Revinty Ellipta

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 92 micrograms/22 micrograms inhalation powder, pre-dispensed 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each single inhalation provides a delivered dose (the dose leaving the mouthpiece) of 92 micrograms of 
fluticasone furoate and 22 micrograms of vilanterol (as trifenatate).This corresponds to a pre-dispensed dose 
of 100 micrograms of fluticasone furoate and 25 micrograms vilanterol (as trifenatate). 
 
Excipients with known effect: 
 
Each delivered dose contains approximately 25 mg of lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Inhalation powder, pre-dispensed 
(Inhalation powder). 
 
White powder in a light grey inhaler with a yellow mouthpiece cover and a dose counter. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Asthma 
Revinty Ellipta is indicated for the regular treatment of asthma in adults and adolescents aged 12 years and 
older where use of a combination medicinal product (long-acting beta2-agonist and inhaled corticosteroid) is 
appropriate: 

 patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled short acting 
beta2-agonists. 

 patients already adequately controlled on both inhaled corticosteroid and long-acting beta2-agonist. 
 

COPD (Chronic Obstructive Pulmonary Disease) 
 
Revinty Ellipta is indicated for the symptomatic treatment of adults with COPD with a FEV1<70% predicted 
normal (post-bronchodilator) with an exacerbation history despite regular bronchodilator therapy.  
 
4.2 Posology and method of administration 
 
Posology 
 
Asthma 
 
Patients with asthma should be given the strength of Revinty Ellipta containing the appropriate fluticasone 
furoate (FF) dosage for the severity of their disease. Prescribers should be aware that in patients with asthma, 
fluticasone furoate (FF) 100 micrograms once daily is approximately equivalent to fluticasone propionate 
(FP) 250 micrograms twice daily, while FF 200 micrograms once daily is approximately equivalent to FP 
500 micrograms twice daily. 
 
Adults and adolescents aged 12 years and over   



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A starting dose of one inhalation of Revinty Ellipta 92/22 micrograms once daily should be considered for 
adults and adolescents 12 years and over who require a low to mid dose of inhaled corticosteroid in 
combination with a long-acting beta2-agonist. If patients are inadequately controlled on Revinty Ellipta 
92/22 micrograms, the dose can be increased to 184/22 micrograms, which may provide additional 
improvement in asthma control. 
 
Patients should be regularly reassessed by a healthcare professional so that the strength of fluticasone 
furoate/vilanterol they are receiving remains optimal and is only changed on medical advice. The dose 
should be titrated to the lowest dose at which effective control of symptoms is maintained. 
 
Revinty Ellipta 184/22 micrograms should be considered for adults and adolescents 12 years and over who 
require a higher dose of inhaled corticosteroid in combination with a long-acting beta2-agonist. 
 
Patients usually experience an improvement in lung function within 15 minutes of inhaling Revinty Ellipta.  
However, the patient should be informed that regular daily usage is necessary to maintain control of asthma 
symptoms and that use should be continued even when asymptomatic. 
 
If symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be used for 
immediate relief. 
 
Children aged under 12 years 
 
The safety and efficacy of Revinty Ellipta in children under 12 years of age has not yet been established in 
the indication for asthma. 
No data are available. 
 
COPD 
 
Adults aged 18 years and over 
 
One inhalation of Revinty Ellipta 92/22 micrograms once daily.  
 
Revinty Ellipta 184/22 micrograms is not indicated for patients with COPD. There is no additional benefit of 
the 184/22 micrograms dose compared to the 92/22 micrograms dose and there is a potential increased risk 
of pneumonia and systemic corticosteroid-related adverse reactions (see sections 4.4 and 4.8). 
 
Patients usually experience an improvement in lung function within 16-17 minutes of inhaling Revinty 
Ellipta. 
 
Paediatric population 
 
There is no relevant use of Revinty Ellipta in the paediatric population for the indication of COPD. 
 
Special populations  
 
Elderly patients (>65 years) 
 
No dose adjustment is required in this population (see section 5.2). 
 
Renal impairment  
 
No dose adjustment is required in this population (see section 5.2). 
 
Hepatic impairment 
 



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Studies in subjects with mild, moderate and severe hepatic impairment showed an increase in systemic 
exposure to fluticasone furoate (both Cmax and AUC) (see section 5.2). 
Caution should be exercised when dosing patients with hepatic impairment who may be more at risk of 
systemic adverse reactions associated with corticosteroids.  
For patients with moderate or severe hepatic impairment the maximum dose is 92/22 micrograms (see 
section 4.4).  
 
Method of administration  
 
Revinty Ellipta is for inhalation use only. 
 
It should be administered at the same time of the day, each day.  
 
The final decision on evening or morning dosing should be left to the discretion of the physician. 
 
If a dose is missed the next dose should be taken at the usual time the next day. 
 
If stored in a refrigerator, the inhaler should be allowed to return to room temperature for at least an hour 
before use. 
 
When the inhaler is used for the first time, there is no need to check that it is working properly, and to 
prepare it for use in any special way. The step-by-step instructions should be followed. 
 
The Ellipta inhaler is packaged in a tray containing a desiccant sachet, to reduce moisture. The desiccant 
sachet should be thrown away and it should not be opened, eaten or inhaled.  
 
The patient should be advised to not open the tray until they are ready to inhale a dose.  
 
When the inhaler is taken out of its tray, it will be in the ‘closed’ position. The “Discard by” date should be 
written on the inhaler label in the space provided. The “Discard by” date is 6 weeks from the date of opening 
the tray. After this date the inhaler should no longer be used. The tray can be discarded after first opening. 
 
After inhalation, patients should rinse their mouth with water without swallowing. 
 
The step-by-step instructions shown below for the 30-dose Ellipta inhaler (30 day supply) also apply to the 
14-dose Ellipta inhaler (14 day supply). 
 
Instructions for use 
 
1. Read this before you start 
 
If the inhaler cover is opened and closed without inhaling the medicine, the dose will be lost. The lost dose 
will be securely held inside the inhaler, but it will no longer be available to be inhaled.  
It is not possible to accidentally take extra medicine or a double dose in one inhalation. 
 



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2. How to prepare a dose 
 
Open the cover when ready to inhale a dose. Do not shake the inhaler. 
 
Slide the cover down until you hear a ‘click’. 
 
The medicine is now ready to be inhaled. The dose counter counts down by 1 to confirm. 
 
If the dose counter does not count down as you hear the ‘click’, the inhaler will not deliver medicine. Take it 
back to a pharmacist for advice. 

 

 
 
3. How to inhale the medicine 
 
Hold the inhaler away from your mouth and breathe out as far as is comfortable. 
 
Do not breathe out into the inhaler. 
 
Put the mouthpiece between your lips and close your lips firmly around it. 
 
Do not block the air-vents with your fingers.  
 
Take one long, steady, deep breath in. Hold this breath for as long as possible (at least 3-4 seconds).  

 Remove the inhaler from your mouth. 



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 Breathe out slowly and gently.  

 
 
It may not be possible to taste or feel the medicine, even when using the inhaler correctly. 
 
If you want to clean the mouthpiece, use a dry tissue, before closing the cover. 
 
 
4. Close the inhaler and rinse your mouth  
 
Slide the cover upwards as far as it will go to cover the mouthpiece. 
 
Rinse your mouth with water after you have used the inhaler, do not swallow. 
 
This will make it less likely to develop a sore mouth or throat as side effects. 

 
 
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 
 
Deterioration of disease 
 



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Fluticasone furoate/vilanterol should not be used to treat acute asthma symptoms or an acute exacerbation in 
COPD, for which a short-acting bronchodilator is required.  Increasing use of short-acting bronchodilators to 
relieve symptoms indicates deterioration of control and patients should be reviewed by a physician.  
 
Patients should not stop therapy with fluticasone furoate/vilanterol in asthma or COPD, without physician 
supervision since symptoms may recur after discontinuation. 
 
Asthma-related adverse events and exacerbations may occur during treatment with fluticasone 
furoate/vilanterol. Patients should be asked to continue treatment but to seek medical advice if asthma 
symptoms remain uncontrolled or worsen after initiation of treatment with Revinty Ellipta. 
 
Paradoxical bronchospasm 
 
Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing.  This should be 
treated immediately with a short-acting inhaled bronchodilator. Revinty Ellipta should be discontinued 
immediately, the patient assessed and alternative therapy instituted if necessary. 
 
Cardiovascular effects 
 
Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may 
be seen with sympathomimetic medicinal products including Revinty Ellipta. In a placebo-controlled study 
in subjects with moderate COPD and a history of, or an increased risk of cardiovascular disease, there was 
no increase in the risk of cardiovascular events in patients receiving fluticasone furoate/vilanterol compared 
with placebo (see section 5.1). However, fluticasone furoate/vilanterol should be used with caution in 
patients with severe cardiovascular disease or heart rhythm abnormalities, thyrotoxicosis, uncorrected 
hypokalaemia or patients predisposed to low levels of serum potassium. 
 
Patients with hepatic impairment 
 
For patients with moderate to severe hepatic impairment, the 92/22 micrograms dose should be used and 
patients should be monitored for systemic corticosteroid-related adverse reactions (see section 5.2). 
 
Systemic corticosteroid effects 
 
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long 
periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects 
include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, 
growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of 
psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, 
depression or aggression (particularly in children). 
 
Fluticasone furoate/vilanterol should be administered with caution in patients with pulmonary tuberculosis or 
in patients with chronic or untreated infections.  
 
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. 
 
Hyperglycaemia 
 
There have been reports of increases in blood glucose levels in diabetic patients and this should be 
considered when prescribing to patients with a history of diabetes mellitus. 



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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. 
 
Pneumonia in patients with asthma 
 
The incidence of pneumonia in patients with asthma was common at the higher dose. The incidence of 
pneumonia in patients with asthma taking fluticasone furoate/vilanterol 184/22 micrograms was numerically 
higher compared with those receiving fluticasone furoate/vilanterol 92/22 micrograms or placebo (see 
section 4.8).  No risk factors were identified. 
 
Excipients 
 
Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-
galactose malabsorption should not use this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Clinically significant drug interactions mediated by fluticasone furoate/vilanterol at clinical doses are 
considered unlikely due to the low plasma concentrations achieved after inhaled dosing. 
 
Interaction with beta-blockers 
 
Beta2-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists. Concurrent use 
of both non-selective and selective beta2-adrenergic blockers should be avoided unless there are compelling 
reasons for their use. 
 
Interaction with CYP3A4 inhibitors 
 
Fluticasone furoate and vilanterol are both rapidly cleared by extensive first pass metabolism mediated by 
the liver enzyme CYP3A4.  
 
Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir, 
cobicistat-containing products) as there is potential for increased systemic exposure to both fluticasone 
furoate and vilanterol. Co-administration should be avoided unless the benefit outweighs the increased risk 
of systemic corticosteroid undesirable effects, in which case patients should be monitored for systemic 
corticosteroid undesirable effects. A repeat dose CYP3A4 drug interaction study was performed in healthy 
subjects with the fluticasone furoate/vilanterol combination (184/22 micrograms) and the strong CYP3A4 
inhibitor ketoconazole (400mg).  Co-administration increased mean fluticasone furoate AUC(0-24) and Cmax by 
36% and 33%, respectively.  The increase in fluticasone furoate exposure was associated with a 27% 
reduction in 0-24 hours weighted mean serum cortisol. Co-administration increased mean vilanterol AUC(0-t) 
and Cmax 65% and 22%, respectively.  The increase in vilanterol exposure was not associated with an 
increase in beta2-agonist related systemic effects on heart rate, blood potassium or QTcF interval.  



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Interaction with P-glycoprotein inhibitors 
 
Fluticasone furoate and vilanterol are both substrates of P-glycoprotein (P-gp). A clinical pharmacology 
study in healthy subjects with co-administered vilanterol and the potent P-gp and moderate CYP3A4 
inhibitor verapamil did not show any significant effect on the pharmacokinetics of vilanterol. Clinical 
pharmacology studies with a specific P-gp inhibitor and fluticasone furoate have not been conducted. 
 
Sympathomimetic medicinal products 
 
Concomitant administration of other sympathomimetic medicinal products (alone or as part of combination 
therapy) may potentiate the adverse reactions of fluticasone furoate/vilanterol.  Revinty Ellipta should not be 
used in conjunction with other long-acting beta2-adrenergic agonists or medicinal products containing long-
acting beta2-adrenergic agonists. 
 
Paediatric population 
 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
Studies in animals have shown reproductive toxicity at exposures which are not clinically relevant (see 
section 5.3). There are no or limited data from the use of fluticasone furoate and vilanterol trifenatate in 
pregnant women. 
 
Administration of fluticasone furoate/vilanterol to pregnant women should only be considered if the 
expected benefit to the mother is greater than any possible risk to the foetus. 
 
Breast-feeding 
 
There is insufficient information on the excretion of fluticasone furoate or vilanterol trifenatate and/or 
metabolites in human milk. However, other corticosteroids and beta2-agonists are detected in human milk 
(see section 5.3). A risk to breastfed newborns/infants cannot be excluded. 
 
A decision must be made whether to discontinue breast-feeding or to discontinue fluticasone 
furoate/vilanterol therapy taking into account the benefit of breast-feeding for the child and the benefit of 
therapy for the woman. 
 
Fertility 
 
There are no fertility data in humans. Animal studies showed no effect of fluticasone furoate/vilanterol 
trifenatate on fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Fluticasone furoate or vilanterol has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Data from large asthma and COPD clinical trials were used to determine the frequency of adverse reactions 
associated with fluticasone furoate/vilanterol. In the asthma clinical development program a total of 7,034 



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patients were included in an integrated assessment of adverse reactions. In the COPD clinical development 
programme a total of 6,237 subjects were included in an integrated assessment of adverse reactions. 
 
The most commonly reported adverse reactions with fluticasone furoate and vilanterol were headache and 
nasopharyngitis. With the exception of pneumonia and fractures, the safety profile was similar in patients 
with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently commonly 
observed in patients with COPD.  
 
Tabulated list of adverse reactions 
 
Adverse reactions are listed by system organ class and frequency. The following convention has been used 
for the classification of frequencies: 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). 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 



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System organ class Adverse reaction(s) Frequency 
Infections and infestations Pneumonia*  

Upper respiratory tract infection 

Bronchitis  

Influenza 

Candidiasis of mouth and throat 

Common 

 

Immune system disorders Hypersensitivity reactions including 
anaphylaxis, angioedema, rash, and 
urticaria. 

Rare 

Metabolism and nutrition 
disorders 

Hyperglycaemia Uncommon 

Psychiatric disorders Anxiety Rare 

Nervous system disorders Headache 

Tremor 

Very common 

Rare 

Eye disorders Vision blurred (see section 4.4) Uncommon 

   

Cardiac disorders Extrasystoles  

Palpitations 

Tachycardia 

Uncommon 

Rare 

Rare 

Respiratory, thoracic and 
mediastinal disorders 

Nasopharyngitis  

Paradoxical bronchospasm 

Oropharyngeal pain 

Sinusitis  

Pharyngitis 

Rhinitis  

Cough  

Dysphonia 

Very common 

Rare 

Common 

 

 

Gastrointestinal disorders Abdominal pain Common 

Musculoskeletal and 
connective tissue disorders 

Arthralgia 

Back pain 

Fractures**  

Muscle spasms 

Common 

 

General disorders and 
administration site conditions 

Pyrexia Common 

 
*, ** See below ‘Description of selected adverse reactions’ 
 
*Pneumonia (see section 4.4) 
 
In an integrated analysis of the two replicate one year studies in moderate to severe COPD (mean predicted 
post-bronchodilator screening FEV1 of 45%, standard deviation (SD) 13%) with an exacerbation in the 
preceding year (n = 3255), the number of pneumonia events per 1000 patient years was 97.9 with FF/VI 



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184/22, 85.7 in the FF/VI 92/22 and 42.3 in the VI 22 group. For severe pneumonia the corresponding 
number of events per 1000 patient years were 33.6, 35.5, and 7.6 respectively, while for serious pneumonia 
the corresponding events per 1000 patient years were 35.1 for FF/VI 184/22, 42.9 with FF/VI 92/22, 12.1 
with VI 22. Finally, the exposure-adjusted cases of fatal pneumonia were 8.8 for FF/VI 184/22 versus 1.5 for 
FF/VI 92/22 and 0 for VI 22.  
 
In a placebo-controlled study (SUMMIT) in subjects with moderate COPD (mean percent post-
bronchodilator screening FEV1 of 60%, SD 6%), and a history of, or an increased risk of cardiovascular 
disease, the incidence of pneumonia with FF/VI, FF, VI and placebo was: adverse events (6%, 5%, 4%, 5%); 
serious adverse events (3%, 4%, 3%, 3%); adjudicated on treatment deaths due to pneumonia (0.3%, 0.2%, 
0.1%, 0.2%); the exposure adjusted rates (per 1000 treatment years) were: adverse events (39.5, 42.4, 27.7, 
38.4); serious adverse events (22.4, 25.1, 16.4, 22.2); adjudicated on-treatment deaths due to pneumonia (1.8, 
1.5, 0.9, 1.4) respectively. 
 
In an integrated analysis of 11 studies in asthma (7,034 patients), the incidence of pneumonia per 1000 
patient years was 18.4 for FF/VI 184/22 versus 9.6 for FF/VI 92/22 and 8.0 in the placebo group. 
 
**Fractures 
 
In two replicate 12 month studies in a total of 3,255 patients with COPD the incidence of bone fractures 
overall was low in all treatment groups, with a higher incidence in all Revinty Ellipta groups (2%) compared 
with the vilanterol 22 micrograms group (<1%).  Although there were more fractures in the Revinty Ellipta 
groups compared with the vilanterol 22 micrograms group, fractures typically associated with corticosteroid 
use (e.g., spinal compression/thoracolumbar vertebral fractures, hip and acetabular fractures) occurred in 
<1% of the Revinty Ellipta and vilanterol treatment arms. 
 
For the SUMMIT study, the incidence of all events of fracture with FF/VI, FF, VI and placebo were 2% in 
each arm; fractures commonly associated with ICS use were less than 1 % in each arm. The exposure-
adjusted rates (per 1000 treatment years) for all fracture events were 13.6, 12.8, 13.2, 11.5 respectively; 
fractures commonly associated with ICS use were 3.4, 3.9, 2.4, 2.1 respectively. 
 
In an integrated analysis of 11 studies in asthma (7,034 patients), the incidence of fractures was <1%, and 
usually associated with trauma. 
 
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 
 
Symptoms and signs 
 
An overdose of fluticasone furoate/vilanterol may produce signs and symptoms due to the individual 
component’s actions, including those seen with overdose of other beta2-agonists and consistent with the 
known inhaled corticosteroid class effects (see section 4.4). 
 
Treatment 
 
There is no specific treatment for an overdose with fluticasone furoate/vilanterol. If overdose occurs, the 
patient should be treated supportively with appropriate monitoring as necessary.  
 
Cardioselective beta-blockade should only be considered for profound vilanterol overdose effects that are 
clinically concerning and unresponsive to supportive measures. Cardioselective beta-blocking medicinal 
products should be used with caution in patients with a history of bronchospasm. 



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Further management should be as clinically indicated or as recommended by the national poisons centre, 
where available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs for obstructive airways diseases, adrenergics in combination with 
corticosteroids or other drugs, excl. anticholinergics, ATC code: R03AK10. 
 
Mechanism of action 
 
Fluticasone furoate and vilanterol represent two classes of medications (a synthetic corticosteroid and a 
selective, long-acting beta2-receptor agonist). 
 
Pharmacodynamic effects 
 
Fluticasone furoate 
 
Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. The 
precise mechanism through which fluticasone furoate affects asthma and COPD symptoms is not known. 
Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g. eosinophils, 
macrophages, lymphocytes) and mediators (e.g. cytokines and chemokines involved in inflammation). 
 
Vilanterol trifenatate 
 
Vilanterol trifenatate is a selective long-acting, beta2-adrenergic agonist (LABA).  
The pharmacologic effects of beta2-adrenoceptor agonist active substances, including vilanterol trifenatate, 
are at least in part attributable to stimulation of intracellular adenylate cyclase, the enzyme that catalyzes the 
conversion of adenosine triphosphate (ATP) to cyclic-3’,5’-adenosine monophosphate (cyclic AMP). 
Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of 
mediators of immediate hypersensitivity from cells, especially from mast cells. 
 
Molecular interactions occur between corticosteroids and LABAs, whereby steroids activate the beta2-
receptor gene, increasing receptor number and sensitivity and LABAs prime the glucocorticoid receptor for 
steroid-dependent activation and enhance cell nuclear translocation. These synergistic interactions are 
reflected in enhanced anti-inflammatory activity, which has been demonstrated in vitro and in vivo in a range 
of inflammatory cells relevant to the pathophysiology of both asthma and COPD. In peripheral blood 
mononuclear cells from subjects with COPD, a larger anti-inflammatory effect was seen in the presence of 
the combination of fluticasone furoate/vilanterol compared with fluticasone furoate alone at concentrations 
achieved with clinical doses. The enhanced anti-inflammatory effect of the LABA component was similar to 
that obtained with other ICS/LABA combinations. 
 
Clinical efficacy and safety 
 
Asthma 
 
Three phase III randomised, double-blind studies (HZA106827, HZA106829 and HZA106837) of different 
durations evaluated the safety and efficacy of fluticasone furoate/vilanterol in adult and adolescent patients 
with persistent asthma.  All subjects were using an ICS (Inhaled corticosteroid) with or without LABA for at 
least 12 weeks prior to visit 1. In HZA106837 all patients had at least one exacerbation that required 
treatment with oral corticosteroids in the year prior to visit 1.  HZA106827 was 12 weeks in duration and 
evaluated the efficacy of fluticasone furoate/vilanterol 92/22 micrograms [n=201] and FF 92 micrograms 
[n=205]) compared with placebo [n=203], all administered once daily. HZA106829 was 24 weeks in 



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duration and evaluated the efficacy of fluticasone furoate/vilanterol 184/22 micrograms [n=197] and FF 
184 micrograms [n=194]) both administered once daily compared with FP 500 micrograms twice daily 
[n=195].  
 
In HZA106827/HZA106829 the co-primary efficacy endpoints were change from baseline in clinic visit 
trough (pre-bronchodilator and pre-dose) FEV1 at the end of the treatment period in all subjects and weighted 
mean serial FEV1 over 0-24 hours post-dose calculated in a subset of subjects at the end of the treatment 
period. Change from baseline in the percentage of rescue-free 24 hour periods during treatment was a 
powered secondary endpoint.  Results for the primary and key secondary endpoints in these studies are 
described in Table 1. 

Table 1 - Results of primary and key secondary endpoints in HZA106827 and HZA106829 

Study No. HZA106829 HZA106827 
Treatment Dose of 
FF/VI*(micrograms) 

FF/VI 184/22 
Once Daily vs 
FF 184 Once 

Daily 

FF/VI 184/22 
Once Daily 
vs FP 500 

Twice Daily 

FF/VI 92/22 
Once Daily 

vs FF 92 
Once Daily 

FF/VI 92/22 
Once Daily 
vs placebo 
Once Daily 

Change from Baseline in Trough FEV1 Last Observation Carried Forward (LOCF) 
Treatment difference 
P value  
(95% CI)  

193mL 
p<0.001 

(108, 277) 

210mL 
p<0.001 

(127, 294) 

36mL 
p=0.405 

(-48, 120) 

172mL 
p<0.001 
(87, 258) 

Weighted Mean Serial FEV1 over 0-24 hours post-dose 
Treatment difference 
P value 
(95% CI) 

136mL 
p=0.048 
(1, 270) 

206mL 
p=0.003 
(73, 339) 

116mL 
p=0.06 

(-5, 236) 

302mL 
p<0.001 

(178, 426) 
Change from Baseline in Percentage of Rescue-Free 24-hour Periods 
Treatment difference 
P value  
(95% CI) 

11.7% 
p<0.001 

(4.9, 18.4) 

6.3% 
p=0.067 

(-0.4, 13.1) 

10.6% 
p<0.001 

(4.3, 16.8) 

19.3% 
p<0.001 

(13.0, 25.6) 
Change from Baseline in Percentage of Symptom-Free 24-hour Periods 
Treatment difference 
P value  
(95% CI) 

8.4% 
p=0.010 

(2.0, 14.8) 

4.9% 
p=0.137 

(-1.6, 11.3) 

12.1% 
p<0.001 

(6.2, 18.1) 

18.0% 
p<0.001 

(12.0, 23.9) 
Change from Baseline in AM Peak Expiratory Flow 
Treatment difference 
P value  
(95% CI) 

33.5L/min 
p<0.001 

(22.3, 41.7) 

32.9L/min 
p<0.001 

(24.8, 41.1) 

14.6L/min 
p<0.001 

(7.9, 21.3) 

33.3L/min 
p<0.001 

(26.5, 40.0) 
Change from Baseline in PM Peak Expiratory Flow 
Treatment difference 
P value  
(95% CI) 

30.7L/min 
p<0.001 

(22.5, 38.9) 

26.2L/min  
p<0.001 

(18.0, 34.3) 

12.3L/min 
p<0.001 

(5.8, 18.8) 

28.2L/min 
p<0.001 

(21.7, 34.8) 
*FF/VI = fluticasone furoate/vilanterol 
 
HZA106837 was of variable treatment duration (from a minimum of 24 weeks to a maximum of 76 weeks 
with the majority of patients treated for at least 52 weeks).  In HZA106837 patients were randomised to 
receive either fluticasone furoate/vilanterol 92/22 micrograms [n=1009] or FF 92 micrograms [n=1010] both 
administered once daily.  In HZA106837 the primary endpoint was the time to first severe asthma 
exacerbation.  A severe asthma exacerbation was defined as deterioration of asthma requiring the use of 
systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency department visit due 
to asthma that required systemic corticosteroids. Adjusted mean change from baseline in trough FEV1 was 
also evaluated as a secondary endpoint. 
 
In HZA106837 the risk of experiencing a severe asthma exacerbation in patients receiving fluticasone 
furoate/vilanterol 92/22 micrograms was reduced by 20% compared with FF 92 micrograms alone (hazard 
ratio 0.795, p=0.036 95% CI 0.642, 0.985). The rate of severe asthma exacerbations per patient per year was 



15 

0.19 in the FF 92 micrograms group (approximately 1 in every 5 years) and 0.14 in the fluticasone 
furoate/vilanterol 92/22 micrograms group (approximately 1 in every 7 years).  The ratio of the exacerbation 
rate for fluticasone furoate/vilanterol 92/22 micrograms versus FF 92 micrograms was 0.755 (95% CI 0.603, 
0.945). This represents a 25% reduction in the rate of severe asthma exacerbations for subjects treated with 
fluticasone furoate/vilanterol 92/22 micrograms compared with FF 92 micrograms(p=0.014). The 24-hour 
bronchodilator effect of fluticasone furoate/vilanterol was maintained throughout a one-year treatment period 
with no evidence of loss in efficacy (no tachyphylaxis). Fluticasone furoate/vilanterol 92/22 micrograms 
consistently demonstrated 83 mL to 95 mL improvements in trough FEV1 at weeks 12, 36 and 52 and 
Endpoint compared with FF 92 micrograms (p<0.001 95% CI 52, 126 mL at Endpoint). Forty four percent of 
patients in the fluticasone furoate/vilanterol 92/22 micrograms group were well controlled (ACQ7 ≤0.75) at 
end of treatment compared to 36% of subjects in the FF 92 micrograms group (p<0.001 95% CI 1.23, 1.82). 
 
Studies versus salmeterol/fluticasone propionate combinations 
 
In a 24 week study (HZA113091) in adult and adolescent patients with uncontrolled persistent asthma both 
fluticasone furoate/vilanterol 92/22 micrograms given once daily in the evening and salmeterol/FP 
50/250 micrograms given twice daily demonstrated improvements from baseline in lung function. Adjusted 
mean treatment increases from baseline in weighted mean 0-24 hours FEV1 of 341 mL (fluticasone 
furoate/vilanterol) and 377 mL (salmeterol/FP) demonstrated an overall improvement in lung function over 
24 hours for both treatments.  The adjusted mean treatment difference of -37 mL between the groups was not 
statistically significant (p=0.162). For trough FEV1 subjects in the fluticasone furoate/vilanterol group 
achieved a LS mean change from baseline of 281 mL and subjects in the salmeterol/FP group a change of 
300 mL; (the difference in adjusted mean of -19 mL (95%CI:-0.073, 0.034) was not statistically significant 
(p=0.485). 
 
A randomised, double-blind, parallel group, 24 week study (201378) was conducted to demonstrate non-
inferiority (using a margin of -100 mL for trough FEV1) of fluticasone furoate/vilanterol 92/22 once daily to 
salmeterol/FP 50/250 twice daily in adults and adolescents whose asthma was well controlled following 4 
weeks of treatment with open-label salmeterol/FP 50/250 twice daily (N=1504). Subjects randomised to 
once-daily FF/VI maintained lung function comparable with those randomised to twice-daily salmeterol/FP 
[difference in trough FEV1 of +19 mL (95% CI: -11, 49)]. 
 
No comparative studies versus salmeterol/FP or versus other ICS/LABA combinations have been conducted 
to appropriately compare the effects on asthma exacerbations. 
 
Fluticasone furoate monotherapy 
 
A 24 week randomised, double-blind placebo controlled study (FFA112059) evaluated the safety and 
efficacy of FF 92 micrograms once daily [n= 114] and FP 250 micrograms twice daily [n=114] versus 
placebo [n=115] in adult and adolescent patients with persistent asthma. All subjects had to have been on a 
stable dose of an ICS for at least 4 weeks prior to visit 1 (screening visit) and the use of LABAs was not 
permitted within 4 weeks of visit 1. The primary efficacy endpoint was change from baseline in clinic visit 
trough (pre-bronchodilator and pre-dose) FEV1 at the end of the treatment period. Change from baseline in 
the percentage of rescue-free 24 hour periods during the 24-week treatment period was a powered secondary.  
At the 24-week time point FF and FP increased trough FEV1 by 146 mL (95% CI 36, 257 mL, p=0.009) and 
145 mL (95% CI 33, 257 mL, p=0.011) respectively compared to placebo. FF and FP both increased the 
percentage of 24 hour rescue free periods by 14.8% (95% CI 6.9, 22.7, p<0.001) and 17.9% (95% CI 10.0, 
25.7, p<0.001) respectively versus placebo.  
 
Allergen challenge study 
 
The bronchoprotective effect of fluticasone furoate/vilanterol 92/22 micrograms on the early and late 
asthmatic response to inhaled allergen was evaluated in a repeat dose, placebo-controlled four-way crossover 
study (HZA113126) in patients with mild asthma.  Patients were randomized to receive fluticasone 
furoate/vilanterol 92/22 micrograms, FF 92 micrograms, vilanterol 22 micrograms or placebo once daily for 
21 days followed by challenge with allergen 1 hour after the final dose. The allergen was house dust mite, cat 



16 

dander, or birch pollen; the selection was based on individual screening tests.  Serial FEV1 measurements 
were compared with pre-allergen challenge values taken after saline inhalation (baseline).  Overall, the 
greatest effects on the early asthmatic response were seen with fluticasone furoate/vilanterol 
92/22 micrograms compared with FF 92 micrograms or vilanterol 22 micrograms alone. Both fluticasone 
furoate/vilanterol 92/22 micrograms and FF 92 micrograms virtually abolished the late asthmatic response 
compared with vilanterol alone. Fluticasone furoate/vilanterol 92/22 micrograms provided significantly 
greater protection against allergen-induced bronchial hyper-reactivity compared with monotherapies FF and 
vilanterol as assessed on Day 22 by methacholine challenge.  
 
Chronic Obstructive Pulmonary Disease  
 
The COPD clinical development programme included a 12-week (HZC113107), two 6-month (HZC112206, 
HZC112207),  two one-year (HZC102970, HZC102871), and one >1 year study (SUMMIT). These were 
randomised controlled studies in patients with a clinical diagnosis of COPD. These studies included 
measures of lung function, dyspnoea and moderate and severe exacerbations. 
 
Six month studies 
 
HZC112206 and HZC112207 were 24 week randomised, double-blind, placebo controlled, parallel group 
studies comparing the effect of the combination to vilanterol and FF alone and placebo.  HZC112206 
evaluated the efficacy of fluticasone furoate/vilanterol 46 /22 micrograms [n=206] and fluticasone 
furoate/vilanterol 92/22 micrograms [n=206] compared with FF 92 micrograms [n=206], vilanterol 
22 micrograms [n=205] and placebo [n = 207], all administered once daily. HZC112207 evaluated the 
efficacy of fluticasone furoate/vilanterol 92/22 micrograms [n=204] and fluticasone furoate/vilanterol 
184/22 micrograms [n=205] compared with FF 92 micrograms [n=204], FF 184 micrograms [n=203] and 
vilanterol 22 micrograms [n=203] and placebo [n = 205], all administered once daily. 
 
All patients were required to have a smoking history of at least 10 pack years; a post-salbutamol FEV1/FVC 
ratio less than or equal to 0.70; post-salbutamol FEV1 less than or equal to 70% predicted and have a 
Modified Medical Research Council (mMRC) dyspnea score 2 (scale 0-4) at screening. At screening, the 
mean pre-bronchodilator FEV1 was 42.6% and 43.6% predicted, and the mean reversibility was 15.9% and 
12.0% in HZC112206 and HZC112207, respectively.  The co-primary endpoints in both studies were 
weighted mean FEV1 from zero to 4 hours post-dose at Day 168 and change from baseline in pre-dose trough 
FEV1 at Day 169. 
 
In an integrated analysis of both studies, fluticasone furoate/vilanterol 92/22 micrograms showed clinically 
meaningful improvements in lung function. At Day 169 fluticasone furoate/vilanterol 92/22 micrograms and 
vilanterol increased adjusted mean trough FEV1 by 129 mL (95% CI: 91, 167 mL, p<0.001) and 83 mL (95% 
CI: 46, 121mL, p<0.001) respectively compared to placebo. Fluticasone furoate/vilanterol 92/22 micrograms 
increased trough FEV1 by 46 mL compared to vilanterol (95% CI: 8, 83mL, p= 0.017). At Day 168 
fluticasone furoate/vilanterol 92/22 micrograms and vilanterol increased adjusted mean weighted mean FEV1 
over 0-4 hours by 193mL (95% CI: 156, 230 mL, p<0.001) and 145 mL (95% CI: 108, 181 mL, p<0.001) 
respectively compared to placebo. Fluticasone furoate/vilanterol 92/22 micrograms increased adjusted mean 
weighted mean FEV1 over 0-4 hours by 148 ml compared to FF alone (95% CI: 112, 184 mL, p< 0.001). 
 
12 month studies 
 
Studies HZC102970 and HZC102871 were 52 week randomised, double-blind, parallel-group, studies 
comparing the effect of fluticasone furoate/vilanterol 184/22 micrograms, fluticasone furoate/vilanterol 
92/22 micrograms, fluticasone furoate/vilanterol 46/22 micrograms with vilanterol 22 micrograms, all 
administered once daily, on the annual rate of moderate/severe exacerbations in subjects with COPD with a 
smoking history of at least 10 pack years and a post-salbutamol FEV1/FVC ratio less than or equal to 0.70 
and post-salbutamol FEV1 less than or equal to 70% predicted and documented history of ≥ 1 COPD 
exacerbation that required antibiotics and/or oral corticosteroids or hospitalisation in the 12 months prior to 
visit 1. The primary endpoint was the annual rate of moderate and severe exacerbations.  Moderate/ severe 
exacerbations were defined as worsening symptoms that required treatment with oral corticosteroids and/or 



17 

antibiotics or in-patient hospitalisation.  Both studies had a 4 week run-in period during which all subjects 
received open-label salmeterol/FP 50/250 twice daily to standardise COPD pharmacotherapy and stabilise 
disease prior to randomisation to blinded study medication for 52 weeks.  Prior to run-in, subjects 
discontinued use of previous COPD medications except short-acting bronchodilators. The use of concurrent 
inhaled long-acting bronchodilators (beta2-agonist and anticholinergic), ipratropium/salbutamol combination 
products, oral beta2-agonists, and theophylline preparations were not allowed during the treatment period. 
Oral corticosteroids and antibiotics were allowed for the acute treatment of COPD exacerbations with 
specific guidelines for use. Subjects used salbutamol on an as-needed basis throughout the studies.  
 
The results of both studies showed that treatment with fluticasone furoate/vilanterol 92/22 micrograms once 
daily resulted in a lower annual rate of moderate/severe COPD exacerbations compared with vilanterol 
(Table 2). 
 

Table 2: Analysis of Exacerbation Rates following 12 months of treatment 

Endpoint 
 

HZC102970 HZC102871 HZC102970 and 
HZC102871 integrated 

Vilanterol 
(n=409) 

fluticasone 
furoate/  

vilanterol 
92/22 

(n=403) 

Vilanterol 
(n=409) 

fluticasone  
furoate/ 

vilanterol  
92/22  

(n=403) 

Vilanterol 
(n=818) 

fluticasone  
furoate/ 

vilanterol 
 92/22 

(n=806) 
Moderate and severe exacerbations 
Adjusted mean 
annual rate  

1.14 0.90 1.05 0.70 1.11 0.81 

Ratio vs VI 
95% CI 
p-value 
% reduction 
(95% CI) 

 0.79 
(0.64,0.97) 

0.024 
21 

(3, 36) 

 0.66 
(0.54, 0.81) 

<0.001 
34 

(19, 46) 

 0.73 
(0.63, 0.84) 

<0.001 
27 

(16, 37) 
Absolute 
difference in 
number per 
year vs VI 
(95% CI) 

  
 
 
 

0.24 
(0.03, 0.41) 

  
 
 
 

0.36 
(0.20, 0.48) 

  
 
 
 

0.30 
(0.18, 0.41) 

Time to first 
exacerbation: 
Hazard ratio 
(95% CI) 
% risk 
reduction 
 
p-value 

  
 

0.80 
(0.66, 0.99) 

20 
 
 

0.036 

  
 

0.72 
(0.59, 0.89) 

28 
 
 

0.002 

  
 

0.76 
(0.66, 0.88) 

24 
 
 

p<0.001 
 
In an integrated analysis of HZC102970 and HZC102871 at week 52, an improvement was seen when 
comparing the fluticasone furoate/vilanterol 92/22 micrograms versus vilanterol 22 micrograms in adjusted 
mean trough FEV1 (42 mL 95% CI: 19, 64mL, p<0.001). The 24-hour bronchodilator effect of fluticasone 
furoate/vilanterol was maintained from the first dose throughout a one-year treatment period with no 
evidence of loss in efficacy (no tachyphylaxis). 
 
Overall, across the two studies combined 2009 (62%) patients had cardiovascular history/risk factors at 
screening.  The incidence of cardiovascular history/risk factors was similar across the treatment groups with 
patients most commonly suffering from hypertension (46%), followed by hypercholesterolemia (29%) and 
diabetes mellitus (12%). Similar effects in reduction of moderate and severe exacerbations were observed in 



18 

this subgroup as compared with the overall population. In patients with a cardiovascular history/risk factors, 
fluticasone furoate/vilanterol  92/22 micrograms resulted in a significantly lower annual rate of 
moderate/severe COPD exacerbations compared with vilanterol (adjusted mean annual rates of 0.83 and 1.18 
respectively, 30% reduction (95% CI 16, 42%, p<0.001)). Improvements were also seen in this subgroup at 
week 52 when comparing the fluticasone furoate/vilanterol 92/22 micrograms vs. vilanterol 22 micrograms 
in adjusted mean trough FEV1 (44 mL 95% CI: 15, 73mL, (p=0.003)). 
 
 
 
Studies > 1 year duration 
 
SUMMIT was a multi-centre, randomised, double-blind study evaluating the effect on survival of fluticasone 
furoate/vilanterol 92/22 micrograms compared with placebo in 16,485 subjects. The primary endpoint was 
all-cause mortality and a secondary endpoint was a composite of cardiovascular events (on-treatment 
cardiovascular death, myocardial infarction, stroke, unstable angina, or transient ischemic attack).  
 
Prior to randomization, subjects were required to discontinue previous COPD medications used at baseline, 
which included long-acting bronchodilators plus inhaled corticosteroids (28%), long-acting bronchodilators 
alone (11%) and inhaled corticosteroids alone (4%). Subjects were then randomized to receive either 
fluticasone furoate/vilanterol 92/22 micrograms, fluticasone furoate 92 micrograms, 
vilanterol 22 micrograms, or placebo, and treated for a mean of 1.7 years (SD = 0.9 years).  
 
Subjects had moderate COPD (mean percent post-bronchodilator screening FEV1 of 60% [SD = 6%]), and a 
history of, or an increased risk of cardiovascular disease. In the 12 months prior to the study, 61% of subjects 
reported no COPD exacerbations and 39% of subjects reported ≥1 moderate/severe COPD exacerbation. 
 
All-cause mortality was: fluticasone furoate/vilanterol, 6.0%; placebo, 6.7%; fluticasone furoate, 6.1%; 
vilanterol, 6.4%. Exposure-adjusted all-cause mortality per 100 patients/year (%/yr) was: fluticasone 
furoate/vilanterol, 3.1 %/yr; placebo, 3.5 %/yr; fluticasone furoate, 3.2 %/yr; and vilanterol, 3.4 %/yr. 
Mortality risk with fluticasone furoate/vilanterol was not significantly different compared with placebo (HR 
0.88; 95% CI: 0.74 to 1.04; p=0.137), fluticasone furoate (HR 0.96; 95% CI: 0.81 to 1.15; p=0.681) or 
vilanterol (HR 0.91; 95% CI: 0.77 to 1.09; p=0.299).  
 
The risk of the cardiovascular composite event with fluticasone furoate/vilanterol was not significantly 
different compared with placebo (HR 0.93; 95% CI: 0.75 to 1.14), fluticasone furoate (HR 1.03; 95% CI: 
0.83 to 1.28) or vilanterol (HR 0.94; 95% CI: 0.76 to 1.16). 
 
Studies versus salmeterol/fluticasone propionate combinations 
 
In a 12 week study (HZC113107) in COPD patients both fluticasone furoate/vilanterol 92/22 micrograms 
given once daily in the morning and salmeterol/FP 50/500 micrograms given twice daily, demonstrated 
improvements from baseline in lung function. Adjusted mean treatment increases from baseline in weighted 
mean 0-24 hours FEV1 of 130 mL (fluticasone furoate/vilanterol) and 108 mL (salmeterol/FP) demonstrated 
an overall improvement in lung function over 24 hours for both treatments. The adjusted mean treatment 
difference of 22 mL (95% CI: -18, 63mL) between the groups was not statistically significant (p=0.282).  
The adjusted mean change from baseline in trough FEV1 on Day 85 was 111 mL in the fluticasone 
furoate/vilanterol group and 88 mL in the salmeterol/FP group; the 23 mL (95% CI: -20, 66) difference 
between the treatment groups was not clinically meaningful or statistically significant (p=0.294). 
No comparative studies versus salmeterol/FP or versus other established bronchodilators have been 
conducted to appropriately compare the effects on COPD exacerbations.  
 



19 

Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with Revinty 
Ellipta in all subsets of the paediatric population in COPD (see section 4.2 for information on paediatric use). 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with Revinty 
Ellipta in one or more subsets of the paediatric population in asthma (see section 4.2 for information on 
paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The absolute bioavailability for fluticasone furoate and vilanterol when administered by inhalation as 
fluticasone furoate/vilanterol was on average 15.2% and 27.3%, respectively. The oral bioavailability of both 
fluticasone furoate and vilanterol was low, on average 1.26% and <2%, respectively. Given this low oral 
bioavailability, systemic exposure for fluticasone furoate and vilanterol following inhaled administration is 
primarily due to absorption of the inhaled portion of the dose delivered to the lung. 
 
Distribution 
 
Following intravenous dosing, both fluticasone furoate and vilanterol are extensively distributed with 
average volumes of distribution at steady state of 661 L and 165 L, respectively. 
Both fluticasone furoate and vilanterol have a low association with red blood cells. In vitro plasma protein 
binding in human plasma of fluticasone furoate and vilanterol was high, on average >99.6% and 93.9%, 
respectively. There was no decrease in the extent of in vitro plasma protein binding in subjects with renal or 
hepatic impairment. 
Fluticasone furoate and vilanterol are substrates for P-glycoprotein (P-gp), however, concomitant 
administration of fluticasone furoate/vilanterol with P-gp inhibitors is considered unlikely to alter fluticasone 
furoate or vilanterol systemic exposure since they are both well absorbed molecules. 
 
Biotransformation 
 
Based on in vitro data, the major routes of metabolism of both fluticasone furoate and vilanterol in human 
are mediated primarily by CYP3A4. 
Fluticasone furoate is primarily metabolised through hydrolysis of the S-fluoromethyl carbothioate group to 
metabolites with significantly reduced corticosteroid activity. Vilanterol is primarily metabolised by 
O-dealkylation to a range of metabolites with significantly reduced 1- and 2-agonist activity. 
 
Elimination 
 
Following oral administration, fluticasone furoate was eliminated in humans mainly by metabolism with 
metabolites being excreted almost exclusively in faeces, with <1% of the recovered radioactive dose 
eliminated in the urine. 
 
Following oral administration, vilanterol was eliminated mainly by metabolism followed by excretion of 
metabolites in urine and faeces approximately 70% and 30% of the radioactive dose respectively in a human 
radiolabel study conducted by the oral route. The apparent plasma elimination half-life of vilanterol 
following single inhaled administration of fluticasone furoate/vilanterol was, on average, 2.5 hours.  The 
effective half-life for accumulation of vilanterol, as determined from inhalation administration of repeat 
doses of vilanterol 25 micrograms, is 16.0 hours in subjects with asthma and 21.3 hours in subjects with 
COPD. 
 
Paediatric population 
 
In adolescents (12 years or older), there are no recommended dose modifications. 



20 

The pharmacokinetics of fluticasone furoate/vilanterol in patients less than 12 years of age has not been 
studied. The safety and efficacy of fluticasone furoate/vilanterol in children under the age of 12 years has not 
yet been established.  
 

Special populations 
 

Elderly patients (> 65 years old) 
 
The effects of age on the pharmacokinetics of fluticasone furoate and vilanterol were determined in phase III 
studies in COPD and asthma. There was no evidence for age (12-84) to affect the pharmacokinetics of 
fluticasone furoate and vilanterol in subjects with asthma. 
 
There was no evidence for age to affect the pharmacokinetics of fluticasone furoate in subjects with COPD 
while there was an increase (37%) in AUC (0-24) of vilanterol over the observed age range of 41 to 84 years. 
For an elderly subject (aged 84 years) with low bodyweight (35 kg) vilanterol AUC (0-24) is predicted to be 
35% higher than the population estimate (subject with COPD aged 60 years and bodyweight of 70 kg), 
whilst Cmax was unchanged. These differences are unlikely to be of clinical relevance. 
In subjects with asthma and subjects with COPD there are no recommended dose modifications. 
 
Renal impairment 
 
A clinical pharmacology study of fluticasone furoate/vilanterol showed that severe renal impairment 
(creatinine clearance <30mL/min) did not result in significantly greater exposure to fluticasone furoate or 
vilanterol or more marked corticosteroid or beta2-agonist systemic effects compared with healthy subjects.  
 
No dose adjustment is required for patients with renal impairment. 
 
The effects of haemodialysis have not been studied. 
 
Hepatic impairment 
 
Following repeat dosing of fluticasone furoate/vilanterol for 7 days, there was an increase in fluticasone 
furoate systemic exposure (up to three-fold as measured by AUC(0–24)) in subjects with hepatic impairment 
(Child-Pugh A, B or C) compared with healthy subjects. The increase in fluticasone furoate systemic 
exposure in subjects with moderate hepatic impairment (Child-Pugh B; fluticasone furoate/vilanterol 
184/22 micrograms) was associated with an average 34% reduction in serum cortisol compared with healthy 
subjects. Dose-normalised fluticasone furoate systemic exposure was similar in subjects with moderate and 
severe hepatic impairment (Child-Pugh B or C). 
 
Following repeat dosing of fluticasone furoate/vilanterol for 7 days, there was no significant increase in 
systemic exposure to vilanterol (Cmax and AUC) in subjects with mild, moderate, or severe hepatic 
impairment (Child-Pugh A, B or C). 
 
There were no clinically relevant effects of the fluticasone furoate/vilanterol combination on beta-adrenergic 
systemic effects (heart rate or serum potassium) in subjects with mild or moderate hepatic impairment 
(vilanterol, 22 micrograms) or with severe hepatic impairment (vilanterol, 12.5 micrograms) compared with 
healthy subjects. 
 
Other special populations 
 
In subjects with asthma, estimates of fluticasone furoate AUC(0-24) for East Asian, Japanese and South East 
Asian subjects (12-13% of subjects) were on average 33% to 53% higher compared with other racial groups. 
However, there was no evidence for the higher systemic exposure in this population to be associated with 
greater effect on 24 hour urinary cortisol excretion. On average, vilanterol Cmax is predicted to be 220 to 
287% higher and AUC(0-24) comparable for those subjects from an Asian heritage compared with subjects 



21 

from other racial groups. However, there was no evidence that this higher vilanterol Cmax resulted in 
clinically significant effects on heart rate. 
In subjects with COPD estimates of fluticasone furoate AUC(0-24) for East Asian, Japanese and South East 
Asian subjects (13-14% subjects) were on average 23% to 30% higher compared with Caucasian subjects. 
However, there was no evidence for the higher systemic exposure in this population to be associated with 
greater effect on 24 hour urinary cortisol excretion. There was no effect of race on pharmacokinetic 
parameter estimates of vilanterol in subjects with COPD. 
 
Gender, weight and BMI 
 
There was no evidence for gender, weight or BMI (body mass index) to influence the pharmacokinetics of 
fluticasone furoate based on a population pharmacokinetic analysis of phase III data in 1213 subjects with 
asthma (712 females) and 1225 subjects with COPD (392 females).  
 
There was no evidence for gender, weight or BMI to influence the pharmacokinetics of vilanterol based on a 
population pharmacokinetic analysis in 856 subjects with asthma (500 females) and 1091 subjects with 
COPD (340 females). 
 
No dosage adjustment is necessary based on gender, weight or BMI. 
 
5.3 Preclinical safety data 
 
Pharmacological and toxicological effects seen with fluticasone furoate or vilanterol in nonclinical studies 
were those typically associated with either glucocorticoids or beta2-agonists. Administration of fluticasone 
furoate combined with vilanterol did not result in any significant new toxicity. 
 
Genotoxicity and carcinogenicity 
 
Fluticasone furoate 
 
Fluticasone furoate was not genotoxic in a standard battery of studies and was not carcinogenic in lifetime 
inhalation studies in rats or mice at exposures similar to those at the maximum recommended human dose, 
based on AUC.  
 
Vilanterol trifenatate 
 
In genetic toxicity studies, vilanterol (as alpha-phenylcinnamate) and triphenylacetic acid were not genotoxic 
indicating that vilanterol (as trifenatate) does not represent a genotoxic hazard to humans.  
 
Consistent with findings for other beta2 agonists, in lifetime inhalation studies vilanterol trifenatate caused 
proliferative effects in the female rat and mouse reproductive tract and rat pituitary gland. There was no 
increase in tumour incidence in rats or mice at exposures 2- or 30-fold, respectively, those at the maximum 
recommended human dose, based on AUC. 
 
Reproductive toxicity  
 
Fluticasone furoate 
 
Effects seen following inhalation administration of fluticasone furoate in combination with vilanterol in rats 
were similar to those seen with fluticasone furoate alone.  
Fluticasone furoate was not teratogenic in rats or rabbits, but delayed development in rats and caused 
abortion in rabbits at maternally toxic doses. There were no effects on development in rats at exposures 
approximately 3-times greater than those at the maximum recommended human dose, based on AUC. 
 
Vilanterol trifenatate 
 



22 

Vilanterol trifenatate was not teratogenic in rats. In inhalation studies in rabbits, vilanterol trifenatate caused 
effects similar to those seen with other beta2 agonists (cleft palate, open eyelids, sternebral fusion and limb 
flexure/malrotation). When given subcutaneously there were no effects at exposures 84-times greater than 
those at the maximum recommended human dose, based on AUC. 
Neither fluticasone furoate nor vilanterol trifenatate had any adverse effects on fertility or pre- and post-natal 
development in rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate  
Magnesium stearate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years 
In-use shelf-life after opening the tray: 6 weeks. 
 
6.4 Special precautions for storage 
 
Do not store above 25°C. If stored in a refrigerator allow the inhaler to return to room temperature for at least 
an hour before use. 
 
Store in the original package in order to protect from moisture. 
 
Write the date the inhaler should be discarded on the label in the space provided. The date should be added 
as soon as the inhaler has been removed from the tray. 

 
6.5 Nature and contents of container  
 
The inhaler consists of a light grey body, a yellow mouthpiece cover and a dose counter, packed into a foil 
laminate tray containing a silica gel desiccant sachet. The tray is sealed with a peelable foil lid.  
 
The inhaler is a multi-component device composed of polypropylene, high density polyethylene, 
polyoxymethylene, polybutylene terephthalate, acrylonitrile butadiene styrene, polycarbonate and stainless 
steel. 
 
The inhaler contains two aluminium foil laminate strips of 14 or 30 doses. 
 
Pack sizes of 14 or 30 dose Inhalers. Multipack of 3 x 30 dose Inhalers. 
 
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.  
 
 



23 

7. MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/929/001 
EU/1/14/929/002 
EU/1/14/929/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 May 2014 
Date of latest renewal: 26 July 2018 
 
 
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. 



24 

1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 184 micrograms/22 micrograms inhalation powder, pre-dispensed 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each single inhalation provides a delivered dose (the dose leaving the mouthpiece) of 184 micrograms of 
fluticasone furoate and 22 micrograms of vilanterol (as trifenatate). This corresponds to a pre-dispensed dose 
of 200 micrograms of fluticasone furoate and 25 micrograms vilanterol (as trifenatate). 
 
Excipients with known effect: 
 
Each delivered dose contains approximately 25 mg of lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Inhalation powder, pre-dispensed 
(Inhalation powder). 
 
White powder in a light grey inhaler with a yellow mouthpiece cover and a dose counter. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Asthma 
Revinty Ellipta is indicated for the regular treatment of asthma in adults and adolescents aged 12 years and 
older where use of a combination medicinal product (long-acting beta2-agonist and inhaled corticosteroid) is 
appropriate: 

 patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled short acting 
beta2-agonists. 

 patients already adequately controlled on both inhaled corticosteroid and long-acting beta2-agonist. 
 

4.2 Posology and method of administration 
 
Posology 
 
Asthma 
 
Patients with asthma should be given the strength of Revinty Ellipta containing the appropriate fluticasone 
furoate (FF) dosage for the severity of their disease. Prescribers should be aware that in patients with asthma, 
fluticasone furoate (FF) 100 micrograms once daily is approximately equivalent to fluticasone propionate 
(FP) 250 micrograms twice daily, while FF 200 micrograms once daily is approximately equivalent to FP 
500 micrograms twice daily. 
 
 
Adults and adolescents aged 12 years and over   
 
A starting dose of one inhalation of Revinty Ellipta 92/22 micrograms once daily should be considered for 
adults and adolescents 12 years and over who require a low to mid dose of inhaled corticosteroid in 
combination with a long-acting beta2-agonist. If patients are inadequately controlled on Revinty Ellipta 



25 

92/22 micrograms, the dose can be increased to 184/22 micrograms, which may provide additional 
improvement in asthma control. 
 
Patients should be regularly reassessed by a healthcare professional so that the strength of fluticasone 
furoate/vilanterol they are receiving remains optimal and is only changed on medical advice. The dose 
should be titrated to the lowest dose at which effective control of symptoms is maintained. 
 
Revinty Ellipta 184/22 micrograms should be considered for adults and adolescents 12 years and over who 
require a higher dose of inhaled corticosteroid in combination with a long-acting beta2-agonist. 
 
Patients usually experience an improvement in lung function within 15 minutes of inhaling Revinty Ellipta.  
However, the patient should be informed that regular daily usage is necessary to maintain control of asthma 
symptoms and that use should be continued even when asymptomatic. 
 
If symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be used for 
immediate relief. 
 
The maximum recommended dose is Revinty Ellipta 184/22 micrograms once daily. 
 
 
Children aged under 12 years 
 
The safety and efficacy of Revinty Ellipta in children under 12 years of age has not yet been established in 
the indication for asthma. 
No data are available. 
 
Special populations  
 
Elderly patients (>65 years) 
 
No dose adjustment is required in this population (see section 5.2). 
 
Renal impairment  
 
No dose adjustment is required in this population (see section 5.2). 
 
Hepatic impairment 
 
Studies in subjects with mild, moderate and severe hepatic impairment showed an increase in systemic 
exposure to fluticasone furoate (both Cmax and AUC) (see section 5.2). 
Caution should be exercised when dosing patients with hepatic impairment who may be more at risk of 
systemic adverse reactions associated with corticosteroids.  
For patients with moderate or severe hepatic impairment the maximum dose is 92/22 micrograms (see 
section 4.4).  
 
Method of administration  
 
Revinty Ellipta is for inhalation use only. 
 
It should be administered at the same time of the day, each day.  
The final decision on evening or morning dosing should be left to the discretion of the physician. 
 
If a dose is missed the next dose should be taken at the usual time the next day. 
 
If stored in a refrigerator, the inhaler should be allowed to return to room temperature for at least an hour 
before use. 
 



26 

When the inhaler is used for the first time, there is no need to check that it is working properly, and to 
prepare it for use in any special way. The step-by-step instructions should be followed. 
 
The Ellipta inhaler is packaged in a tray containing a desiccant sachet, to reduce moisture. The desiccant 
sachet should be thrown away and it should not be opened, eaten or inhaled. 
 
The patient should be advised to not open the tray until they are ready to inhale a dose.  
 
When the inhaler is taken out of its tray, it will be in the ‘closed’ position. The “Discard by” date should be 
written on the inhaler label in the space provided. The “Discard by” date is 6 weeks from the date of opening 
the tray. After this date the inhaler should no longer be used. The tray can be discarded after first opening. 
 
After inhalation, patients should rinse their mouth with water without swallowing. 
 
The step-by-step instructions shown below for the 30-dose Ellipta inhaler (30 day supply) also apply to the 
14-dose Ellipta inhaler (14 day supply). 
 
Instructions for use 
 
1. Read this before you start 
 
If the inhaler cover is opened and closed without inhaling the medicine, the dose will be lost. The lost dose 
will be securely held inside the inhaler, but it will no longer be available to be inhaled.  
It is not possible to accidentally take extra medicine or a double dose in one inhalation. 
 

 
 

 
2. How to prepare a dose 
 
Open the cover when ready to inhale a dose. Do not shake the inhaler. 
 
Slide the cover down until you hear a ‘click’. 
 
The medicine is now ready to be inhaled. The dose counter counts down by 1 to confirm. 
 
If the dose counter does not count down as you hear the ‘click’, the inhaler will not deliver medicine. Take it 
back to a pharmacist for advice. 

 



27 

 
 

 
3. How to inhale the medicine 
 
Hold the inhaler away from your mouth and breathe out as far as is comfortable. 
 
Do not breathe out into the inhaler. 
 
Put the mouthpiece between your lips and close your lips firmly around it. 
 
Do not block the air-vents with your fingers.  
 
Take one long, steady, deep breath in. Hold this breath for as long as possible (at least 3-4 seconds).  

 Remove the inhaler from your mouth. 
 Breathe out slowly and gently.  

 
 
It may not be possible to taste or feel the medicine, even when using the inhaler correctly. 
 
If you want to clean the mouthpiece, use a dry tissue, before closing the cover. 
 
 
 



28 

4. Close the inhaler and rinse your mouth  
 
 
Slide the cover upwards as far as it will go to cover the mouthpiece. 
 
Rinse your mouth with water after you have used the inhaler, do not swallow. 
 
This will make it less likely to develop a sore mouth or throat as side effects. 
 
 

 
 
 
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 
 
Deterioration of disease 
 
Fluticasone furoate/vilanterol should not be used to treat acute asthma symptoms, for which a short-acting 
bronchodilator is required.  Increasing use of short-acting bronchodilators to relieve symptoms indicates 
deterioration of control and patients should be reviewed by a physician.  
 
Patients should not stop therapy with fluticasone furoate/vilanterol in asthma, without physician supervision 
since symptoms may recur after discontinuation. 
 
Asthma-related adverse events and exacerbations may occur during treatment with fluticasone 
furoate/vilanterol. Patients should be asked to continue treatment but to seek medical advice if asthma 
symptoms remain uncontrolled or worsen after initiation of treatment with Revinty Ellipta. 
 
Paradoxical bronchospasm 
 
Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing.  This should be 
treated immediately with a short-acting inhaled bronchodilator. Revinty Ellipta should be discontinued 
immediately, the patient assessed and alternative therapy instituted if necessary. 
 



29 

Cardiovascular effects 
 
Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may 
be seen with sympathomimetic medicinal products including Revinty Ellipta. In a placebo-controlled study 
in subjects with moderate COPD and a history of, or an increased risk of cardiovascular disease, there was 
no increase in the risk of cardiovascular events in patients receiving fluticasone furoate/vilanterol compared 
with placebo (see section 5.1). However, fluticasone furoate/vilanterol should be used with caution in 
patients with severe cardiovascular disease or heart rhythm abnormalities, thyrotoxicosis, uncorrected 
hypokalaemia or patients predisposed to low levels of serum potassium. 
 
Patients with hepatic impairment 
 
For patients with moderate to severe hepatic impairment, the 92/22 micrograms dose should be used and 
patients should be monitored for systemic corticosteroid-related adverse reactions (see section 5.2). 
 
Systemic corticosteroid effects 
 
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long 
periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects 
include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, 
growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of 
psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, 
depression or aggression (particularly in children). 
 
Fluticasone furoate/vilanterol should be administered with caution in patients with pulmonary tuberculosis or 
in patients with chronic or untreated infections.  
 
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. 
 
Hyperglycaemia 
 
There have been reports of increases in blood glucose levels in diabetic patients and this should be 
considered when prescribing to patients with a history of diabetes mellitus. 
 
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. 
 



30 

Pneumonia in patients with asthma 
 
The incidence of pneumonia in patients with asthma was common at the higher dose. The incidence of 
pneumonia in patients with asthma taking fluticasone furoate/vilanterol 184/22 micrograms was numerically 
higher compared with those receiving fluticasone furoate/vilanterol 92/22 micrograms or placebo (see 
section 4.8).  No risk factors were identified. 
 
Excipients 
 
Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-
galactose malabsorption should not use this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Clinically significant drug interactions mediated by fluticasone furoate/vilanterol at clinical doses are 
considered unlikely due to the low plasma concentrations achieved after inhaled dosing. 
 
Interaction with beta-blockers 
 
Beta2-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists. Concurrent use 
of both non-selective and selective beta2-adrenergic blockers should be avoided unless there are compelling 
reasons for their use. 
 
Interaction with CYP3A4 inhibitors 
 
Fluticasone furoate and vilanterol are both rapidly cleared by extensive first pass metabolism mediated by 
the liver enzyme CYP3A4.  
 
Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir, 
cobicistat-containing products) as there is potential for increased systemic exposure to both fluticasone 
furoate and vilanterol. Co-administration should be avoided unless the benefit outweighs the increased risk 
of systemic corticosteroid undesirable effects, in which case patients should be monitored for systemic 
corticosteroid undesirable effects. A repeat dose CYP3A4 drug interaction study was performed in healthy 
subjects with the fluticasone furoate/vilanterol combination (184/22 micrograms) and the strong CYP3A4 
inhibitor ketoconazole (400mg).  Co-administration increased mean fluticasone furoate AUC(0-24) and Cmax by 
36% and 33%, respectively.  The increase in fluticasone furoate exposure was associated with a 27% 
reduction in 0-24 hours weighted mean serum cortisol. Co-administration increased mean vilanterol AUC(0-t) 
and Cmax 65% and 22%, respectively.  The increase in vilanterol exposure was not associated with an 
increase in beta2-agonist related systemic effects on heart rate, blood potassium or QTcF interval.  
 
Interaction with P-glycoprotein inhibitors 
 
Fluticasone furoate and vilanterol are both substrates of P-glycoprotein (P-gp). A clinical pharmacology 
study in healthy subjects with co-administered vilanterol and the potent P-gp and moderate CYP3A4 
inhibitor verapamil did not show any significant effect on the pharmacokinetics of vilanterol. Clinical 
pharmacology studies with a specific P-gp inhibitor and fluticasone furoate have not been conducted. 
 
Sympathomimetic medicinal products 
 
Concomitant administration of other sympathomimetic medicinal products (alone or as part of combination 
therapy) may potentiate the adverse reactions of fluticasone furoate/vilanterol.  Revinty Ellipta should not be 
used in conjunction with other long-acting beta2-adrenergic agonists or medicinal products containing long-
acting beta2-adrenergic agonists. 
 



31 

Paediatric population 
 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
Studies in animals have shown reproductive toxicity at exposures which are not clinically relevant (see 
section 5.3). There are no or limited data from the use of fluticasone furoate and vilanterol trifenatate in 
pregnant women. 
 
Administration of fluticasone furoate/vilanterol to pregnant women should only be considered if the 
expected benefit to the mother is greater than any possible risk to the foetus. 
 
Breast-feeding 
 
There is insufficient information on the excretion of fluticasone furoate or vilanterol trifenatate and/or 
metabolites in human milk. However, other corticosteroids and beta2-agonists are detected in human milk 
(see section 5.3). A risk to breastfed newborns/infants cannot be excluded. 
 
A decision must be made whether to discontinue breast-feeding or to discontinue fluticasone 
furoate/vilanterol therapy taking into account the benefit of breast-feeding for the child and the benefit of 
therapy for the woman. 
 
Fertility 
 
There are no fertility data in humans. Animal studies showed no effect of fluticasone furoate/vilanterol 
trifenatate on fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Fluticasone furoate or vilanterol has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Data from large asthma and COPD clinical trials were used to determine the frequency of adverse reactions 
associated with fluticasone furoate/vilanterol. In the asthma clinical development program a total of 7,034 
patients were included in an integrated assessment of adverse reactions. In the COPD clinical development 
programme a total of 6,237 subjects were included in an integrated assessment of adverse reactions. 
 
The most commonly reported adverse reactions with fluticasone furoate and vilanterol were headache and 
nasopharyngitis. With the exception of pneumonia and fractures, the safety profile was similar in patients 
with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently commonly 
observed in patients with COPD.  
 
Tabulated list of adverse reactions 
 
Adverse reactions are listed by system organ class and frequency. The following convention has been used 
for the classification of frequencies: 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).Within each frequency grouping, 
adverse reactions are presented in order of decreasing seriousness. 
 



32 

System organ class Adverse reaction(s) Frequency 
Infections and infestations Pneumonia*  

Upper respiratory tract infection 

Bronchitis  

Influenza 

Candidiasis of mouth and throat 

Common 

 

Immune system disorders Hypersensitivity reactions including 
anaphylaxis, angioedema, rash, and 
urticaria. 

Rare 

Metabolism and nutrition 
disorders 

Hyperglycaemia Uncommon 

Psychiatric disorders Anxiety Rare 

Nervous system disorders Headache 

Tremor 

Very common 

Rare 

Eye disorders Vision blurred (see section 4.4) Uncommon 

   

Cardiac disorders Extrasystoles  

Palpitations 

Tachycardia 

Uncommon  

Rare 

Rare 

Respiratory, thoracic and 
mediastinal disorders 

Nasopharyngitis  

Paradoxical bronchospasm 

Oropharyngeal pain 

Sinusitis  

Pharyngitis 

Rhinitis  

Cough  

Dysphonia 

Very common 

Rare 

Common 

 

 

Gastrointestinal disorders Abdominal pain Common 

Musculoskeletal and 
connective tissue disorders 

Arthralgia 

Back pain 

Fractures**  

Muscle spasms 

Common 

 

General disorders and 
administration site conditions 

Pyrexia  Common 

 
*, ** See below ‘Description of selected adverse reactions’ 
 
*Pneumonia (see section 4.4) 
 
In an integrated analysis of the two replicate one year studies in moderate to severe COPD (mean predicted 
post-bronchodilator screening FEV1 of 45%, standard deviation (SD) 13%) with an exacerbation in the 
preceding year (n = 3255), the number of pneumonia events per 1000 patient years was 97.9  with FF/VI 



33 

184/22, 85.7 in the FF/VI 92/22 and 42.3 in the VI 22 group. For severe pneumonia the corresponding 
number of events per 1000 patient years were 33.6, 35.5, and 7.6 respectively, while for serious pneumonia 
the corresponding events per 1000 patient years were 35.1 for FF/VI 184/22, 42.9 with FF/VI 92/22, 12.1 
with VI 22. Finally, the exposure-adjusted cases of fatal pneumonia were 8.8 for FF/VI 184/22 versus 1.5 for 
FF/VI 92/22 and 0 for VI 22.  
 
In a placebo-controlled study (SUMMIT) in subjects with moderate COPD (mean percent post-
bronchodilator screening FEV1 of 60%, SD 6%), and a history of, or an increased risk of cardiovascular 
disease, the incidence of pneumonia with FF/VI, FF, VI and placebo was: adverse events (6%, 5%, 4%, 5%); 
serious adverse events (3%, 4%, 3%, 3%); adjudicated on treatment deaths due to pneumonia (0.3%, 0.2%, 
0.1%, 0.2%); the exposure adjusted rates (per 1000 treatment years) were: adverse events (39.5, 42.4, 27.7, 
38.4); serious adverse events (22.4, 25.1, 16.4, 22.2); adjudicated on-treatment deaths due to pneumonia (1.8, 
1.5, 0.9, 1.4) respectively. 
 
In an integrated analysis of 11 studies in asthma (7,034 patients), the incidence of pneumonia per 1000 
patient years was 18.4 for FF/VI 184/22 versus 9.6 for FF/VI 92/22 and 8.0 in the placebo group. 
 
**Fractures 
 
In two replicate 12 month studies in a total of 3,255 patients with COPD the incidence of bone fractures 
overall was low in all treatment groups, with a higher incidence in all Revinty Ellipta groups (2%) compared 
with the vilanterol 22 micrograms group (<1%).  Although there were more fractures in the Revinty Ellipta 
groups compared with the vilanterol 22 micrograms group, fractures typically associated with corticosteroid 
use (e.g., spinal compression/thoracolumbar vertebral fractures, hip and acetabular fractures) occurred in 
<1% of the Revinty Ellipta and vilanterol treatment arms. 
 
For the SUMMIT study, the incidence of all events of fracture with FF/VI, FF, VI and placebo were 2% in 
each arm; fractures commonly associated with ICS use were less than 1 % in each arm. The exposure-
adjusted rates (per 1000 treatment years) for all fracture events were 13.6, 12.8, 13.2, 11.5 respectively; 
fractures commonly associated with ICS use were 3.4, 3.9, 2.4, 2.1 respectively. 
 
In an integrated analysis of 11 studies in asthma (7,034 patients), the incidence of fractures was <1%, and 
usually associated with trauma. 
 
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 
 
Symptoms and signs 
 
An overdose of fluticasone furoate/vilanterol may produce signs and symptoms due to the individual 
component’s actions, including those seen with overdose of other beta2-agonists and consistent with the 
known inhaled corticosteroid class effects (see section 4.4). 
 
Treatment 
 
There is no specific treatment for an overdose with fluticasone furoate/vilanterol. If overdose occurs, the 
patient should be treated supportively with appropriate monitoring as necessary.  
 
Cardioselective beta-blockade should only be considered for profound vilanterol overdose effects that are 
clinically concerning and unresponsive to supportive measures. Cardioselective beta-blocking medicinal 
products should be used with caution in patients with a history of bronchospasm. 



34 

 
Further management should be as clinically indicated or as recommended by the national poisons centre, 
where available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs for obstructive airways diseases, adrenergics in combination with 
corticosteroids or other drugs, excl. anticholinergics, ATC code: R03AK10. 
 
Mechanism of action 
 
Fluticasone furoate and vilanterol represent two classes of medications (a synthetic corticosteroid and a 
selective, long-acting beta2-receptor agonist). 
 
Pharmacodynamic effects 
 
Fluticasone furoate 
 
Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. The 
precise mechanism through which fluticasone furoate affects asthma and COPD symptoms is not known. 
Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g. eosinophils, 
macrophages, lymphocytes) and mediators (e.g. cytokines and chemokines involved in inflammation). 
 
Vilanterol trifenatate 
 
Vilanterol trifenatate is a selective long-acting, beta2-adrenergic agonist (LABA).  
The pharmacologic effects of beta2-adrenoceptor agonist active substance, including vilanterol trifenatate, 
are at least in part attributable to stimulation of intracellular adenylate cyclase, the enzyme that catalyzes the 
conversion of adenosine triphosphate (ATP) to cyclic-3’,5’-adenosine monophosphate (cyclic AMP). 
Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of 
mediators of immediate hypersensitivity from cells, especially from mast cells. 
 
Molecular interactions occur between corticosteroids and LABAs, whereby steroids activate the beta2-
receptor gene, increasing receptor number and sensitivity and LABAs prime the glucocorticoid receptor for 
steroid-dependent activation and enhance cell nuclear translocation. These synergistic interactions are 
reflected in enhanced anti-inflammatory activity, which has been demonstrated in vitro and in vivo in a range 
of inflammatory cells relevant to the pathophysiology of both asthma and COPD.  In peripheral blood 
mononuclear cells from subjects with COPD, a larger anti-inflammatory effect was seen in the presence of 
the combination of fluticasone furoate/vilanterol compared with fluticasone furoate alone at concentrations 
achieved with clinical doses. The enhanced anti-inflammatory effect of the LABA component was similar to 
that obtained with other ICS/LABA combinations. 
 
Clinical efficacy and safety 
 
Asthma 
 
Three phase III randomised, double-blind studies (HZA106827, HZA106829 and HZA106837) of different 
durations evaluated the safety and efficacy of fluticasone furoate/vilanterol in adult and adolescent patients 
with persistent asthma.  All subjects were using an ICS (Inhaled corticosteroid) with or without LABA for at 
least 12 weeks prior to visit 1. In HZA106837 all patients had at least one exacerbation that required 
treatment with oral corticosteroids in the year prior to visit 1.  HZA106827 was 12 weeks in duration and 
evaluated the efficacy of fluticasone furoate/vilanterol 92/22 micrograms [n=201] and FF 92 micrograms 
[n=205]) compared with placebo [n=203], all administered once daily. HZA106829 was 24 weeks in 



35 

duration and evaluated the efficacy of fluticasone furoate/vilanterol 184/22 micrograms [n=197] and FF 
184 micrograms [n=194]) both administered once daily compared with FP 500 micrograms twice daily 
[n=195].  
 
In HZA106827/HZA106829 the co-primary efficacy endpoints were change from baseline in clinic visit 
trough (pre-bronchodilator and pre-dose) FEV1 at the end of the treatment period in all subjects and weighted 
mean serial FEV1 over 0-24 hours post-dose calculated in a subset of subjects at the end of the treatment 
period. Change from baseline in the percentage of rescue-free 24 hour periods during treatment was a 
powered secondary endpoint.  Results for the primary and key secondary endpoints in these studies are 
described in Table 1. 

Table 1 - Results of primary and key secondary endpoints in HZA106827 and HZA106829 

Study No. HZA106829 HZA106827 
Treatment Dose of 
FF/VI*(micrograms) 

FF/VI 184/22 
Once Daily vs 
FF 184 Once 

Daily 

FF/VI 184/22 
Once Daily 
vs FP 500 

Twice Daily 

FF/VI 92/22 
Once Daily 

vs FF 92 
Once Daily 

FF/VI 92/22 
Once Daily 
vs placebo 
Once Daily 

Change from Baseline in Trough FEV1 Last Observation Carried Forward (LOCF) 
Treatment difference 
P value  
(95% CI)  

193mL 
p<0.001 

(108, 277) 

210mL 
p<0.001 

(127, 294) 

36mL 
p=0.405 

(-48, 120) 

172mL 
p<0.001 
(87, 258) 

Weighted Mean Serial FEV1 over 0-24 hours post-dose 
Treatment difference 
P value 
(95% CI) 

136mL 
p=0.048 
(1, 270) 

206mL 
p=0.003 
(73, 339) 

116mL 
p=0.06 

(-5, 236) 

302mL 
p<0.001 

(178, 426) 
Change from Baseline in Percentage of Rescue-Free 24-hour Periods 
Treatment difference 
P value  
(95% CI) 

11.7% 
p<0.001 

(4.9, 18.4) 

6.3% 
p=0.067 

(-0.4, 13.1) 

10.6% 
p<0.001 

(4.3, 16.8) 

19.3% 
p<0.001 

(13.0, 25.6) 
Change from Baseline in Percentage of Symptom-Free 24-hour Periods 
Treatment difference 
P value  
(95% CI) 

8.4% 
p=0.010 

(2.0, 14.8) 

4.9% 
p=0.137 

(-1.6, 11.3) 

12.1% 
p<0.001 

(6.2, 18.1) 

18.0% 
p<0.001 

(12.0, 23.9) 
Change from Baseline in AM Peak Expiratory Flow 
Treatment difference 
P value  
(95% CI) 

33.5L/min 
p<0.001 

(22.3, 41.7) 

32.9L/min 
p<0.001 

(24.8, 41.1) 

14.6L/min 
p<0.001 

(7.9, 21.3) 

33.3L/min 
p<0.001 

(26.5, 40.0) 
Change from Baseline in PM Peak Expiratory Flow 
Treatment difference 
P value  
(95% CI) 

30.7L/min 
p<0.001 

(22.5, 38.9) 

26.2L/min  
p<0.001 

(18.0, 34.3) 

12.3L/min 
p<0.001 

(5.8, 18.8) 

28.2L/min 
p<0.001 

(21.7, 34.8) 
*FF/VI = fluticasone furoate/vilanterol 
 
HZA106837 was of variable treatment duration (from a minimum of 24 weeks to a maximum of 76 weeks 
with the majority of patients treated for at least 52 weeks).  In HZA106837 patients were randomised to 
receive either fluticasone furoate/vilanterol 92/22 micrograms [n=1009] or FF 92 micrograms [n=1010] both 
administered once daily.  In HZA106837 the primary endpoint was the time to first severe asthma 
exacerbation.  A severe asthma exacerbation was defined as deterioration of asthma requiring the use of 
systemic corticosteroids for at least 3 days or an inpatient hospitalization or emergency department visit due 
to asthma that required systemic corticosteroids. Adjusted mean change from baseline in trough FEV1 was 
also evaluated as a secondary endpoint. 
 
In HZA106837 the risk of experiencing a severe asthma exacerbation in patients receiving fluticasone 
furoate/vilanterol 92/22 micrograms was reduced by 20% compared with FF 92 micrograms alone (hazard 
ratio 0.795, p=0.036 95% CI 0.642, 0.985). The rate of severe asthma exacerbations per patient per year was 



36 

0.19 in the FF 92 group (approximately 1 in every 5 years) and 0.14 in the fluticasone furoate/vilanterol 
92/22 micrograms group (approximately 1 in every 7 years).  The ratio of the exacerbation rate for 
fluticasone furoate/vilanterol 92/22 micrograms versus FF 92 was 0.755 (95% CI 0.603, 0.945). This 
represents a 25% reduction in the rate of severe asthma exacerbations for subjects treated with fluticasone 
furoate/vilanterol 92/22 micrograms compared with FF 92 (p=0.014). The 24-hour bronchodilator effect of 
fluticasone furoate/vilanterol was maintained throughout a one-year treatment period with no evidence of 
loss in efficacy (no tachyphylaxis). Fluticasone furoate/vilanterol 92 /22 micrograms consistently 
demonstrated 83 mL to 95 mL improvements in trough FEV1 at weeks 12, 36 and 52 and Endpoint compared 
with FF 92 micrograms (p<0.001 95% CI 52, 126 mL at Endpoint).  Forty four percent of patients in the 
fluticasone furoate/vilanterol 92/22 group were well controlled (ACQ7 ≤0.75) at end of treatment compared 
to 36% of subjects in the FF 92 micrograms group (p<0.001 95% CI 1.23, 1.82). 
 
Studies versus salmeterol/fluticasone propionate combinations 
 
In a 24 week study (HZA113091) in adult and adolescent patients with uncontrolled persistent asthma both 
fluticasone furoate/vilanterol 92/22 micrograms given once daily in the evening and salmeterol/FP 
50/250 micrograms given twice daily demonstrated improvements from baseline in lung function. Adjusted 
mean treatment increases from baseline in weighted mean 0-24 hours FEV1 of 341 mL (fluticasone 
furoate/vilanterol) and 377 mL (salmeterol/FP) demonstrated an overall improvement in lung function over 
24 hours for both treatments.  The adjusted mean treatment difference of -37 mL between the groups was not 
statistically significant (p=0.162). For trough FEV1 subjects in the fluticasone furoate/vilanterol group 
achieved a LS mean change from baseline of 281 mL and subjects in the salmeterol/FP group a change of 
300 mL; (the difference in adjusted mean of -19 mL (95%CI:-0.073, 0.034) was not statistically significant 
(p=0.485). 
 
A randomised, double-blind, parallel group, 24 week study (201378) was conducted to demonstrate non-
inferiority (using a margin of -100 mL for trough FEV1) of fluticasone furoate/vilanterol 92/22 once daily to 
salmeterol/FP 50/250 twice daily in adults and adolescents whose asthma was well controlled following 4 
weeks of treatment with open-label salmeterol/FP 50/250 twice daily (N=1504). Subjects randomised to 
once-daily FF/VI maintained lung function comparable with those randomised to twice-daily salmeterol/FP 
[difference in trough FEV1 of +19 mL (95% CI: -11, 49)]. 
 
No comparative studies versus salmeterol/FP or versus other ICS/LABA combinations have been conducted 
to appropriately compare the effects of asthma exacerbations. 
 
Fluticasone furoate monotherapy 
 
A 24 week randomised, double-blind placebo controlled study (FFA112059) evaluated the safety and 
efficacy of FF 92 micrograms once daily [n= 114] and FP 250 micrograms twice daily [n=114] versus 
placebo [n=115] in adult and adolescent patients with persistent asthma.  All subjects had to have been on a 
stable dose of an ICS for at least 4 weeks prior to visit 1 (screening visit) and the use of LABAs was not 
permitted within 4 weeks of visit 1. The primary efficacy endpoint was change from baseline in clinic visit 
trough (pre-bronchodilator and pre-dose) FEV1 at the end of the treatment period. Change from baseline in 
the percentage of rescue-free 24 hour periods during the 24-week treatment period was a powered secondary.  
At the 24-week time point FF and FP increased trough FEV1 by 146 mL (95% CI 36, 257 mL, p=0.009) and 
145 mL (95% CI 33, 257 mL, p=0.011) respectively compared to placebo. FF and FP both increased the 
percentage of 24 hour rescue free periods by 14.8% (95% CI 6.9, 22.7, p<0.001) and 17.9% (95% CI 10.0, 
25.7, p<0.001) respectively versus placebo.  
 
Allergen challenge study 
 
The bronchoprotective effect of fluticasone furoate/vilanterol 92/22 micrograms on the early and late 
asthmatic response to inhaled allergen was evaluated in a repeat dose, placebo-controlled four-way crossover 
study (HZA113126) in patients with mild asthma.  Patients were randomized to receive fluticasone 
furoate/vilanterol 92/22 micrograms, FF 92 micrograms, vilanterol 22 micrograms or placebo once daily for 
21 days followed by challenge with allergen 1 hour after the final dose. The allergen was house dust mite, cat 



37 

dander, or birch pollen; the selection was based on individual screening tests.  Serial FEV1 measurements 
were compared with pre-allergen challenge values taken after saline inhalation (baseline).  Overall, the 
greatest effects on the early asthmatic response were seen with fluticasone furoate/vilanterol 
92/22 micrograms compared with FF 92 micrograms or vilanterol 22 micrograms alone. Both fluticasone 
furoate/vilanterol 92/22 micrograms and FF 92 micrograms virtually abolished the late asthmatic response 
compared with vilanterol alone. Fluticasone furoate/vilanterol 92/22 micrograms provided significantly 
greater protection against allergen-induced bronchial hyper-reactivity compared with monotherapies FF and 
vilanterol as assessed on Day 22 by methacholine challenge. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with Revinty 
Ellipta in one or more subsets of the paediatric population in asthma (see section 4.2 for information on 
paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The absolute bioavailability for fluticasone furoate and vilanterol when administered by inhalation as 
fluticasone furoate/vilanterol was on average 15.2% and 27.3%, respectively. The oral bioavailability of both 
fluticasone furoate and vilanterol was low, on average 1.26% and <2%, respectively. Given this low oral 
bioavailability, systemic exposure for fluticasone furoate and vilanterol following inhaled administration is 
primarily due to absorption of the inhaled portion of the dose delivered to the lung. 
 
Distribution 
 
Following intravenous dosing, both fluticasone furoate and vilanterol are extensively distributed with 
average volumes of distribution at steady state of 661 L and 165 L, respectively. 
Both fluticasone furoate and vilanterol have a low association with red blood cells. In vitro plasma protein 
binding in human plasma of fluticasone furoate and vilanterol was high, on average >99.6% and 93.9%, 
respectively. There was no decrease in the extent of in vitro plasma protein binding in subjects with renal or 
hepatic impairment. 
Fluticasone furoate and vilanterol are substrates for P-glycoprotein (P-gp), however, concomitant 
administration of fluticasone furoate/vilanterol with P-gp inhibitors is considered unlikely to alter fluticasone 
furoate or vilanterol systemic exposure since they are both well absorbed molecules. 
 
Biotransformation 
 
Based on in vitro data, the major routes of metabolism of both fluticasone furoate and vilanterol in human 
are mediated primarily by CYP3A4. 
Fluticasone furoate is primarily metabolised through hydrolysis of the S-fluoromethyl carbothioate group to 
metabolites with significantly reduced corticosteroid activity. Vilanterol is primarily metabolised by 
O-dealkylation to a range of metabolites with significantly reduced 1- and 2-agonist activity. 
 
Elimination 
 
Following oral administration, fluticasone furoate was eliminated in humans mainly by metabolism with 
metabolites being excreted almost exclusively in faeces, with <1% of the recovered radioactive dose 
eliminated in the urine. 
 
Following oral administration, vilanterol was eliminated mainly by metabolism followed by excretion of 
metabolites in urine and faeces approximately 70% and 30% of the radioactive dose respectively in a human 
radiolabel study conducted by the oral route. The apparent plasma elimination half-life of vilanterol 
following single inhaled administration of fluticasone furoate/vilanterol was, on average, 2.5 hours.  The 
effective half-life for accumulation of vilanterol, as determined from inhalation administration of repeat 



38 

doses of vilanterol 25 micrograms, is 16.0 hours in subjects with asthma and 21.3 hours in subjects with 
COPD. 
 
Paediatric population 
 
In adolescents (12 years or older), there are no recommended dose modifications. 
The pharmacokinetics of fluticasone furoate/vilanterol in patients less than 12 years of age has not been 
studied. The safety and efficacy of fluticasone furoate/vilanterol in children under the age of 12 years has not 
yet been established.  
 

Special populations 
 

Elderly patients (> 65 years old) 
 
The effects of age on the pharmacokinetics of fluticasone furoate and vilanterol were determined in phase III 
studies in COPD and asthma. There was no evidence for age (12-84) to affect the pharmacokinetics of 
fluticasone furoate and vilanterol in subjects with asthma. 
 
In subjects with asthma and subjects with COPD there are no recommended dose modifications. 
 
Renal impairment 
 
A clinical pharmacology study of fluticasone furoate/vilanterol showed that severe renal impairment 
(creatinine clearance <30mL/min) did not result in significantly greater exposure to fluticasone furoate or 
vilanterol or more marked corticosteroid or beta2-agonist systemic effects compared with healthy subjects.  
 
No dose adjustment is required for patients with renal impairment. 
 
The effects of haemodialysis have not been studied. 
 
Hepatic impairment 
 
Following repeat dosing of fluticasone furoate/vilanterol for 7 days, there was an increase in fluticasone 
furoate systemic exposure (up to three-fold as measured by AUC(0–24)) in subjects with hepatic impairment 
(Child-Pugh A, B or C) compared with healthy subjects. The increase in fluticasone furoate systemic 
exposure in subjects with moderate hepatic impairment (Child-Pugh B; fluticasone furoate/vilanterol 
184/22 micrograms) was associated with an average 34% reduction in serum cortisol compared with healthy 
subjects. Dose-normalised fluticasone furoate systemic exposure was similar in subjects with moderate and 
severe hepatic impairment (Child-Pugh B or C). 
 
Following repeat dosing of fluticasone furoate/vilanterol for 7 days, there was no significant increase in 
systemic exposure to vilanterol (Cmax and AUC) in subjects with mild, moderate, or severe hepatic 
impairment (Child-Pugh A, B or C). 
 
There were no clinically relevant effects of the fluticasone furoate/vilanterol combination on beta-adrenergic 
systemic effects (heart rate or serum potassium) in subjects with mild or moderate hepatic impairment 
(vilanterol, 22 micrograms) or with severe hepatic impairment (vilanterol, 12.5 micrograms) compared with 
healthy subjects. 
 
Other special populations 
 
In subjects with asthma, estimates of fluticasone furoate AUC(0-24) for East Asian, Japanese and South East 
Asian subjects (12-13% of subjects) were on average 33% to 53% higher compared with other racial groups. 
However, there was no evidence for the higher systemic exposure in this population to be associated with 
greater effect on 24 hour urinary cortisol excretion. On average, vilanterol Cmax is predicted to be 220 to 



39 

287% higher and AUC(0-24) comparable for those subjects from an Asian heritage compared with subjects 
from other racial groups. However, there was no evidence that this higher vilanterol Cmax resulted in 
clinically significant effects on heart rate. 
 
Gender, weight and BMI 
 
There was no evidence for gender, weight or BMI (body mass index) to influence the pharmacokinetics of 
fluticasone furoate based on a population pharmacokinetic analysis of phase III data in 1213 subjects with 
asthma (712 females).  
 
There was no evidence for gender, weight or BMI to influence the pharmacokinetics of vilanterol based on a 
population pharmacokinetic analysis in 856 subjects with asthma (500 females). 
 
No dosage adjustment is necessary based on gender, weight or BMI. 
 
5.3 Preclinical safety data 
 
Pharmacological and toxicological effects seen with fluticasone furoate or vilanterol in nonclinical studies 
were those typically associated with either glucocorticoids or beta2-agonists. Administration of fluticasone 
furoate combined with vilanterol did not result in any significant new toxicity. 
 
Genotoxicity and carcinogenicity 
 
Fluticasone furoate 
 
Fluticasone furoate was not genotoxic in a standard battery of studies and was not carcinogenic in lifetime 
inhalation studies in rats or mice at exposures similar to those at the maximum recommended human dose, 
based on AUC.  
 
Vilanterol trifenatate 
 
In genetic toxicity studies, vilanterol (as alpha-phenylcinnamate) and triphenylacetic acid were not genotoxic 
indicating that vilanterol (as trifenatate) does not represent a genotoxic hazard to humans.  
 
Consistent with findings for other beta2 agonists, in lifetime inhalation studies vilanterol trifenatate caused 
proliferative effects in the female rat and mouse reproductive tract and rat pituitary gland. There was no 
increase in tumour incidence in rats or mice at exposures 2- or 30-fold, respectively, those at the maximum 
recommended human dose, based on AUC. 
 
Reproductive toxicity  
 
Fluticasone furoate 
 
Effects seen following inhalation administration of fluticasone furoate in combination with vilanterol in rats 
were similar to those seen with fluticasone furoate alone.  
Fluticasone furoate was not teratogenic in rats or rabbits, but delayed development in rats and caused 
abortion in rabbits at maternally toxic doses. There were no effects on development in rats at exposures 
approximately 3-times greater than those at the maximum recommended human dose, based on AUC. 
 
Vilanterol trifenatate 
 
Vilanterol trifenatate was not teratogenic in rats. In inhalation studies in rabbits, vilanterol trifenatate caused 
effects similar to those seen with other beta2 agonists (cleft palate, open eyelids, sternebral fusion and limb 
flexure/malrotation). When given subcutaneously there were no effects at exposures 84-times greater than 
those at the maximum recommended human dose, based on AUC. 



40 

Neither fluticasone furoate nor vilanterol trifenatate had any adverse effects on fertility or pre- and post-natal 
development in rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate  
Magnesium stearate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years 
In-use shelf-life after opening the tray: 6 weeks. 
 
6.4 Special precautions for storage 
 
Do not store above 25°C. If stored in a refrigerator allow the inhaler to return to room temperature for at least 
an hour before use. 
 
Store in the original package in order to protect from moisture. 
 
Write the date the inhaler should be discarded on the label in the space provided. The date should be added 
as soon as the inhaler has been removed from the tray. 

 
6.5 Nature and contents of container  
 
The inhaler consists of a light grey body, a yellow mouthpiece cover and a dose counter, packed into a foil 
laminate tray containing a silica gel desiccant sachet. The tray is sealed with a peelable foil lid.  
 
The inhaler is a multi-component device composed of polypropylene, high density polyethylene, 
polyoxymethylene, polybutylene terephthalate, acrylonitrile butadiene styrene, polycarbonate and stainless 
steel. 
 
The inhaler contains two aluminium foil laminate strips of 14 or 30 doses. 
 
Pack sizes of 14 or 30 dose Inhalers. Multipack of 3 x 30 dose Inhalers. 
 
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.  
 
 
 



41 

7. MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/929/004 
EU/1/14/929/005 
EU/1/14/929/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 May 2014 
Date of latest renewal: 26 July 2018 
 
 
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 



42 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 



43 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturers responsible for batch release 

Glaxo Operations UK Ltd. (trading as Glaxo Wellcome Operations) 
Priory Street 
Ware, Hertfordshire SG12 0DJ 
United Kingdom. 

Glaxo Operations UK Ltd. (trading as Glaxo Wellcome Operations), 
Harmire Road, 
Barnard Castle,  
County Durham DL12 8DT  
United Kingdom. 

 
  Glaxo Wellcome Production 
  Zone Industrielle No.2, 
  23 Rue Lavoisier,  
  27000 Evreux,  
  France 
 

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 products 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 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.  

 
 



44 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 



45 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



46 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON (SINGLE PACKS) 
 
92/22 micrograms  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 92 micrograms/22 micrograms inhalation powder, pre-dispensed  
 
fluticasone furoate/vilanterol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each delivered dose contains 92 micrograms of fluticasone furoate and 22 micrograms of vilanterol (as 
trifenatate). 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and magnesium stearate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder, pre-dispensed. 
14 doses 
30 doses 
1 inhaler of 14 doses 
1 inhaler of 30 doses 

 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
ONCE DAILY 
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 



47 

In use shelf-life: 6 weeks. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from moisture. 
 
 
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 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
GlaxoSmithKline (Ireland) Limited logo 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/929/001 
EU/1/14/929/002 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
revinty ellipta 92:22  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



48 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
BUNDLE LABEL (WITH BLUE BOX- MULTIPACK) 
 
92/22 micrograms  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 92 micrograms/22 micrograms inhalation powder, pre-dispensed  
fluticasone furoate/vilanterol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each delivered dose contains 92 micrograms of fluticasone furoate and 22 micrograms of vilanterol (as 
trifenatate). 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and magnesium stearate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder, pre-dispensed. 
Multipack: 90 (3 packs of 30) doses 

 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
ONCE DAILY 
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 
In use shelf-life: 6 weeks. 
 
 



49 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from moisture. 
 
 
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 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
GlaxoSmithKline (Ireland) Limited logo 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/929/003 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
revinty ellipta 92:22  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



50 

 
PARTICULARS TO APPEAR ON  THE OUTER PACKAGING  
 
OUTER CARTON (SINGLE PACK) 
 
184/22 micrograms  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 184 micrograms/22 micrograms inhalation powder, pre-dispensed 
 
fluticasone furoate/vilanterol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each delivered dose contains 184 micrograms of fluticasone furoate and 22 micrograms of vilanterol (as 
trifenatate).  
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and magnesium stearate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder, pre-dispensed. 
14 doses 
30 doses 
1 inhaler of 14 doses  
1 inhaler of 30 doses  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
ONCE DAILY 
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 
In use shelf-life: 6 weeks. 



51 

 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from moisture. 
 
 
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 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
GlaxoSmithKline (Ireland) Limited logo 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/929/004 
EU/1/14/929/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
revinty ellipta 184:22 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN:



52 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
BUNDLE LABEL (WITH BLUE BOX- MULTIPACK) 
 
184/22 micrograms  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 184 micrograms/22 micrograms inhalation powder, pre-dispensed 
fluticasone furoate/vilanterol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each delivered dose contains 184 micrograms of fluticasone furoate and 22 micrograms of vilanterol (as 
trifenatate).  
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and magnesium stearate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Inhalation powder, pre-dispensed. 
Multipack: 90 (3 packs of 30) doses 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
ONCE DAILY 
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 
In use shelf-life: 6 weeks. 
 
 



53 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from moisture. 
 
 
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 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
GlaxoSmithKline (Ireland) Limited logo 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/929/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
revinty ellipta 184:22 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN:



54 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
INTERMEDIATE OUTER CARTON (WITHOUT BLUE BOX- MULTIPACK ONLY) 
 
92/22 micrograms 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 92 micrograms/22 micrograms inhalation powder, pre-dispensed 
 
fluticasone furoate/vilanterol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each delivered dose contains 92 micrograms of fluticasone furoate and 22 micrograms of vilanterol (as 
trifenatate). 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and magnesium stearate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 doses 
1 inhaler of 30 doses. 
Component of a multipack, can’t be sold separately.  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
ONCE DAILY 
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 
In use shelf-life: 6 weeks. 
 
 



55 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C 
Store in the original package in order to protect from moisture. 
 
 
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 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
GlaxoSmithKline (Ireland) Limited logo 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/929/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
revinty ellipta 92:22  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 



56 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
INTERMEDIATE OUTER CARTON (WITHOUT BLUE BOX- MULTIPACK ONLY) 
 
184/22 micrograms 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 184 micrograms/22 micrograms inhalation powder, pre-dispensed 
 
fluticasone furoate /vilanterol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each delivered dose contains 184 micrograms of fluticasone furoate and 22 micrograms of vilanterol (as 
trifenatate). 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and magnesium stearate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 doses 
1 inhaler of 30 doses. 
Component of a multipack,  can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
ONCE DAILY 
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 
In use shelf-life: 6 weeks. 
 
 



57 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from moisture. 
 
 
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 
 
GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland 
GlaxoSmithKline (Ireland) Limited logo 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/929/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
revinty ellipta 184:22  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 
 



58 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY LABEL 
 
92/22 micrograms 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 92 micrograms/22 micrograms inhalation powder, pre-dispensed 
 
fluticasone furoate/vilanterol 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER  
 
GSK Logo 
GlaxoSmithKline (Ireland) Limited  
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. OTHER  
 
Do not open until ready to inhale. 
In use shelf-life: 6 weeks. 
 
14 doses 
30 doses 
 



59 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY LABEL 
 
184/22 micrograms 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Revinty Ellipta 184 micrograms/22 micrograms inhalation powder, pre-dispensed 
 
fluticasone furoate/vilanterol 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
GSK Logo 
GlaxoSmithKline (Ireland) Limited  
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. OTHER  
 
Do not open until ready to inhale. 
In use shelf-life: 6 weeks. 
 
14 doses 
30 doses 
 



60 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
DEVICE LABEL 
 
92/22 micrograms 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Revinty Ellipta 92 micrograms/22 micrograms inhalation powder 
 
fluticasone furoate/vilanterol 
 
Inhalation use 
 
 
2. EXPIRY DATE 
 
EXP 
In use shelf-life: 6 weeks 
Discard by: 
 
 
3. BATCH NUMBER 
 
Lot 
 
 
4. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
14 doses 
30 doses 



61 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
DEVICE LABEL 
 
184/22 micrograms 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Revinty Ellipta 184 micrograms/22 micrograms inhalation powder 
 
fluticasone furoate/vilanterol 
 
Inhalation use 
 
 
2. EXPIRY DATE 
 
EXP 
In use shelf-life: 6 weeks 
Discard by: 
 
 
3. BATCH NUMBER 
 
Lot 
 
 
4. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
14 doses 
30 doses 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



62 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



63 

Package leaflet: Information for the user 

Revinty Ellipta 92 micrograms/22 micrograms inhalation powder, pre-dispensed 
Revinty Ellipta 184 micrograms/22 micrograms inhalation powder, pre-dispensed 

 
Fluticasone furoate/vilanterol 

 
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 Revinty Ellipta is and what it is used for 
2. What you need to know before you use Revinty Ellipta 
3. How to use Revinty Ellipta 
4. Possible side effects 
5. How to store Revinty Ellipta 
6. Contents of the pack and other information 

Step-by-step instructions 
 
 

1. What Revinty Ellipta is and what it is used for  
 
Revinty Ellipta contains two active substances: fluticasone furoate and vilanterol. Two different strengths of 
Revinty Ellipta are available: fluticasone furoate 92 micrograms/vilanterol 22 micrograms and fluticasone 
furoate 184 micrograms/vilanterol 22 micrograms.  
 
The 92/22 micrograms strength is used for the regular treatment of chronic obstructive pulmonary disease 
(COPD) in adults, and asthma in adults and adolescents 12 years and over.  
 
The 184/22 micrograms strength is used to treat asthma in adults and adolescents aged 12 years and older. 
The 184/22 micrograms strength is not approved for the treatment of COPD. 
 
 Revinty Ellipta should be used every day and not only when you have breathing problems or         

other symptoms of COPD and asthma. It should not be used to relieve a sudden attack of 
breathlessness or wheezing. If you get this sort of attack you must use a quick-acting inhaler (such as 
salbutamol). If you do not have a quick-acting inhaler contact your doctor. 

 
Fluticasone furoate belongs to a group of medicines called corticosteroids, often simply called steroids. 
Corticosteroids reduce inflammation. They reduce the swelling and irritation in the small air passages in the 
lungs and so gradually ease breathing problems. Corticosteroids also help to prevent attacks of asthma and 
aggravation of COPD. 
 
Vilanterol belongs to a group of medicines called long acting bronchodilators. It relaxes the muscles of the 
small air passages in the lungs. This helps to open the airways and makes it easier for air to get in and out of 
the lungs. When it is taken regularly, it helps the small air passages to remain open. 
 
When you take these two active substances together regularly, they will help to control your breathing 
difficulties more than either medicine alone. 



64 

 
Asthma is a serious, long term lung disease where the muscles surrounding the smaller airways become tight 
(bronchoconstriction) and swollen and irritated (inflammation). Symptoms come and go and include 
shortness of breath, wheezing, chest tightness and cough. Revinty Ellipta has been shown to reduce flare-ups 
and symptoms of asthma.  
 
Chronic obstructive pulmonary disease (COPD) is a serious, long term lung disease where the airways 
become inflamed and thickened. Symptoms include shortness of breath, cough, chest discomfort and 
coughing up mucus. Revinty Ellipta has been shown to reduce flare-ups of COPD symptoms. 
 
 
2. What you need to know before you use Revinty Ellipta  
 
Do not use Revinty Ellipta 
- if you are allergic to fluticasone furoate, vilanterol or any other ingredients of this medicine (listed in 

section 6). 
- if you think the above applies to you, don’t use Revinty Ellipta until you have checked with your 

doctor. 
 
Warnings and precautions 
Talk to your doctor before you use Revinty Ellipta: 
- if you have liver disease, as you may be more likely to have side effects. If you have moderate or 

severe liver disease, your doctor will limit your dose to the lower strength of Revinty Ellipta 
(92/22 micrograms once daily). 

- if you have heart problems or high blood pressure. 
- if you have tuberculosis (TB) of the lung, or any long standing or untreated infections. 
- if you have ever been told you have diabetes or high blood sugar. 
-  if you have thyroid gland problems. 
-            if you have low potassium in your blood. 
-  if you experience blurred vision or other visual disturbances. 
 
 
 Check with your doctor before you use this medicine if you think any of these applies to you. 
 
While you’re using Revinty Ellipta 
 
- Contact your doctor if you experience blurred vision or other visual disturbances. 
- Contact your doctor if you experience increased thirst, frequent urination or unexplained tiredness 

(signs of high blood sugar). 
 
Immediate breathing difficulties 
If your breathing or wheezing gets worse straight after using Revinty Ellipta, stop using it and get medical 
help immediately. 
 
Infection of the lung 
If you are using this medicine for COPD you may be at an increased risk of developing an infection of the 
lungs known as pneumonia. See section 4 for information on symptoms to look out for while you are using 
this medicine. Tell your doctor as soon as possible if you develop any of these symptoms. 
 
Children and adolescents 
Do not give this medicine to children under the age of 12 years for the treatment of asthma, or in children 
and adolescents of any age for the treatment of COPD. 
 
Other medicines and Revinty Ellipta 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicinesn. If 
you are not sure what your medicine contains talk to your doctor or pharmacist. 



65 

 
Some medicines may affect how this medicine works, or make it more likely that you will have side effects. 
These include: 
-  beta-blockers, such as metoprolol, used to treat high blood pressure or a heart condition.  
- ketoconazole, to treat fungal infections. 
- ritonavir or cobicistat, to treat HIV infections. 
- long-acting beta2-adrenergic agonists, such as salmeterol 
 
Tell your doctor or pharmacist if you are taking any of these medicines. Your doctor may wish to monitor 
you carefully if you are taking any of these medicines as they may increase the side effects of 
Revinty Ellipta.  
 
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 for advice before taking this medicine.  Don’t use this medicine if you are pregnant unless your doctor 
tells you that you can.  
 
It is not known whether the ingredients of this medicine can pass into breast milk.  If you are breast-feeding, 
you must check with your doctor before you use Revinty Ellipta.  Don’t use this medicine if you are breast-
feeding unless your doctor tells you that you can.  
 
If you are breast-feeding, check with your doctor before you use Revinty Ellipta.  

Driving and using machines 
This medicine is unlikely to affect your ability to drive or use machines. 
 
Revinty Ellipta contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, or to milk protein, contact 
to your doctor before using this medicine. 
 
 
3. How to use Revinty Ellipta  
 
Always use this medicine exactly as your doctor has told you to. Check with your doctor, nurse or 
pharmacist if you are not sure. 
 
How much to use 
 
Asthma 
The recommended dose to treat asthma is one inhalation (92 micrograms of fluticasone furoate and 
22 micrograms of vilanterol) once daily at the same time each day. 
 
If you have severe asthma, your doctor may decide that you should use one inhalation of the higher strength 
inhaler (184 micrograms fluticasone furoate and 22 micrograms of vilanterol). This dose is also used once 
daily at the same time each day. 
 
COPD 
The recommended dose to treat COPD is one inhalation (92 micrograms of fluticasone furoate and 
22 micrograms of vilanterol) once daily at the same time each day. 
 
The higher strength of Revinty Ellipta (184 micrograms fluticasone furoate and 22 micrograms of vilanterol) 
is not suitable for the treatment of COPD. 
 
Revinty Ellipta is for inhalation use. 
 



66 

Use Revinty Ellipta at the same time each day as it is effective over 24 hours 
It is very important that you use this medicine every day, as instructed by your doctor. This will help to keep 
you free of symptoms throughout the day and night. 
 
Revinty Ellipta should not be used to relieve a sudden attack of breathlessness or wheezing. If you get 
this sort of attack you must use a quick-acting inhaler (such as salbutamol). 
 
If you feel you are getting breathless or wheezy more often than normal, or if you are using your quick-
acting inhaler more than usual, see your doctor. 
 
How to use Revinty Ellipta 
See ‘Step-by-step instructions’ after section 6 of this leaflet for full information. 
 
You do not need to prepare Revinty Ellipta in any special way, not even the first time you use it. 
 
If your symptoms do not improve 
If your symptoms (breathlessness, wheezing, cough) do not improve or get worse, or if you are using your 
quick-acting inhaler more often  
 
 contact your doctor as soon as possible. 
 
If you use more Revinty Ellipta than you should  
If you accidentally take more Revinty Ellipta than your doctor has instructed, talk to your doctor or 
pharmacist. You may notice that your heart is beating faster than usual, you feel shaky or have a headache. 
  
If you have used more than instructed for a long period of time, it is particularly important that you 
ask your doctor or pharmacist for advice. This is because larger doses of Revinty Ellipta may reduce the 
amount of steroid hormones produced naturally by your body.  
 
If you forget to use Revinty Ellipta  
Do not take a double dose to make up for a forgotten dose. Just take your next dose at the usual time. 
 
If you become wheezy or breathless, or develop any other symptoms of an asthma attack, use your 
quick-acting inhaler (e.g. salbutamol), then seek medical advice.  
 
Do not stop using Revinty Ellipta without advice 
Use this medicine for as long as your doctor recommends. It will only be effective as long as you are using it. 
Do not stop unless your doctor advises you to, even if you feel better. 
 
If you have further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 



67 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
Allergic Reactions 
 
Allergic reactions to Revinty Ellipta are rare (may affect up to 1 in 1,000 people).  
If you have any of the following symptoms after taking Revinty Ellipta stop taking this medicine and tell 
your doctor immediately. 
 skin rash (hives) or redness  
 swelling, sometimes of the face or mouth (angioedema) 
 becoming very wheezy, coughing or having difficulty in breathing 
 suddenly feeling weak or light headed (which may lead to collapse or loss of consciousness) 
 
Immediate breathing difficulties 
 
Immediate breathing difficulties after using Revinty Ellipta are rare. 
If your breathing or wheezing gets worse straight after using this medicine, stop using it and get medical 
help immediately. 
 
Pneumonia (infection of the lung) (common side effect, may affect up to 1 in 10 people) 
Tell your doctor if you have any of the following while taking Revinty Ellipta – they could be symptoms of 
a lung infection:  

 fever or chills 
 increased mucus production, change in mucus colour 
 increased cough or increased breathing difficulties 

 
Other side effects include: 
 
Very common side effects 
These may affect more than 1 in 10 people: 

 headache 
 common cold  

 
Common side effects 
These may affect up to 1 in 10 people:  

 sore, raised patches in the mouth or throat caused by a fungal infection (candidiasis). Rinsing your 
mouth out with water immediately after using Revinty Ellipta may help stop this side effect 
developing. 

 inflammation of the lungs (bronchitis) 
 infection of the nose sinuses or throat 
 flu (influenza)  
 pain and irritation in the back of the mouth and throat 
 inflammation of the sinuses 
 itchy, runny or blocked nose  
 cough 
 voice disorders 
 weakening of the bones, leading to fractures 
 stomach pain  
 back pain 
 high temperature (fever) 
 joint pain 
 muscle spasms 

 



68 

Uncommon side effects 
This may affect up to 1 in 100 people:  

 irregular heartbeat  
 blurred vision 
 increase in blood sugar (hyperglycaemia) 

 
 
Rare side effects 
These may affect up to 1 in 1,000 people:  

 heart beating faster (tachycardia) 
 awareness of heart beat (palpitations) 
 tremor
 anxiety

 
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 Revinty Ellipta 
 
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 pack after EXP. The expiry date refers 
to the last day of that month. 
 
Do not store above 25°C. 
 
Keep the inhaler inside the sealed tray to protect from moisture and only remove immediately before first 
use. Once the tray is opened, the inhaler can be used for up to 6 weeks, starting from the date of opening the 
tray. Write the date the inhaler should be thrown away on the label in the space provided. The date should be 
added as soon as the inhaler has been removed from the tray. 
 
If you store in a refrigerator, allow the inhaler to return to room temperature for at least an hour before 
use.  
 
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. 
 
 
6. Contents of the pack and other information 
 
What Revinty Ellipta contains 

- The active substances are fluticasone furoate and vilanterol.  
- For the 92/22mcg dose: each single inhalation provides a delivered dose (the dose leaving the 

mouthpiece) of 92  micrograms of fluticasone furoate and 22 micrograms of vilanterol (as trifenatate). 
- For the 184/22 dose: each single inhalation provides a delivered dose (the dose leaving the 

mouthpiece) of 184 micrograms of fluticasone furoate and 22 micrograms of vilanterol (as trifenatate). 
- The other ingredients are lactose monohydrate (See section 2) and magnesium stearate. 

 
What Revinty Ellipta looks like and contents of the pack 
The Ellipta device itself is a light grey inhaler with a yellow mouthpiece cover and a dose counter. It is 
packaged in a foil laminate tray with a peelable foil lid. The tray contains a desiccant sachet, to reduce 



69 

moisture in the packaging. Once you have opened the lid of the tray, throw the desiccant away – do not eat or 
inhale it. The device does not need to be stored in the foil laminate tray once it has been opened.   

The inhaler contains two aluminium foil laminate strips of 14 or 30 doses. Multipacks contain 3 x 30 dose 
inhalers. 
 
 
Marketing Authorisation Holder: 
 
GlaxoSmithKline (Ireland) Limited  
12 Riverwalk  
Citywest Business Campus 
Dublin 24 
Ireland 
 
Manufacturer: 
 
Glaxo Operations UK Limited (trading as Glaxo Wellcome Operations),  
Priory Street, 
Ware,  
Hertfordshire, SG12 0DJ  
United Kingdom. 
 
Glaxo Operations UK Limited (trading as Glaxo Wellcome Operations), 
Harmire Road, 
Barnard Castle, 
County Durham DL12 8DT 
United Kingdom. 
 
Glaxo Wellcome Production 
Zone Industrielle No.2, 
23 Rue Lavoisier,  
27000 Evreux,  
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 (0) 10 85 52 00 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

България 
ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 52 00 
 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 

Danmark 
GlaxoSmithKline Pharma A/S 

Malta 
GlaxoSmithKline Malta 



70 

Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Tel: + 356 21 238131 

Deutschland 
BERLIN-CHEMIE AG 
Tel: +49 (0) 30 67070 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 6938100 
nlinfo@gsk.com 



71 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
firmapost@gsk.no 

Ελλάδα 
Menarini Hellas Α.Ε. 
Τηλ. + 30 210 8316111-13 
 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
FAES FARMA, S.A. 
Tel: + 34 900 460 153 
aweber@faes.es  

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 
 

France 
MENARINI France 
Tél: + 33 (0)1 45 60 77 20 
 
 

Portugal  
BIAL, Portela & Ca. SA. 
Tel: + 351 22 986 61 00 
info@bial.com 
 

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: + 385 1 6051 999 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 

Italia 
A. Menarini Industrie Farmaceutiche Riunite s.r.l.
Tel: +39-055 56801 
 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 

United Kingdom 
GlaxoSmithKline UK 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com  
  



72 

This leaflet

Carton 

Tray lid 

Inhaler 

Desiccant 

Tray 

Desiccant 

This leaflet was last revised in <{MM/YYYY}>  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
Step by step instructions 
 
What is the Ellipta inhaler? 
When you first use the Ellipta inhaler you do not need to check that it is working properly, and you do not 
need to prepare it for use in any special way. Just follow these step-by-step instructions. 
 
Your Revinty Ellipta inhaler carton contains 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

The inhaler is packaged in a tray. Don’t open the tray until you are ready to start using your new 
inhaler.  When you are ready to use your inhaler, peel back the lid to open the tray.  The tray contains a 
desiccant sachet, to reduce moisture. Throw this desiccant sachet away – don’t open, eat or inhale it. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



73 

 
When you take the inhaler out of its tray, it will be in the ‘closed’ position. Don’t open the inhaler until 
you are ready to inhale a dose of medicine. When the tray is opened, write the “Discard by” date on the 
inhaler label in the space provided. The “Discard by” date is 6 weeks from the date you opened the tray. 
After this date the inhaler should no longer be used. The tray can be discarded after first opening. 
 
The step-by-step instructions shown below for the 30-dose Ellipta inhaler (30 day supply) also apply to the 
14-dose Ellipta inhaler (14 day supply). 
 
 
1. Read this before you start 
 
If you open and close the cover without inhaling the medicine, you will lose the dose.  
The lost dose will be securely held inside the inhaler, but it will no longer be available. 
It is not possible to accidentally take extra medicine or a double dose in one inhalation. 
 

 
 
2. Prepare a dose  
 
 Wait to open the cover until you are ready to take your dose. Do not shake the inhaler. 

 Slide the cover down until you hear a “click”. 

 
Your medicine is now ready to be inhaled. 
The dose counter counts down by 1 to confirm. 

 If the dose counter does not count down as you hear the “click”, the inhaler will not deliver 
medicine. Take it back to your pharmacist for advice. 



74 

 
3. Inhale your medicine 
 

 While holding the inhaler away from your mouth, breathe out as far as is comfortable.  
       Don’t breathe out into the inhaler. 
 

 Put the mouthpiece between your lips, and close your lips firmly around it. 
      Don’t block the air vent with your fingers. 

 
 Take one long, steady, deep breath in. Hold this breath for as long as possible (at least 

3-4 seconds). 
 

 Remove the inhaler from your mouth. 
 

 Breathe out slowly and gently. 
 
You may not be able to taste or feel the medicine, even when you are using the inhaler correctly. 

If you want to clean the mouthpiece, use a dry tissue, before you close the cover. 
 
4. Close the inhaler and rinse your mouth  
 

 Slide the cover upwards as far as it will go, to cover the mouthpiece. 

 
 Rinse your mouth with water after you have used the inhaler, do not swallow.  

 This will make it less likely that you will develop a sore mouth or throat as side effects. 
 


	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 MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVEUSE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET