Fluticasone Propionate and Salmeterol HFA

1 INDICATIONS AND USAGE Fluticasone Propionate and Salmeterol HFA is indicated for treatment of asthma in adult and adolescent patients aged 12 years and older. Fluticasone Propionate and Salmeterol HFA should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ICS) or whose disease warrants initiation of treatment with both an ICS and long-acting beta 2 -adrenergic agonist (LABA). Limitations of Use Fluticasone Propionate and Salmeterol HFA is not indicated for the relief of acute bronchospasm. Fluticasone Propionate and Salmeterol HFA is a combination of fluticasone propionate, an inhaled corticosteroid, and salmeterol, a long-acting beta 2 ‐adrenergic agonist (LABA), indicated for treatment of asthma in adult and adolescent patients aged 12 years and older. ( 1 ) Limitations of use: Not indicated for relief of acute bronchospasm. ( 1 )

2 DOSAGE AND ADMINISTRATION • For oral inhalation only. ( 2.1 ) • Adult and adolescent patients aged 12 years and older: 2 inhalations of Fluticasone Propionate and Salmeterol HFA 45 mcg/21 mcg, Fluticasone Propionate and Salmeterol HFA 115 mcg/21 mcg, or Fluticasone Propionate and Salmeterol HFA 230 mcg/21 mcg twice daily. ( 2.2 ) • Starting dosage is based on asthma severity. ( 2.2 ) 2.1 Administration Information Fluticasone Propionate and Salmeterol HFA should be administered by the orally inhaled route only. After inhalation, rinse mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis. Priming Prime Fluticasone Propionate and Salmeterol HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 4 weeks or when it has been dropped, prime the inhaler again by releasing 2 sprays into the air away from the face, shaking well for 5 seconds before each spray. Avoid spraying in eyes. 2.2 Recommended Dosage Adult and adolescent patients aged 12 years and older: 2 oral inhalations twice daily, approximately 12 hours apart. The maximum recommended dosage is 2 inhalations of Fluticasone Propionate and Salmeterol HFA 230 mcg/21 mcg twice daily. General Dosing Recommendation When choosing the starting dosage strength of Fluticasone Propionate and Salmeterol HFA, consider the patients’ disease severity, based on their previous asthma therapy, including the ICS dosage, as well as the patients’ current control of asthma symptoms and risk of future exacerbation. If asthma symptoms arise in the period between doses, an inhaled, short-acting beta 2 -agonist should be used for immediate relief. Improvement in asthma control following inhaled administration of Fluticasone Propionate and Salmeterol HFA can occur within 30 minutes of beginning treatment, although maximum benefit may not be achieved for 1 week or longer after starting treatment. Individual patients will experience a variable time to onset and degree of symptom relief. For patients who do not respond adequately to the starting dosage after 2 weeks of therapy, replacing the current strength of Fluticasone Propionate and Salmeterol HFA with a higher strength may provide additional improvement in asthma control. If a previously effective dosage regimen fails to provide adequate improvement in asthma control, the therapeutic regimen should be reevaluated and additional therapeutic options (e.g., replacing the current strength of Fluticasone Propionate and Salmeterol HFA with a higher strength, adding additional ICS, initiating oral corticosteroids) should be considered. More frequent administration or a greater number of inhalations (more than 2 inhalations twice daily) of the prescribed strength of Fluticasone Propionate and Salmeterol HFA is not recommended as some patients are more likely to experience adverse effects with higher doses of salmeterol. Patients using Fluticasone Propionate and Salmeterol HFA should not use additional LABA for any reason. [See Warnings and Precautions ( 5.3 , 5.12 ).]

3 DOSAGE FORMS AND STRENGTHS Inhalation aerosol: purple plastic inhaler with a light purple cap containing a pressurized metered-dose aerosol canister containing 120 metered inhalations and fitted with a counter. • 45 mcg fluticasone propionate/21 mcg salmeterol from the mouthpiece per actuation • 115 mcg fluticasone propionate/21 mcg salmeterol from the mouthpiece per actuation • 230 mcg fluticasone propionate/21 mcg salmeterol from the mouthpiece per actuation Inhalation aerosol: • 45 mcg fluticasone propionate/21 mcg salmeterol per actuation (3) • 115 mcg fluticasone propionate/21 mcg salmeterol per actuation (3) • 230 mcg fluticasone propionate/21 mcg salmeterol per actuation (3)

4 CONTRAINDICATIONS Fluticasone Propionate and Salmeterol HFA is contraindicated in the following conditions: • Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required [see Warnings and Precautions ( 5.2 )] . • Hypersensitivity to any of the ingredients [see Warnings and Precautions ( 5.11 ), Adverse Reactions ( 6.2 ), Description ( 11 )] . • Primary treatment of status asthmaticus or acute episodes of asthma requiring intensive measures. ( 4 ) • Hypersensitivity to any ingredient. (4)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Serious asthma-related events – hospitalizations, intubations, death [see Warnings and Precautions ( 5.1 )] • Oropharyngeal candidiasis [see Warnings and Precautions ( 5.4 )] • Pneumonia in patients with COPD [see Warnings and Precautions ( 5.5 )] • Immunosuppression and risk of infections [see Warnings and Precautions ( 5.6 )] • Hypercorticism and adrenal suppression [see Warnings and Precautions ( 5.8 )] • Cardiovascular and central nervous system effects [see Warnings and Precautions ( 5.12 )] • Reduction in bone mineral density [see Warnings and Precautions ( 5.13 )] • Growth effects [see Warnings and Precautions ( 5.14 )] • Glaucoma and cataracts [see Warnings and Precautions ( 5.15 )] Most common adverse reactions (incidence ≥3%) include: upper respiratory tract infection or inflammation, throat irritation, dysphonia, headache, dizziness, nausea and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Prasco Laboratories at 1-866-525-0688 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult and Adolescent Subjects Aged 12 Years and Older The incidence of adverse reactions associated with fluticasone propionate and salmeterol HFA in Table 2 is based upon two 12-week, placebo-controlled, U.S. clinical trials (Trials 1 and 3) and 1 active-controlled 12-week U.S. clinical trial (Trial 2). A total of 1,008 adult and adolescent subjects with asthma (556 females and 452 males) previously treated with albuterol alone, salmeterol, or ICS were treated twice daily with 2 inhalations of fluticasone propionate and salmeterol HFA 45 mcg/21 mcg or fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, fluticasone propionate CFC inhalation aerosol (44- or 110-mcg doses), salmeterol CFC inhalation aerosol 21 mcg, or placebo HFA inhalation aerosol. The average duration of exposure was 71 to 81 days in the active treatment groups compared with 51 days in the placebo group. Table 2. Adverse Reactions with Fluticasone Propionate and Salmeterol HFA with ≥3% Incidence in Adult and Adolescent Subjects with Asthma Adverse Event Fluticasone Propionate and Salmeterol HFA Fluticasone Propionate CFC Inhalation Aerosol Salmeterol CFC Inhalation Aerosol Placebo HFA Inhalation Aerosol 45 mcg/21 mcg (n = 187) % 115 mcg/21 mcg (n = 94) % 44 mcg (n = 186) % 110 mcg (n = 91) % 21 mcg (n = 274) % (n = 176) % Ear, nose, and throat Upper respiratory tract infection 16 24 13 15 17 13 Throat irritation 9 7 12 13 9 7 Upper respiratory inflammation 4 4 3 7 5 3 Hoarseness/dysphonia 3 1 2 0 1 0 Lower respiratory Viral respiratory infection 3 5 4 5 3 4 Neurology Headache 21 15 24 16 20 11 Dizziness 4 1 1 0 <1 0 Gastrointestinal Nausea and vomiting 5 3 4 2 2 3 Viral gastrointestinal infection 4 2 2 0 1 2 Gastrointestinal signs and symptoms 3 2 2 1 1 1 Musculoskeletal Musculoskeletal pain 5 7 8 2 4 4 Muscle pain 4 1 1 1 3 <1 The incidence of common adverse reactions reported in Trial 4, a 12-week non-U.S. clinical trial in 509 subjects previously treated with ICS who were treated twice daily with 2 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg, fluticasone propionate CFC inhalation aerosol 220 mcg, or 1 inhalation of ADVAIR DISKUS 500 mcg/50 mcg was similar to the incidences reported in Table 2. Additional Adverse Reactions Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that occurred in the groups receiving fluticasone propionate and salmeterol HFA with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo include the following …

7 DRUG INTERACTIONS Fluticasone propionate and salmeterol HFA has been used concomitantly with other drugs, including short-acting beta 2 -agonists, methylxanthines, and nasal corticosteroids, commonly used in patients with asthma without adverse drug reactions [see Clinical Pharmacology ( 12.2 )] . No formal drug interaction trials have been performed with fluticasone propionate and salmeterol HFA. • Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. May increase risk of systemic corticosteroid and cardiovascular effects. ( 7.1 ) • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of salmeterol on vascular system. ( 7.2 ) • Beta-blockers: Use with caution. May block bronchodilatory effects of beta-agonists and produce severe bronchospasm. ( 7.3 ) • Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists. ( 7.4 ) 7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone propionate and salmeterol, the individual components of Fluticasone Propionate and Salmeterol HFA, are substrates of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate and Salmeterol HFA is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur. Ritonavir Fluticasone Propionate: A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Clinical Pharmacology ( 12.3 )] . During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression. Ketoconazole Fluticasone Propionate: Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone propionate exposure and a 45% decrease in plasma cortisol area under the curve (AUC), but had no effect on urinary excretion of cortisol. Salmeterol: In a drug interaction trial in 20 healthy subjects, coadministration of inhaled salmeterol (50 mcg twice daily) and oral ketoconazole (400 mg once daily) for 7 days resulted in greater systemic exposure to salmeterol (AUC increased 16-fold and C max increased 1.4-fold). Three (3) subjects were withdrawn due to beta 2 -agonist side effects (2 with prolonged QTc and 1 with palpitations and sinus tachycardia). Although there was no statistical effect on the mean QTc, coadministration of salmeterol and ketoconazole was associated with more frequent increases in QTc duration compared with salmeterol and placebo administration. 7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Fluticasone Propionate and Salmeterol HFA should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of salmeterol, a component of Fluticasone Propionate and Salmeterol HFA, on the vascular system may be potentiated by these agents. 7.3 Beta-adrenergic Receptor Blocking Agents Beta-blockers not only block the pulmonary effect of beta-agonists, such as salmeterol, a component of Fluticasone Propionate and Salmeterol HFA, but may also produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, there may be no acceptable alternatives to the use …

8 USE IN SPECIFIC POPULATIONS Hepatic impairment: Monitor patients for signs of increased drug exposure. (8.6) 8.1 Pregnancy Risk Summary There are insufficient data on the use of fluticasone propionate and salmeterol HFA or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. There are clinical considerations with the use of fluticasone propionate and salmeterol HFA in pregnant women. (See Clinical Considerations.) In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits, was observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the maximum recommended human daily inhaled dose (MRHDID) on a mcg/m 2 basis. (See Data.) However, fluticasone propionate administered via inhalation to rats decreased fetal body weight but did not induce teratogenicity at a maternal toxic dose less than the MRHDID on a mcg/m 2 basis. (See Data.) Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. Oral administration of salmeterol to pregnant rabbits caused teratogenicity characteristic of beta-adrenoceptor stimulation at maternal doses approximately 25 times the MRHDID on an AUC basis. These adverse effects generally occurred at large multiples of the MRHDID when salmeterol was administered by the oral route to achieve high systemic exposures. No such effects occurred at an oral salmeterol dose approximately 10 times the MRHDID. (See Data.) The estimated risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma. Labor and Delivery: There are no human studies evaluating the effects of fluticasone propionate and salmeterol HFA during labor and delivery. Because of the potential for beta-agonist interference with uterine contractility, use of Fluticasone Propionate and Salmeterol HFA during labor should be restricted to those patients in whom the benefits clearly outweigh the risks. Data Human Data: Fluticasone Propionate: Following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery. Animal Data: Fluticasone Propionate and Salmeterol: In an embryofetal development study with pregnant rats that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,000; 30/0; 10/100; 30/1,000; and 100/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. Omphalocele, increased embryofetal deaths, decreased body weight, and skeletal variations were observed in rat fetuses in the presence of maternal toxicity when combining fluticasone propionate at a dose approximately equivalent to the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 100 mcg/kg/day) and salmeterol at a dose approximately 1,200 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 10,000 mcg/kg/day). The rat no observed adverse effect level (NOAEL) was observed when combining fluticasone propionate at a dose less than the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 30 mcg/kg/day) and salmeterol at a dose approximately 12 …

12.1 Mechanism of Action Fluticasone Propionate and Salmeterol HFA Fluticasone Propionate and Salmeterol HFA contains both fluticasone propionate and salmeterol. The mechanisms of action described below for the individual components apply to Fluticasone Propionate and Salmeterol HFA. These drugs represent 2 different classes of medications (a synthetic corticosteroid and a LABA) that have different effects on clinical, physiologic, and inflammatory indices of asthma. Fluticasone Propionate Fluticasone propionate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Fluticasone propionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is 18 times that of dexamethasone, almost twice that of beclomethasone-17-monopropionate (BMP), the active metabolite of beclomethasone dipropionate, and over 3 times that of budesonide. Data from the McKenzie vasoconstrictor assay in man are consistent with these results. The clinical significance of these findings is unknown. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma. Salmeterol Xinafoate Salmeterol is a selective LABA. In vitro studies show salmeterol to be at least 50 times more selective for beta 2 ‐adrenoceptors than albuterol. Although beta 2 -adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -adrenoceptors are the predominant receptors in the heart, there are also beta 2 -adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these receptors has not been established, but their presence raises the possibility that even selective beta 2 -agonists may have cardiac effects. The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including salmeterol, are at least in part attributable to stimulation of intracellular adenyl 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. In vitro tests show that salmeterol is a potent and long-lasting inhibitor of the release of mast cell mediators, such as histamine, leukotrienes, and prostaglandin D 2 , from human lung. Salmeterol inhibits histamine-induced plasma protein extravasation and inhibits platelet-activating factor–induced eosinophil accumulation in the lungs of guinea pigs when administered by the inhaled route. In humans, single doses of salmeterol administered via inhalation aerosol attenuate allergen-induced bronchial hyper-responsiveness.

11 DESCRIPTION Fluticasone Propionate and Salmeterol HFA 45 mcg/21 mcg inhalation aerosol, Fluticasone Propionate and Salmeterol HFA inhalation aerosol 115 mcg/21 mcg, and Fluticasone Propionate and Salmeterol HFA inhalation aerosol 230 mcg/21 mcg are combinations of fluticasone propionate and salmeterol xinafoate. One active component of Fluticasone Propionate and Salmeterol HFA is fluticasone propionate, a corticosteroid having the chemical name S- (fluoromethyl) 6α,9-difluoro-11β,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, 17-propionate and the following chemical structure: Fluticasone propionate is a white powder with a molecular weight of 500.6, and the empirical formula is C 25 H 31 F 3 O 5 S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol. The other active component of Fluticasone Propionate and Salmeterol HFA is salmeterol xinafoate, a beta 2 -adrenergic bronchodilator. Salmeterol xinafoate is the racemic form of the 1-hydroxy-2-naphthoic acid salt of salmeterol. It has the chemical name 4-hydroxy-α 1 -[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol, 1-hydroxy-2-naphthalenecarboxylate and the following chemical structure: Salmeterol xinafoate is a white powder with a molecular weight of 603.8, and the empirical formula is C 25 H 37 NO 4 •C 11 H 8 O 3 . It is freely soluble in methanol; slightly soluble in ethanol, chloroform, and isopropanol; and sparingly soluble in water. Fluticasone Propionate and Salmeterol HFA is a purple plastic inhaler with a light purple cap containing a pressurized metered-dose aerosol canister fitted with a counter. Each canister contains a microcrystalline suspension of micronized fluticasone propionate and micronized salmeterol xinafoate in propellant HFA-134a (1,1,1,2-tetrafluoroethane). It contains no other excipients. After priming, each actuation of the inhaler delivers 50, 125, or 250 mcg of fluticasone propionate and 25 mcg of salmeterol in 75 mg of suspension from the valve. Each actuation delivers 45, 115, or 230 mcg of fluticasone propionate and 21 mcg of salmeterol from the actuator. Twenty-one micrograms (21 mcg) of salmeterol base is equivalent to 30.45 mcg of salmeterol xinafoate. The actual amount of drug delivered to the lung will depend on patient factors, such as the coordination between the actuation of the inhaler and inspiration through the delivery system. Prime Fluticasone Propionate and Salmeterol HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 4 weeks or when it has been dropped, prime the inhaler again by releasing 2 sprays into the air away from the face, shaking well for 5 seconds before each spray. Avoid spraying in eyes. Fluticasone chemical structure Salmeterol chemical structure

10 OVERDOSAGE No human overdosage data has been reported for fluticasone propionate and salmeterol HFA. Fluticasone Propionate and Salmeterol HFA contains both fluticasone propionate and salmeterol; therefore, the risks associated with overdosage for the individual components described below apply to Fluticasone Propionate and Salmeterol HFA. Treatment of overdosage consists of discontinuation of Fluticasone Propionate and Salmeterol HFA together with institution of appropriate symptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. Cardiac monitoring is recommended in cases of overdosage. Fluticasone Propionate Chronic overdosage of fluticasone propionate may result in signs/symptoms of hypercorticism [see Warnings and Precautions ( 5.8 )] . Salmeterol The expected signs and symptoms with overdosage of salmeterol are those of excessive beta‐adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms of beta-adrenergic stimulation (e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, metabolic acidosis). Overdosage with salmeterol can lead to clinically significant prolongation of the QTc interval, which can produce ventricular arrhythmias. As with all inhaled sympathomimetic medicines, cardiac arrest and even death may be associated with an overdose of salmeterol.

16 HOW SUPPLIED/STORAGE AND HANDLING Fluticasone Propionate and Salmeterol HFA is supplied in the following boxes of 1 as a pressurized aluminum canister fitted with a counter and supplied with a purple plastic actuator with a light purple cap: • Fluticasone Propionate and Salmeterol HFA 45 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 66993-086-96) • Fluticasone Propionate and Salmeterol HFA 115 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 66993-087-96) • Fluticasone Propionate and Salmeterol HFA 230 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 66993-088-96) Each inhaler is packaged with a Patient Information leaflet. The purple actuator supplied with Fluticasone Propionate and Salmeterol HFA should not be used with any other product canisters, and actuators from other products should not be used with a Fluticasone Propionate and Salmeterol HFA canister. Counter Fluticasone Propionate and Salmeterol HFA has a counter attached to the canister. The counter starts at 124 and counts down each time a spray is released. The correct amount of medication in each actuation cannot be assured after the counter reads 000, even though the canister is not completely empty and will continue to operate. The inhaler should be discarded when the counter reads 000. Contents under Pressure Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw canister into fire or incinerator. Storage Store at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C) [See USP Controlled Room Temperature]. Store the inhaler with the mouthpiece down. For best results, the inhaler should be at room temperature before use.