Advair Hfa Generic Name & Formulations
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).
Store the inhaler with the mouthpiece down.
Do not use or store near heat or open flame.
Advair Hfa Indications
Limitations of Use
Advair Hfa Dosage and Administration
Advair Hfa Contraindications
Advair Hfa Boxed Warnings
Advair Hfa Warnings/Precautions
Serious Asthma-Related Events – Hospitalizations, Intubations, Death
- Long-acting beta2-adrenergic agonists (LABA) as monotherapy (without inhaled corticosteroids [ICS]) for asthma can increase risk of asthma-related events.
- The increased risk of asthma-related death is considered a class effect of the LABA.
- Available data do not suggest an increased risk of serious asthma-related events with use of LABA in fixed-dose combination with ICS compared with ICS alone in asthma patients.
Deterioration of Disease and Acute Episodes
- Do not initiate Advair HFA with acutely deteriorating asthma; use in this setting is inappropriate.
- Not for relief of acute symptoms; acute symptoms should be treated with inhaled short-acting beta2-agonist.
- When beginning treatment with Advair HFA, patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (eg, 4 x daily) should be instructed to discontinue the regular use of these drugs.
Avoid Excessive Use of Advair HFA and Avoid Use with Other Long-acting Beta2-agonists
- Do not exceed the recommended dose.
- Fatalities have been reported with excessive use of inhaled sympathomimetic drugs.
- Patients using Advair HFA should not use another medicine containing a LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.
- Localized Infections of the mouth and pharynx with Candida albicans has occurred in clinical trials. Infections should be treated with appropriate local or systemic antifungal therapy while remaining on Advair HFA, though Advair HFA may need to be interrupted in some cases.
- Patients should rinse the mouth after inhalation of Advair HFA.
Immunosuppression and Risk of Infections
- Patients who are using drugs that suppress the immune system are more susceptible to infections. For patients who have not previously had chickenpox or measles or been vaccinated against these diseases, consider immunoglobulin prophylactic therapy if exposure occurs. Treatment with antivirals should be considered if chickenpox develops.
- Inhaled corticosteroids should be used with caution in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
Transferring patients from systemic corticosteroids:
- Particular care is needed for patients who are transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically-available ICS.
- Patients who have been previously maintained on 20mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn.
- During this period of HPA suppression, patients may exhibit signs/symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss.
- In recommended doses, Advair HFA supplies less than normal physiological amounts of corticosteroid systemically and does not provide the mineralocorticoid activity that is necessary for coping with these emergencies.
- Patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately during periods of stress or a severe asthma attack.
- Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to Advair HFA.
- Monitor lung function, beta-agonist use, and asthma symptoms during withdrawal.
- Observe patients for signs/symptoms of adrenal insufficiency (eg, fatigue, lassitude, weakness, nausea, vomiting, hypotension).
- Transfer from systemic corticosteroids may unmask allergic conditions.
- Some patients may experience systemically active steroid withdrawal, despite maintenance of improvement of respiratory function.
Hypercorticism and Adrenal Suppression
- Monitor for hypercorticism and HPA axis suppression (if occur, reduce dose gradually).
Paradoxical Bronchospasm and Upper Airway Symptoms
- Discontinue if paradoxical bronchospasm occurs; alternative therapy should be started.
Hypersensitivity Reactions, including Anaphylaxis
- Immediate hypersensitivity reactions (eg, urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Advair HFA.
Cardiovascular and Central Nervous System Effects
- Cardiovascular disorders (esp. coronary insufficiency, arrhythmias, hypertension).
- Beta2-agonists can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic and/or diastolic blood pressure, and/or symptoms.
- ECG changes have also been reported.
- Use with caution in patients with cardiovascular disorders.
- Consider discontinuing treatment if significant cardiovascular effects occur.
Reduction in Bone Mineral Density
- Decreases in bone mineral density have been observed with long-term administration of ICS; patients with risk factors should be monitored and treated appropriately.
Effect on Growth
- Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients.
- Monitor the growth of pediatric patients receiving Advair HFA routinely (eg, via stadiometry).
- To minimize the systemic effects of orally inhaled corticosteroids, including Advair HFA, titrate each patient’s dosage to the lowest dosage that effectively controls his/her symptoms.
Glaucoma and Cataracts
- Glaucoma, increased intraocular pressure, and cataracts have been reported following administration of inhaled corticosteroids, including Advair HFA.
- Consider referral to an ophthalmologist in those who develop ocular symptoms or use Advair HFA long term.
Eosinophilic Conditions and Churg-Strauss Syndrome
- In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions. Some of these patients have clinical features of vasculitis consistent with ChurgStrauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually have been associated with the reduction and/or withdrawal of oral corticosteroid therapy after the use of fluticasone propionate.
- Cases of serious eosinophilic conditions have also been reported with other ICS in this clinical setting.
- Be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established.
- Use with caution in patients with convulsive disorders.
- Use with caution in patients with thyrotoxicosis.
- Use with caution in patients who are unusually responsive to sympathomimetic amines.
- Large doses of the related beta2-agonist albuterol, when given intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.
Hypokalemia and Hyperglycemia
- Beta-agonists may produce significant hypokalemia in some patients.
- This is usually transient and does not require supplementation.
- Clinically significant changes in blood glucose and/or serum potassium were infrequent during clinical trials with Advair HFA at recommended doses.
There is insufficient data on the use of Advair HFA or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women.
Pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma.
There are no human studies evaluating the effects of Advair HFA during labor and delivery. Due to the potential for beta-agonist interference with uterine contractility, use of Advair HFA during labor should be restricted to those in whom the benefits clearly outweigh the risks.
Nursing Mother Considerations
There is no available data on the presence of fluticasone propionate or salmeterol in human milk, the effects on the breastfed child, or the effects on milk production. Other corticosteroids have been detected in human milk. However, fluticasone propionate and salmeterol concentrations in plasma after inhaled therapeutic doses are low; therefore concentrations in human breast milk are likely to be correspondingly low.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Advair HFA and any potential adverse effects on the breastfed child from Advair HFA or from the underlying maternal condition.
The safety and effectiveness of Advair HFA in pediatric patients <12 years have not been established.
ICS, including fluticasone propionate, a component of Advair HFA, may cause a reduction in growth velocity in children and adolescents. The growth of pediatric patients receiving orally inhaled corticosteroids, including Advair HFA, should be monitored.
To minimize the systemic effects of orally inhaled corticosteroids, including Advair HFA, patients should be titrated to the lowest strength that effectively controls his/her asthma.
Clinical trials of Advair HFA did not include sufficient numbers of subjects aged ≥65 years 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 beta2-agonists, special caution should be observed when using Advair HFA in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta2-agonists.
Hepatic Impairment Considerations
Both fluticasone propionate and salmeterol are predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate and salmeterol in plasma. Therefore, patients with hepatic disease should be closely monitored.
Advair Hfa Pharmacokinetics
Fluticasone Propionate: After intravenous administration, the initial disposition phase for fluticasone propionate was rapid and consistent with its high lipid solubility and tissue binding. The volume of distribution averaged 4.2 L/kg. The percentage of fluticasone propionate bound to human plasma proteins averages 99%.
Salmeterol: The percentage of salmeterol bound to human plasma proteins averages 96% in vitro.
Fluticasone Propionate: After intravenous dosing, fluticasone propionate had a terminal elimination half-life of ~7.8 hours. Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites. Terminal half-life estimates of fluticasone propionate averaged 5.6 hours.
Salmeterol: In 2 healthy adult subjects who received 1 mg of radiolabeled salmeterol (as salmeterol xinafoate) orally, approximately 25% and 60% of the radiolabeled salmeterol was eliminated in urine and feces, respectively, over a period of 7 days. The terminal elimination half-life was about 5.5 hours (1 volunteer only).
The xinafoate moiety has no apparent pharmacologic activity.
The xinafoate moiety is highly protein bound (>99%) and has a long elimination half-life of 11 days. No terminal half-life estimates were calculated for salmeterol following administration of Advair HFA.
Advair Hfa Interactions
Advair Hfa Adverse Reactions
Upper respiratory tract infection or inflammation, throat irritation, dysphonia, headache, dizziness, nausea, vomiting; oral candidiasis, pneumonia, hypersensitivity reactions.
Advair Hfa Clinical Trials
Four (4) double-blind, parallel-group clinical trials were conducted with Advair HFA in 1,517 adult and adolescent patients (aged ≥12 years, 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 mcg/21 mcg
- A placebo-controlled, 12-week, US 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 FEV1 and withdrawals due to worsening asthma.
- This trial was stratified according to baseline asthma therapy: patients using beta-agonists (albuterol alone or salmeterol) or ICS.
- Baseline FEV1 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, 2.27 L.
- Predefined withdrawal criteria for lack of efficacy, an indicator of worsening asthma, were utilized for this placebo-controlled trial.
Results showed statistically significantly fewer patients who received Advair HFA 45 mcg/21 mcg were withdrawn due to worsening asthma (2%) compared with salmeterol (25%) and placebo (28%). Fewer patients who received Advair HFA 45 mcg/21 mcg were withdrawn due to worsening asthma (2%) compared with fluticasone propionate 44 mcg (8%); however, the difference was not statistically significant.
The FEV1 results at endpoint showed that patients who received Advair HFA 45 mcg/21 mcg 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 mcg/21 mcg were achieved regardless of baseline asthma therapy (albuterol alone, salmeterol, or ICS).
The subjective impact of asthma on patients’ 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). Patients receiving Advair HFA 45 mcg/21 mcg had clinically meaningful improvements in overall asthma-specific quality of life as defined by a difference between groups of ≥0.5 points in change from baseline AQLQ scores (difference in AQLQ score of 1.14 [95% CI, 0.85-1.44] vs placebo).
Trial 2: Clinical Trial with Advair HFA 45 mcg/21 mcg
- An active-controlled, 12-week, US trial compared Advair HFA 45 mcg/21 mcg with fluticasone propionate CFC inhalation aerosol 44 mcg and salmeterol CFC inhalation aerosol 21 mcg, each given as 2 inhalations twice daily, in 283 patients using as-needed albuterol alone.
- The primary efficacy endpoint was predose FEV1. Baseline FEV1 measurements were similar across treatments: Advair HFA 45 mcg/21 mcg, 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. Patients who received Advair HFA 45 mcg/21 mcg 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 mcg/21 mcg
- A placebo-controlled, 12-week, US trial compared Advair HFA 115 mcg/21 mcg with fluticasone propionate CFC inhalation aerosol 110 mcg or salmeterol CFC inhalation aerosol 21 mcg, each given as 2 inhalations twice daily, in 365 patients using ICS.
- The primary efficacy endpoints were predose FEV1 and withdrawals due to worsening asthma. Baseline FEV1 measurements were similar across treatments: Advair HFA 115 mcg/21 mcg, 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. Patients who received Advair HFA 115 mcg/21 mcg 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 patients who received Advair HFA 115 mcg/21 mcg were withdrawn from this trial for worsening asthma (7%) compared with salmeterol (24%) and placebo (54%). Fewer patients who received Advair HFA 115 mcg/21 mcg 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 mcg/21 mcg
- A active-controlled, 12-week, non-US trial compared Advair HFA 230 mcg/21 mcg with fluticasone propionate CFC inhalation aerosol 220 mcg, each given as 2 inhalations twice daily, and with Advair Diskus 500 mcg /50 mcg given as 1 inhalation twice daily in 509 patients using ICS.
- The primary efficacy endpoint was morning peak expiratory flow (PEF). Baseline morning PEF measurements were similar across treatments: Advair HFA 230 mcg/21 mcg, 327 L/min; Advair Diskus 500 mcg/50 mcg, 341 L/min; and fluticasone propionate 220 mcg, 345 L/min.
Results showed that the morning PEF improved significantly with Advair HFA 230 mcg/21 mcg compared with fluticasone propionate 220 mcg over the 12-week treatment period. Improvements in morning PEF observed with Advair HFA 230 mcg/21 mcg were similar to improvements observed with Advair Diskus 500 mcg/50 mcg.
One-Year Safety Trial: Clinical Trial with Advair HFA 45 mcg/21 mcg, 115 mcg/21 mcg, and 230 mcg/21 mcg
- A 1-year, open-label, non-U.S. trial evaluated the safety of Advair HFA 45 mcg/21 mcg, 115 mcg/21 mcg, and 230 mcg/21 mcg given as 2 inhalations twice daily in 325 patients.
- This trial was stratified into 3 groups according to baseline asthma therapy: patients using short-acting beta2-agonists alone (n = 42), salmeterol (n = 91), or ICS (n = 277).
- Patients treated with short-acting beta2-agonists alone, salmeterol, or low doses of ICS with or without concurrent salmeterol received Advair HFA 45 mcg/21 mcg.
- Patients treated with moderate doses of ICS with or without concurrent salmeterol received Advair HFA 115 mcg/21 mcg.
- Patients treated with high doses of ICS with or without concurrent salmeterol received Advair HFA 230 mcg/21 mcg.
- Baseline FEV1 measurements ranged from 2.3 to 2.6 L.
At study endpoint, 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 patients (3%) were withdrawn due to worsening asthma over 1 year.
Advair Hfa Note
Advair Hfa Patient Counseling
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.
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.
- 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 (ie, 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.
- Patients with COPD have a higher risk of pneumonia; instruct them to contact their healthcare providers if they develop symptoms of pneumonia.
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.
Hypercorticism and Adrenal Suppression
- Advise patients that Advair HFA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression.
- 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.
Hypersensitivity Reactions, including Anaphylaxis
- Advise patients that immediate hypersensitivity reactions (eg, urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Advair HFA. Patients should discontinue Advair HFA if such reactions occur.
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.
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.
Glaucoma and Cataracts
- Advise patients that long-term use of ICS may increase the risk of some eye problems (cataracts or glaucoma); consider regular eye examinations.