AIRSUPRA is indicated for the as-needed treatment or prevention of bronchoconstriction and for the prevention of exacerbations in patients with asthma 18 years of age and older.

AIRSUPRA is also indicated for the prevention of exercise-induced bronchoconstriction in patients with asthma 18 years of age and older.

Posology

Recommended dosage for treatment or prevention of bronchoconstriction and for the prevention of exacerbations

Adult (18 years of age and older): salbutamol 180 mcg and budesonide 160 mcg (administered as 2 actuations of AIRSUPRA [salbutamol/budesonide 90 mcg/80 mcg]) as needed by oral inhalation.

Recommended dosage for prevention of exercise-induced bronchoconstriction

Adult patients (18 years of age and older): salbutamol 180 mcg and budesonide 160 mcg (administered as 2 actuations of AIRSUPRA [salbutamol/budesonide 90 mcg/80 mcg]) by oral inhalation 15 to 30 minutes before exercise.

Do not take more than 6 doses (12 inhalations) in a 24-hour period.

Special populations

Renal impairment

There are no data available for use of AIRSUPRA in patients with renal impairment.

Hepatic impairment

No dosage adjustment is necessary for patients with hepatic impairment (see section 5.2). As budesonide is primarily eliminated via hepatic metabolism, an increased exposure can be expected in patients with severe liver diseases.

Elderly population

No dosage adjustment is necessary for elderly patients (see section 5.2).

Paediatric population

The safety and effectiveness of AIRSUPRA have not been established in paediatric patients aged 12 - 17.

Method of administration

For oral inhalation use.

For detailed instructions, refer to the patient leaflet/instructions for use.

Patients should be instructed how to administer the product correctly and advised to read the instructions for use carefully.

Patient inhaler technique should be checked to make sure that aerosol actuation is synchronised with inspiration of breath for optimum delivery of drug to the lungs.

Increasing use of bronchodilators to relieve symptoms indicates deterioration of asthma control. The patient should be instructed to seek medical advice if treatment with AIRSUPRA becomes less effective, or more inhalations than usual are required. In this situation the patient should be assessed and the treatment regimen should be evaluated.

Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with salbutamol. Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving salbutamol should be warned to

seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin. AIRSUPRA should be used with caution in severe and untreated hypertension.

AIRSUPRA should be administered cautiously to patients with thyrotoxicosis.

Potentially serious hypokalaemia may result from beta2-agonist therapy, mainly from parenteral and nebulised administration. Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics. Serum potassium levels should be monitored in such situations.

As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with an alternative product containing a fast-acting inhaled bronchodilator. AIRSUPRA should be discontinued immediately, the patient assessed, and a different fast-acting bronchodilator product instituted.

Reduced liver function may affect the elimination of glucocorticosteroids. The intravenous pharmacokinetics of budesonide however are similar in cirrhotic patients and in healthy subjects. The pharmacokinetics after oral ingestion of budesonide were affected by compromised liver function as evidenced by increased systemic availability. This is however of limited clinical importance for AIRSUPRA, as after inhalation the oral contribution to the systemic availability is relatively small.

Special caution is necessary in patients with active or quiescent pulmonary tuberculosis, and in patients with fungal or viral infections in the airways.

In vivo studies have shown that oral administration of ketoconazole and itraconazole (known inhibitors of CYP3A4 activity in the liver and in the intestinal mucosa, see also section 4.5 Interactions) may cause an increase of the systemic exposure to budesonide. This is of limited clinical importance for short-term (1-2 weeks) treatment but should be taken into consideration during long-term treatment.

The long-term local and systemic effects of budesonide are not completely known. Physicians should closely monitor the growth of children taking corticosteroids by any route and weigh the benefit of corticosteroid therapy and asthma control against the possibility of growth suppression.

No formal drug interaction studies have been performed with AIRSUPRA.

Salbutamol and non-selective beta-blocking drugs such as propranolol, should not usually be prescribed together.

The metabolism of budesonide is primarily mediated by CYP3A4, a subfamily of cytochrome P450. Inhibitors of this enzyme, e.g., ketoconazole and itrakonazole, can therefore increase systemic exposure to budesonide, see section 4.4 Special warnings and special precautions for use.

Pregnancy

Because of the potential for beta-agonist interference with uterine contractility, use of AIRSUPRA during labour should be restricted to those patients in whom the benefits clearly outweigh the risk. AIRSUPRA has not been approved for the management of pre-term labour. Serious adverse reactions, including pulmonary oedema, have been reported during or following treatment of premature labour with beta2-agonists, including salbutamol.

Studies in animals have shown reproductive toxicity (see section 5.3) of salbutamol. Safety in pregnant women has not been established. No controlled clinical trials with salbutamol have been conducted in pregnant women. Rare reports of various congenital anomalies following intrauterine exposure to salbutamol (including cleft palate, limb defects and cardiac disorders) have been received. Some of the mothers were taking multiple medications during their pregnancies. AIRSUPRA should not be used during pregnancy unless clearly necessary.

Despite a large amount of data (more than 1000 pregnancy outcomes) on pregnant women, there is insufficient robust evidence to indicate malformative toxicity of inhaled budesonide.

Breast-feeding

As salbutamol is probably secreted in breast milk, its use in nursing mothers requires careful consideration. It is not known whether salbutamol has a harmful effect on the neonate, and so its use should be restricted to situations where the expected benefit to the mother is likely to outweigh any potential risk to the neonate.

Budesonide is excreted in breast milk. However, at therapeutic doses of AIRSUPRA no effects on the suckling child are anticipated.

Fertility

There is no information on the effects of salbutamol on human fertility. There were no adverse effects on fertility in animals (see section 5.3).

Budesonide did not cause any adverse effects on fertility in rats. It is unlikely that AIRSUPRA administered at the recommended dose will affect fertility in humans.

AIRSUPRA is not expected to adversely affect the ability to drive or use machines.

Overall summary of the safety profile

Since AIRSUPRA contains both salbutamol and budesonide, the safety profile is related to the individual components of the combination. No increased incidence of adverse reactions has been seen

following concurrent administration of the two compounds. The most common drug related adverse reactions are pharmacologically predictable side effects of beta2-agonist therapy, such as tremor.

Adverse Drug Reactions

Adverse drug reactions (ADRs) are organised by MedDRA System Organ Class (SOC). Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness.

Frequencies of occurrence of adverse reactions are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000) and not known (cannot be estimated from available data).

Adverse drug reactions which have been associated with the individual components of AIRSUPRA, either alone or in combination, as evaluated in clinical trials, literature reports, or in a post-marketing setting, are given in Table 1.

Description of selected adverse reaction

Symptoms of systemic glucocorticosteroid effect, including hypofunction of the adrenal gland and reduction of growth rate, may occur with inhaled glucocorticosteroids, probably depending on dose, exposure time, concomitant and previous glucocorticosteroid exposure, and individual sensitivity.

To report any side effect (s)

Saudi Arabia

Other GCC States:

AIRSUPRA contains both salbutamol and budesonide; therefore, the risks associated with overdosage for the individual components described below apply to AIRSUPRA.

Salbutamol

The most common signs and symptoms of overdose with salbutamol are transient beta agonist pharmacologically mediated events, including tachycardia, tremor, hyperactivity and metabolic effects including hypokalaemia (see sections 4.4 and 4.8).

Hypokalaemia may occur following overdose with salbutamol. Serum potassium levels should be monitored. Lactic acidosis has been reported in association with high therapeutic doses as well as overdoses of short-acting beta-agonist therapy, therefore monitoring for elevated serum lactate and consequent metabolic acidosis (particularly if there is persistence or worsening of tachypnoea despite resolution of other signs of bronchospasm such as wheezing) may be indicated in the setting of overdose.

Budesonide

Acute overdosage with budesonide is not expected to be a clinical problem.

Mechanism of action

AIRSUPRA contains both salbutamol and budesonide; therefore, the mechanisms of action described below for the individual components apply to AIRSUPRA. These drugs represent two classes of medications (a short-acting selective beta2-adrenergic agonist and a synthetic corticosteroid) that have different effects on clinical, physiological, and inflammatory indices of asthma.

Salbutamol is a selective beta2-adrenoceptor agonist. At therapeutic doses it acts on the

beta2-adrenoceptors of bronchial muscle providing short acting (4-6 hour) bronchodilation with a fast onset (within 5 minutes) in reversible airways obstruction.

Budesonide is a glucocorticosteroid which when inhaled has a rapid (within hours) and dose-dependent anti-inflammatory action in the airways, resulting in reduced symptoms and fewer asthma exacerbations. Inhaled budesonide has a lower incidence and severity of adverse effects than those seen with oral corticosteroids. The exact mechanism responsible for the anti-inflammatory effect of glucocorticosteroids is unknown.

Clinical efficacy and safety

The efficacy of AIRSUPRA was evaluated in the 3 clinical randomized, double-blind, multicenter studies MANDALA, DENALI, and TYREE in subjects with mild to severe asthma as described below.

MANDALA

The efficacy of AIRSUPRA 180 mcg/160 mcg was evaluated in patients 12 years of age and older with moderate to severe asthma in MANDALA, a randomised, double-blind, multicentre study.

MANDALA was a variable length exacerbation study with at least 24 weeks duration.

Patients 12 years of age and older were randomised (1:1:1) and received at least one dose of AIRSUPRA, salbutamol/budesonide 180 mcg/80 mcg or salbutamol 180 mcg as needed. Patients were required to be receiving medium to high dose inhaled corticosteroids (ICS) or low to high dose ICS/long-acting beta2-adrenergic agonists (LABA), with or without another controller medicine as maintenance therapy. All patients continued their own maintenance therapy throughout the trial.

MANDALA was conducted in symptomatic patients with moderate to severe asthma, a history of at least 1 severe asthma exacerbation in the year prior to screening, pre-bronchodilator FEV1 ≥ 40 to < 90% of predicted normal (for patients aged 12 to < 18 years old, ≥ 60%) and a confirmed reversibility to salbutamol.

The efficacy population (n=3040) in MANDALA had a mean age of 51 years (range: 12 to 84 years), with 66% female, 82% Caucasian, and 25% of Hispanic or Latino ethnicity. The median duration of asthma was 20 years (range: 1 to 80 years) since the first diagnosis of asthma. The mean pre- bronchodilator percent predicted FEV1 was 68% (range 22% to 126%).

The overall patterns of use of AIRSUPRA and salbutamol 180 mcg were similar during the randomised treatment period.

The primary efficacy endpoint was the time to first severe asthma exacerbation (defined as worsening or onset of asthma symptoms that required systemic corticosteroids for at least 3 days or an emergency room visit that led to the use of systemic corticosteroids for at least 3 days or a hospitalisation for at least 24 hours due to asthma).

Treatment with AIRSUPRA, compared with salbutamol 180 mcg, demonstrated statistically significant reductions in the risk of severe asthma exacerbations, as assessed by the time to first severe asthma exacerbation as described in Figure 1. Compared with salbutamol 180 mcg, patients receiving AIRSUPRA experienced a statistically significant 27% reduction (Hazard Ratio

[HR] 0.73; 95% CI: 0.61, 0.88) in the risk of a severe asthma exacerbation (p<0.001).

Figure 1. Kaplan-Meier cumulative incidence curve for time to first exacerbation*

^*Curve truncated when < 1% of patient population remained at risk.

There were reductions in severe asthma exacerbation risk regardless of exacerbation history (1 or > 1 in the past year), baseline lung function, and asthma severity (defined by background maintenance therapy) compared with salbutamol 180 mcg.

Treatment with AIRSUPRA demonstrated a statistically significant reduction in the annual rate of severe asthma exacerbations by 24% compared with salbutamol 180 mcg as shown in Table 2.

Table 2. Annualized rate of severe exacerbations in patients 12 years of age and older with moderate to severe asthma

The annualised total systemic corticosteroid (SCS) dose due to asthma was calculated for each patient during the study period. For patients treated with AIRSUPRA, the annualised total SCS dose when compared with salbutamol 180 mcg demonstrated a statistically significant reduction in mean annualized dose of 43 mg per patient [AIRSUPRA (86 mg) vs salbutamol 180 mcg (129 mg)].

Asthma control was assessed using the Asthma Control Questionnaire (ACQ-5) responder analysis. Responders were defined as patients with an improvement of 0.5 or more in overall ACQ-5 score at Week 24 compared to baseline. The percentage of ACQ-5 responders at Week 24 for AIRSUPRA was 67% compared with 62% for salbutamol 180 mcg (odds ratio 1.22; 95% CI: 1.02, 1.47).

Asthma quality of life was assessed using the Asthma Quality of Life Questionnaire (AQLQ+12). Responders were defined as those with an improvement of 0.5 or more in AQLQ score at Week 24 compared to baseline. The percentage of responders at Week 24 for AIRSUPRA was 51% compared with 46% for salbutamol 180 mcg (odds ratio 1.23; 95% CI: 1.02, 1.48).

DENALI

The efficacy of AIRSUPRA on lung function was evaluated in patients 12 years of age and older with mild to moderate asthma who were previously treated with as-needed short-acting beta2-agonists (SABA) alone or with low-dose ICS maintenance therapy plus as-needed SABA. DENALI was a double-blind, active-comparator and placebo-controlled lung function study conducted over 12 weeks. Patients were randomized 1:1:1:1:1 to receive AIRSUPRA, salbutamol/budesonide 180 mcg/80 mcg, budesonide 160 mcg, salbutamol 180 mcg, or placebo, all administered 4 times daily. Only the results for the approved dose of AIRSUPRA are described below.

The study population (n=989) had a mean age of 49 years (range: 12 to 90 years) with 62% female, 89% Caucasian, and 28% of Hispanic or Latino ethnicity, and a median duration of asthma of 21 years. At screening, subjects had a pre-bronchodilator FEV1 of 50 to < 85% predicted normal value for subjects 18 years of age and older and ≥ 50% predicted normal value for subjects 12 to 17 years of age. All subjects were required to demonstrate reversibility to salbutamol. The mean pre-bronchodilator percent predicted FEV1 was 66% (range: 45 to 107%).

The dual primary endpoints were change from baseline in FEV1 AUC0-6 hours over the 12-week treatment period comparing AIRSUPRA with budesonide 160 mcg and change from baseline in trough FEV1 at Week 12 comparing AIRSUPRA with salbutamol 180 mcg.

For FEV1 AUC0-6 hours, AIRSUPRA showed statistically significantly greater improvements compared with budesonide 160 mcg (80.7 mL; 95% CI: 28.4, 132.9; p-value=0.003).

For trough FEV1, AIRSUPRA showed statistically significantly greater improvements compared with salbutamol 180 mcg (132.8 mL; 95% CI: 63.6, 201.9; p-value <0.001).

Onset of bronchodilation (as defined by a ≥ 15% increase in FEV1 post-dose within 30 minutes on Day 1) was observed in 50% of subjects treated with AIRSUPRA and 43% of subjects treated with salbutamol 180 mcg. Following a single dose on Day 1, the median time to onset and mean duration of bronchodilation were 7.5 and 186.9 minutes with AIRSUPRA and 9.5 and 168.2 minutes with salbutamol 180 mcg, respectively.

No diminution in the 6-hour bronchodilator effect was observed with AIRSUPRA as assessed by FEV1 following 12 weeks of treatment (Figures 2 and 3). Post-dose FEV1 AUC0-6 for AIRSUPRA was at Day One 240.8 mL and after 12 weeks 247.9 mL, compared to 212.6 mL and 137.5 mL respectively for salbutamol 180 mcg.

Figure 2. Mean change from baseline FEV1 on Day 1 (≥ 12 years of age)^*

*Baseline FEV1 is defined as the average of the 60- and 30-minute pre-dose results on the date of randomization. Error bars represent the standard error of mean estimates.

Figure 3. Mean change from baseline FEV1 at Week 12 (≥ 12 years of age)^*

*Baseline FEV1 is defined as the average of the 60- and 30-minute pre-dose results on the date of randomization. Error bars represent the standard error of mean estimates.

Subjects receiving AIRSUPRA demonstrated an improvement from baseline in trough FEV1 at Week 1 when compared with salbutamol 180 mcg (107.9 mL; 95% CI: 48.1, 167.8).

Asthma control was assessed in subjects who were uncontrolled at baseline using the ACQ-7 responder analysis. Responders were defined as those with an improvement of 0.5 or more from baseline to Week 12. The percentage of responders for AIRSUPRA were 66% compared with 47% for salbutamol 180 mcg (odds ratio 2.3; 95% CI: 1.47, 3.69).

The incidence of severe exacerbations was an exploratory endpoint in DENALI. The number (percentage) of subjects with at least 1 severe asthma exacerbation was lower in AIRSUPRA and budesonide 160 mcg treatment groups at 4 (2.0%), and 4 (2.0%), respectively when compared with

salbutamol 180 mcg at 20 (10.2%) and placebo at 14 (7.1%).

TYREE

TYREE was a randomized, single-dose, cross-over study in patients 12 years of age and older with asthma and exercise-induced bronchoconstriction (EIB). Patients receiving either as-needed SABA alone or low-to-medium-dose ICS maintenance therapy and as-needed SABA were included. The study population (n=60) had a mean age of 40 years (range: 15 to 67 years) with 63% female, 65%

Caucasian, and 5% of Hispanic or Latino ethnicity, and had a mean pre-bronchodilator percent predicted pre-exercise challenge FEV1 of 81% (range 71% - 129%).

When AIRSUPRA or placebo was taken 30 minutes prior to exercise, the mean maximum percentage fall from post-dose pre-exercise challenge FEV1 in the overall population was 5.5% compared with 19.0%, respectively. Additionally, 47/60 (78.3%) patients were fully protected from EIB (as defined by reduction in FEV1 less than 10% of post-dose, pre-exercise baseline values) when dosed with AIRSUPRA, versus 17/60 (28.3%) patients treated with placebo. Similar effects were seen in subjects on SABA alone and in subjects on ICS maintenance with as-needed SABA.

Absorption

Salbutamol

Following inhaled administration of AIRSUPRA in healthy subjects, the median tmax of salbutamol was 1.00 hour (individual values ranged from 0.08 to 6.05 hours). Geometric mean Cmax was 472.2 pg/mL (individual values ranged from 38.4 to 971 pg/mL).

Budesonide

Following inhaled administration in healthy subjects of AIRSUPRA, the median tmax of budesonide was 0.33 hours (individual values ranged from 0.08 to 4.00 hours). Geometric mean Cmax was 272.8 pg/mL (individual values ranged from 51.7 to 819 pg/mL). Systemic exposure to budesonide with AIRSUPRA did not exceed that from inhaled budesonide via a dry powder inhaler comparator in healthy subjects.

Distribution

Salbutamol

Following inhaled administration of AIRSUPRA in healthy subjects, the mean apparent volume of distribution (Vz/F) of salbutamol was 565.7 L. Salbutamol is bound to plasma proteins to the extent of 10%.

Budesonide

Following inhaled administration of AIRSUPRA in healthy subjects, the mean apparent volume of distribution (Vz/F) of budesonide administered in AIRSUPRA was 1002.0 L. Budesonide plasma protein binding averages 85-90%.

Biotransformation

Salbutamol

Salbutamol administered intravenously is cleared partly renally and partly by metabolism to the inactive 4'-O-sulfate (phenolic sulfate).

Budesonide

Budesonide undergoes an extensive degree (»90%) of biotransformation on first passage through the liver to metabolites of low glucocorticosteroid activity. The glucocorticosteroid activity of the major

metabolites, 6b-hydroxybudesonide and 16a-hydroxyprednisolone, is less than 1% of that of budesonide. The metabolism of budesonide is primarily mediated by CYP3A, a subfamily of cytochrome p450.

Elimination

Following inhaled single-dose administration with AIRSUPRA in healthy subjects, the mean terminal half-life of salbutamol was estimated to be 7.1 hours (individual values ranged from 4.62 to 10.0 hours) and the mean terminal half-life of budesonide was estimated to be 4.1 hours (individual values ranges from 2.46 to 6.15 hours).

Linearity/non-linearity

The kinetics of budesonide is dose-proportional at clinically relevant doses. Special populations

Specific studies to examine the effects of age, sex, gender/ethnicity, or body weight on the pharmacokinetics of AIRSUPRA have not been conducted.

Elderly patients

Based on available data, no adjustment of the dosage of AIRSUPRA in elderly patients is necessary.

The confirmatory trial of AIRSUPRA for asthma included 566 subjects aged 65 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

Renal impairment

There are no data regarding the specific use of AIRSUPRA in patients with renal impairment.

Hepatic impairment

There are no data regarding the specific use of AIRSUPRA in patients with hepatic impairment.

However, because budesonide is primarily eliminated via hepatic metabolism, an increased exposure can be expected in patients with severe liver impairment.

Paediatric patients

The pharmacokinetics of salbutamol and budesonide in paediatric patients 12 to 17 years old have not been specifically evaluated in a dedicated study with AIRSUPRA.

Drug-Drug Interaction

Inhibitors of cytochrome P450 enzymes

Ketoconazole: As a strong inhibitor of cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4), the main metabolic enzyme for corticosteroids, ketoconazole increased plasma levels of orally ingested budesonide.

Cimetidine: At recommended doses, cimetidine, a nonspecific inhibitor of CYP enzymes, had a slight but clinically insignificant effect on the pharmacokinetics of oral budesonide.

Non-clinical data reveal no specific hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.

The toxicity observed in animal studies with budesonide and salbutamol were associated with pharmacological actions or minor adaptive responses commonly observed in inhalation toxicology studies and dose-dependent.

No non-clinical repeat dose toxicology, genotoxicity, carcinogenicity or reproductive toxicology studies have been conducted with AIRSUPRA.

Salbutamol

In common with other potent selective beta2-agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of foetuses were found to have cleft palate at 2.5 mg/kg dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50 mg/kg/day orally throughout pregnancy resulted in no significant foetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as the result of lack of maternal care.

Reproductive studies in the rabbit at doses of 50 mg/kg/day orally (900 times higher than the maximum dose in humans on a mcg/m2 basis) have shown foetuses with treatment related changes; these included open eyelids (ablepharia), secondary palate clefts (palatoschisis), changes in ossification of the frontal bones of the cranium (cranioschisis) and limb flexure.

In an oral fertility and general reproductive performance study in rats at doses of 2 and 50 mg/kg/day (450 times higher than the maximum dose in humans on a mcg/m2 basis), with the exception of a reduction in number of weanlings surviving to day 21 post-partum at 50 mg/kg/day, there were no adverse effects on fertility, embryofoetal development, litter size, birth weight or growth rate.

AIRSUPRA contains the excipients 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and calcium chloride as part of the spray-dried porous particle technology in the pressurised liquid propellant HFA- 134a. The safety of HFA-134a has been fully evaluated in preclinical studies. DSPC and calcium chloride have a long history of safe use in man and are approved excipients worldwide.

Budesonide

In animal reproduction studies, glucocorticosteroids such as budesonide have been shown to induce malformations (cleft palate, skeletal malformations). However, these animal experimental results are not relevant in humans at the recommended doses (see section 4.6). Budesonide demonstrated no tumourigenic potential in mice. In rats, an increased incidence of hepatocellular tumours was observed, considered to be a class-effect in rats from long-term exposure to corticosteroids.

HFA-134a

1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) Calcium chloride

Not applicable.

Do not store above 30°C. Store in a dry place.

A pressurised metered dose inhaler, comprising an internally-coated aluminium canister, sealed with a metering valve, fitted with an attached dose indicator and fitted into a white plastic actuator body with a frosted clear plastic dust cap. Each inhaler is individually packaged in a foil laminate pouch containing a desiccant sachet and placed into a carton.

The canister should not be broken, punctured or burnt, even when apparently empty. Do not use or store near heat or open flames. Do not expose to temperatures above 49^oC.

See also section 4.2 Posology and method of administration, and the patient information leaflet.