SEEBRI BREEZHALER 44mcg capsules with inhalation powder medication leaflet

Seebri Breezhaler 44 micrograms inhalation powder, hard capsules

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

Each delivered dose (the dose that leaves the mouthpiece of the inhaler) contains 55 micrograms ofglycopyrronium bromide equivalent to 44 micrograms of glycopyrronium.

Each capsule contains 23.6 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

Inhalation powder, hard capsule (inhalation powder).

Transparent orange capsules containing a white powder, with the product code “GPL50” printed inblack above and the company logo ( ) printed in black below a black bar.

Seebri Breezhaler is indicated as a maintenance bronchodilator treatment to relieve symptoms in adultpatients with chronic obstructive pulmonary disease (COPD).

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

Breezhaler inhaler.

Seebri Breezhaler is recommended to be administered, at the same time of the day each day. If a doseis missed, the next dose should be taken as soon as possible. Patients should be instructed not to takemore than one dose in a day.

Seebri Breezhaler can be used at the recommended dose in elderly patients (75 years of age and older)(see section 4.8).

Seebri Breezhaler can be used at the recommended dose in patients with mild to moderate renalimpairment. In patients with severe renal impairment or end-stage renal disease requiring dialysis

Seebri Breezhaler should be used only if the expected benefit outweighs the potential risk since thesystemic exposure to glycopyrronium may be increased in this population (see sections 4.4 and 5.2).

No studies have been conducted in patients with hepatic impairment. Glycopyrronium ispredominantly cleared by renal excretion and therefore no major increase in exposure is expected inpatients with hepatic impairment. No dose adjustment is required in patients with hepatic impairment.

There is no relevant use of Seebri Breezhaler in the paediatric population (under 18 years) in theindication COPD.

For inhalation use only.

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

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

The capsules must not be swallowed.

Patients should be instructed on how to administer the medicinal product correctly. Patients who donot experience improvement in breathing should be asked if they are swallowing the medicinalproduct rather than inhaling it.

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

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

Seebri Breezhaler is a once-daily, long-term maintenance treatment and is not indicated for the initialtreatment of acute episodes of bronchospasm, i.e. as a rescue therapy.

Immediate hypersensitivity reactions have been reported after administration of Seebri Breezhaler. Ifsigns suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathingor swallowing, swelling of the tongue, lips, and face), urticaria or skin rash, treatment should bediscontinued immediately and alternative therapy instituted.

In clinical studies with Seebri Breezhaler, paradoxical bronchospasm was not observed. However,paradoxical bronchospasm has been observed with other inhalation therapy and can belife-threatening. If this occurs, treatment should be discontinued immediately and alternative therapyinstituted.

Anticholinergic effect

Seebri Breezhaler should be used with caution in patients with narrow-angle glaucoma or urinaryretention.

Patients should be informed about the signs and symptoms of acute narrow-angle glaucoma andshould be informed to stop using Seebri Breezhaler and to contact their doctor immediately should anyof these signs or symptoms develop.

Patients with severe renal impairment

A moderate mean increase in total systemic exposure (AUClast) of up to 1.4-fold was seen in subjectswith mild and moderate renal impairment and up to 2.2-fold in subjects with severe renal impairmentand end-stage renal disease. In patients with severe renal impairment (estimated glomerular filtrationrate below 30 ml/min/1.73 m2), including those with end-stage renal disease requiring dialysis, Seebri

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

These patients should be monitored closely for potential adverse reactions.

Patients with a history of cardiovascular disease

Patients with unstable ischaemic heart disease, left ventricular failure, history of myocardial infarction,arrhythmia (excluding chronic stable atrial fibrillation), a history of long QT syndrome or whose QTc(Fridericia method) was prolonged (>450 ms for males or >470 ms for females) were excluded fromthe clinical trials, and therefore the experience in these patient groups is limited. Seebri Breezhalershould be used with caution in these patient groups.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

The co-administration of Seebri Breezhaler with other anticholinergic-containing medicinal productshas not been studied and is therefore not recommended.

Although no formal drug interaction studies have been performed, Seebri Breezhaler has been usedconcomitantly with other medicinal products commonly used in the treatment of COPD withoutclinical evidence of drug interactions. These include sympathomimetic bronchodilators,methylxanthines, and oral and inhaled steroids.

In a clinical study in healthy volunteers, cimetidine, an inhibitor of organic cation transport which isthought to contribute to the renal excretion of glycopyrronium, increased total exposure (AUC) toglycopyrronium by 22% and decreased renal clearance by 23%. Based on the magnitude of thesechanges, no clinically relevant drug interaction is expected when glycopyrronium is co-administeredwith cimetidine or other inhibitors of organic cation transport.

Concomitant administration of glycopyrronium and orally inhaled indacaterol, a beta2-adrenergicagonist, under steady-state conditions of both active substances did not affect the pharmacokinetics ofeither medicinal product.

There are no data from the use of Seebri Breezhaler in pregnant women. Animal studies do notindicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Glycopyrronium should only be used during pregnancy if the expected benefit to the patient justifiesthe potential risk to the foetus.

It is unknown whether glycopyrronium bromide is excreted in human milk. However, glycopyrroniumbromide (including its metabolites) was excreted in the milk of lactating rats (see section 5.3). The useof glycopyrronium by breast-feeding women should only be considered if the expected benefit to thewoman is greater than any possible risk to the infant (see section 5.3).

Reproduction studies and other data in animals do not indicate a concern regarding fertility in eithermales or females (see section 5.3).

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

The most common anticholinergic adverse reaction was dry mouth (2.4%). The majority of the reportsof dry mouth were suspected to be related to the medicinal product and were mild, with none beingsevere.

The safety profile is further characterised by other symptoms related to the anticholinergic effects,including signs of urinary retention, which were uncommon. Gastrointestinal effects includinggastroenteritis and dyspepsia were also observed. Adverse reactions related to local tolerabilityincluded throat irritation, nasopharyngitis, rhinitis and sinusitis.

Adverse reactions reported during the first six months of two pooled pivotal Phase III trials of 6 and12 months duration are listed by MedDRA system organ class (Table 1). Within each system organclass, the adverse reactions are ranked by frequency, with the most frequent reactions first. Withineach frequency grouping, adverse reactions are presented in order of decreasing seriousness. Inaddition, the corresponding frequency category for each adverse reaction is based on the followingconvention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare(≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the availabledata).

Table 1 Adverse reactions

Adverse reactions Frequency category

Nasopharyngitis1) Common

Rhinitis Uncommon

Cystitis Uncommon

Hypersensitivity Uncommon

Angioedema2) Uncommon

Hyperglycaemia Uncommon

Insomnia Common

Headache3) Common

Hypoaesthesia Uncommon

Atrial fibrillation Uncommon

Palpitations Uncommon

Sinus congestion Uncommon

Productive cough Uncommon

Throat irritation Uncommon

Epistaxis Uncommon

Dysphonia2) Uncommon

Paradoxical bronchospasm2) Not known

Dry mouth Common

Gastroenteritis Common

Nausea2) Uncommon

Vomiting1) 2) Uncommon

Dyspepsia Uncommon

Dental caries Uncommon

Rash Uncommon

Pruritus2) Uncommon

Musculoskeletal pain1) 2) Common

Pain in extremity Uncommon

Musculoskeletal chest pain Uncommon

Urinary tract infection3) Common

Dysuria Uncommon

Urinary retention Uncommon

Fatigue Uncommon

Asthenia Uncommon1) More frequent for glycopyrronium than placebo in the 12 months database only.

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

Seebri Breezhaler. These were reported voluntarily from a population of uncertain size, and it istherefore not always possible to reliably estimate the frequency or establish a causal relationship todrug exposure. Therefore the frequency was calculated from clinical trial experience.

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

In the pooled 6-month database the frequency of dry mouth was 2.2% versus 1.1%, of insomnia 1.0%versus 0.8%, and of gastroenteritis 1.4% versus 0.9%, for Seebri Breezhaler and placebo respectively.

Dry mouth was reported mainly during the first 4 weeks of treatment with a median duration of fourweeks in the majority of patients. However in 40% of cases symptoms continued for the entire 6-month period. No new cases of dry mouth were reported in months 7-12.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

High doses of glycopyrronium may lead to anticholinergic signs and symptoms for whichsymptomatic treatment may be indicated.

Acute intoxication by inadvertent oral ingestion of Seebri Breezhaler capsules is unlikely due to thelow oral bioavailability (about 5%).

Peak plasma levels and total systemic exposure following intravenous administration of150 micrograms glycopyrronium bromide (equivalent to 120 micrograms glycopyrronium) in healthyvolunteers were respectively about 50-fold and 6-fold higher than the peak and total exposure atsteady-state achieved with the recommended dose (44 micrograms once daily) of Seebri Breezhalerand were well tolerated.

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

R03BB06

Glycopyrronium is an inhaled long-acting muscarinic receptor antagonist (anticholinergic) foronce-daily maintenance bronchodilator treatment of COPD. Parasympathetic nerves are the majorbronchoconstrictive neural pathway in airways, and cholinergic tone is the key reversible componentof airflow obstruction in COPD. Glycopyrronium works by blocking the bronchoconstrictor action ofacetylcholine on airway smooth muscle cells, thereby dilating the airways.

Glycopyrronium bromide is a high affinity muscarinic receptor antagonist. A greater than 4-foldselectivity for the human M3 receptors over the human M2 receptor has been demonstrated usingradioligand binding studies. It has a rapid onset of action as evidenced by observed receptorassociation/dissociation kinetic parameters and the onset of action after inhalation in clinical studies.

The long duration of action can be partly attributed to sustained concentrations of active substance inthe lung as reflected by the prolonged terminal elimination half-life of glycopyrronium after inhalationvia the Seebri Breezhaler inhaler in contrast to the half life after intravenous administration (seesection 5.2).

The clinical Phase III development programme included two phase III studies: a 6-monthplacebo-controlled study and a 12-month placebo and active-controlled (open label tiotropium18 micrograms once daily) study, both in patients with clinical diagnosis of moderate to severe COPD.

Seebri Breezhaler 44 micrograms once daily provided consistently statistically significantimprovement in lung function (forced expiratory volume in one second, FEV1, forced vital capacity,

FVC, and inspiratory capacity, IC) in a number of clinical studies. In phase III studies, bronchodilatoreffects were seen within 5 minutes after the first dose and were maintained over the 24-hour dosinginterval from the first dose. There was no attenuation of the bronchodilator effect over time in the 6-and 12-month studies. The magnitude of the effect was dependent on the degree of reversibility ofairflow limitation at baseline (tested by administration of a short-acting muscarinic antagonistbronchodilator): Patients with the lowest degree of reversibility at baseline (<5%) generally exhibiteda lower bronchodilator response than patients with a higher degree of reversibility at baseline (≥5%).

At 12 weeks (primary endpoint), Seebri Breezhaler increased trough FEV1 by 72 ml in patients withthe lowest degree of reversibility (<5%) and by 113 ml in those patients with a higher degree ofreversibility at baseline (≥5%) compared to placebo (both p<0.05).

In the 6-month study, Seebri Breezhaler increased FEV1 after the first dose with an improvement of93 ml within 5 minutes and 144 ml within 15 minutes of dosing, compared to placebo (both p<0.001).

In the 12-month study, the improvements were 87 ml at 5 minutes and 143 ml at 15 minutes (bothp<0.001). In the 12-month study, Seebri Breezhaler produced statistically significant improvements in

FEV1 compared to tiotropium in the first 4 hours after dosing on day 1 and at week 26, andnumerically greater values for FEV1 in the first 4 hours after dosing than tiotropium at week 12 andweek 52.

The values for FEV1 at the end of the dosing interval (24 h post dose) were similar between the firstdose and those seen after 1 year of dosing. At 12 weeks (primary endpoint), Seebri Breezhalerincreased trough FEV1 by 108 ml in the 6-month study and by 97 ml in the 12-month study comparedto placebo (both p<0.001). In the 12-month study, the improvement versus placebo for tiotropium was83 ml (p<0.001).

Symptomatic outcomes

Seebri Breezhaler administered at 44 micrograms once daily statistically significantly reducedbreathlessness as evaluated by the Transitional Dyspnoea Index (TDI). In a pooled analysis of the 6-and 12-month pivotal studies a statistically significantly higher percentage of patients receiving Seebri

Breezhaler responded with a 1 point or greater improvement in the TDI focal score at week 26compared to placebo (58.4% and 46.4% respectively, p<0.001). These findings were similar to thoseseen in patients receiving tiotropium, 53.4% of whom responded with 1 point or greater improvement(p=0.009 compared to placebo).

Seebri Breezhaler once daily has also shown a statistically significant effect on health-related qualityof life measured using the St. George’s Respiratory Questionnaire (SGRQ). A pooled analysis of the6- and 12-month pivotal studies found a statistically significantly higher percentage of patientsreceiving Seebri Breezhaler responded with a 4 point or greater improvement in SGRQ compared toplacebo at week 26 (57.8% and 47.6% respectively, p<0.001). For patients receiving tiotropium,61.0% responded with a 4 point or greater improvement in SGRQ (p=0.004 compared to placebo).

COPD exacerbations reduction

COPD exacerbation data was collected in the 6- and 12-month pivotal studies. In both studies, thepercentage of patients experiencing a moderate or severe exacerbation (defined as requiring treatmentwith systemic corticosteroids and/or antibiotics or hospitalisation) was reduced. In the 6-month study,the percentage of patients experiencing a moderate or severe exacerbation was 17.5% for Seebri

Breezhaler and 24.2% for placebo (Hazard ratio: 0.69, p=0.023), and in the 12-month study it was32.8% for Seebri Breezhaler and 40.2% for placebo (Hazard ratio: 0.66, p=0.001). In a pooled analysisof the first 6 months of treatment in the 6- and 12-month studies, compared to placebo Seebri

Breezhaler statistically significantly prolonged time to first moderate or severe exacerbation andreduced the rate of moderate or severe COPD exacerbations (0.53 exacerbations/year versus0.77exacerbations /year, p<0.001). The pooled analysis also showed fewer patients treated with Seebri

Breezhaler than with placebo experienced an exacerbation requiring hospitalisation (1.7% versus4.2%, p=0.003).

Other effects

Seebri Breezhaler once daily statistically significantly reduced the use of rescue medication(salbutamol) by 0.46 puffs per day (p=0.005) over 26 weeks and by 0.37 puffs per day (p=0.039) over52 weeks, compared to placebo for the 6- and 12-month studies, respectively.

In a 3-week study where exercise tolerance was tested via cycle ergometer at submaximal (80%)workload (submaximal exercise tolerance test), Seebri Breezhaler, dosed in the morning, reduceddynamic hyperinflation and improved the length of time exercise could be maintained from the firstdose onwards. On the first day of treatment inspiratory capacity under exercise was improved by230 ml and exercise endurance time was improved by 43 seconds (an increase of 10%) compared toplacebo. After three weeks of treatment the improvement in inspiratory capacity with Seebri

Breezhaler was similar to the first day (200 ml), exercise endurance time however had increased by89 seconds (an increase of 21%) compared to placebo. Seebri Breezhaler was found to decreasedyspnoea and leg discomfort when exercising as measured using Borg scales. Seebri Breezhaler alsoreduced dyspnoea at rest measured using the Transitional Dyspnoea Index.

Secondary pharmacodynamic effects

No change in mean heart rate or QTc interval was observed with Seebri Breezhaler in doses up to176 micrograms in COPD patients. In a thorough QT study in 73 healthy volunteers, a single inhaleddose of glycopyrronium 352 micrograms (8 times the therapeutic dose) did not prolong the QTcinterval and slightly reduced heart rate (maximal effect -5.9 bpm; average effect over24 hours -2.8 bpm) when compared to placebo. The effect on heart rate and QTc interval of150 micrograms glycopyrronium bromide (equivalent to 120 micrograms glycopyrronium)administered intravenously was investigated in young healthy subjects. Peak exposures (Cmax) about50-fold higher than after inhalation of glycopyrronium 44 micrograms at steady state were achievedand did not result in tachycardia or QTc prolongation. A slight reduction in heart rate (mean differenceover 24 h -2 bpm when compared to placebo), which is a known effect of low exposures toanticholinergic compounds in young healthy subjects, was observed.

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

Breezhaler in all subsets of the paediatric population in COPD (see section 4.2 for information onpaediatric use).

Following oral inhalation using the Seebri Breezhaler inhaler, glycopyrronium was rapidly absorbedand reached peak plasma levels at 5 minutes post dose.

The absolute bioavailability of glycopyrromium inhaled via Seebri Breezhaler was estimated to beabout 45% of the delivered dose. About 90% of systemic exposure following inhalation is due to lungabsorption and 10% is due to gastrointestinal absorption.

In patients with COPD, pharmacokinetic steady-state of glycopyrronium was reached within one weekof the start of treatment. The steady-state mean peak and trough plasma concentrations ofglycopyrronium for a 44 micrograms once-daily dosing regimen were 166 picograms/ml and8 picograms/ml, respectively. Steady-state exposure to glycopyrronium (AUC over the 24-hour dosinginterval) was about 1.4- to 1.7-fold higher than after the first dose.

After intravenous dosing, the steady-state volume of distribution of glycopyrronium was 83 litres andthe volume of distribution in the terminal phase was 376 litres. The apparent volume of distribution inthe terminal phase following inhalation was almost 20-fold larger, which reflects the much slowerelimination after inhalation. The in vitro human plasma protein binding of glycopyrronium was 38%to 41% at concentrations of 1 to 10 nanograms/ml.

In vitro metabolism studies showed consistent metabolic pathways for glycopyrronium bromidebetween animals and humans. Hydroxylation resulting in a variety of mono-and bis-hydroxylatedmetabolites and direct hydrolysis resulting in the formation of a carboxylic acid derivative (M9) wereseen. In vivo, M9 is formed from the swallowed dose fraction of inhaled glycopyrronium bromide.

Glucuronide and/or sulfate conjugates of glycopyrronium were found in urine of humans afterrepeated inhalation, accounting for about 3% of the dose.

Multiple CYP isoenzymes contribute to the oxidative biotransformation of glycopyrronium. Inhibitionor induction of the metabolism of glycopyrronium is unlikely to result in a relevant change of systemicexposure to the active substance.

In vitro inhibition studies demonstrated that glycopyrronium bromide has no relevant capacity toinhibit CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4/5, theefflux transporters MDR1, MRP2 or MXR, and the uptake transporters OCT1 or OCT2. In vitroenzyme induction studies did not indicate a clinically relevant induction by glycopyrronium bromidefor cytochrome P450 isoenzymes, or for UGT1A1 and the transporters MDR1 and MRP2.

After intravenous administration of [3H]-labelled glycopyrronium bromide to humans, the meanurinary excretion of radioactivity in 48 hours amounted to 85% of the dose. A further 5% of the dosewas found in the bile.

Renal elimination of parent drug accounts for about 60 to 70% of total clearance of systemicallyavailable glycopyrronium whereas non-renal clearance processes account for about 30 to 40%. Biliaryclearance contributes to the non-renal clearance, but the majority of non-renal clearance is thought tobe due to metabolism.

Mean renal clearance of glycopyrronium following inhalation was in the range of 17.4 and24.4 litres/h. Active tubular secretion contributes to the renal elimination of glycopyrronium. Up to23% of the delivered dose was found in urine as parent drug.

Glycopyrronium plasma concentrations declined in a multi-phasic manner. The mean terminalelimination half-life was much longer after inhalation (33 to 57 hours) than after intravenous(6.2 hours) and oral (2.8 hours) administration. The elimination pattern suggests sustained lungabsorption and/or transfer of glycopyrronium into the systemic circulation at and beyond 24 hoursafter inhalation.

In COPD patients both systemic exposure and total urinary excretion of glycopyrronium atpharmacokinetic steady state increased about dose-proportionally over the dose range of 44 to176 micrograms.

A population pharmacokinetic analysis of data in COPD patients identified body weight and age asfactors contributing to inter-patient variability in systemic exposure. Seebri Breezhaler 44 microgramsonce daily can be safely used in all age and body weight groups.

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

There were no major differences in total systemic exposure (AUC) between Japanese and Caucasiansubjects following inhalation of glycopyrronium bromide. Insufficient pharmacokinetic data isavailable for other ethnicities or races.

Clinical studies have not been conducted in patients with hepatic impairment. Glycopyrronium iscleared predominantly from the systemic circulation by renal excretion. Impairment of the hepaticmetabolism of glycopyrronium is not thought to result in a clinically relevant increase of systemicexposure.

Renal impairment has an impact on the systemic exposure to glycopyrronium bromide. A moderatemean increase in total systemic exposure (AUClast) of up to 1.4-fold was seen in subjects with mild andmoderate renal impairment and up to 2.2-fold in subjects with severe renal impairment and end-stagerenal disease. In COPD patients with mild and moderate renal impairment (estimated glomerularfiltration rate, eGFR ≥30 ml/min/1.73 m2) Seebri Breezhaler can be used at the recommended dose. Inpatients with severe renal impairment (eGFR <30 ml/min/1.73 m2), including those with end-stagerenal disease requiring dialysis, Seebri Breezhaler should only be used if the expected benefitoutweighs the potential risk (see section 4.4).

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproductionand development.

Effects attributable to the muscarinic receptor antagonist properties of glycopyrronium bromideincluded mild to moderate increases in heart rate in dogs, lens opacities in rats and, reversible changesassociated with reduced glandular secretions in rats and dogs. Mild irritancy or adaptive changes in therespiratory tract were seen in rats. All these findings occurred at exposures sufficiently in excess ofthose anticipated in humans.

Glycopyrronium was not teratogenic in rats or rabbits following inhalation administration. Fertilityand pre- and post-natal development were not affected in rats. Glycopyrronium bromide and itsmetabolites did not significantly cross the placental barrier of pregnant mice, rabbits and dogs.

Glycopyrronium bromide (including its metabolites) was excreted into the milk of lactating rats andreached up to 10-fold higher concentrations in the milk than in the blood of the dam.

Genotoxicity studies did not reveal any mutagenic or clastogenic potential for glycopyrroniumbromide. Carcinogenicity studies in transgenic mice using oral administration and in rats usinginhalation administration revealed no evidence of carcinogenicity at systemic exposures (AUC) ofapproximately 53-fold higher in mice and 75-fold higher in rats than the maximum recommended doseof 44 micrograms once daily for humans.

Lactose monohydrate

Magnesium stearate

Not applicable.

2 years

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

Do not store above 25°C.

The capsules must always be stored in the original blister in order to protect from moisture. Thecapsules must only be removed immediately before use.

Seebri Breezhaler is a single-dose inhaler. Inhaler body and cap are made from acrylonitrile butadienestyrene, push buttons are made from methyl metacrylate acrylonitrile butadiene styrene. Needles andsprings are made from stainless steel. Each blister strip contains either 6 or 10 hard capsules.

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

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

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

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

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

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

Not all pack sizes may be marketed.

The inhaler provided with each new prescription should be used. Each inhaler should be disposed ofafter all capsules have been used.

Instructions for handling and use

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

Insert Pierce and release Inhale deeply Check capsule is empty

Chec1 2 3k

Step 1a: Step 2a: Step 3a: Check capsule is empty

Pull off cap Pierce capsule once Breathe out fully Open the inhaler to see if

Hold the inhaler upright. Do not blow into the any powder is left in the

Pierce capsule by firmly inhaler. capsule.

pressing both sidebuttons at the same time.

You should hear a noise If there is powder left inas the capsule is pierced. the capsule:

Only pierce the capsule - Close the inhaler.once. - Repeat steps 3a to 3c.

Step 1b: Step 3b:

Open inhaler Inhale medicine deeply

Powder Empty

Hold the inhaler asremainingshown in the picture.

Place the mouthpiece inyour mouth and closeyour lips firmly around

Step 2b: it.

Release side buttons Do not press the sidebuttons.

Breathe in quickly and asdeeply as you can.

During inhalation youwill hear a whirringnoise.

You may taste themedicine as you inhale.

Step 1c: Remove empty capsule

Remove capsule Put the empty capsule in

Separate one of the your household waste.

blisters from the blister Close the inhaler andcard. replace the cap.

Peel open the blister andremove the capsule.

Do not push the capsule

Step 3c:

through the foil.

Hold breath

Do not swallow the

Hold your breath for upcapsule.to 5 seconds.

Important Information

- Seebri Breezhalercapsules must always bestored in the blister cardand only removedimmediately before use.

Step 1d: - Do not push the capsule

Insert capsule through the foil to

Never place a capsule remove it from thedirectly into the blister.mouthpiece. - Do not swallow thecapsule.

- Do not use the Seebri

Breezhaler capsules withany other inhaler.

- Do not use the Seebri

Breezhaler inhaler totake any other capsulemedicine.

Step 1e: - Never place the capsule

Close inhaler into your mouth or themouthpiece of theinhaler.

- Do not press the sidebuttons more than once.

- Do not blow into themouthpiece.

- Do not press the sidebuttons while inhalingthrough the mouthpiece.

- Do not handle capsuleswith wet hands.

- Never wash your inhalerwith water.

Your Seebri Breezhaler Inhaler pack contains: Frequently Asked Cleaning the inhaler

- One Seebri Breezhaler inhaler Questions Wipe the mouthpiece

- One or more blister cards, each containing either inside and outside with a6 or 10 Seebri Breezhaler capsules to be used in Why didn’t the inhaler clean, dry, lint-free cloth tothe inhaler make a noise when I remove any powderinhaled? residue. Keep the inhaler

Capsule The capsule may be stuck dry. Never wash your

Mouthpiece

Cap chamber in the capsule chamber. If inhaler with water.

this happens, carefully

Screenloosen the capsule by

Side tapping the base of thebuttons

Base Blister inhaler. Inhale themedicine again by

Inhaler Inhaler base Blister Cardrepeating steps 3a to 3c.

Disposing of the inhaler

What should I do if there after useis powder left inside the Each inhaler should becapsule? disposed of after all

You have not received capsules have been used.

enough of your medicine. Ask your pharmacist how

Close the inhaler and to dispose of medicinesrepeat steps 3a to 3c. and inhalers that are nolonger required.

I coughed after inhaling- does this matter?

This may happen. As longas the capsule is emptyyou have received enoughof your medicine.

I felt small pieces of thecapsule on my tongue -does this matter?

This can happen. It is notharmful. The chances ofthe capsule breaking intosmall pieces will beincreased if the capsule ispierced more than once.

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

EU/1/12/788/001-008

Date of first authorisation: 28 September 2012

Date of latest renewal: 19 July 2017

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

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