remove the inhaler from your mouth and 
breathe out slowly. Do not breathe out into the inhaler. 

6. Check that the dose counter (60/120 puffs) has moved down by one or that the dose indicator 
(180 puffs) has rotated by a small amount. 

 
For the second puff, keep the inhaler in the upright position for about half a minute, then repeat steps 2 
to 5. 
 
If you see 'mist' coming from the top of the inhaler or the sides of your mouth, this means that 
Trydonis will not be getting into your lungs as it should. Take another puff, following the instructions 
starting again from step 2. 
 



 

37 

After use, replace the protective cap. 
 
To prevent a fungal infection in the mouth and throat, rinse your mouth or gargle with water without 
swallowing it or brush your teeth after each use of your inhaler. 
 
When to get a new inhaler 
You should get a replacement when the counter or indicator shows the number 20. Stop using the 
inhaler when the counter or indicator shows 0, as any medicine left in the inhaler may not be enough 
to give you a full puff. 
 
If you have a weak grip, it may be easier to hold the inhaler with both hands: hold the upper part of the 
inhaler with both index fingers and its lower part with both thumbs. 
 
If you find it difficult to use the inhaler while starting to breathe in, you may use the AeroChamber 
Plus spacer device. Ask your doctor or pharmacist about this device. 
It is important that you read the package leaflet which is supplied with your AeroChamber Plus spacer 
device and that you carefully follow the instructions on how to use the AeroChamber Plus spacer 
device and how to clean it. 
 
Cleaning of the Trydonis inhaler 
You should clean your inhaler once a week.  
1. Do not remove the pressurised container from the inhaler and do not use water or other liquids to 

clean your inhaler. 
2. Remove the protective cap from the mouthpiece by pulling it away from your inhaler. 
3. Wipe inside and outside of the mouthpiece and the inhaler with a clean, dry cloth or tissue. 
4. Replace the mouthpiece cap. 
 
If you use more Trydonis than you should 
It is important that you take your dose as advised by your doctor. Do not exceed your prescribed dose 
without talking to your doctor. 
If you use more Trydonis than you should, side effects, as described in section 4, may occur.  
Tell your doctor if you have used more Trydonis than you should and if you experience any of these 
symptoms. Your doctor may wish to carry out some blood tests. 
 
Tell your doctor if you have any of these symptoms.  
 
If you forget to use Trydonis 
Use it as soon as you remember. If it is almost time for your next dose, do not take the dose you have 
missed, but just take the next dose at the correct time. Do not double the dose. 
 
If you stop using Trydonis 
It is important to use Trydonis every day. Do not stop using Trydonis or lower the dose, even if you are 
feeling better or you have no symptoms. If you want to do this, talk to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
There is a risk of worsening shortness of breath and wheezing immediately after using Trydonis and 
this is known as paradoxical bronchospasm (may affect up to 1 in 1,000 people). If this occurs you 
should stop using Trydonis and use your quick-acting “reliever” inhaler straightaway to treat the 
shortness of breath and wheezing. You should contact your doctor straightaway. 
 



 

38 

Tell your doctor immediately 
• if you experience any allergic reactions like skin allergies, hives, skin itching, skin rash (may 

affect up to 1 in 100 people), reddening of the skin, swelling of the skin or mucous membranes 
especially of the eyes, face, lips and throat (may affect up to 1 in 1,000 people). 

• 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 (may affect up to 1 in 10,000 people). 

 
Tell your doctor if you have any of the following while using Trydonis as they could be symptoms of 
a lung infection (may affect up to 1 in 10 people): 
• fever or chills 
• increased mucus production, change in mucus colour 
• increased cough or increased breathing difficulties. 
 
Possible side effects are listed below according to their frequency.  
 
Common (may affect up to 1 in 10 people): 
• sore throat 
• runny or stuffy nose and sneezing 
• fungal infections of the mouth. Rinsing your mouth or gargling with water and brushing your 

teeth immediately after inhalation may help to prevent these side effects 
• hoarseness 
• headache 
• urinary tract infection. 
 
Uncommon (may affect up to 1 in 100 people): 
• flu 
• inflammation of the sinuses 
• itchy, runny or blocked nose 
• fungal infections of the throat or of the 

food pipe (oesophagus)  
• fungal infections of the vagina 
• restlessness 
• trembling 
• dizziness 
• abnormal or reduced sense of taste 
• numbness 
• inflammation of the ear 
• irregular heart beat 
• changes in the electrocardiogram (heart 

trace) 
• unusually fast heart beat and disorders of 

the heart rhythm 
• palpitations (feeling of abnormal beating of 

the heart) 
• reddening of the face 
• increased blood flow to some tissues in the 

body 
• cough and productive cough 

• irritation of the throat 
• nose bleeds 
• dry mouth 
• diarrhoea 
• swallowing difficulties 
• feeling sick 
• upset stomach 
• stomach discomfort after meals 
• burning sensation of the lips 
• tooth decay 
• skin rash, hives, skin itching 
• inflammation of the mucous membrane of 

the mouth with or without ulcers 
• increased sweating 
• muscle cramps and pain in muscles 
• pain in arms or legs 
• pain in muscles, bones or joints of the chest 
• tiredness 
• increase of blood pressure 
• fall in the level of some constituents of your 

blood: of certain white blood cells called 
granulocytes, of potassium or of cortisol 

• increase in the level of some constituents of 
your blood: glucose, C-reactive protein, 
number of platelets, insulin, free fatty acid 
or ketones. 

 



 

39 

Rare (may affect up to 1 in 1,000 people): 
• fungal infections of the chest 
• decreased appetite 
• sleep disorders (sleeping too little or too 

long) 
• crushing chest pain 
• sensation of a missed heart beat, unusually 

slow heart beat 

• leakage of blood from a vessel into the 
tissues surrounding it 

• decrease of blood pressure 
• weakness 
• pain in the back of the mouth and throat 
• inflammation and redness of the pharynx 
• dry throat 
• painful and frequent urination 
• difficulty and pain when passing urine 
• inflammation of the kidneys. 

 
Very rare (may affect up to 1 in 10,000 people): 
• low level in the number of certain blood cells called platelets 
• feeling breathless or short of breath 
• swelling of the hands and feet 
• growth retardation in children and adolescents. 
 
Not known (frequency cannot be estimated from the available data): 
• blurred vision. 
 
Using high-dose inhaled corticosteroids over a long time can cause in very rare cases effects on 
the body: 
• problems with how your adrenal glands work (adrenal suppression) 
• decrease in bone mineral density (thinning of the bones) 
• clouding of the lens of your eyes (cataract). 
 
Trydonis does not contain a high-dose inhaled corticosteroid, but your doctor may wish to measure the 
cortisol levels in your blood from time to time. 
 
The following side effects can also occur with high-dose inhaled corticosteroids used over a long time, 
but the frequency is not known (frequency cannot be estimated from the available data) at present: 
• depression 
• feeling worried, nervous, over-excited or irritable. 
These events are more likely to occur in children. 
 
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 Trydonis 
 
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 label and carton after EXP. The 
expiry date refers to the last day of that month.  
 
Prior to dispensing: 
Store in a refrigerator (2°C-8°C). 
 
Do not freeze.  
Do not expose to temperatures higher than 50°C.  
Do not pierce the pressurised container. 



 

40 

 
60 actuation pressurised container:  After dispensing, the inhaler may be stored at a 

temperature up to 25°C for a maximum of 2 months.  
120 and 180 actuation pressurised container:  After dispensing, the inhaler may be stored at a 

temperature up to 25°C for a maximum of 4 months.  
 
Medicines should not be disposed of via waste water or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. Content of the pack and other information 
 
What Trydonis contains 
The active substances are: beclometasone dipropionate, formoterol fumarate dihydrate and 
glycopyrronium. 
 
Each delivered dose (the dose leaving the mouthpiece) contains 87 micrograms of beclometasone 
dipropionate, 5 micrograms of formoterol fumarate dihydrate and 9 micrograms of glycopyrronium (as 
11 micrograms glycopyrronium bromide). 
 
Each metered dose (the dose leaving the valve) contains 100 micrograms of beclometasone 
dipropionate, 6 micrograms of formoterol fumarate dihydrate and 10 micrograms of glycopyrronium 
(as 12.5 micrograms of glycopyrronium bromide). 
 
The other ingredients are: ethanol anhydrous, hydrochloric acid, propellant: norflurane. 
 
What Trydonis looks like and contents of the pack 
Trydonis is a pressurised inhalation, solution. 
Trydonis comes in a pressurised container (coated aluminium), with a metering valve. The pressurised 
container is inserted in a plastic inhaler. This incorporates a mouthpiece provided with a plastic 
protective cap, and either a dose counter (containers with 60 and 120 puffs) or a dose indicator 
(containers with 180 puffs). 
 
Each pack contains one pressurised container either providing 60 puffs, 120 puffs or 180 puffs. 
Additional there are multipacks containing either 2 or 3 pressurised containers with 120 puffs, each. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Chiesi Farmaceutici S.p.A. 
Via Palermo 26/A 
43122 Parma 
Italy 
 
Manufacturers 
Chiesi Farmaceutici S.p.A. 
Via San Leonardo 96 
43122 Parma 
Italy 
 
Chiesi SAS 
2 rue des Docteurs Alberto et Paolo Chiesi 
41260 La Chaussée Saint Victor 
France 
 



 

41 

Chiesi Pharmaceuticals GmbH 
Gonzagagasse 16/16 
1010 Wien  
Austria 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Chiesi sa/nv  
Tél/Tel: + 32 (0)2 788 42 00 
 

Lietuva 
Chiesi Pharmaceuticals GmbH  
Tel: + 43 1 4073919 
 

България 
Chiesi Bulgaria EOOD  
Teл.: + 359 29201205 
 

Luxembourg/Luxemburg 
Chiesi sa/nv  
Tél/Tel: + 32 (0)2 788 42 00 

Česká republika 
Chiesi CZ s.r.o.  
Tel: + 420 261221745 
 

Magyarország 
Chiesi Hungary Kft.  
Tel.: + 36-1-429 1060 

Danmark 
Chiesi Pharma AB  
Tlf: + 46 8 753 35 20 
 

Malta 
Chiesi Farmaceutici S.p.A.  
Tel: + 39 0521 2791 

Deutschland 
Chiesi GmbH  
Tel: + 49 40 89724-0 
 

Nederland 
Chiesi Pharmaceuticals B.V.  
Tel: + 31 88 501 64 00 
 

Eesti 
Chiesi Pharmaceuticals GmbH  
Tel: + 43 1 4073919 
 

Norge 
Chiesi Pharma AB  
Tlf: + 46 8 753 35 20 

Ελλάδα 
Chiesi Hellas AEBE  
Τηλ: + 30 210 6179763 
 

Österreich 
Chiesi Pharmaceuticals GmbH  
Tel: + 43 1 4073919 

España 
Atreiza Laboratorios S.L.U. 
Tel: + 34 91 277 10 76 
 

Polska 
Chiesi Poland Sp. z.o.o.  
Tel.: + 48 22 620 1421 

France 
Chiesi S.A.S.  
Tél: + 33 1 47688899 
 

Portugal 
Chiesi Farmaceutici S.p.A.  
Tel: + 39 0521 2791 

Hrvatska 
Chiesi Pharmaceuticals GmbH  
Tel: + 43 1 4073919 
 

România 
Chiesi Romania S.R.L.  
Tel: + 40 212023642 

Ireland 
Chiesi Farmaceutici S.p.A.  
Tel: + 39 0521 2791 
 

Slovenija 
Chiesi Slovenija d.o.o.  
Tel: + 386-1-43 00 901 

Ísland 
Chiesi Pharma AB  
Sími: +46 8 753 35 20 
 

Slovenská republika 
Chiesi Slovakia s.r.o.  
Tel: + 421 259300060 



 

42 

Italia 
Marco Antonetto Farmaceutici S.p.A. 
Tel: + 39 011 5613031 
 

Suomi/Finland 
Chiesi Pharma AB  
Puh/Tel: +46 8 753 35 20 

Κύπρος 
Chiesi Farmaceutici S.p.A.  
Τηλ: + 39 0521 2791 
 

Sverige 
Chiesi Pharma AB  
Tel: +46 8 753 35 20 

Latvija 
Chiesi Pharmaceuticals GmbH  
Tel: + 43 1 4073919 
 

United Kingdom 
Chiesi Ltd  
Tel: + 44 (0)161 488 5555 
 

 
This leaflet was last revised in {month YYYY}. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu.  
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS 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