Advair

Name: Advair

Commonly used brand name(s)

In the U.S.

  • Advair Diskus
  • Advair Diskus 100/50
  • Advair Diskus 250/50
  • Advair Diskus 500/50
  • Advair HFA
  • Advair HFA 115/21
  • Advair HFA 230/21
  • Advair HFA 45/21
  • Airduo Respiclick

In Canada

  • Advair
  • Advair Inhalation Aerosol

Available Dosage Forms:

  • Powder
  • Aerosol Liquid
  • Disk
  • Aerosol Powder

Therapeutic Class: Antiasthma, Anti-Inflammatory/Bronchodilator Combination

Pharmacologic Class: Fluticasone

Before Using Advair

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of Advair® Diskus® to treat asthma in children older than 4 years of age. Safety and efficacy have not been established in children younger than 4 years of age.

Appropriate studies have not been performed on the relationship of age to the effects of Advair® HFA oral inhalation or Airduo™ Respiclick® in children younger than 12 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of fluticasone and salmeterol combination in the elderly. However, elderly people with heart and blood vessel problems may require special caution when receiving fluticasone and salmeterol combination.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Desmopressin
  • Fluconazole
  • Posaconazole

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Alfuzosin
  • Amiodarone
  • Amprenavir
  • Apomorphine
  • Arsenic Trioxide
  • Asenapine
  • Astemizole
  • Atazanavir
  • Azithromycin
  • Bemiparin
  • Boceprevir
  • Bupropion
  • Ceritinib
  • Chloroquine
  • Chlorpromazine
  • Ciprofloxacin
  • Citalopram
  • Clarithromycin
  • Clozapine
  • Cobicistat
  • Conivaptan
  • Darunavir
  • Dasabuvir
  • Dasatinib
  • Disopyramide
  • Dofetilide
  • Dolasetron
  • Domperidone
  • Droperidol
  • Fingolimod
  • Flecainide
  • Fosamprenavir
  • Gatifloxacin
  • Gemifloxacin
  • Granisetron
  • Halofantrine
  • Haloperidol
  • Ibutilide
  • Idelalisib
  • Iloperidone
  • Indinavir
  • Itraconazole
  • Ketoconazole
  • Lapatinib
  • Lopinavir
  • Lumacaftor
  • Lumefantrine
  • Mefloquine
  • Mifepristone
  • Nadroparin
  • Nefazodone
  • Nelfinavir
  • Netupitant
  • Nilotinib
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Ombitasvir
  • Ondansetron
  • Paliperidone
  • Paritaprevir
  • Pixantrone
  • Posaconazole
  • Procainamide
  • Prochlorperazine
  • Promethazine
  • Propafenone
  • Quinidine
  • Quinine
  • Ranolazine
  • Ritonavir
  • Saquinavir
  • Sodium Phosphate
  • Sodium Phosphate, Dibasic
  • Sodium Phosphate, Monobasic
  • Solifenacin
  • Sorafenib
  • Sunitinib
  • Telaprevir
  • Telavancin
  • Telithromycin
  • Tetrabenazine
  • Tipranavir
  • Toremifene
  • Trazodone
  • Trifluoperazine
  • Vardenafil
  • Voriconazole

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Erythromycin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Asthma attack, acute or
  • Bronchospasm (difficulty with breathing), acute or
  • COPD flare-up or
  • Milk protein allergy, severe—Should not be used in patients with these conditions.
  • Blood vessel disease (eg, Churg-Strauss syndrome) or
  • Bone problems (eg, osteoporosis) or
  • Cataracts or
  • Diabetes or
  • Glaucoma or
  • Heart disease or
  • Heart rhythm problems (eg, arrhythmia) or
  • Hypertension (high blood pressure) or
  • Hyperthyroidism (overactive thyroid) or
  • Hypokalemia (low potassium in the blood) or
  • Ketoacidosis (high ketones in the blood) or
  • Seizures, history of—Use with caution. May make these conditions worse.
  • Chickenpox (including recent exposure) or
  • Herpes simplex (virus) infection of the eye or
  • Infections (virus, bacteria, or fungus) or
  • Measles or
  • Tuberculosis, active or history of—Inhaled fluticasone can reduce the body's ability to fight off these infections.
  • Infection or
  • Stress or
  • Surgery or
  • Trauma—Supplementary oral corticosteroids may be needed. Check with your doctor.
  • Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

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 Inhalation Aerosol 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.

Trials 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 FEV1 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 45/21 Inhalation Aerosol

This placebo-controlled 12-week, U.S. trial compared Advair HFA 45/21 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 FEV1 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 inhaled corticosteroids [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 FEV1 measurements were similar across treatments: Advair HFA 45/21, 2.29 L; fluticasone propionate 44 mcg, 2.20 L; salmeterol, 2.33 L; and placebo, 2.27 L.

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 FEV1 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 45/21 were withdrawn due to worsening asthma compared with salmeterol and placebo. Fewer subjects receiving Advair HFA 45/21 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 Beta2-agonists (Albuterol or Salmeterol) or Inhaled Corticosteroids (Trial 1)

Advair HFA 45/21 Inhalation Aerosol

(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 FEV1 results are displayed in Figure 2. Because this trial used predetermined criteria for worsening asthma, which caused more subjects in the placebo group to be withdrawn, FEV1 results at Endpoint (last available FEV1 result) are also provided. Subjects receiving Advair HFA 45/21 had significantly greater improvements in FEV1 (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 FEV1 with Advair HFA 45/21 were achieved regardless of baseline asthma therapy (albuterol alone, salmeterol, or inhaled corticosteroids).

Figure 2. Mean Percent Change from Baseline in FEV1 in Subjects Previously Treated with Either Beta2-agonists (Albuterol or Salmeterol) or Inhaled Corticosteroids (Trial 1)

The effect of Advair HFA 45/21 on the secondary efficacy parameters, including morning and evening PEF, usage of VENTOLIN Inhalation Aerosol, and asthma symptoms over 24 hours on a scale of 0 to 5 is shown in Table 4.

Table 4. Secondary Efficacy Variable Results for Subjects Previously Treated with Beta2-agonists (Albuterol or Salmeterol) or Inhaled Corticosteroids (Trial 1)

Efficacy Variablea

Advair HFA 45/21 Inhalation Aerosol

(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)

AM PEF (L/min)

  Baseline

377

369

381

382

  Change from baseline

58

27

25

1

PM PEF (L/min)

  Baseline

397

387

402

407

  Change from baseline

48

20

16

3

Use of VENTOLIN Inhalation Aerosol (inhalations/day)

  Baseline

3.1

2.4

2.7

2.7

  Change from baseline

-2.1

-0.4

-0.8

0.2

Asthma symptom score/day

  Baseline

1.8

1.6

1.7

1.7

  Change from baseline

-1.0

-0.3

-0.4

0

aChange from baseline = change from baseline at Endpoint (last available data).

The subjective impact of asthma on subjects’ perception of health was evaluated through use of an instrument called the Asthma Quality of Life Questionnaire (AQLQ) (based on a 7-point scale where 1 = maximum impairment and 7 = none). Subjects receiving Advair HFA 45/21 had clinically meaningful improvements in overall asthma-specific quality of life as defined by a difference between groups of greater than or equal to 0.5 points in change from baseline AQLQ scores (difference in AQLQ score of 1.14 [95% CI: 0.85, 1.44] compared with placebo).

Trial 2: Clinical Trial with Advair HFA 45/21 Inhalation Aerosol

This active-controlled, 12-week, U.S. trial compared Advair HFA 45/21 with fluticasone propionate CFC inhalation aerosol 44 mcg and salmeterol CFC inhalation aerosol 21 mcg, each given as 2 inhalations twice daily, in 283 subjects using as-needed albuterol alone. The primary efficacy endpoint was predose FEV1. Baseline FEV1 measurements were similar across treatments: Advair HFA 45/21, 2.37 L; fluticasone propionate 44 mcg, 2.31 L; and salmeterol, 2.34 L.

Efficacy results in this trial were similar to those observed in Trial 1. Subjects receiving Advair HFA 45/21 had significantly greater improvements in FEV1 (0.69 L, 33%) compared with fluticasone propionate 44 mcg (0.51 L, 25%) and salmeterol (0.47 L, 22%).

Trial 3: Clinical Trial with Advair HFA 115/21 Inhalation Aerosol

This placebo-controlled, 12-week, U.S. trial compared Advair HFA 115/21 with fluticasone propionate CFC inhalation aerosol 110 mcg or salmeterol CFC inhalation aerosol 21 mcg, each given as 2 inhalations twice daily, in 365 subjects using inhaled corticosteroids (daily doses of beclomethasone dipropionate 378 to 840 mcg; budesonide 800 to 1,200 mcg; flunisolide 1,250 to 2,000 mcg; fluticasone propionate inhalation aerosol 440 to 660 mcg; fluticasone propionate inhalation powder 400 to 600 mcg; or triamcinolone acetonide 900 to 1,600 mcg). The primary efficacy endpoints were predose FEV1 and withdrawals due to worsening asthma. Baseline FEV1 measurements were similar across treatments: Advair HFA 115/21, 2.23 L; fluticasone propionate 110 mcg, 2.18 L; salmeterol, 2.22 L; and placebo, 2.17 L.

Efficacy results in this trial were similar to those observed in Trials 1 and 2. Subjects receiving Advair HFA 115/21 had significantly greater improvements in FEV1 (0.41 L, 20%) compared with fluticasone propionate 110 mcg (0.19 L, 9%), salmeterol (0.15 L, 8%), and placebo (-0.12 L, -6%). Significantly fewer subjects receiving Advair HFA 115/21 were withdrawn from this trial for worsening asthma (7%) compared with salmeterol (24%) and placebo (54%). Fewer subjects receiving Advair HFA 115/21 were withdrawn due to worsening asthma (7%) compared with fluticasone propionate 110 mcg (11%); however, the difference was not statistically significant.

Trial 4: Clinical Trial with Advair HFA 230/21 Inhalation Aerosol

This active-controlled 12-week non-U.S. trial compared Advair HFA 230/21 with fluticasone propionate CFC inhalation aerosol 220 mcg, each given as 2 inhalations twice daily, and with Advair DISKUS 500/50 given as 1 inhalation twice daily in 509 subjects using inhaled corticosteroids (daily doses of beclomethasone dipropionate CFC inhalation aerosol 1,500 to 2,000 mcg; budesonide 1,500 to 2,000 mcg; flunisolide 1,500 to 2,000 mcg; fluticasone propionate inhalation aerosol 660 to 880 mcg; or fluticasone propionate inhalation powder 750 to 1,000 mcg). The primary efficacy endpoint was morning PEF.

Baseline morning PEF measurements were similar across treatments: Advair HFA 230/21, 327 L/min; Advair DISKUS 500/50, 341 L/min; and fluticasone propionate 220 mcg, 345 L/min. As shown in Figure 3, morning PEF improved significantly with Advair HFA 230/21 compared with fluticasone propionate 220 mcg over the 12-week treatment period. Improvements in morning PEF observed with Advair HFA 230/21 were similar to improvements observed with Advair DISKUS 500/50.

Figure 3. Mean Percent Change from Baseline in Morning Peak Expiratory Flow in Subjects Previously Treated with Inhaled Corticosteroids (Trial 4)

One-Year Safety Trial

Clinical Trial with Advair HFA 45/21, 115/21, and 230/21 Inhalation Aerosol

This 1-year, open-label, non-U.S. trial evaluated the safety of Advair HFA 45/21, 115/21, and 230/21 given as 2 inhalations twice daily in 325 subjects. This trial was stratified into 3 groups according to baseline asthma therapy: subjects using short-acting beta2-agonists alone (n = 42), salmeterol (n = 91), or inhaled corticosteroids (n = 277). Subjects treated with short-acting beta2-agonists alone, salmeterol, or low doses of inhaled corticosteroids with or without concurrent salmeterol received Advair HFA 45/21. Subjects treated with moderate doses of inhaled corticosteroids with or without concurrent salmeterol received Advair HFA 115/21. Subjects treated with high doses of inhaled corticosteroids with or without concurrent salmeterol received Advair HFA 230/21. Baseline FEV1 measurements ranged from 2.3 to 2.6 L.

Improvements in FEV1 (0.17 to 0.35 L at 4 weeks) were seen across all 3 treatments and were sustained throughout the 52-week treatment period. Few subjects (3%) were withdrawn due to worsening asthma over 1 year.

Onset of Action and Progression of Improvement in Control

The onset of action and progression of improvement in asthma control were evaluated in 2 placebo-controlled U.S. trials and 1 active-controlled U.S. trial. Following the first dose, the median time to onset of clinically significant bronchodilatation (greater than or equal to 15% improvement in FEV1) in most subjects was seen within 30 to 60 minutes. Maximum improvement in FEV1 occurred within 4 hours, and clinically significant improvement was maintained for 12 hours (Figure 4).

Following the initial dose, predose FEV1 relative to Day 1 baseline improved markedly over the first week of treatment and continued to improve over the 12 weeks of treatment in all 3 trials.

No diminution in the 12-hour bronchodilator effect was observed with either Advair HFA 45/21 (Figures 4 and 5) or Advair HFA 230/21 as assessed by FEV1 following 12 weeks of therapy.

Figure 4. Percent Change in Serial 12-Hour FEV1 in Subjects Previously Using Either Beta2-agonists (Albuterol or Salmeterol) or Inhaled Corticosteroids (Trial 1)

First Treatment Day

Figure 5. Percent Change in Serial 12-Hour FEV1 in Subjects Previously Using Either Beta2-agonists (Albuterol or Salmeterol) or Inhaled Corticosteroids (Trial 1)

Last Treatment Day (Week 12)

Reduction in asthma symptoms and use of rescue VENTOLIN Inhalation Aerosol and improvement in morning and evening PEF also occurred within the first day of treatment with Advair HFA, and continued to improve over the 12 weeks of therapy in all 3 trials.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Asthma-Related Death

Inform patients that salmeterol, one of the active ingredients in Advair HFA, increases the risk of asthma-related death and may increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Also inform them that currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA.

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 beta2-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 beta2-agonists • Need for more inhalations than usual of inhaled, short-acting beta2-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.

Do Not Use Additional Long-acting Beta2-agonists

Instruct patients not to use other LABA for asthma.

Local Effects

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.

Pneumonia

Patients with COPD have a higher risk of pneumonia; instruct them to contact their healthcare providers if they develop symptoms of pneumonia.

Immunosuppression

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.

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.

Immediate Hypersensitivity Reactions

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.

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.

Reduced Growth Velocity

Inform patients that orally inhaled corticosteroids, including fluticasone propionate, may cause a reduction in growth velocity when administered to pediatric patients. Physicians should closely follow the growth of children and adolescents taking corticosteroids by any route.

Ocular Effects

Inform patients that long-term use of inhaled corticosteroids may increase the risk of some eye problems (cataracts or glaucoma); consider regular eye examinations.

Risks Associated with Beta-agonist Therapy

Inform patients of adverse effects associated with beta2‑agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness.

Advair, Advair DISKUS, DISKUS, FLONASE, FLOVENT, ROTADISK, SEREVENT, and VENTOLIN are registered trademarks of the GSK group of companies.

GlaxoSmithKline

Research Triangle Park, NC 27709

©2017 the GSK group of companies. All rights reserved.

ADH:11PI

MEDICATION GUIDE

Advair® [ad′ vair] HFA

(fluticasone propionate and salmeterol)

inhalation aerosol

for oral inhalation

What is the most important information I should know about Advair HFA?

Advair HFA can cause serious side effects, including:

• People with asthma who take long-acting beta2-adrenergic agonist (LABA) medicines, such as salmeterol (one of the medicines in Advair HFA), have an increased risk of death from asthma problems. It is not known whether fluticasone propionate, the other medicine in Advair HFA, reduces the risk of death from asthma problems seen with salmeterol. • Call your healthcare provider if breathing problems worsen over time while using Advair HFA. You may need different treatment. • Get emergency medical care if: • your breathing problems worsen quickly. • you use your rescue inhaler, but it does not relieve your breathing problems. • Advair HFA should be used only if your healthcare provider decides that your asthma is not well controlled with a long-term asthma control medicine, such as an inhaled corticosteroid. • When your asthma is well controlled, your healthcare provider may tell you to stop taking Advair HFA. Your healthcare provider will decide if you can stop Advair HFA without loss of asthma control. Your healthcare provider may prescribe a different asthma control medicine for you, such as an inhaled corticosteroid. • Children and adolescents who take LABA medicines may have an increased risk of being hospitalized for asthma problems.

What is Advair HFA?

• Advair HFA combines the inhaled corticosteroid (ICS) medicine fluticasone propionate and the LABA medicine salmeterol. • ICS medicines such as fluticasone propionate help to decrease inflammation in the lungs. Inflammation in the lungs can lead to breathing problems. • 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. • 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: • 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. • Advair HFA contains salmeterol, the same medicine found in SEREVENT® DISKUS® (salmeterol xinafoate inhalation powder). LABA medicines such as salmeterol increase the risk of death from asthma problems. • 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 inhaled corticosteroid medicine.

Who should not use Advair HFA?

Do not use Advair HFA if you:

• are allergic to fluticasone propionate, salmeterol, or any of the ingredients in Advair HFA. See “What are the ingredients in Advair HFA?” below for a complete list of ingredients.

What should I tell my healthcare provider before using Advair HFA?

Tell your healthcare provider about all of your health 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 eye problems such as glaucoma or cataracts. • are allergic to any of the ingredients in Advair HFA or any other medicines. See “What are the ingredients in Advair HFA?” below for a complete list of ingredients. • have any type of viral, bacterial, or fungal infection. • are exposed to chickenpox or measles. • have any other medical conditions. • are pregnant or planning 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 Medication Guide.

What should I avoid while using Advair HFA?

• 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. Take your next dose at your usual time. Do not take 2 doses at 1 time. • If you take too much Advair HFA, call your healthcare provider or go to the nearest hospital emergency room right away if you have any unusual symptoms, such as worsening shortness of breath, chest pain, increased heart rate, or shakiness. • Do not use other medicines that contain a LABA for any reason. Ask your healthcare provider or pharmacist if any of your other medicines are LABA medicines. • Do not stop using Advair HFA, even if you are feeling better, unless your healthcare provider tells you to. • Talk to your healthcare provider right away if you stop using Advair HFA. • Advair HFA does not relieve sudden breathing problems. Always have a rescue inhaler with you to treat sudden symptoms. If you do not have a rescue inhaler, call your healthcare provider to have one prescribed for you. • Call your healthcare provider or get medical care right away if: • your breathing problems get worse. • you need to use your rescue inhaler more often than usual. • your rescue inhaler does not work as well to relieve your symptoms. • you need to use 4 or more inhalations of your rescue inhaler in 24 hours for 2 or more days in a row. • you use 1 whole canister of your rescue inhaler in 8 weeks. • your peak flow meter results decrease. Your healthcare provider will tell you the numbers that are right for you. • you have asthma and your symptoms do not improve after using Advair HFA regularly for 1 week.

What are the possible side effects of Advair HFA?

Advair HFA can cause serious side effects, including:

• See “What is the most important information I should know about Advair HFA?” • fungal infection in your mouth or throat (thrush). Rinse your mouth with water without swallowing after using Advair HFA to help decrease your chance of getting thrush. • pneumonia. Advair HFA contains the same medicine found in Advair DISKUS® (fluticasone propionate and salmeterol inhalation powder). Advair DISKUS is used to treat people with asthma and people with chronic obstructive pulmonary disease (COPD). People with COPD have a higher chance of getting pneumonia. Advair DISKUS may increase the chance of you getting pneumonia. It is not known if Advair HFA is safe and effective in people with COPD. Call your healthcare provider right away if you have any of the following symptoms:

         •  increase in mucus (sputum) production                           •  chills

         •  change in mucus color                                                     •  increased cough

         •  fever                                                                                 •  increased breathing problems

• weakened immune system and increased chance of getting infections (immunosuppression). • reduced adrenal function (adrenal insufficiency). Adrenal insufficiency is a condition where the adrenal glands do not make enough steroid hormones. This can happen when you stop taking oral corticosteroid medicines (such as prednisone) and start taking a medicine containing an inhaled steroid (such as Advair HFA). During this transition period, when your body is under stress such as from fever, trauma (such as a car accident), infection, surgery, or worse COPD symptoms, adrenal insufficiency can get worse and may cause death. • Symptoms of adrenal insufficiency include:

         •  feeling tired                                                                      •  nausea and vomiting

         •  lack of energy                                                                   •  low blood pressure

         •  weakness

• sudden breathing problems immediately after inhaling your medicine. If you have sudden breathing problems immediately after inhaling your medicine, stop using Advair HFA and call your healthcare provider right away. • serious allergic reactions. Call your healthcare provider or get emergency medical care if you get any of the following symptoms of a serious allergic reaction:

         •  rash                                                                                   •  swelling of your face, mouth and tongue

         •  hives                                                                                 •  breathing problems

• effects on heart.

         •  increased blood pressure                                                  •  chest pain

         •  a fast or irregular heartbeat

• effects on nervous system.

         •  tremor                                                                               •  nervousness

• bone thinning or weakness (osteoporosis). • slowed growth in children. A child’s growth should be checked often. • eye problems including glaucoma and cataracts. You should have regular eye exams while using Advair HFA. • changes in laboratory blood levels (sugar, potassium, certain types of white blood cells).

Common side effects of Advair HFA include:

         •  upper respiratory tract infection                                       •  headache

         •  throat irritation                                                                 •  dizziness

         •  hoarseness and voice changes                                          •  nausea and vomiting

Tell your healthcare provider about any side effect that bothers you or that does not go away.

These are not all the side effects with Advair HFA. Ask your healthcare provider or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Advair HFA?

• Store Advair HFA at room temperature between 68°F and 77°F (20°C and 25°C) with the mouthpiece down. • The contents of your Advair HFA are under pressure: Do not puncture. Do not use or store near heat or open flame. Temperatures above 120°F may cause the canister to burst. • Do not throw into fire or an incinerator. • Safely throw away Advair HFA in the trash when the counter reads 000. • Keep Advair HFA and all medicines out of the reach of children.

General information about the safe and effective use of Advair HFA.

Medicines are sometimes prescribed for purposes not mentioned in a Medication Guide. Do not use Advair HFA for a condition for which it was not prescribed. Do not give your Advair HFA to other people, even if they have the same condition that you have. It may harm them.

This Medication Guide summarizes the most important information about Advair HFA. If you would like more information, talk with your healthcare provider or pharmacist. You can ask your healthcare provider or pharmacist for information about Advair HFA that was written for healthcare professionals.

What are the ingredients in Advair HFA?

Active ingredients: fluticasone propionate, salmeterol xinafoate

Inactive ingredient: propellant HFA-134a

For more information about Advair HFA, call 1-888-825-5249 or visit our website at www.Advair.com.

Advair, Advair DISKUS, DISKUS, and SEREVENT are registered trademarks of the GSK group of companies.

GlaxoSmithKline

Research Triangle Park, NC 27709

©2017 the GSK group of companies. All rights reserved.

ADH:11MG

  This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: February 2017

INSTRUCTIONS FOR USE

Advair® [ad′ vair] HFA

(fluticasone propionate and salmeterol)

inhalation aerosol

for oral inhalation

Your Advair HFA inhaler

• The metal canister holds the medicine. See Figure A.

Figure A

• The 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 actuator. See Figure B.

Figure B

• 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 canister. • The purple plastic actuator sprays the medicine from the canister. The actuator has a protective cap that covers the mouthpiece. See Figure A. Keep the protective cap on the mouthpiece when the canister is not in use. The strap keeps the cap attached to the actuator. • Do not use the actuator with a canister of medicine from any other inhaler. • Do not use an Advair HFA canister with an actuator from any other inhaler.

Before using your Advair HFA inhaler

• Take Advair HFA out of the foil pouch just before you use it for the first time. Safely throw away the pouch and the drying packet that comes inside the pouch. • The inhaler should be at room temperature before you use it.

Priming your Advair HFA inhaler

• 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 prime the inhaler, take the cap off the mouthpiece and shake the inhaler well for 5 seconds. Then spray the inhaler 1 time into the air away from your face. See Figure C. Avoid spraying in eyes.

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.

Figure D

• You must prime your inhaler again if you have not used it in more than 4 weeks or if you drop it. Take the cap off the mouthpiece and 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.

  Step 1. Make sure the canister fits firmly in the actuator. The counter should show through the window in the actuator.   Shake the inhaler well for 5 seconds before each spray.   Take the cap off the mouthpiece of the actuator. Look inside the mouthpiece for foreign objects, and take out any you see.   Step 2. Hold the inhaler with the mouthpiece down. See Figure E.

Figure E

  Step 3. Breathe out through your mouth and push as much air from your lungs as you can. Put the mouthpiece in your mouth and close your lips around it. See Figure F.   Step 4. Push the top of the canister all the way down while you breathe in deeply and slowly through your mouth. See Figure F.

Figure F

  Step 5. After the spray comes out, take your finger off the 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 steps 2 through 6.   Step 7. Rinse your mouth with water after breathing in the medicine. Spit out the water. Do not swallow it. See Figure G.

Figure G

  Step 8. Put the cap back on the mouthpiece after every time you use the inhaler. Make sure it snaps firmly into place.

Cleaning your Advair HFA inhaler

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 H.

Figure H

  Step 9. Take the cap off the mouthpiece. The strap on the cap will stay attached to the actuator. Do not take the canister out of the plastic actuator.   Step 10. Use a dry cotton swab to clean the small circular opening where the medicine sprays out of the canister. Carefully twist the swab in a circular motion to take off any medicine. See Figure I.

Figure I

  Step 11. Wipe the inside of the mouthpiece with a clean tissue dampened with water. Let the actuator air-dry overnight.

Step 12. Put the cap back on the mouthpiece after the actuator has dried.

Replacing your Advair HFA inhaler

• When the counter reads 020, you should refill your prescription or ask your healthcare provider if you need another prescription for Advair HFA. • When the counter reads 000, throw the inhaler away. You should not keep using the inhaler when the counter reads 000 because you may not receive the right amount of medicine. • Do not use the inhaler after the expiration date, which is on the packaging it comes in.

For correct use of your Advair HFA inhaler, remember:

• The canister should always fit firmly in the actuator. • Breathe in deeply and slowly to make sure you get all the medicine. • Hold your breath for about 10 seconds after breathing in the medicine. Then breathe out fully. • After each dose, rinse your mouth with water and spit it out. Do not swallow the water. • Do not take the inhaler apart. • Always keep the protective cap on the mouthpiece when your inhaler is not in use. • Always store your inhaler with the mouthpiece pointing down. • Clean your inhaler at least 1 time each week.

If you have questions about Advair HFA or how to use your inhaler, call GlaxoSmithKline (GSK) at 1-888-825-5249 or visit www.Advair.com.

Advair is a registered trademark of the GSK group of companies.

GlaxoSmithKline

Research Triangle Park, NC 27709

©2017 the GSK group of companies. All rights reserved.

ADH:1IFU

  This Instructions for Use has been approved by the U.S. Food and Drug Administration Revised: February 2017

PRINCIPAL DISPLAY PANEL

NDC 0173-0715-20

Advair® HFA 45/21

(fluticasone propionate 45 mcg and salmeterol 21 mcg*)

Inhalation Aerosol

12 g

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.

Federal Law requires the dispensing of Advair HFA with the Medication Guide inside the carton.

See prescribing information for dosage information.

RX only

With Counter

120 Metered Actuations

©2015, the GSK group of companies

  10000000132553 Rev. 3/15

PRINCIPAL DISPLAY PANEL

NDC 0173-0716-20

Advair® HFA 115/21

(fluticasone propionate 115 mcg and salmeterol 21 mcg*)

Inhalation Aerosol

12 g

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.

Federal Law requires the dispensing of Advair HFA with the Medication Guide inside the carton.

See prescribing information for dosage information.

RX only

With Counter

120 Metered Actuations

©2015, the GSK group of companies

  10000000132527 Rev. 3/15

PRINCIPAL DISPLAY PANEL

NDC 0173-0717-20

Advair® HFA 230/21

(fluticasone propionate 230 mcg and salmeterol 21 mcg*)

Inhalation Aerosol

12 g

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.

Federal Law requires the dispensing of Advair HFA with the Medication Guide inside the carton.

See prescribing information for dosage information.

RX only

With Counter

120 Metered Actuations

©2015, the GSK group of companies

  10000000132528 Rev. 3/15
Advair HFA 
fluticasone propionate and salmeterol xinafoate aerosol, metered
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0173-0715
Route of Administration RESPIRATORY (INHALATION) DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
FLUTICASONE PROPIONATE (FLUTICASONE) FLUTICASONE PROPIONATE 45 ug
SALMETEROL XINAFOATE (SALMETEROL) SALMETEROL 21 ug
Inactive Ingredients
Ingredient Name Strength
NORFLURANE  
Packaging
# Item Code Package Description
1 NDC:0173-0715-20 1 INHALER in 1 CARTON
1 120 AEROSOL, METERED in 1 INHALER
2 NDC:0173-0715-22 1 INHALER in 1 CARTON
2 60 AEROSOL, METERED in 1 INHALER
3 NDC:0173-0715-61 1 INHALER in 1 CARTON
3 60 AEROSOL, METERED in 1 INHALER
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021254 09/29/2008
Advair HFA 
fluticasone propionate and salmeterol xinafoate aerosol, metered
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0173-0716
Route of Administration RESPIRATORY (INHALATION) DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
FLUTICASONE PROPIONATE (FLUTICASONE) FLUTICASONE PROPIONATE 115 ug
SALMETEROL XINAFOATE (SALMETEROL) SALMETEROL 21 ug
Inactive Ingredients
Ingredient Name Strength
NORFLURANE  
Packaging
# Item Code Package Description
1 NDC:0173-0716-20 1 INHALER in 1 CARTON
1 120 AEROSOL, METERED in 1 INHALER
2 NDC:0173-0716-22 1 INHALER in 1 CARTON
2 60 AEROSOL, METERED in 1 INHALER
3 NDC:0173-0716-61 1 INHALER in 1 CARTON
3 60 AEROSOL, METERED in 1 INHALER
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021254 09/29/2008
Advair HFA 
fluticasone propionate and salmeterol xinafoate aerosol, metered
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0173-0717
Route of Administration RESPIRATORY (INHALATION) DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
FLUTICASONE PROPIONATE (FLUTICASONE) FLUTICASONE PROPIONATE 230 ug
SALMETEROL XINAFOATE (SALMETEROL) SALMETEROL 21 ug
Inactive Ingredients
Ingredient Name Strength
NORFLURANE  
Packaging
# Item Code Package Description
1 NDC:0173-0717-20 1 INHALER in 1 CARTON
1 120 AEROSOL, METERED in 1 INHALER
2 NDC:0173-0717-22 1 INHALER in 1 CARTON
2 60 AEROSOL, METERED in 1 INHALER
3 NDC:0173-0717-61 1 INHALER in 1 CARTON
3 60 AEROSOL, METERED in 1 INHALER
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021254 03/06/2009
Labeler - GlaxoSmithKline LLC (167380711)
Revised: 02/2017   GlaxoSmithKline LLC

What happens if I miss a dose?

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

For the Consumer

Applies to fluticasone / salmeterol: inhalation aerosol liquid, inhalation aerosol powder, inhalation disk, inhalation powder

Along with its needed effects, fluticasone / salmeterol may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking fluticasone / salmeterol:

More common
  • Black, tarry stools
  • blindness
  • blurred vision
  • burning, tingling, numbness, or pain in the hands, arms, feet, or legs
  • chills
  • cough
  • decreased vision
  • difficulty with breathing or swallowing
  • eye pain
  • fast heartbeat
  • fever
  • headache
  • hives or welts, skin itching, rash, or redness
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • nausea or vomiting
  • noisy breathing
  • painful or difficult urination
  • sensation of pins and needles
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • stabbing pain in the arms or legs
  • swelling of the face, throat, or tongue
  • swollen glands
  • tearing
  • unusual bleeding or bruising
Incidence not known
  • Abdominal or stomach pain
  • backache
  • bruising
  • darkening of the skin
  • decrease in height
  • diarrhea
  • difficulty with moving
  • dizziness
  • facial hair growth in females
  • fainting
  • fast, slow, pounding, or irregular heartbeat or pulse
  • flushed, dry skin
  • fractures
  • fruit-like breath odor
  • full or round face, neck, or trunk
  • heavy bleeding
  • increased hunger
  • increased thirst or urination
  • irritability
  • large, flat, blue, or purplish patches in the skin
  • loss of sexual desire or ability
  • menstrual irregularities
  • mental depression
  • muscle pain or stiffness
  • muscle wasting
  • pain in the back, ribs, arms, or legs
  • pain in the joints
  • sweating
  • troubled breathing
  • unexplained weight loss
  • unusual tiredness or weakness
  • weight gain

Get emergency help immediately if any of the following symptoms of overdose occur while taking fluticasone / salmeterol:

Symptoms of overdose
  • Chest pain or tightness
  • confusion
  • convulsions (seizures)
  • decreased urine output
  • dry mouth
  • faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • general feeling of discomfort or illness
  • high blood pressure
  • loss of appetite
  • mood changes
  • nervousness
  • numbness or tingling in the hands, feet, or lips
  • sudden sweating
  • tremors
  • trouble with sleeping

Some side effects of fluticasone / salmeterol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Body aches or pain
  • choking
  • congestion
  • dryness of the throat
  • high-pitched noise when breathing
  • hoarseness
  • runny nose
  • sneezing
  • trouble with swallowing
  • voice changes
Less common
  • Cough-producing mucus
  • flu-like symptoms
  • irritation or inflammation of the eye
  • muscle pain
  • pain or tenderness around the eyes and cheekbones
  • sleep disorders
  • stuffy nose
  • white patches in the mouth or throat or on the tongue

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