Advair HFA fluticasone propionate and salmeterol xinafoate 230 ug; 21 ug Aerosol, Metered — NDC 0173-0717-22 (Billing 00173-0717-22)
This is a package of Advair HFA fluticasone propionate and salmeterol xinafoate 230 ug; 21 ug Aerosol, Metered from GlaxoSmithKline LLC, marketed since Mar 2009 and currently FDA-listed; retail pharmacies pay about $30.53 per g (NADAC).
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 061345
- GCN: 97137
- GPI-14 (Medi-Span): 44209902703270
- HICL (First Databank): 019963
- AHFS class code: 12:12.08.12
- RxCUI (RxNorm): 896231
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the beta2-Adrenergic Agonist class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
The combination of fluticasone and salmeterol (Advair® Diskus, Advair® HFA, AirDuo® Respiclick) is used to treat difficulty breathing, wheezing, shortness of breath, coughing, and chest tightness caused by asthma. The combination of fluticasone and salmeterol (Advair® Diskus) is also used to prevent and treat wheezing, shortness of breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema). The combination of fluticasone and salmeterol (Advair® Diskus) is used in adults and children 4 yea...
Read the full MedlinePlus article ↗- It's a twice-daily controller for asthma in people 4 and older. The inhalation powder is also used for COPD maintenance. It's not for sudden attacks, so keep your rescue inhaler cl...
- Take one inhalation twice a day, about 12 hours apart, and don't take extra. Rinse your mouth with water afterward and spit it out. That helps prevent a yeast infection in your mou...
- Use your short-acting rescue inhaler, not extra doses of this one. If you need the rescue inhaler more and more, call your doctor, since that can mean your asthma is getting worse.
- What if I feel short of breath between doses?
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per g | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $30.531 | — |
| Medicaid paysCMS SDUD · 12 mo | $29.73 | — |
| Medicare drug plans payPart D · Q2 2026 | $19.94 | — |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q4 2025
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 00173-0717-20 0173-0717-20 Main listing | 1 INHALER in 1 CARTON / 120 AEROSOL, METERED in 1 INHALER | $35.02 / g | — | 2009-03-06 | — | Active |
| 00173-0717-22 You're viewing this | 1 INHALER in 1 CARTON / 60 AEROSOL, METERED in 1 INHALER | $30.53 / g | — | 2009-03-06 | — | Active |
This pack has the lowest per-g cost of the 2 priced pack sizes ($30.53 NADAC).
Pack size FAQ
What quantity is in this package?
What NDC number is used to bill for this package of Advair HFA fluticasone propionate and salmeterol xinafoate 230 ug; 21 ug Aerosol, Metered?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Fluticasone Propionate and Salmeterol HFA 230 ug/1; 21 ug 66993-0088-96 | Prasco | 1 inhaler | $26.746 | — | Availability likely | save 12% |
| Advair Hfa 230 ug/1; 21 ugthis 00173-0717-22 | GlaxoSmithKline | 1 inhaler | $30.531 | — | Availability likely | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII DH9E53K1Y8
A synthetic fluorinated hydrocarbon used primarily as a propellant or aerosol dispersant in pressurized inhaler formulations to help deliver medication to the lungs.
1 inactive ingredient listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE ADVAIR HFA is indicated for treatment of asthma in adult and adolescent patients aged 12 years and older. ADVAIR 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 ADVAIR HFA is not indicated for the relief of acute bronchospasm.
ADVAIR 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 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • For oral inhalation only. ( 2.1 ) • Adult and adolescent patients aged 12 years and older: 2 inhalations of ADVAIR HFA 45 mcg/21 mcg, ADVAIR HFA 115 mcg/21 mcg, or ADVAIR HFA 230 mcg/21 mcg twice daily. ( 2.2 ) • Starting dosage is based on asthma severity. ( 2.2 )
2.1Administration Information ADVAIR 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 ADVAIR 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.
2.2Recommended 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 ADVAIR HFA 230 mcg/21 mcg twice daily. General Dosing Recommendation When choosing the starting dosage strength of ADVAIR 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 ADVAIR 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 ADVAIR 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 ADVAIR 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 ADVAIR HFA is not recommended as some patients are more likely to experience adverse effects with higher doses of salmeterol. Patients using ADVAIR HFA should not use additional LABA for any reason. [See Warnings and Precautions ( 5.3 , 5.12 ).]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Inhalation aerosol: purple plastic inhaler with a light purple cap containing a pressurized metered-dose aerosol canister containing 60 or 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)
⛔ Contraindications ▾
4 CONTRAINDICATIONS ADVAIR 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)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • LABA monotherapy increases the risk of serious asthma-related events. (5.1) • Do not initiate in acutely deteriorating asthma or to treat acute symptoms. (5.2) • Do not use in combination with an additional medicine containing a LABA because of risk of overdose.
(5.3) • Candida albicans infection of the mouth and pharynx may occur. Monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after inhalation to help reduce the risk.
( 5.4 ) • Increased risk of pneumonia in patients with COPD. Monitor patients for signs and symptoms of pneumonia. ( 5.5 ) • Potential worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infections; ocular herpes simplex).
Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. ( 5.6 ) • Risk of impaired adrenal function when transferring from systemic corticosteroids.
Taper patients slowly from systemic corticosteroids if transferring to ADVAIR HFA. ( 5.7 ) • Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue ADVAIR HFA slowly.
( 5.8 ) • If paradoxical bronchospasm occurs, discontinue ADVAIR HFA and institute alternative therapy. ( 5.10 ) • Use with caution in patients with cardiovascular or central nervous system disorders because of beta-adrenergic stimulation. ( 5.12 ) • Assess for decrease in bone mineral density initially and periodically thereafter.
( 5.13 ) • Monitor growth of pediatric patients. ( 5.14 ) • Glaucoma and cataracts may occur with long-term use of inhaled corticosteroids. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ADVAIR HFA long term.
( 5.15 ) • Be alert to eosinophilic conditions, hypokalemia, and hyperglycemia. ( 5.16 , 5.18 ) • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis. ( 5.17 )
5.1Serious Asthma-Related Events – Hospitalizations, Intubations, Death Use of LABA as monotherapy (without ICS) for asthma is associated with an increased risk of asthma-related death [see Salmeterol Multicenter Asthma Research Trial (SMART)] . Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy.
When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone (see Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists) . Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists Four (4) large, 26-week, randomized, double-blind, active-controlled clinical safety trials were conducted to evaluate the risk of serious asthma-related events when LABA were used in fixed‑dose combination with ICS compared with ICS alone in subjects with asthma.
Three (3) trials included adult and adolescent subjects aged 12 years and older: 1 trial compared fluticasone propionate/salmeterol inhalation powder with fluticasone propionate inhalation powder, 1 trial compared mometasone furoate/formoterol with mometasone furoate, and 1 trial compared budesonide/formoterol with budesonide. The fourth trial included pediatric subjects aged 4 to 11 years and compared fluticasone propionate/salmeterol inhalation powder with fluticasone propionate inhalation powder. The primary safety endpoint for all 4 trials was serious asthma-related events (hospitalizations, intubations, death).
A blinded adjudication committee determined whether events were asthma related. The 3 adult and ado… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
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 GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 ADVAIR 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 ADVAIR HFA 45 mcg/21 mcg or ADVAIR 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 ADVAIR HFA with ≥3% Incidence in Adult and Adolescent Subjects with Asthma Adverse Event ADVAIR 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 ADVAIR 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 ADVAIR HFA with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo include the following: tachycardia, arrhythmias, myocardial infarction, postoperative complications, wounds and lacerations, soft tissue injuries, ear signs and symptoms, rhinorrhea/postnasal drip, epistaxis, nasal congestion/blockage, laryngitis, unspecified… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS ADVAIR 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 ADVAIR 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 )
7.1Inhibitors of Cytochrome P450 3A4 Fluticasone propionate and salmeterol, the individual components of ADVAIR HFA, are substrates of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with ADVAIR 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.
7.2Monoamine Oxidase Inhibitors and Tricyclic Antidepressants ADVAIR 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 ADVAIR HFA, on the vascular system may be potentiated by these agents.
7.3Beta-adrenergic Receptor Blocking Agents Beta-blockers not only block the pulmonary effect of beta-agonists, such as salmeterol, a component of ADVAIR 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 of beta-adrenergic blocking agents for these patients; cardioselective beta-blockers could be considered, although they should be administered with caution.
7.4Non–Potassium-Sparing Diuretics The ECG changes and/or hypok… [Excerpted — this section continues on DailyMed.]
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Hepatic impairment: Monitor patients for signs of increased drug exposure. (8.6)
8.1Pregnancy Risk Summary There are insufficient data on the use of ADVAIR HFA or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. There are clinical considerations with the use of ADVAIR 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 ADVAIR HFA during labor and delivery. Because of the potential for beta-agonist interference with uterine contractility, use of ADVAIR 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 120 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 1,000 mcg/kg/day). In an embryofetal development study wit… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are insufficient data on the use of ADVAIR HFA or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. There are clinical considerations with the use of ADVAIR 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 ADVAIR HFA during labor and delivery. Because of the potential for beta-agonist interference with uterine contractility, use of ADVAIR 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 120 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 1,000 mcg/kg/day). In an embryofetal development study with pregnant mice that received the combination of subcutaneous administration of fluticasone propionate and oral… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of ADVAIR HFA have been established in pediatric patients aged 12 years and older. Use of ADVAIR HFA in this age group is supported by evidence from adequate and well-controlled studies in adults with additional data from thirty-eight (38) subjects aged 12 to 17 years were treated with ADVAIR HFA in U.S. pivotal clinical trials. Subjects in this age group demonstrated efficacy results similar to those observed in subjects aged 18 years and older.
There were no obvious differences in the type or frequency of adverse events reported in this age group compared with subjects aged 18 years and older. In a 12-week trial, the safety of ADVAIR HFA 45 mcg/21 mcg given as 2 inhalations twice daily was compared with that of fluticasone propionate 44 mcg HFA (FLOVENT HFA) 2 inhalations twice daily in 350 subjects aged 4 to 11 years with persistent asthma currently being treated with ICS. No new safety concerns were observed in children aged 4 to 11 years treated for 12 weeks with ADVAIR HFA 45 mcg/21 mcg compared with adults and adolescents aged 12 years and older.
Common adverse reactions (≥3%) seen in children aged 4 to 11 years treated with ADVAIR HFA 45 mcg/21 mcg but not reported in the adult and adolescent clinical trials of ADVAIR HFA include: pyrexia, cough, pharyngolaryngeal pain, rhinitis, and sinusitis [see Adverse Reactions (6.1)] . This trial was not designed to assess the effect of salmeterol, a component of ADVAIR HFA, on asthma hospitalizations and death in subjects aged 4 to 11 years. The pharmacokinetics and pharmacodynamic effect on serum cortisol of 21 days of treatment with ADVAIR HFA 45 mcg/21 mcg (2 inhalations twice daily with or without a spacer) or ADVAIR DISKUS 100 mcg/50 mcg (1 inhalation twice daily) was evaluated in a trial of 31 children aged 4 to 11 years with mild asthma.
Systemic exposure to salmeterol xinafoate was similar for ADVAIR HFA, ADVAIR HFA delivered with a spacer, and ADVAIR DISKUS while the systemic exposure to fluticasone propionate was lower with ADVAIR HFA compared with that of ADVAIR HFA delivered with a spacer or ADVAIR DISKUS. There were reductions in serum cortisol from baseline in all treatment groups (14%, 22%, and 13% for ADVAIR HFA, ADVAIR HFA delivered with a spacer, and ADVAIR DISKUS, respectively) [see Clinical Pharmacology (12.2, 12.3)] . The safety and effectiveness of ADVAIR HFA in pediatric patients younger than 12 years have not been established.
Effects on Growth ICS, including fluticasone propionate, a component of ADVAIR HFA, may cause a reduction in growth velocity in children and adolescents [see Warnings and Precautions (5.14)] . The growth of pediatric patients receiving orally inhaled corticosteroids, including ADVAIR HFA, should be monitored. A 52-week placebo-controlled trial to assess the potential growth effects of fluticasone propionate inhalation powder (FLOVENT ROTADISK) at 50 and 100 mcg twice daily was conducted in the U.S. in 325 prepubescent children (244 males and 81 females) aged 4 to 11 years.
The mean growth velocities at 52 weeks observed in the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the 50-mcg group (n = 98), and 5.66 cm/year in the 100-mcg group (n = 89). An imbalance in the proportion of children entering puberty between groups and a higher dropout rate in the placebo group due to poorly controlled asthma may be confounding factors in interpreting these data. A separate subset analysis of children who remained prepubertal during the trial revealed growth rates at 52 weeks of 6.10 cm/year in the placebo group (n = 57), 5.91 cm/year in the 50-mcg group (n = 74), and 5.67 cm/year in the 100-mcg group (n = 79).
In children aged 8.5 years, the mean age of children in this trial, the range for expected growth velocity is: boys – 3 rd percentile = 3.8 cm/year, 50 th percentile = 5.4 cm/year, and 97 th percentile = 7.0 cm/year; girls – 3 rd percentile = 4.2… [Excerpted — this section continues on DailyMed.]
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical trials of ADVAIR HFA did not include sufficient numbers of subjects aged 65 years and older to determine whether older subjects respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In addition, as with other products containing beta 2 -agonists, special caution should be observed when using ADVAIR HFA in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta 2 -agonists.
🆘 Overdosage ▾
10 OVERDOSAGE No human overdosage data has been reported for ADVAIR HFA. ADVAIR HFA contains both fluticasone propionate and salmeterol; therefore, the risks associated with overdosage for the individual components described below apply to ADVAIR HFA. Treatment of overdosage consists of discontinuation of ADVAIR 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action ADVAIR HFA ADVAIR HFA contains both fluticasone propionate and salmeterol. The mechanisms of action described below for the individual components apply to ADVAIR 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.
12.2Pharmacodynamics ADVAIR HFA Healthy Subjects: Cardiovascular Effects: Since systemic pharmacodynamic effects of salmeterol are not normally seen at the therapeutic dose, higher doses were used to produce measurable effects. Four (4) placebo-controlled crossover trials were conducted with healthy subjects: (1) a cumulative-dose trial using 42 to 336 mcg of salmeterol CFC inhalation aerosol given alone or as ADVAIR HFA 115 mcg/21 mcg, (2) a single-dose trial using 4 inhalations of ADVAIR HFA 230 mcg/21 mcg, salmeterol CFC inhalation aerosol 21 mcg, or fluticasone propionate CFC inhalation aerosol 220 mcg, (3) a single-dose trial using 8 inhalations of ADVAIR HFA 45 mcg/21 mcg, ADVAIR HFA 115 mcg/21 mcg, or ADVAIR HFA 230 mcg/21 mcg, and (4) a single-dose trial using 4 inhalations of ADVAIR HFA 230 mcg/21 mcg; 2 inhalations of ADVAIR DISKUS 500 mcg/50 mcg; 4 inhalations of fluticasone propionate CFC inhalation aerosol 220 mcg; or 1,010 mcg of fluticasone propionate gi… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action ADVAIR HFA ADVAIR HFA contains both fluticasone propionate and salmeterol. The mechanisms of action described below for the individual components apply to ADVAIR 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING ADVAIR 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: • ADVAIR HFA 45 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 0173-0715-20) • ADVAIR HFA 45 mcg/21 mcg: 8-g canister containing 60 actuations (NDC 0173-0715-22) • ADVAIR HFA 115 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 0173-0716-20) • ADVAIR HFA 115 mcg/21 mcg: 8-g canister containing 60 actuations (NDC 0173-0716-22) • ADVAIR HFA 230 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 0173-0717-20) • ADVAIR HFA 230 mcg/21 mcg: 8-g canister containing 60 actuations (NDC 0173-0717-22) Each inhaler is packaged with a Patient Information leaflet.
The purple actuator supplied with ADVAIR HFA should not be used with any other product canisters, and actuators from other products should not be used with an ADVAIR HFA canister. Counter ADVAIR HFA has a counter attached to the canister. The counter starts at 124 or 064 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.
📋 Description ▾
11 DESCRIPTION ADVAIR HFA 45 mcg/21 mcg, ADVAIR HFA 115 mcg/21 mcg, and ADVAIR HFA 230 mcg/21 mcg are combinations of fluticasone propionate and salmeterol xinafoate. One active component of ADVAIR 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 ADVAIR 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. ADVAIR 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 ADVAIR 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
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Serious Asthma-Related Events Inform patients with asthma that LABA when used alone increases the risk of asthma-related hospitalization or asthma-related death. Available data show that when ICS and LABA are used together, such as with ADVAIR HFA, there is not a significant increase in the risk of these events. [See Warnings and Precautions (5.1).] Not for Acute Symptoms Inform patients that ADVAIR HFA is not meant to relieve acute asthma symptoms and extra doses should not be used for that purpose.
Advise patients to treat acute asthma symptoms with an inhaled, short-acting beta 2 -agonist such as albuterol. Provide patients with such medication and instruct them in how it should be used. Instruct patients to seek medical attention immediately if they experience any of the following: • Decreasing effectiveness of inhaled, short-acting beta 2 -agonists • Need for more inhalations than usual of inhaled, short-acting beta 2 -agonists • Significant decrease in lung function as outlined by the physician Tell patients they should not stop therapy with ADVAIR HFA without physician/provider guidance since symptoms may recur after discontinuation. [See Warnings and Precautions (5.2).] Do Not Use Additional Long-acting Beta 2 -agonists Instruct patients not to use other LABA for asthma. [See Warnings and Precautions (5.3).] Oropharyngeal Candidiasis Inform patients that localized infections with Candida albicans occurred in the mouth and pharynx in some patients.
If oropharyngeal candidiasis develops, treat it with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with ADVAIR HFA, but at times therapy with ADVAIR HFA may need to be temporarily interrupted under close medical supervision. Advise patients to rinse the mouth with water without swallowing after inhalation to help reduce the risk of thrush. [See Warnings and Precautions (5.4).] Pneumonia Patients with COPD have a higher risk of pneumonia; instruct them to contact their healthcare providers if they develop symptoms of pneumonia. [See Warnings and Precautions (5.5).] Immunosuppression and Risk of Infections Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay.
Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. [See Warnings and Precautions (5.6).] Hypercorticism and Adrenal Suppression Advise patients that ADVAIR HFA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, inform patients that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids. Patients should taper slowly from systemic corticosteroids if transferring to ADVAIR HFA. [See Warnings and Precautions (5.8).] Hypersensitivity Reactions, including Anaphylaxis Advise patients that immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of ADVAIR HFA.
Patients should discontinue ADVAIR HFA if such reactions occur. [See Warnings and Precautions (5.11).] Risks Associated with Beta-agonist Therapy Inform patients of adverse effects associated with beta 2 -agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness. [See Warnings and Precautions (5.12).] Reduction in Bone Mineral Density Advise patients who are at an increased risk for decreased BMD that the use of corticosteroids may pose an additional risk. [See Warnings and Precautions (5.13).] Reduced Growth Velocity Inform patients that orally inhaled corticosteroids, including fluticasone propionate, may cause a reduction in growth velocity when administered to… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption Fluticasone Propionate: Healthy Subjects: Fluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed.
Three (3) single-dose, placebo-controlled, crossover trials were conducted in healthy subjects: (1) a trial using 4 inhalations of ADVAIR HFA 230 mcg/21 mcg, salmeterol CFC inhalation aerosol 21 mcg, or fluticasone propionate CFC inhalation aerosol 220 mcg, (2) a trial using 8 inhalations of ADVAIR HFA 45 mcg/21 mcg, ADVAIR HFA 115 mcg/21 mcg, or ADVAIR HFA 230 mcg/21 mcg, and (3) a trial using 4 inhalations of ADVAIR HFA 230 mcg/21 mcg; 2 inhalations of ADVAIR DISKUS 500 mcg/50 mcg; 4 inhalations of fluticasone propionate CFC inhalation aerosol 220 mcg; or 1,010 mcg of fluticasone propionate given intravenously.
Peak plasma concentrations of fluticasone propionate were achieved in 0.33 to 1.5 hours and those of salmeterol were achieved in 5 to 10 minutes. Peak plasma concentrations of fluticasone propionate (N = 20 subjects) following 8 inhalations of ADVAIR HFA 45 mcg/21 mcg, ADVAIR HFA 115 mcg/21 mcg, and ADVAIR HFA 230 mcg/21 mcg averaged 41, 108, and 173 pg/mL, respectively. Systemic exposure (N = 20 subjects) from 4 inhalations of ADVAIR HFA 230 mcg/21 mcg was 53% of the value from the individual inhaler for fluticasone propionate CFC inhalation aerosol and 42% of the value from the individual inhaler for salmeterol CFC inhalation aerosol.
Peak plasma concentrations from ADVAIR HFA for fluticasone propionate (86 versus 120 pg/mL) and salmeterol (170 versus 510 pg/mL) were significantly lower compared with individual inhalers. In 15 healthy subjects, systemic exposure to fluticasone propionate from 4 inhalations of ADVAIR HFA 230 mcg/21 mcg (920/84 mcg) and 2 inhalations of ADVAIR DISKUS 500 mcg/50 mcg (1,000/100 mcg) was similar between the 2 inhalers (i.e., 799 versus 832 pg•h/mL, respectively), but approximately half the systemic exposure from 4 inhalations of fluticasone propionate CFC inhalation aerosol 220 mcg (880 mcg, AUC = 1,543 pg•h/mL).
Similar results were observed for peak fluticasone propionate plasma concentrations (186 and 182 pg/mL from ADVAIR HFA and ADVAIR DISKUS, respectively, and 307 pg/mL from the fluticasone propionate CFC inhalation aerosol). Absolute bioavailability of fluticasone propionate was 5.3% and 5.5% following administration of ADVAIR HFA and ADVAIR DISKUS, respectively. Subjects with Asthma: A double-blind crossover trial was conducted in 13 adult subjects with asthma to evaluate the steady-state pharmacokinetics of fluticasone propionate and salmeterol following administration of 2 inhalations of ADVAIR HFA 115 mcg/21 mcg twice daily or 1 inhalation of ADVAIR DISKUS 250 mcg/50 mcg twice daily for 4 weeks.
Systemic exposure (AUC) to fluticasone propionate was similar for ADVAIR HFA (274 pg•h/mL [95% CI: 150, 502]) and ADVAIR DISKUS (338 pg•h/mL [95% CI: 197, 581]). The effect of 21 days of treatment with ADVAIR HFA 45 mcg/21 mcg (2 inhalations twice daily with or without a spacer) or ADVAIR DISKUS 100 mcg/50 mcg (1 inhalation twice daily) was evaluated in a trial of 31 children aged 4 to 11 years with mild asthma. Systemic exposure to fluticasone propionate was similar with ADVAIR DISKUS and ADVAIR HFA with a spacer (138 pg•h/mL [95% CI: 69, 273] and 107 pg•h/mL [95% CI: 46, 252], respectively) and lower with ADVAIR HFA without a spacer (24 pg•h/mL [95% CI: 10, 60]).
Salmeterol Xinafoate: Healthy Subjects: Salmeterol xinafoate, an ionic salt, dissociates in solution so that the salmeterol and 1-hydroxy-2-naphthoic acid (xinafoate) moieties are absorbed, distribut… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics ADVAIR HFA Healthy Subjects: Cardiovascular Effects: Since systemic pharmacodynamic effects of salmeterol are not normally seen at the therapeutic dose, higher doses were used to produce measurable effects. Four (4) placebo-controlled crossover trials were conducted with healthy subjects: (1) a cumulative-dose trial using 42 to 336 mcg of salmeterol CFC inhalation aerosol given alone or as ADVAIR HFA 115 mcg/21 mcg, (2) a single-dose trial using 4 inhalations of ADVAIR HFA 230 mcg/21 mcg, salmeterol CFC inhalation aerosol 21 mcg, or fluticasone propionate CFC inhalation aerosol 220 mcg, (3) a single-dose trial using 8 inhalations of ADVAIR HFA 45 mcg/21 mcg, ADVAIR HFA 115 mcg/21 mcg, or ADVAIR HFA 230 mcg/21 mcg, and (4) a single-dose trial using 4 inhalations of ADVAIR HFA 230 mcg/21 mcg; 2 inhalations of ADVAIR DISKUS 500 mcg/50 mcg; 4 inhalations of fluticasone propionate CFC inhalation aerosol 220 mcg; or 1,010 mcg of fluticasone propionate given intravenously.
In these trials pulse rate, blood pressure, QTc interval, glucose, and/or potassium were measured. Comparable or lower effects were observed for ADVAIR HFA compared with ADVAIR DISKUS or salmeterol alone. The effect of salmeterol on pulse rate and potassium was not altered by the presence of different amounts of fluticasone propionate in ADVAIR HFA.
Hypothalamic-Pituitary-Adrenal Axis Effects: The potential effect of salmeterol on the effects of fluticasone propionate on the HPA axis was also evaluated in 3 of these trials. Compared with fluticasone propionate CFC inhalation aerosol, ADVAIR HFA had less effect on 24-hour urinary cortisol excretion and less or comparable effect on 24-hour serum cortisol. In these crossover trials in healthy subjects, ADVAIR HFA and ADVAIR DISKUS had similar effects on urinary and serum cortisol.
Subjects with Asthma: Cardiovascular Effects: In clinical trials with ADVAIR HFA in adult and adolescent subjects aged 12 years and older with asthma, systemic pharmacodynamic effects of salmeterol (pulse rate, blood pressure, QTc interval, potassium, and glucose) were similar to or slightly lower in patients treated with ADVAIR HFA compared with patients treated with salmeterol CFC inhalation aerosol 21 mcg. In 61 adult and adolescent subjects with asthma given ADVAIR HFA (45 mcg/21 mcg or 115 mcg/21 mcg), continuous 24-hour electrocardiographic monitoring was performed after the first dose and after 12 weeks of twice-daily therapy, and no clinically significant dysrhythmias were noted.
The effect of 21 days of treatment with ADVAIR HFA 45 mcg/21 mcg (2 inhalations twice daily with or without a spacer) or ADVAIR DISKUS 100 mcg/50 mcg (1 inhalation twice daily) was evaluated in 31 children aged 4 to 11 years with mild asthma. There were no notable changes from baseline for QTc, heart rate, or systolic and diastolic blood pressure. Hypothalamic-Pituitary-Adrenal Axis Effects: A 4-way crossover trial in 13 subjects with asthma compared pharmacodynamics at steady state following 4 weeks of twice-daily treatment with 2 inhalations of ADVAIR HFA 115 mcg/21 mcg, 1 inhalation of ADVAIR DISKUS 250 mcg/50 mcg, 2 inhalations of fluticasone propionate HFA inhalation aerosol 110 mcg, and placebo.
No significant differences in serum cortisol AUC were observed between active treatments and placebo. Mean 12-hour serum cortisol AUC ratios comparing active treatment with placebo ranged from 0.9 to 1.2. No statistically or clinically significant increases in heart rate or QTc interval were observed for any active treatment compared with placebo.
In a 12-week trial in adult and adolescent subjects with asthma, ADVAIR HFA 115 mcg/21 mcg was compared with the individual components, fluticasone propionate CFC inhalation aerosol 110 mcg and salmeterol CFC inhalation aerosol 21 mcg, and placebo [see Clinical Studies (14.1)] . All treatments were administered as 2 inhalations twice daily. After 12 weeks of treatment with these therapeutic doses… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
14 CLINICAL STUDIES ADVAIR HFA has been studied in subjects with asthma aged 12 years and older. ADVAIR HFA has not been studied in subjects younger than 12 years or in subjects with COPD. In clinical trials comparing ADVAIR HFA with its individual components, improvements in most efficacy endpoints were greater with ADVAIR HFA than with the use of either fluticasone propionate or salmeterol alone.
In addition, clinical trials showed comparable results between ADVAIR HFA and ADVAIR DISKUS.
14.1Trials Comparing ADVAIR HFA with Fluticasone Propionate Alone or Salmeterol Alone Four (4) double-blind, parallel-group clinical trials were conducted with ADVAIR HFA in 1,517 adult and adolescent subjects (aged 12 years and older, mean baseline FEV 1 65% to 75% of predicted normal) with asthma that was not optimally controlled on their current therapy. All metered-dose inhaler treatments were inhalation aerosols given as 2 inhalations twice daily, and other maintenance therapies were discontinued. Trial 1: Clinical Trial with ADVAIR HFA 45 mcg/21 mcg This placebo-controlled, 12-week, U.S. trial compared ADVAIR HFA 45 mcg/21 mcg with fluticasone propionate CFC inhalation aerosol 44 mcg or salmeterol CFC inhalation aerosol 21 mcg, each given as 2 inhalations twice daily.
The primary efficacy endpoints were predose FEV 1 and withdrawals due to worsening asthma. This trial was stratified according to baseline asthma therapy: subjects using beta-agonists (albuterol alone [n = 142], salmeterol [n = 84], or ICS [n = 134] [daily doses of beclomethasone dipropionate 252 to 336 mcg; budesonide 400 to 600 mcg; flunisolide 1,000 mcg; fluticasone propionate inhalation aerosol 176 mcg; fluticasone propionate inhalation powder 200 mcg; or triamcinolone acetonide 600 to 800 mcg]). Baseline FEV 1 measurements were similar across treatments: ADVAIR HFA 45 mcg/21 mcg,
2.29 L; fluticasone propionate 44 mcg,
2.20 L; salmeterol,
2.33 L; and placebo,
2.27L. Predefined withdrawal criteria for lack of efficacy, an indicator of worsening asthma, were utilized for this placebo-controlled trial. Worsening asthma was defined as a clinically important decrease in FEV 1 or PEF, increase in use of VENTOLIN (albuterol, USP) Inhalation Aerosol, increase in night awakenings due to asthma, emergency intervention or hospitalization due to asthma, or requirement for asthma medicine not allowed by the protocol.
As shown in Table 3, statistically significantly fewer subjects receiving ADVAIR HFA 45 mcg/21 mcg were withdrawn due to worsening asthma compared with salmeterol and placebo. Fewer subjects receiving ADVAIR HFA 45 mcg/21 mcg were withdrawn due to worsening asthma compared with fluticasone propionate 44 mcg; however, the difference was not statistically significant. Table 3.
Percent of Subjects Withdrawn due to Worsening Asthma in Subjects Previously Treated with Beta 2 -agonists (Albuterol or Salmeterol) or Inhaled Corticosteroids (Trial 1) ADVAIR HFA 45 mcg/21 mcg (n = 92) Fluticasone Propionate CFC Inhalation Aerosol 44 mcg (n = 89) Salmeterol CFC Inhalation Aerosol 21 mcg (n = 92) Placebo HFA Inhalation Aerosol (n = 87) 2% 8% 25% 28% The FEV 1 results are displayed in Figure 1. Because this trial used predetermined criteria for worsening asthma, which caused more subjects in the placebo group to be withdrawn, FEV 1 results at Endpoint (last available FEV 1 result) are also provided.
Subjects receiving ADVAIR HFA 45 mcg/21 mcg had significantly greater improvements in FEV 1 (0.58 L, 27%) compared with fluticasone propionate 44 mcg (0.36 L, 18%), salmeterol (0.25 L, 12%), and placebo (0.14 L, 5%). These improvements in FEV 1 with ADVAIR HFA 45 mcg/21 mcg were achieved regardless of baseline asthma therapy (albuterol alone, salmeterol, or ICS). Figure 1.
Mean Percent Change from Baseline in FEV1 in Subjects Previously Treated with Either Beta 2 ‑agonists (Albuterol or Salmeterol) or Inhaled Corticosteroids (Trial 1) The effect of ADVAIR HFA 45 mcg/21 mcg on the sec… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Fluticasone Propionate Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 5 times the MRHDID on a mcg/m 2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 0.5 times the MRHDID on a mcg/m 2 basis) for 104 weeks. Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the in vivo mouse micronucleus test.
Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 0.5 times the MRHDID for adults on a mcg/m 2 basis). Salmeterol In an 18-month carcinogenicity study in CD-mice, salmeterol at oral doses of 1,400 mcg/kg and above (approximately 10 times the MRHDID based on comparison of the plasma AUCs) caused a dose-related increase in the incidence of smooth muscle hyperplasia, cystic glandular hyperplasia, leiomyomas of the uterus, and ovarian cysts.
No tumors were seen at 200 mcg/kg (approximately 2 times the MRHDID for adults based on comparison of the AUCs). In a 24-month oral and inhalation carcinogenicity study in Sprague Dawley rats, salmeterol caused a dose-related increase in the incidence of mesovarian leiomyomas and ovarian cysts at doses of 680 mcg/kg and above (approximately 80 times the MRHDID on a mcg/m 2 basis). No tumors were seen at 210 mcg/kg (approximately 25 times the MRHDID on a mcg/m 2 basis).
These findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown. Salmeterol produced no detectable or reproducible increases in microbial and mammalian gene mutation in vitro.
No clastogenic activity occurred in vitro in human lymphocytes or in vivo in a rat micronucleus test. Fertility and reproductive performance were unaffected in male and female rats at oral doses up to 2,000 mcg/kg (approximately 230 times the MRHDID for adults on a mcg/m 2 basis).
13.2Animal Toxicology and/or Pharmacology Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical relevance of these findings is unknown.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Fluticasone Propionate Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 5 times the MRHDID on a mcg/m 2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 0.5 times the MRHDID on a mcg/m 2 basis) for 104 weeks. Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the in vivo mouse micronucleus test.
Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 0.5 times the MRHDID for adults on a mcg/m 2 basis). Salmeterol In an 18-month carcinogenicity study in CD-mice, salmeterol at oral doses of 1,400 mcg/kg and above (approximately 10 times the MRHDID based on comparison of the plasma AUCs) caused a dose-related increase in the incidence of smooth muscle hyperplasia, cystic glandular hyperplasia, leiomyomas of the uterus, and ovarian cysts.
No tumors were seen at 200 mcg/kg (approximately 2 times the MRHDID for adults based on comparison of the AUCs). In a 24-month oral and inhalation carcinogenicity study in Sprague Dawley rats, salmeterol caused a dose-related increase in the incidence of mesovarian leiomyomas and ovarian cysts at doses of 680 mcg/kg and above (approximately 80 times the MRHDID on a mcg/m 2 basis). No tumors were seen at 210 mcg/kg (approximately 25 times the MRHDID on a mcg/m 2 basis).
These findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown. Salmeterol produced no detectable or reproducible increases in microbial and mammalian gene mutation in vitro.
No clastogenic activity occurred in vitro in human lymphocytes or in vivo in a rat micronucleus test. Fertility and reproductive performance were unaffected in male and female rats at oral doses up to 2,000 mcg/kg (approximately 230 times the MRHDID for adults on a mcg/m 2 basis).
📄 Patient Package Insert ▾
PATIENT INFORMATION ADVAIR (AD vair) HFA (fluticasone propionate and salmeterol inhalation aerosol) for oral inhalation use What is ADVAIR HFA? • ADVAIR HFA combines the inhaled corticosteroid (ICS) medicine fluticasone propionate and the long-acting beta 2 -adrenergic agonist (LABA) medicine salmeterol. o ICS medicines such as fluticasone propionate help to decrease inflammation in the lungs. Inflammation in the lungs can lead to breathing problems. o LABA medicines such as salmeterol help the muscles around the airways in your lungs stay relaxed to prevent symptoms, such as wheezing, cough, chest tightness, and shortness of breath.
These symptoms can happen when the muscles around the airways tighten. This makes it hard to breathe. • ADVAIR HFA is not used to relieve sudden breathing problems and will not replace a rescue inhaler. • It is not known if ADVAIR HFA is safe and effective in children younger than 12 years of age. • ADVAIR HFA is used for asthma as follows: o ADVAIR HFA is a prescription medicine used to control symptoms of asthma and to prevent symptoms such as wheezing in adults and adolescents aged 12 years and older. o ADVAIR HFA contains salmeterol, the same medicine found in SEREVENT DISKUS (salmeterol xinafoate inhalation powder).
LABA medicines such as salmeterol when used alone increase the risk of hospitalizations and death from asthma problems. ADVAIR HFA contains an ICS and a LABA. When an ICS and LABA are used together, there is not a significant increased risk in hospitalizations and death from asthma problems. o ADVAIR HFA is not for adults and adolescents with asthma who are well controlled with an asthma control medicine, such as a low to medium dose of an ICS medicine.
ADVAIR HFA is for adults and adolescents with asthma who need both an ICS and LABA medicine. Do not use ADVAIR HFA: • to relieve sudden breathing problems. • as a rescue inhaler. • if you are allergic to fluticasone propionate, salmeterol, or any of the ingredients in ADVAIR HFA. See the end of this Patient Information for a complete list of ingredients in ADVAIR HFA.
Before using ADVAIR HFA, tell your healthcare provider about all of your medical conditions, including if you: • have heart problems. • have high blood pressure. • have seizures. • have thyroid problems. • have diabetes. • have liver problems. • have weak bones (osteoporosis). • have an immune system problem. • have or have had eye problems such as glaucoma, increased pressure in your eye, cataracts, or other changes in vision. • have any type of viral, bacterial, or fungal infection. • are exposed to chickenpox or measles. • are pregnant or plan to become pregnant.
It is not known if ADVAIR HFA may harm your unborn baby. • are breastfeeding. It is not known if the medicines in ADVAIR HFA pass into your milk and if they can harm your baby. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
ADVAIR HFA and certain other medicines may interact with each other. This may cause serious side effects. Especially tell your healthcare provider if you take antifungal or anti-HIV medicines.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use ADVAIR HFA?
Read the step-by-step instructions for using ADVAIR HFA at the end of this Patient Information. • Do not use ADVAIR HFA unless your healthcare provider has taught you how to use the inhaler and you understand how to use it correctly. • ADVAIR HFA comes in 3 different strengths. Your healthcare provider prescribed the strength that is best for you. • Use ADVAIR HFA exactly as your healthcare provider tells you to use it. Do not use ADVAIR HFA more often than prescribed. • Use 2 inhalations of ADVAIR HFA 2 times each day.
Use ADVAIR HFA at the same time each day, about 12 hours apart. • If you miss a dose of ADVAIR HFA, just skip that dose. Ta… [Excerpted — this section continues on DailyMed.]
📖 Instructions for Use ▾
INSTRUCTIONS FOR USE ADVAIR (AD vair) HFA (fluticasone propionate and salmeterol inhalation aerosol) for oral inhalation use Your ADVAIR HFA inhaler Figure A • The metal canister holds the medicine. See Figure A. • The metal canister has a counter to show how many sprays of medicine you have left. The number shows through a window in the back of the purple plastic actuator.
See Figure A. • The counter starts at either 124 or 064 , depending on which size inhaler you have. The number will count down by 1 each time you spray the inhaler. The counter will stop counting at 000 . • Do not try to change the numbers or take the counter off the metal canister.
The counter cannot be reset, and it is permanently attached to the metal canister. • The purple plastic actuator sprays the medicine from the metal canister. The plastic actuator has a light purple protective cap that covers the mouthpiece. See Figure A.
Keep the protective cap on the mouthpiece when the metal canister is not in use. • Do not use the plastic actuator with a canister of medicine from any other inhaler. • Do not use an ADVAIR HFA metal canister with an actuator from any other inhaler. Before using your ADVAIR HFA inhaler • The inhaler should be at room temperature before you use it. Priming your ADVAIR HFA inhaler Figure B Figure C Figure D Before you use ADVAIR HFA for the first time, you must prime the inhaler so that you will get the right amount of medicine when you use it. • To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out.
See Figure B. • Shake the inhaler well for 5 seconds. • Spray the inhaler 1 time into the air away from your face. Avoid spraying in eyes. See Figure C. • Shake and spray the inhaler like this 3 more times to finish priming it.
The counter should now read 120 or 060 , depending on which size inhaler you have. See Figure D. • You must prime your inhaler again if you have not used it in more than 4 weeks or if you have dropped it. To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out.
Shake the inhaler well for 5 seconds. Then spray it 1 time into the air away from your face. Shake and spray the inhaler like this 1 more time to finish priming it.
How to use your ADVAIR HFA inhaler Follow these steps every time you use ADVAIR HFA. Figure E Figure F Figure G Figure H Step 1. Make sure the metal canister fits firmly in the plastic actuator.
The counter should show through the window in the actuator. To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out. Look inside the mouthpiece for foreign objects and take out any you see.
Step 2. Hold the inhaler with the mouthpiece down and shake it well for 5 seconds . See Figure E.
Step 3. Breathe out through your mouth and push as much air from your lungs as you can. See Figure F.
Step 4. Put the mouthpiece in your mouth and close your lips around it. Push the top of the metal canister firmly all the way down while you breathe in deeply and slowly through your mouth.
See Figure G. Step 5. After the spray comes out, take your finger off the metal canister.
After you have breathed in all the way, take the inhaler out of your mouth and close your mouth. Step 6. Hold your breath for about 10 seconds, or for as long as is comfortable.
Breathe out slowly as long as you can. Wait about 30 seconds and shake the inhaler well for 5 seconds. Repeat Step 2 through Step 6.
Step 7. Rinse your mouth with water after breathing in the medicine. Spit out the water.
Do not swallow it. See Figure H. Step 8.
Put the cap back on the mouthpiece after you finish using the inhaler. Make sure it snaps firmly into place. Cleaning your ADVAIR HFA inhaler Figure I Figure J Clean your inhaler at least 1 time each week after your evening dose.
You may not see any medicine build-up on the inhaler, but it is important to keep it clean so medicine build-up will not block the spray. See Figure I. Step 9.
Take the cap off the mo… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL NDC 0173-0715-20 ADVAIR HFA (fluticasone propionate and salmeterol inhalation aerosol) 45 mcg/21 mcg For oral inhalation with ADVAIR HFA actuator only. Contents: Each canister contains a microcrystalline suspension of fluticasone propionate and salmeterol xinafoate in propellant HFA-134a(1,1,1,2,-tetrafluoroethane). Each actuation delivers 45 mcg of fluticasone propionate and 30.45 mcg of salmeterol xinafoate equivalent to 21 mcg of salmeterol base from the mouthpiece.
See prescribing information for dosage information. R X only 120 Metered Actuations Net Wt. 12 g GSK Made in France ©2026 GSK group of companies or its licensor.
62000000103038 Rev. 03/26 Advair HFA 45mcg 120 dose carton
PRINCIPAL DISPLAY PANEL NDC 0173-0716-20 ADVAIR HFA (fluticasone propionate and salmeterol inhalation aerosol) 115 mcg/21 mcg For oral inhalation with ADVAIR HFA actuator only. Contents: Each canister contains a microcrystalline suspension of fluticasone propionate and salmeterol xinafoate in propellant HFA-134a(1,1,1,2,-tetrafluoroethane). Each actuation delivers 115 mcg of fluticasone propionate and 30.45 mcg of salmeterol xinafoate equivalent to 21 mcg of salmeterol base from the mouthpiece.
See prescribing information for dosage information. R X only 120 Metered Actuations Net Wt. 12 g GSK Made in France ©2026 GSK group of companies or its licensor.
62000000103039 Rev. 03/26 Advair HFA 115mcg 120 dose carton
PRINCIPAL DISPLAY PANEL NDC 0173-0717-20 ADVAIR HFA (fluticasone propionate and salmeterol inhalation aerosol) 230 mcg/21 mcg For oral inhalation with ADVAIR HFA actuator only. Contents: Each canister contains a microcrystalline suspension of fluticasone propionate and salmeterol xinafoate in propellant HFA-134a(1,1,1,2,-tetrafluoroethane). Each actuation delivers 230 mcg of fluticasone propionate and 30.45 mcg of salmeterol xinafoate equivalent to 21 mcg of salmeterol base from the mouthpiece.
See prescribing information for dosage information. R X only 120 Metered Actuations Net Wt. 12 g GSK Made in France ©2026 GSK group of companies or its licensor.
62000000103041 Rev. 03/26 Advair HFA 230mcg 120 dose carton