Medicine guide

Fluticasone Propionate and Salmeterol

113 ug + 14 ug · Powder, Metered

Prescription only
Corticosteroid

Active substance: Fluticasone Propionate and Salmeterol
Used in: Breathing, airways, allergies and cough
Made by: Bryant Ranch Prepack
Source: Official label

Quoted from the official source. Not yet reviewed by Mediclarum — the leaflet in your pack is authoritative.

At a glance

Quoted from the official label · 2024-04-04

What it is

Corticosteroid

Used for

Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhaler (FS MDPI) is indicated for the treatment of asthma in adult and pediatric patients aged 12 years and older.

The label’s usual adult dose

( 2.2 ) 1 inhalation of Fluticasone Propionate/Salmeterol 55 mcg/14 mcg, 113 mcg/14 mcg, or 232 mcg/14 mcg twice daily.

Do not use more than two times every 24 hours.

Full directions ↓

Do not take it if

Fluticasone Propionate/Salmeterol MDPI is contraindicated in:

All warnings ↓

Good to know

Prescription only
FDA enforcement reports list no ongoing recall, and none from the last two years, for this product code · checked 2026-10-02

46other products contain Fluticasone Propionate and Salmeterol — compare makers, forms and strengths

Every line above is selected, not written, from the official label. Nothing is reworded. DailyMed

What it is for

Limitations of Use :

Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhaler (FS MDPI) is indicated for the treatment of asthma in adult and pediatric patients aged 12 years and older.
Fluticasone Propionate/Salmeterol MDPI should be used for patients not adequately controlled on a long term asthma control medication such as an inhaled corticosteroid or whose disease warrants initiation of treatment with both an inhaled corticosteroid and long acting beta 2 -adrenergic agonist (LABA).
Fluticasone Propionate/Salmeterol MDPI is not indicated for the relief of acute bronchospasm.
Fluticasone Propionate/Salmeterol Multi-Dose Dry Powder Inhaler (MDPI) is a combination of fluticasone propionate, a corticosteroid, and salmeterol, a long-acting beta 2 -adrenergic agonist (LABA), indicated for treatment of asthma in adult and pediatric patients aged 12 years and older.
Fluticasone Propionate/Salmeterol inhalation powder should be used for patients not adequately controlled on a long term asthma control medication such as an inhaled corticosteroid or whose disease warrants initiation of treatment with both an inhaled corticosteroid and long acting beta 2 -adrenergic agonist (LABA).
( 1 ) Limitations of Use : Not indicated for the relief of acute bronchospasm.
( 1 )

From the official label · 2024-04-04 · DailyMed

How it works

From this product’s own US prescribing label.

This product contains both fluticasone propionate and salmeterol.
The mechanisms of action described below for the individual components apply to this combination product.

Half-life7.8 h

Mostly cleared after≈ 39 hfive half-lives — our arithmetic

How the body breaks it down

Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate was negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver.

How it leaves the body

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.

Quoted from the prescribing label, sections “Mechanism of Action” and “Pharmacokinetics”. DailyMed · 2024-04-04

Do not take it if

Fluticasone Propionate/Salmeterol MDPI is contraindicated in:
the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required [see Warnings and Precautions ( 5.2 )] . patients with known severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to fluticasone propionate or any of the excipients [see Warnings and Precautions ( 5.10 ) and Description ( 11 )] .
Primary treatment of status asthmaticus or acute episodes of asthma requiring intensive measures.
( 4 ) Severe hypersensitivity to milk proteins or any ingredients of Fluticasone Propionate/Salmeterol MDPI.
( 4 )

Quoted from the official label, section “Contraindications”.

How to take it

These directions are for this exact strength and form. Another one is different.

For oral inhalation only.
( 2.1 ) Starting dosage is based on prior asthma therapy and disease severity.
( 2.2 ) 1 inhalation of Fluticasone Propionate/Salmeterol 55 mcg/14 mcg, 113 mcg/14 mcg, or 232 mcg/14 mcg twice daily.
( 2.2 ) Do not use with a spacer or volume holding chamber.
( 2.2 )
2.1 Administration Instructions Fluticasone Propionate/Salmeterol MDPI is for oral inhalation and does not require priming.
Do not use Fluticasone Propionate/Salmeterol MDPI with a spacer or volume holding chamber.
Do not use more than two times every 24 hours.
More frequent administration or a greater number of daily inhalations (more than one inhalation twice daily) is not recommended as some patients are more likely to experience adverse reactions with higher salmeterol dosages.
Avoid the concomitant use of other long acting beta 2 -adrenergic agonist (LABAs) [see Warnings and Precautions ( 5.3 , 5.11 )].
If asthma symptoms arise in the period between doses, an inhaled, short-acting beta 2 -agonist should be taken for immediate relief.
2.2 Recommended Dosage Administer 1 inhalation of Fluticasone Propionate/Salmeterol MDPI twice daily by oral inhalation (approximately 12 hours apart at the same time every day).
Rinse the mouth with water without swallowing after each inhalation.
Dosage Selection The recommended starting dosage for Fluticasone Propionate/Salmeterol MDPI is based on asthma severity and current inhaled corticosteroid use and strength.
Patients not taking inhaled corticosteroids (ICS) (with less severe asthma):
1 inhalation of 55 mcg/14 mcg Fluticasone Propionate/Salmeterol MDPI dose strength (55 mcg of fluticasone propionate and 14 mcg of salmeterol), twice daily by oral inhalation.
Patients with greater asthma severity, use the higher dose strengths:
1 inhalation of 113 mcg/14 mcg Fluticasone Propionate/Salmeterol MDPI (113 mcg of fluticasone propionate and 14 mcg of salmeterol) twice daily; or 1 inhalation of 232 mcg/14 mcg Fluticasone Propionate/Salmeterol MDPI (232 mcg of fluticasone propionate and 14 mcg of salmeterol) twice daily Patients switching to Fluticasone Propionate/Salmeterol MDPI from another inhaled corticosteroid or combination product:
1 inhalation of low (55 mcg/14 mcg), medium (113 mcg/14 mcg) or high (232 mcg/14 mcg) Fluticasone Propionate/Salmeterol MDPI twice daily by oral inhalation based on the strength of the previous inhaled corticosteroid product, or the strength of the inhaled corticosteroid from a combination product, and disease severity.
The maximum recommended dosage of Fluticasone Propionate/Salmeterol MDPI is 232 mcg/14 mcg twice daily.
General Dosing Information Improvement in asthma control following Fluticasone Propionate/Salmeterol MDPI administration can occur within 15 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 dose of Fluticasone Propionate/Salmeterol MDPI after 2 weeks of therapy, consider increasing the strength (replace with higher strength) to possibly provide additional improvement in asthma control.
If a previously effective dosage regimen fails to provide adequate improvement in asthma control, re-evaluate the therapeutic regimen, including patient compliance and inhaler technique, and consider additional therapeutic options (e.g., increasing the dose of Fluticasone Propionate/Salmeterol MDPI with a higher strength, adding additional controller therapies).
After asthma stability has been achieved, it is desirable to titrate to the lowest effective dosage to reduce the risk of adverse reactions.
2.3 Storing and Cleaning the Inhaler Keep the inhaler in a cool dry place.
Routine maintenance is not required.
If the mouthpiece needs cleaning, gently wipe the mouthpiece with a dry cloth or tissue as needed.
Never wash or put any part of the inhaler in water.
2.4 Dose Counter The Fluticasone Propionate/Salmeterol MDPI has a dose counter:
The number 60 is displayed (prior to use).
The dose counter will count down each time the mouthpiece is opened and closed [see Patient Counseling Information ( 17 )].
2.1 Administration Instructions Fluticasone Propionate/Salmeterol MDPI is for oral inhalation and does not require priming.
Do not use Fluticasone Propionate/Salmeterol MDPI with a spacer or volume holding chamber.
Do not use more than two times every 24 hours.
More frequent administration or a greater number of daily inhalations (more than one inhalation twice daily) is not recommended as some patients are more likely to experience adverse reactions with higher salmeterol dosages.
Avoid the concomitant use of other long acting beta 2 -adrenergic agonist (LABAs) [see Warnings and Precautions ( 5.3 , 5.11 )].
If asthma symptoms arise in the period between doses, an inhaled, short-acting beta 2 -agonist should be taken for immediate relief.
2.2 Recommended Dosage Administer 1 inhalation of Fluticasone Propionate/Salmeterol MDPI twice daily by oral inhalation (approximately 12 hours apart at the same time every day).
Rinse the mouth with water without swallowing after each inhalation.
Dosage Selection The recommended starting dosage for Fluticasone Propionate/Salmeterol MDPI is based on asthma severity and current inhaled corticosteroid use and strength.
Patients not taking inhaled corticosteroids (ICS) (with less severe asthma):
1 inhalation of 55 mcg/14 mcg Fluticasone Propionate/Salmeterol MDPI dose strength (55 mcg of fluticasone propionate and 14 mcg of salmeterol), twice daily by oral inhalation.
Patients with greater asthma severity, use the higher dose strengths:
1 inhalation of 113 mcg/14 mcg Fluticasone Propionate/Salmeterol MDPI (113 mcg of fluticasone propionate and 14 mcg of salmeterol) twice daily; or 1 inhalation of 232 mcg/14 mcg Fluticasone Propionate/Salmeterol MDPI (232 mcg of fluticasone propionate and 14 mcg of salmeterol) twice daily Patients switching to Fluticasone Propionate/Salmeterol MDPI from another inhaled corticosteroid or combination product:
1 inhalation of low (55 mcg/14 mcg), medium (113 mcg/14 mcg) or high (232 mcg/14 mcg) Fluticasone Propionate/Salmeterol MDPI twice daily by oral inhalation based on the strength of the previous inhaled corticosteroid product, or the strength of the inhaled corticosteroid from a combination product, and disease severity.
The maximum recommended dosage of Fluticasone Propionate/Salmeterol MDPI is 232 mcg/14 mcg twice daily.
General Dosing Information Improvement in asthma control following Fluticasone Propionate/Salmeterol MDPI administration can occur within 15 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 dose of Fluticasone Propionate/Salmeterol MDPI after 2 weeks of therapy, consider increasing the strength (replace with higher strength) to possibly provide additional improvement in asthma control.
If a previously effective dosage regimen fails to provide adequate improvement in asthma control, re-evaluate the therapeutic regimen, including patient compliance and inhaler technique, and consider additional therapeutic options (e.g., increasing the dose of Fluticasone Propionate/Salmeterol MDPI with a higher strength, adding additional controller therapies).
After asthma stability has been achieved, it is desirable to titrate to the lowest effective dosage to reduce the risk of adverse reactions.
2.3 Storing and Cleaning the Inhaler Keep the inhaler in a cool dry place.
Routine maintenance is not required.
If the mouthpiece needs cleaning, gently wipe the mouthpiece with a dry cloth or tissue as needed.
Never wash or put any part of the inhaler in water.
2.4 Dose Counter The Fluticasone Propionate/Salmeterol MDPI has a dose counter:
The number 60 is displayed (prior to use). The dose counter will count down each time the mouthpiece is opened and closed [see Patient Counseling Information ( 17 )].

Quoted from the official label, section “Dosage & Administration”.

Other warnings

LABA monotherapy increases the risk of serious asthma-related events.
( 5.1 ) Deterioration of asthma and acute episodes:
Do not use for relief of acute symptoms.
Patients require immediate re-evaluation during rapidly deteriorating asthma.
( 5.2 )
Do not use in combination with an additional medicine containing LABA because of risk of overdose.
( 5.3 ) Localized infections:
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 ) Immunosuppression:
Potential worsening of existing tuberculosis, fungal, bacterial, viral, parasitic infection, or 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.
( 5.5 ) Transferring patients from systemic corticosteroids:
Risk of impaired adrenal function when transferring from systemic corticosteroids.
Taper patients slowly from systemic corticosteroids if transferring to Fluticasone Propionate/Salmeterol.
( 5.6 ) Hypercorticism and adrenal suppression:
May occur with very high dosages or at the regular dosage in susceptible individuals.
If such changes occur, discontinue Fluticasone Propionate/Salmeterol slowly.
( 5.7 ) Paradoxical bronchospasm:
Discontinue Fluticasone Propionate/Salmeterol and institute alternative therapy if paradoxical bronchospasm occurs.
( 5.9 ) Use with caution in patients with cardiovascular or central nervous system disorders because of beta adrenergic stimulation.
( 5.11 ) Decreases in bone mineral density:
Monitor patients with major risk factors for decreased bone mineral content.
( 5.12 ) Monitor growth of pediatric patients.
( 5.13 ) Close monitoring for glaucoma and cataracts is warranted.
( 5.14 ) Be alert to eosinophilic conditions, hypokalemia, and hyperglycemia.
( 5.15 , 5.17 ) Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.
( 5.16 )
5.1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death Use of LABA as monotherapy [without inhaled corticosteroids (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 large, 26-week, randomized, blinded, 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 budesonide/formoterol to budesonide, 1 trial compared fluticasone propionate/salmeterol inhalation powder to fluticasone propionate inhalation powder, and 1 trial compared mometasone furoate/formoterol to mometasone furoate.
The fourth trial included pediatric subjects aged 4 to 11 years and compared fluticasone propionate/salmeterol inhalation powder to 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 adolescent trials were designed to rule out a risk margin of 2.0, and the pediatric trial was designed to rule out a risk margin of 2.7.
Each individual trial met its pre-specified objective and demonstrated non-inferiority of ICS/LABA to ICS alone.
A meta-analysis of the 3 adult and adolescent trials did not show a significant increase in risk of a serious asthma-related event with ICS/LABA fixed-dose combination compared with ICS alone (Table 1).
These trials were not designed to rule out all risk for serious asthma-related events with ICS/LABA compared with ICS.
Table 1.
Meta-analysis of Serious Asthma-Related Events in Subjects with Asthma Aged 12 Years and Older ICS/LABA (n =17,537) a ICS (n = 17,552) a ICS/LABA vs.
ICS Hazard Ratio (95% CI) b Serious asthma-related event c 116 105 1.10 (0.85, 1.44) Asthma-related death 2 0 Asthma-related intubation (endotracheal) 1 2 Asthma-related hospitalization (≥24-hour stay) 115 105 ICS = Inhaled Corticosteroid;
LABA = Long-acting Beta 2 -adrenergic Agonist. a Randomized subjects who had taken at least 1 dose of study drug.
Planned treatment used for analysis. b Estimated using a Cox proportional hazards model for time to first event with baseline hazards stratified by each of the 3 trials. c Number of subjects with events that occurred within 6 months after the first use of study drug or 7 days after the last date of study drug, whichever date was later.
Subjects can have one or more events, but only the first event was counted for analysis.
A single, blinded, independent adjudication committee determined whether events were asthma related.
The pediatric safety trial included 6,208 pediatric patients aged 4 to 11 years who received ICS/LABA (fluticasone propionate/salmeterol inhalation powder) or ICS (fluticasone propionate inhalation powder).
In this trial 27/3,107 (0.9%) of patients treated with ICS/LABA and 21/3,101 (0.7%) of patients treated with ICS experienced a serious asthma‑related event.
There were no asthma-related deaths or intubations.
ICS/LABA did not show a significantly increased risk of a serious asthma-related event compared to ICS based on the prespecified risk margin (2.7), with an estimated hazard ratio of time to first event of 1.29 (95% CI:
0.73, 2.27).
Salmeterol Multicenter Asthma Research Trial (SMART) A 28-week, placebo-controlled, U.S. trial that compared the safety of salmeterol with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in subjects receiving salmeterol (13/13,176 in subjects treated with salmeterol versus 3/13,179 in subjects treated with placebo; relative risk:
4.37 [95% CI:
1.25, 15.34]).
Use of background ICS was not required in SMART.
The increased risk of asthma‑related death is considered a class effect of LABA monotherapy.
5.2 Deterioration of Disease and Acute Episodes Fluticasone Propionate/Salmeterol MDPI should not be initiated in patients during rapidly deteriorating or potentially life‑threatening episodes of asthma.
Fluticasone Propionate/Salmeterol MDPI has not been studied in subjects with acutely deteriorating asthma.
The initiation of Fluticasone Propionate/Salmeterol MDPI in this setting is not appropriate.
Serious acute respiratory events, including fatalities, have been reported when salmeterol, a component of this product, has been initiated in patients with significantly worsening or acutely deteriorating asthma.
In most cases, these have occurred in patients with severe asthma (e.g., patients with a history of corticosteroid dependence, low pulmonary function, intubation, mechanical ventilation, frequent hospitalizations, previous life‑threatening acute asthma exacerbations) and in some patients with acutely deteriorating asthma (e.g., patients with significantly increasing symptoms; increasing need for inhaled, short‑acting beta 2 ‑agonists; decreasing response to usual medications; increasing need for systemic corticosteroids; recent emergency room visits; deteriorating lung function).
However, these events have occurred in a few patients with less severe asthma as well.
It was not possible from these reports to determine whether salmeterol contributed to these events.
Increasing use of inhaled, short‑acting beta 2 ‑agonists is a marker of deteriorating asthma.
In this situation, the patient requires immediate reevaluation with reassessment of the treatment regimen, giving special consideration to the possible need for replacing the current strength of Fluticasone Propionate/Salmeterol MDPI with a higher strength, adding additional inhaled corticosteroid, or initiating systemic corticosteroids.
Patients should not use more than 1 inhalation twice daily of Fluticasone Propionate/Salmeterol MDPI.
Fluticasone Propionate/Salmeterol MDPI should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm.
An inhaled, short‑acting beta 2 ‑agonist, not Fluticasone Propionate/Salmeterol MDPI, should be used to relieve acute symptoms such as shortness of breath.
When prescribing Fluticasone Propionate/Salmeterol MDPI, the healthcare provider should also prescribe an inhaled, short‑acting beta 2 -agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice‑daily use of Fluticasone Propionate/Salmeterol MDPI.
When beginning treatment with Fluticasone Propionate/Salmeterol MDPI, patients who have been taking oral or inhaled, short‑acting beta 2 ‑agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs.
5.3
Avoid Excessive Use of Fluticasone Propionate/Salmeterol and
Avoid Use with Other Long-Acting Beta 2 -Agonists Fluticasone Propionate/Salmeterol MDPI should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result.
Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.
Patients using Fluticasone Propionate/Salmeterol MDPI should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.
5.4 Oropharyngeal Candidiasis In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with Fluticasone Propionate/Salmeterol MDPI.
When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with Fluticasone Propionate/Salmeterol MDPI continues, but at times therapy with Fluticasone Propionate/Salmeterol MDPI may need to be interrupted.
Advise the patient to rinse his/her mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.
5.5 Immunosuppression and Risk of Infections Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals.
Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible adolescents or
adults using corticosteroids.
In such patients who have not had these diseases or who have not been properly immunized, particular care should be taken to
avoid exposure.
How the dose, route and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known.
The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known.
If a patient is exposed to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG) may be indicated.
If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated.
(See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.
Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
5.6 Transferring Patients from Systemic Corticosteroid Therapy HPA Suppression/Adrenal Insufficiency Particular care is needed for patients who are transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.
After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic‑pituitary‑adrenal (HPA) function.
Patients who have been previously maintained on 20 mg or more 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 and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss.
Although Fluticasone Propionate/Salmeterol MDPI may improve control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies.
During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physician for further instruction.
These patients should also be instructed to carry a medical identification warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.
Patients requiring systemic corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to Fluticasone Propionate/Salmeterol MDPI.
Lung function (mean forced expiratory volume in 1 second [FEV 1 ] or morning peak expiratory flow [AM PEF]), beta‑agonist use, and asthma symptoms should be carefully monitored during withdrawal of systemic corticosteroids.
In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.
Unmasking of Allergic Conditions Previously Suppressed by Systemic Corticosteroids Transfer of patients from systemic corticosteroid therapy to Fluticasone Propionate/Salmeterol MDPI may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).
Corticosteroid Withdrawal Symptoms During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.
5.7 Hypercorticism and Adrenal Suppression Fluticasone propionate, a component of Fluticasone Propionate/Salmeterol MDPI, will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone.
Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of Fluticasone Propionate/Salmeterol MDPI in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose.
A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol.
Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing Fluticasone Propionate/Salmeterol MDPI.
Because of the possibility of significant systemic absorption of inhaled corticosteroids, patients treated with Fluticasone Propionate/Salmeterol MDPI should be observed carefully for any evidence of systemic corticosteroid effects.
Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.
It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects.
If such effects occur, Fluticasone Propionate/Salmeterol MDPI should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and for management of asthma symptoms.
5.8 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate/Salmeterol MDPI is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )].
5.9 Paradoxical Bronchospasm and Upper Airway Symptoms As with other inhaled medicines, Fluticasone Propionate/Salmeterol MDPI can produce paradoxical bronchospasm, which may be life‑threatening.
If paradoxical bronchospasm occurs following dosing with inhaled fluticasone propionate/salmeterol medicines, it should be treated immediately with an inhaled, short-acting bronchodilator; inhaled fluticasone propionate/salmeterol medicines should be discontinued immediately; and alternative therapy should be instituted.
Upper airway symptoms of laryngeal spasm, irritation, or swelling, such as stridor and choking, have been reported in patients receiving inhaled fluticasone propionate/salmeterol medicines.
5.10 Hypersensitivity Reactions, Including Anaphylaxis Immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Fluticasone Propionate/Salmeterol MDPI.
There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder products containing lactose; therefore, patients with severe milk protein allergy should not use Fluticasone Propionate/Salmeterol MDPI [see Contraindications ( 4 )].
5.11 Cardiovascular and Central Nervous System Effects Excessive beta‑adrenergic stimulation has been associated with seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, palpitation, nausea, dizziness, fatigue, malaise, and insomnia [see Overdosage ].
Therefore, Fluticasone Propionate/Salmeterol MDPI, like all products containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Salmeterol, a component of Fluticasone Propionate/Salmeterol MDPI, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms.
Although such effects are uncommon after administration of salmeterol at recommended doses, if they occur, the drug may need to be discontinued.
In addition, beta‑agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.
The clinical significance of these findings is unknown.
Large doses of inhaled or oral salmeterol (12 to 20 times the recommended dose) have been associated with clinically significant prolongation of the QTc interval, which has the potential for producing ventricular arrhythmias.
Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.
5.12 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long‑term administration of products containing inhaled corticosteroids.
The clinical significance of small changes in BMD with regard to long‑term consequences such as fracture is unknown.
Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care.
5.13 Effect on Growth Orally inhaled corticosteroids, including Fluticasone Propionate/Salmeterol MDPI, may cause a reduction in growth velocity when administered to pediatric patients.
Monitor the growth of pediatric patients receiving Fluticasone Propionate/Salmeterol MDPI routinely (e.g., via stadiometry).
To minimize the systemic effects of orally inhaled corticosteroids, including Fluticasone Propionate/Salmeterol MDPI, titrate each patient’s dosage to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration ( 2 ), Use in Specific Populations ( 8.4 )] .
5.14 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of inhaled corticosteroids, including fluticasone propionate, a component of Fluticasone Propionate/Salmeterol MDPI.
Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.
Effects of treatment with other fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg, fluticasone propionate 500 mcg, salmeterol 50 mcg, or placebo on development of cataracts or glaucoma was evaluated in a subset of 658 subjects with COPD in the 3-year survival trial.
Ophthalmic examinations were conducted at baseline and at 48, 108, and 158 weeks.
Conclusions about cataracts cannot be drawn from this trial because the high incidence of cataracts at baseline (61% to 71%) resulted in an inadequate number of subjects treated with other fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg who were eligible and available for evaluation of cataracts at the end of the trial (n = 53).
The incidence of newly diagnosed glaucoma was 2% with other fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg, 5% with fluticasone propionate, 0% with salmeterol, and 2% with placebo.
5.15 Eosinophilic Conditions and Churg-Strauss Syndrome In rare cases, patients on inhaled fluticasone propionate, a component of Fluticasone Propionate/Salmeterol MDPI, may present with systemic eosinophilic conditions.
Some of these patients have clinical features of vasculitis consistent with Churg‑Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy.
These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate.
Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting.
Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients.
A causal relationship between fluticasone propionate and these underlying conditions has not been established.
5.16 Coexisting Conditions Fluticasone Propionate/Salmeterol MDPI, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines.
Doses of the related beta 2 ‑adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.
5.17 Hypokalemia and Hyperglycemia Beta‑adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects [see Clinical Pharmacology ( 12.2 )] .
The decrease in serum potassium is usually transient, not requiring supplementation.
Clinically significant changes in blood glucose and/or serum potassium were seen infrequently during clinical trials with Fluticasone Propionate/Salmeterol MDPI at recommended doses.
5.1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death Use of LABA as monotherapy [without inhaled corticosteroids (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 large, 26-week, randomized, blinded, 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 budesonide/formoterol to budesonide, 1 trial compared fluticasone propionate/salmeterol inhalation powder to fluticasone propionate inhalation powder, and 1 trial compared mometasone furoate/formoterol to mometasone furoate.
The fourth trial included pediatric subjects aged 4 to 11 years and compared fluticasone propionate/salmeterol inhalation powder to 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 adolescent trials were designed to rule out a risk margin of 2.0, and the pediatric trial was designed to rule out a risk margin of 2.7.
Each individual trial met its pre-specified objective and demonstrated non-inferiority of ICS/LABA to ICS alone.
A meta-analysis of the 3 adult and adolescent trials did not show a significant increase in risk of a serious asthma-related event with ICS/LABA fixed-dose combination compared with ICS alone (Table 1).
These trials were not designed to rule out all risk for serious asthma-related events with ICS/LABA compared with ICS.
Table 1.
Meta-analysis of Serious Asthma-Related Events in Subjects with Asthma Aged 12 Years and Older ICS/LABA (n =17,537) a ICS (n = 17,552) a ICS/LABA vs.
ICS Hazard Ratio (95% CI) b Serious asthma-related event c 116 105 1.10 (0.85, 1.44) Asthma-related death 2 0 Asthma-related intubation (endotracheal) 1 2 Asthma-related hospitalization (≥24-hour stay) 115 105 ICS = Inhaled Corticosteroid;
LABA = Long-acting Beta 2 -adrenergic Agonist. a Randomized subjects who had taken at least 1 dose of study drug.
Planned treatment used for analysis. b Estimated using a Cox proportional hazards model for time to first event with baseline hazards stratified by each of the 3 trials. c Number of subjects with events that occurred within 6 months after the first use of study drug or 7 days after the last date of study drug, whichever date was later.
Subjects can have one or more events, but only the first event was counted for analysis.
A single, blinded, independent adjudication committee determined whether events were asthma related.
The pediatric safety trial included 6,208 pediatric patients aged 4 to 11 years who received ICS/LABA (fluticasone propionate/salmeterol inhalation powder) or ICS (fluticasone propionate inhalation powder).
In this trial 27/3,107 (0.9%) of patients treated with ICS/LABA and 21/3,101 (0.7%) of patients treated with ICS experienced a serious asthma‑related event.
There were no asthma-related deaths or intubations.
ICS/LABA did not show a significantly increased risk of a serious asthma-related event compared to ICS based on the prespecified risk margin (2.7), with an estimated hazard ratio of time to first event of 1.29 (95% CI:
0.73, 2.27).
Salmeterol Multicenter Asthma Research Trial (SMART) A 28-week, placebo-controlled, U.S. trial that compared the safety of salmeterol with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in subjects receiving salmeterol (13/13,176 in subjects treated with salmeterol versus 3/13,179 in subjects treated with placebo; relative risk:
4.37 [95% CI:
1.25, 15.34]).
Use of background ICS was not required in SMART.
The increased risk of asthma‑related death is considered a class effect of LABA monotherapy.
5.2 Deterioration of Disease and Acute Episodes Fluticasone Propionate/Salmeterol MDPI should not be initiated in patients during rapidly deteriorating or potentially life‑threatening episodes of asthma.
Fluticasone Propionate/Salmeterol MDPI has not been studied in subjects with acutely deteriorating asthma.
The initiation of Fluticasone Propionate/Salmeterol MDPI in this setting is not appropriate.
Serious acute respiratory events, including fatalities, have been reported when salmeterol, a component of this product, has been initiated in patients with significantly worsening or acutely deteriorating asthma.
In most cases, these have occurred in patients with severe asthma (e.g., patients with a history of corticosteroid dependence, low pulmonary function, intubation, mechanical ventilation, frequent hospitalizations, previous life‑threatening acute asthma exacerbations) and in some patients with acutely deteriorating asthma (e.g., patients with significantly increasing symptoms; increasing need for inhaled, short‑acting beta 2 ‑agonists; decreasing response to usual medications; increasing need for systemic corticosteroids; recent emergency room visits; deteriorating lung function).
However, these events have occurred in a few patients with less severe asthma as well.
It was not possible from these reports to determine whether salmeterol contributed to these events.
Increasing use of inhaled, short‑acting beta 2 ‑agonists is a marker of deteriorating asthma.
In this situation, the patient requires immediate reevaluation with reassessment of the treatment regimen, giving special consideration to the possible need for replacing the current strength of Fluticasone Propionate/Salmeterol MDPI with a higher strength, adding additional inhaled corticosteroid, or initiating systemic corticosteroids.
Patients should not use more than 1 inhalation twice daily of Fluticasone Propionate/Salmeterol MDPI.
Fluticasone Propionate/Salmeterol MDPI should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm.
An inhaled, short‑acting beta 2 ‑agonist, not Fluticasone Propionate/Salmeterol MDPI, should be used to relieve acute symptoms such as shortness of breath.
When prescribing Fluticasone Propionate/Salmeterol MDPI, the healthcare provider should also prescribe an inhaled, short‑acting beta 2 -agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice‑daily use of Fluticasone Propionate/Salmeterol MDPI.
When beginning treatment with Fluticasone Propionate/Salmeterol MDPI, patients who have been taking oral or inhaled, short‑acting beta 2 ‑agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs.
5.3
Avoid Excessive Use of Fluticasone Propionate/Salmeterol and
Avoid Use with Other Long-Acting Beta 2 -Agonists Fluticasone Propionate/Salmeterol MDPI should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result.
Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.
Patients using Fluticasone Propionate/Salmeterol MDPI should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.
5.4 Oropharyngeal Candidiasis In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with Fluticasone Propionate/Salmeterol MDPI.
When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with Fluticasone Propionate/Salmeterol MDPI continues, but at times therapy with Fluticasone Propionate/Salmeterol MDPI may need to be interrupted.
Advise the patient to rinse his/her mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.
5.5 Immunosuppression and Risk of Infections Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals.
Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible adolescents or
adults using corticosteroids.
In such patients who have not had these diseases or who have not been properly immunized, particular care should be taken to
avoid exposure.
How the dose, route and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known.
The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known.
If a patient is exposed to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG) may be indicated.
If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated.
(See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.
Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
5.6 Transferring Patients from Systemic Corticosteroid Therapy HPA Suppression/Adrenal Insufficiency Particular care is needed for patients who are transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.
After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic‑pituitary‑adrenal (HPA) function.
Patients who have been previously maintained on 20 mg or more 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 and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss.
Although Fluticasone Propionate/Salmeterol MDPI may improve control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies.
During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physician for further instruction.
These patients should also be instructed to carry a medical identification warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.
Patients requiring systemic corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to Fluticasone Propionate/Salmeterol MDPI.
Lung function (mean forced expiratory volume in 1 second [FEV 1 ] or morning peak expiratory flow [AM PEF]), beta‑agonist use, and asthma symptoms should be carefully monitored during withdrawal of systemic corticosteroids.
In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.
Unmasking of Allergic Conditions Previously Suppressed by Systemic Corticosteroids Transfer of patients from systemic corticosteroid therapy to Fluticasone Propionate/Salmeterol MDPI may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).
Corticosteroid Withdrawal Symptoms During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.
5.7 Hypercorticism and Adrenal Suppression Fluticasone propionate, a component of Fluticasone Propionate/Salmeterol MDPI, will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone.
Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of Fluticasone Propionate/Salmeterol MDPI in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose.
A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol.
Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing Fluticasone Propionate/Salmeterol MDPI.
Because of the possibility of significant systemic absorption of inhaled corticosteroids, patients treated with Fluticasone Propionate/Salmeterol MDPI should be observed carefully for any evidence of systemic corticosteroid effects.
Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.
It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects.
If such effects occur, Fluticasone Propionate/Salmeterol MDPI should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and for management of asthma symptoms.
with Strong Cytochrome P450 3A4 Inhibitors The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate/Salmeterol MDPI is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )].
5.9 Paradoxical Bronchospasm and Upper Airway Symptoms As with other inhaled medicines, Fluticasone Propionate/Salmeterol MDPI can produce paradoxical bronchospasm, which may be life‑threatening.
If paradoxical bronchospasm occurs following dosing with inhaled fluticasone propionate/salmeterol medicines, it should be treated immediately with an inhaled, short-acting bronchodilator; inhaled fluticasone propionate/salmeterol medicines should be discontinued immediately; and alternative therapy should be instituted.
Upper airway symptoms of laryngeal spasm, irritation, or swelling, such as stridor and choking, have been reported in patients receiving inhaled fluticasone propionate/salmeterol medicines.
5.10 Hypersensitivity Reactions, Including Anaphylaxis Immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Fluticasone Propionate/Salmeterol MDPI.
There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder products containing lactose; therefore, patients with severe milk protein allergy should not use Fluticasone Propionate/Salmeterol MDPI [see Contraindications ( 4 )].
5.11 Cardiovascular and Central Nervous System Effects Excessive beta‑adrenergic stimulation has been associated with seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, palpitation, nausea, dizziness, fatigue, malaise, and insomnia [see Overdosage ].
Therefore, Fluticasone Propionate/Salmeterol MDPI, like all products containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Salmeterol, a component of Fluticasone Propionate/Salmeterol MDPI, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms.
Although such effects are uncommon after administration of salmeterol at recommended doses, if they occur, the drug may need to be discontinued.
In addition, beta‑agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.
The clinical significance of these findings is unknown.
Large doses of inhaled or oral salmeterol (12 to 20 times the recommended dose) have been associated with clinically significant prolongation of the QTc interval, which has the potential for producing ventricular arrhythmias.
Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.
5.12 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long‑term administration of products containing inhaled corticosteroids.
The clinical significance of small changes in BMD with regard to long‑term consequences such as fracture is unknown.
Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care.
5.13 Effect on Growth Orally inhaled corticosteroids, including Fluticasone Propionate/Salmeterol MDPI, may cause a reduction in growth velocity when administered to pediatric patients.
Monitor the growth of pediatric patients receiving Fluticasone Propionate/Salmeterol MDPI routinely (e.g., via stadiometry).
To minimize the systemic effects of orally inhaled corticosteroids, including Fluticasone Propionate/Salmeterol MDPI, titrate each patient’s dosage to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration ( 2 ), Use in Specific Populations ( 8.4 )] .
5.14 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of inhaled corticosteroids, including fluticasone propionate, a component of Fluticasone Propionate/Salmeterol MDPI.
Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.
Effects of treatment with other fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg, fluticasone propionate 500 mcg, salmeterol 50 mcg, or placebo on development of cataracts or glaucoma was evaluated in a subset of 658 subjects with COPD in the 3-year survival trial.
Ophthalmic examinations were conducted at baseline and at 48, 108, and 158 weeks.
Conclusions about cataracts cannot be drawn from this trial because the high incidence of cataracts at baseline (61% to 71%) resulted in an inadequate number of subjects treated with other fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg who were eligible and available for evaluation of cataracts at the end of the trial (n = 53).
The incidence of newly diagnosed glaucoma was 2% with other fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg, 5% with fluticasone propionate, 0% with salmeterol, and 2% with placebo.
5.15 Eosinophilic Conditions and Churg-Strauss Syndrome In rare cases, patients on inhaled fluticasone propionate, a component of Fluticasone Propionate/Salmeterol MDPI, may present with systemic eosinophilic conditions.
Some of these patients have clinical features of vasculitis consistent with Churg‑Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy.
These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate.
Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting.
Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients.
A causal relationship between fluticasone propionate and these underlying conditions has not been established.
5.16 Coexisting Conditions Fluticasone Propionate/Salmeterol MDPI, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines.
Doses of the related beta 2 ‑adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.
5.17 Hypokalemia and Hyperglycemia Beta‑adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects [see Clinical Pharmacology ( 12.2 )] .
The decrease in serum potassium is usually transient, not requiring supplementation.
Clinically significant changes in blood glucose and/or serum potassium were seen infrequently during clinical trials with Fluticasone Propionate/Salmeterol MDPI at recommended doses.

Quoted from the official label, section “Warnings”.

Pregnancy and breastfeeding

Risk Summary There are no randomized clinical studies of fluticasone propionate/salmeterol MDPI or individual monoproducts, fluticasone propionate and salmeterol, in pregnant women.
There are clinical considerations with the use of Fluticasone Propionate/Salmeterol MDPI in pregnant women [see Clinical Considerations] .
Animal reproduction studies are available with the combination of fluticasone propionate and salmeterol as well as individual components.
In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits were 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 700 times the MRHDID on a mcg/m 2 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 420 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 Embryo/Fetal Risk In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.
Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.
Data Animal Data Fluticasone Propionate and Salmeterol:
In an embryo/fetal development study with pregnant rats that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1000, 30/0, 10/100, 30/1000, 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 embryo/fetal 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 2 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 100 mcg/kg/day) and a dose of salmeterol at approximately 3500 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 0.6 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 30 mcg/kg/day) and a dose of salmeterol at approximately 350 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 1000 mcg/kg/day).
In an embryo/fetal development study with pregnant mice that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1400, 40/0, 10/200, 40/1400, or 150/10,000 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.
Cleft palate, fetal death, increased implantation loss, and delayed ossification were observed in mouse fetuses when combining fluticasone propionate at a dose approximately 1.4 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 150 mcg/kg/day) and salmeterol at a dose approximately 1470 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 10,000 mcg/kg/day).
No developmental toxicity was observed at combination doses of fluticasone propionate up to approximately 0.8 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 40 mcg/kg) and doses of salmeterol up to approximately 420 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 1400 mcg/kg).
Fluticasone Propionate:
In embryo/fetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species.
Omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately 2 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 100 mcg/kg/day).
The rat NOAEL was observed at approximately 0.6 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 30 mcg/kg/day).
Cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately 0.5 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 45 mcg/kg/day).
The mouse NOAEL was observed with a dose approximately 0.16 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 15 mcg/kg/day).
In an embryo/fetal development study with pregnant rats dosed by the inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately 0.5 times the MRHDID (on a mcg/m 2 basis with a maternal inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity.
The NOAEL was observed with a dose approximately 0.1 times the MRHDID (on a mcg/m 2 basis with a maternal inhalation dose of 5.5 mcg/kg/day).
In an embryo/fetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity at doses approximately 0.02 times the MRHDID and higher (on a mcg/m 2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day).
Teratogenicity was evident based upon a finding of cleft palate for 1 fetus at a dose approximately 0.2 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 4 mcg/kg/day).
The NOAEL was observed in rabbit fetuses with a dose approximately 0.004 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day).
In a pre- and post-natal development study in pregnant rats dosed by the subcutaneous route from late gestation through delivery and lactation (Gestation Day 17 to Postpartum Day 22), fluticasone propionate was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to approximate equivalence to the MRHDID (on a mcg/m 2 basis with maternal subcutaneous doses up to 50 mcg/kg/day).
Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits.
Salmeterol:
In three embryo/fetal development studies, pregnant rabbits received oral administration of salmeterol at doses ranging from 100 to 10,000 mcg/kg/day during the period of organogenesis.
In pregnant Dutch rabbits administered salmeterol doses approximately 700 times the MRHDID (on a mcg/m 2 basis at maternal oral doses of 1000 mcg/kg/day and higher), fetal toxic effects were observed characteristically resulting from beta‑adrenoceptor stimulation.
These included precocious eyelid openings, cleft palate, sternebral fusion, limb and paw flexures, and delayed ossification of the frontal cranial bones.
No such effects occurred at a salmeterol dose approximately 420 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 600 mcg/kg/day).
New Zealand White rabbits were less sensitive since only delayed ossification of the frontal cranial bones was seen at a salmeterol dose approximately 7,000 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 10,000 mcg/kg/day).
In two embryo/fetal development studies, pregnant rats received salmeterol by oral administration at doses ranging from 100 to 10,000 mcg/kg/day during the period of organogenesis.
Salmeterol produced no maternal toxicity or embryo/fetal effects at doses up to 3500 times the MRHDID (on a mcg/m 2 basis at maternal oral doses up to 10,000 mcg/kg/day).
In a peri-and post-natal development study in pregnant rats dosed by the oral route from late gestation through delivery and lactation, salmeterol at a dose 3500 times the MRHDID (on mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day) was fetotoxic and decreased the fertility of survivors.
Salmeterol xinafoate crossed the placenta following oral administration to mice and rats.
IN SPECIFIC POPULATIONS Hepatic impairment: Monitor for systemic corticosteroid effects.
( 8.6 )
8.1 Pregnancy Risk Summary There are no randomized clinical studies of fluticasone propionate/salmeterol MDPI or individual monoproducts, fluticasone propionate and salmeterol, in pregnant women.
There are clinical considerations with the use of Fluticasone Propionate/Salmeterol MDPI in pregnant women [see Clinical Considerations] .
Animal reproduction studies are available with the combination of fluticasone propionate and salmeterol as well as individual components.
In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits were 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 700 times the MRHDID on a mcg/m 2 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 420 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 Embryo/Fetal Risk In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.
Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.
Data Animal Data Fluticasone Propionate and Salmeterol:
In an embryo/fetal development study with pregnant rats that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1000, 30/0, 10/100, 30/1000, 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 embryo/fetal 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 2 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 100 mcg/kg/day) and a dose of salmeterol at approximately 3500 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 0.6 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 30 mcg/kg/day) and a dose of salmeterol at approximately 350 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 1000 mcg/kg/day).
In an embryo/fetal development study with pregnant mice that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1400, 40/0, 10/200, 40/1400, or 150/10,000 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.
Cleft palate, fetal death, increased implantation loss, and delayed ossification were observed in mouse fetuses when combining fluticasone propionate at a dose approximately 1.4 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 150 mcg/kg/day) and salmeterol at a dose approximately 1470 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 10,000 mcg/kg/day).
No developmental toxicity was observed at combination doses of fluticasone propionate up to approximately 0.8 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 40 mcg/kg) and doses of salmeterol up to approximately 420 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 1400 mcg/kg).
Fluticasone Propionate:
In embryo/fetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species.
Omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately 2 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 100 mcg/kg/day).
The rat NOAEL was observed at approximately 0.6 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 30 mcg/kg/day).
Cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately 0.5 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 45 mcg/kg/day).
The mouse NOAEL was observed with a dose approximately 0.16 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 15 mcg/kg/day).
In an embryo/fetal development study with pregnant rats dosed by the inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately 0.5 times the MRHDID (on a mcg/m 2 basis with a maternal inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity.
The NOAEL was observed with a dose approximately 0.1 times the MRHDID (on a mcg/m 2 basis with a maternal inhalation dose of 5.5 mcg/kg/day).
In an embryo/fetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity at doses approximately 0.02 times the MRHDID and higher (on a mcg/m 2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day).
Teratogenicity was evident based upon a finding of cleft palate for 1 fetus at a dose approximately 0.2 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 4 mcg/kg/day).
The NOAEL was observed in rabbit fetuses with a dose approximately 0.004 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day).
In a pre- and post-natal development study in pregnant rats dosed by the subcutaneous route from late gestation through delivery and lactation (Gestation Day 17 to Postpartum Day 22), fluticasone propionate was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to approximate equivalence to the MRHDID (on a mcg/m 2 basis with maternal subcutaneous doses up to 50 mcg/kg/day).
Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits.
Salmeterol:
In three embryo/fetal development studies, pregnant rabbits received oral administration of salmeterol at doses ranging from 100 to 10,000 mcg/kg/day during the period of organogenesis.
In pregnant Dutch rabbits administered salmeterol doses approximately 700 times the MRHDID (on a mcg/m 2 basis at maternal oral doses of 1000 mcg/kg/day and higher), fetal toxic effects were observed characteristically resulting from beta‑adrenoceptor stimulation.
These included precocious eyelid openings, cleft palate, sternebral fusion, limb and paw flexures, and delayed ossification of the frontal cranial bones.
No such effects occurred at a salmeterol dose approximately 420 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 600 mcg/kg/day).
New Zealand White rabbits were less sensitive since only delayed ossification of the frontal cranial bones was seen at a salmeterol dose approximately 7,000 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 10,000 mcg/kg/day).
In two embryo/fetal development studies, pregnant rats received salmeterol by oral administration at doses ranging from 100 to 10,000 mcg/kg/day during the period of organogenesis.
Salmeterol produced no maternal toxicity or embryo/fetal effects at doses up to 3500 times the MRHDID (on a mcg/m 2 basis at maternal oral doses up to 10,000 mcg/kg/day).
In a peri-and post-natal development study in pregnant rats dosed by the oral route from late gestation through delivery and lactation, salmeterol at a dose 3500 times the MRHDID (on mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day) was fetotoxic and decreased the fertility of survivors.
Salmeterol xinafoate crossed the placenta following oral administration to mice and rats.
8.2 Lactation Risk Summary There are 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 and therefore concentrations in human breast milk are likely to be correspondingly low [see Clinical Pharmacology (12.3)] .
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Fluticasone Propionate/Salmeterol MDPI and any potential adverse effects on the breastfed child from Fluticasone Propionate/Salmeterol MDPI or from the underlying maternal condition.
Data Animal Data Subcutaneous administration of tritiated fluticasone propionate at a dose in lactating rats approximately 0.2 times the MRHDID for
adults (on a mcg/m 2 basis) resulted in measurable levels in milk.
Oral administration of salmeterol at a dose in lactating rats approximately 2900 times the MRHDID for
adults (on a mcg/m 2 basis) resulted in measurable levels in milk .
8.4 Pediatric Use The safety and effectiveness of Fluticasone Propionate/Salmeterol MDPI have been established for the treatment of asthma in pediatric patients aged 12 years and older whose asthma (1) is inadequately controlled on a long term asthma control medication or (2) warrants initiation of treatment with both an ICS and a LABA.
Use of Fluticasone Propionate/Salmeterol MDPI in pediatric patients aged 12 to 17 years for this indication is supported by evidence from two adequate and well-controlled trials in pediatric patients 12 years old and older with persistent symptomatic asthma despite ICS or ICS/LABA therapy (Trials 1 and 2) [see Clinical Studies ( 14 )].
In these trials, 58 adolescents received Fluticasone Propionate/Salmeterol MDPI one inhalation twice daily.
The safety and effectiveness of Fluticasone Propionate/Salmeterol MDPI have not been established in pediatric patients younger than 12 years of age for the treatment of asthma.
Effectiveness was not demonstrated in one adequate and well-controlled study conducted in 211 patients aged 4 to 11 years with persistent asthma on a stable asthma regimen who were treated with Fluticasone Propionate/Salmeterol MDPI 55 mcg/14 mcg one inhalation twice daily.
Effect on Growth Inhaled corticosteroids, including fluticasone propionate, a component of this product, may cause a reduction in growth velocity in adolescents [see Warning and Precautions ( 5.13 )] .
The growth of pediatric patients receiving ICS, including Fluticasone Propionate/Salmeterol MDPI, should be monitored.
If an adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect of corticosteroids should be considered.
In such patients, the potential growth effects of prolonged ICS treatment should be weighed against the clinical benefits obtained.
To minimize the systemic effects of ICS, including Fluticasone Propionate/Salmeterol MDPI, each patient should be titrated to the lowest strength that effectively controls his/her asthma [see Dosage and Administration ( 2 )].
8.5 Geriatric Use No overall differences in safety or effectiveness were observed in data collected in 54 subjects aged 65 years and older versus younger subjects who were treated with Fluticasone Propionate/Salmeterol MDPI in placebo-controlled Phase 2 and 3 asthma studies.
8.6 Hepatic Impairment Formal pharmacokinetic studies using Fluticasone Propionate/Salmeterol MDPI have not been conducted in patients with hepatic impairment.
However, since both fluticasone propionate and salmeterol are predominantly cleared by hepatic metabolism [see Clinical Pharmacology ( 12.3 )] , impairment of liver function may lead to accumulation of fluticasone propionate and salmeterol in plasma.
Therefore, patients with hepatic impairment should be closely monitored.
8.7 Renal Impairment Formal pharmacokinetic studies using Fluticasone Propionate/Salmeterol MDPI have not been conducted in patients with renal impairment.

Quoted from the official label, section “OTC — Pregnancy or Breast Feeding”.

Other medicines

Fluticasone Propionate/Salmeterol MDPI has been used concomitantly with other drugs, including short‑acting beta 2 ‑agonists, and intranasal corticosteroids, commonly used in patients with asthma without adverse drug reactions [see Clinical Pharmacology ( 12.2 )] .
No formal drug interaction trials have been performed with Fluticasone Propionate/Salmeterol MDPI.
Avoid strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole):
May increase risk of systemic corticosteroid and cardiovascular effects.
( 7.1 ) Monoamine oxidase inhibitors and tricyclic antidepressants:
Use with extreme caution.
May potentiate effect of salmeterol on vascular system.
( 7.2 ) Beta‑blockers: Use with caution.
May block bronchodilatory effects of beta‑agonists and produce severe bronchospasm.
( 7.3 ) Diuretics: Use with caution.
Electrocardiographic changes and/or hypokalemia associated with non‑potassium‑sparing diuretics may worsen with concomitant beta‑agonists.
( 7.4 )
7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone propionate and salmeterol, the individual components of this product, are substrates of CYP3A4.
The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate/Salmeterol MDPI 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 [see Clinical Pharmacology ( 12.3 )] .
7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Fluticasone Propionate/Salmeterol MDPI 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 this product, on the vascular system may be potentiated by these agents.
7.3 Beta-Adrenergic Receptor Blocking Agents Beta‑blockers not only block the pulmonary effect of beta‑agonists, such as salmeterol, a component of this product, 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.
7.4 Non-Potassium-Sparing Diuretics The ECG changes and/or hypokalemia that may result from the administration of non–potassium‑sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta‑agonists, such as salmeterol, a component of this product, especially when the recommended dose of the beta‑agonist is exceeded.
Although the clinical significance of these effects is not known, caution is advised in the coadministration of Fluticasone Propionate/Salmeterol MDPI with non-potassium‑sparing diuretics.
7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone propionate and salmeterol, the individual components of this product, are substrates of CYP3A4.
The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate/Salmeterol MDPI 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 [see Clinical Pharmacology ( 12.3 )] .
7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Fluticasone Propionate/Salmeterol MDPI 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 this product, on the vascular system may be potentiated by these agents.
7.3 Beta-Adrenergic Receptor Blocking Agents Beta‑blockers not only block the pulmonary effect of beta‑agonists, such as salmeterol, a component of this product, 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.
7.4 Non-Potassium-Sparing Diuretics The ECG changes and/or hypokalemia that may result from the administration of non–potassium‑sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta‑agonists, such as salmeterol, a component of this product, especially when the recommended dose of the beta‑agonist is exceeded.
Although the clinical significance of these effects is not known, caution is advised in the coadministration of Fluticasone Propionate/Salmeterol MDPI with non-potassium‑sparing diuretics.

Quoted from the official label, section “Drug Interactions”.

If you take too much

In an emergency, call your local emergency number or a poison control centre.

This product contains both fluticasone propionate and salmeterol; therefore, the risks associated with overdosage for the individual components described below apply to Fluticasone Propionate/Salmeterol MDPI.
Treatment of overdosage consists of discontinuation of Fluticasone Propionate/Salmeterol MDPI 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 ( 5.7 )] .
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.

Quoted from the official label, section “Overdosage”.

Use in children

The safety and effectiveness of Fluticasone Propionate/Salmeterol MDPI have been established for the treatment of asthma in pediatric patients aged 12 years and older whose asthma (1) is inadequately controlled on a long term asthma control medication or (2) warrants initiation of treatment with both an ICS and a LABA.
Use of Fluticasone Propionate/Salmeterol MDPI in pediatric patients aged 12 to 17 years for this indication is supported by evidence from two adequate and well-controlled trials in pediatric patients 12 years old and older with persistent symptomatic asthma despite ICS or ICS/LABA therapy (Trials 1 and 2) [see Clinical Studies ( 14 )].
In these trials, 58 adolescents received Fluticasone Propionate/Salmeterol MDPI one inhalation twice daily.
The safety and effectiveness of Fluticasone Propionate/Salmeterol MDPI have not been established in pediatric patients younger than 12 years of age for the treatment of asthma.
Effectiveness was not demonstrated in one adequate and well-controlled study conducted in 211 patients aged 4 to 11 years with persistent asthma on a stable asthma regimen who were treated with Fluticasone Propionate/Salmeterol MDPI 55 mcg/14 mcg one inhalation twice daily.
Effect on Growth Inhaled corticosteroids, including fluticasone propionate, a component of this product, may cause a reduction in growth velocity in adolescents [see Warning and Precautions ( 5.13 )] .
The growth of pediatric patients receiving ICS, including Fluticasone Propionate/Salmeterol MDPI, should be monitored.
If an adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect of corticosteroids should be considered.
In such patients, the potential growth effects of prolonged ICS treatment should be weighed against the clinical benefits obtained.
To minimize the systemic effects of ICS, including Fluticasone Propionate/Salmeterol MDPI, each patient should be titrated to the lowest strength that effectively controls his/her asthma [see Dosage and Administration ( 2 )].

Quoted from the official label, section “Pediatric Use”.

Use in older people

No overall differences in safety or effectiveness were observed in data collected in 54 subjects aged 65 years and older versus younger subjects who were treated with Fluticasone Propionate/Salmeterol MDPI in placebo-controlled Phase 2 and 3 asthma studies.

Quoted from the official label, section “Geriatric Use”.

Side effects

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 )] Immunosuppression and risk of infections [see Warnings and Precautions ( 5.5 )] Hypercorticism and adrenal suppression [see Warnings and Precautions ( 5.7 )] Cardiovascular and central nervous system effects [see Warnings and Precautions ( 5.11 )] Reduction in bone mineral density [see Warnings and Precautions ( 5.12 )] Growth effects in pediatrics [see Warnings and Precautions ( 5.13 )] Glaucoma and cataracts [see Warnings and Precautions ( 5.14 )] Most common adverse reactions (greater than or equal to 3%):
nasopharyngitis, oral candidiasis, headache, cough and back pain.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience in Asthma Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In two placebo-controlled, 12-week, clinical studies (Trials 1 and 2) [see Clinical Studies ( 14 )] , a total of 1,364 adolescent and adult patients with persistent symptomatic asthma despite ICS or ICS/LABA therapy were treated twice daily with either placebo; fluticasone propionate MDPI 55 mcg, 113 mcg, 232 mcg; or fluticasone propionate/salmeterol MDPI 55 mcg/14 mcg, 113 mcg/14 mcg, 232 mcg/14 mcg.
Sixty percent of patients were female and 80% of patients were white.
The average duration of exposure was 82 to 84 days in the fluticasone propionate MDPI and fluticasone propionate/salmeterol MDPI treatment groups compared with 75 days in the placebo group.
Table 2 displays the incidence of most common adverse reactions in pooled Trials 1 and 2.
Table 2:
Adverse Reactions with ≥3% Incidence with Fluticasone Propionate/Salmeterol MDPI, and More Common than Placebo in Subjects with Asthma (Trials 1 and 2) Adverse Reaction Fluticasone Propionate MDPI 55 mcg(n=129)% Fluticasone Propionate MDPI 113 mcg(n=274)% Fluticasone Propionate MDPI 232 mcg(n=146)% Fluticasone Propionate /Salmeterol MDPI 55 mcg/14 mcg(n=128)% Fluticasone Propionate /Salmeterol MDPI 113 mcg/14 mcg(n=269)% Fluticasone Propionate /Salmeterol MDPI232 mcg/14 mcg (n=145)% Placebo(n=273)% Nasopharyngitis 5.4 5.8 4.8 8.6 4.8 6.9
4.4 Oral candidiasis* 3.1 2.9 4.8 1.6 2.2 3.4
0.7 Headache 1.6 7.3 4.8 5.5 4.8 2.8
4.4 Cough 1.6 1.8 3.4 2.3 3.7 0.7
2.6 Back pain 0 1.5 1.4 3.1 0.7 0 1.8 *Oral candidiasis includes oropharyngeal candidiasis, oral fungal infection, and oropharyngitis fungal Other adverse reactions not previously listed (and occurring in <3% of patients and in three or more patients on Fluticasone Propionate/Salmeterol MDPI) that were reported more frequently by patients with asthma treated with Fluticasone Propionate/Salmeterol MDPI compared with patients treated with placebo include the following:
Sinusitis, oropharyngeal pain, pharyngitis, dizziness, influenza, rhinitis allergic, respiratory tract infection, rhinitis, nasal congestion, abdominal pain upper, myalgia, pain in extremity, dyspepsia, laceration, dermatitis contact, and palpitations.
Long Term Safety Study:
This was a 26-week, open labeled study of 674 patients previously treated with ICS who were treated twice daily with fluticasone propionate MDPI 113 mcg or 232 mcg; fluticasone propionate/salmeterol MDPI 113 mcg/14 mcg or 232 mcg/14 mcg; fluticasone propionate inhalation aerosol 110 mcg or 220 mcg; fluticasone propionate and salmeterol inhalation powder (250 mcg/50 mcg), or fluticasone propionate and salmeterol inhalation powder (500 mcg/50 mcg).
The types of adverse reactions were similar to those reported above in placebo controlled studies.
6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during post approval use of fluticasone propionate and/or salmeterol regardless of indication.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone propionate and/or salmeterol or a combination of these factors.
Cardiac Disorders :
Arrhythmias (including atrial fibrillation, extrasystoles, supraventricular tachycardia), ventricular tachycardia.
Endocrine Disorders :
Cushing’s syndrome, Cushingoid features, growth velocity reduction in children/adolescents, hypercorticism.
Eye Disorders : Glaucoma, blurred vision and central serous chorioretinopathy.
Gastrointestinal Disorders : Abdominal pain, dyspepsia, xerostomia.
Immune System Disorders :
Immediate and delayed hypersensitivity reaction (including very rare anaphylactic reaction).
Very rare anaphylactic reaction in patients with severe milk protein allergy.
Infections and Infestations : Esophageal candidiasis.
Metabolic and Nutrition Disorders : Hyperglycemia, weight gain.
Musculoskeletal, Connective Tissue, and Bone Disorders :
Arthralgia, cramps, myositis, osteoporosis.
Nervous System Disorders : Paresthesia, restlessness.
Psychiatric Disorders : Agitation, aggression, depression.
Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.
Reproductive System and Breast Disorders : Dysmenorrhea.
Respiratory, Thoracic, and Mediastinal Disorders :
Chest congestion; chest tightness, dyspnea; facial and oropharyngeal edema, immediate bronchospasm; paradoxical bronchospasm; tracheitis; wheezing; reports of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking.
Skin and Subcutaneous Tissue Disorders : Ecchymoses, photodermatitis.
Vascular Disorders : Pallor.

Quoted from the official label, section “Adverse Reactions”.

What to discuss with your doctor

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Patients should be given the following information:
Serious Asthma Events Inform patients with asthma that LABA when used alone increases the risk of asthma-related hospitalization and asthma-related death.
Available data show that when ICS and LABA are used together, such as with Fluticasone Propionate/Salmeterol MDPI, 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 Fluticasone Propionate/Salmeterol MDPI 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 [see Warnings and Precautions ( 5.2 )] .
Instruct patients to seek medical attention 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 Fluticasone Propionate/Salmeterol without physician/provider guidance since symptoms may recur after discontinuation.
Avoid 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 Fluticasone Propionate/Salmeterol MDPI, but at times therapy with Fluticasone Propionate/Salmeterol MDPI may need to be temporarily interrupted under close medical supervision.
Rinsing the mouth with water without swallowing after inhalation is advised to help reduce the risk of thrush [see Warnings and Precautions ( 5.4 )] .
Immunosuppression and 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 ( 5.5 )] .
Hypercorticism and Adrenal Suppression Advise patients that Fluticasone Propionate/Salmeterol MDPI 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 Fluticasone Propionate/Salmeterol MDPI [see Warnings and Precautions ( 5.7 )] .
Immediate Hypersensitivity Reactions Advise patients that immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Fluticasone Propionate/Salmeterol MDPI.
Patients should discontinue Fluticasone Propionate/Salmeterol MDPI if such reactions occur and contact their healthcare provider or get emergency medical help.
There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of powder products containing lactose; therefore, patients with severe milk protein allergy should not take Fluticasone Propionate/Salmeterol MDPI [see Warnings and Precautions ( 5.10 )] .
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 ( 5.12 )] .
Reduced Growth Velocity Inform patients that orally inhaled corticosteroids, including fluticasone propionate, may cause a reduction in growth velocity when administered to adolescent patients.
Physicians should closely follow the growth of adolescents taking corticosteroids by any route [see Warnings and Precautions ( 5.13 )] .
Ocular Effects Long-term use of inhaled corticosteroids may increase the risk of some eye problems (cataracts or glaucoma); consider regular eye examinations [see Warnings and Precautions ( 5.14 )] .
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 ( 5.11 )] .
Pregnancy Inform patients who are pregnant or nursing that they should contact their physician about the use of Fluticasone Propionate/Salmeterol MDPI [see Use in Specific Populations ( 8.1 )] .
Use Daily for Best Effect Patients should use Fluticasone Propionate/Salmeterol MDPI at regular intervals as directed.
The daily dosage of Fluticasone Propionate/Salmeterol MDPI should not exceed 1 inhalation twice a day.
Advise patients, if they miss a dose, to take their next dose at the same time they normally do and to not
take 2 doses at one time.
Individual patients will experience a variable time to onset and degree of symptom relief and full benefit may not be achieved until treatment has been administered for 1 to 2 weeks or longer.
Patients should not increase the prescribed dosage but should contact their physicians
if symptoms do not improve or if the condition worsens.
Instruct patients not to stop use of Fluticasone Propionate/Salmeterol MDPI abruptly.
Patients should contact their physicians immediately if they discontinue use of Fluticasone Propionate/Salmeterol MDPI.
Dose Counter Instruct patients that Fluticasone Propionate/Salmeterol MDPI has a dose counter that displays the number of actuations (inhalations) left in the inhaler.
When the patient receives a new inhaler, the number 60 will be displayed.
The dose counter will count down each time the mouthpiece is opened and closed.
When the dose counter reaches 20, the color of the numbers will change to red to remind the patient to contact their pharmacist or healthcare provider for a refill of their medication.
When the dose counter reaches 0, the patient should stop using the inhaler, and dispose of it in accordance with state and local regulations.
Caring for and Storing the Inhaler Instruct patients to not open their inhaler unless they are taking a dose.
Repeated opening and closing the cover without taking medication will waste medication and may damage the inhaler.
Advise patients to keep their inhaler dry and clean at all times.
Never wash or put any part of the inhaler in water.
Patient should replace inhaler if washed or placed in water.
Advise patients to immediately replace inhaler if mouthpiece cover is damaged or broken.
Gently wipe the mouthpiece with a dry cloth or tissue as needed.
Instruct patients to store the inhaler at room temperature and to
avoid exposure to extreme heat, cold, or humidity.
Instruct patients to never take the inhaler apart.
Inform patients to discard this product when the dose counter displays 0, 30 days after opening the foil pouch or after the expiration date on the product, whichever comes first.
Distributed by: Teva Pharmaceuticals USA, Inc.
Parsippany, NJ 07054 ©2021 Teva Respiratory, LLC.
All rights reserved.
United States Patent Nos. 6701917, 6718972, 6748947, 6871646, 7540282, 8006690, 8651103, 8714149, 8978966, 9066957, 9216260, 9415008, 9463288, 9616024, 9731087, 9987229, 10022510, 10124131, 10195375, 10561808, 10765820.
FPSPI-005 Revised: July 2021

Quoted from the official label, section “Patient Counseling Information”.

Strengths and forms

FORMS AND STRENGTHS Inhalation powder:
an inhalation-driven, multidose, dry powder inhaler (MDPI) for oral inhalation that meters 55 mcg, 113 mcg, or 232 mcg of fluticasone propionate with 14 mcg of salmeterol from the device reservoir and delivers 49 mcg, 100 mcg, or 202 mcg of fluticasone propionate with 12.75 mcg of salmeterol, respectively, from the mouthpiece per actuation.
The Fluticasone Propionate/Salmeterol MDPI is a white inhaler with a yellow cap, and is provided in a sealed foil pouch with desiccant [see How Supplied/Storage and Handling ( 16 )] .
Inhalation powder:
55 mcg/14 mcg, 113 mcg/14 mcg, or 232 mcg/14 mcg of fluticasone propionate/salmeterol in each actuation ( 3 ).

Quoted from the official label, section “Dosage Forms & Strengths”.

What it looks like and how it is packed

How Supplied Fluticasone Propionate/Salmeterol MDPI inhalation powder:
a multidose, dry-powder inhaler (MDPI) each inhaler is white, has a yellow cap and is packaged individually in a foil pouch with a dessicant, each pouch is packed in a carton each inhaler contains 0.45 grams of the formulation and provides 60 actuations STRENGTH NDC CODE Fluticasone Propionate/Salmeterol 113 mcg/14 mcg (medium) 63629-8809-1 Each Fluticasone Propionate/Salmeterol MDPI has a dose counter attached to the actuator.
Patients should never try to alter the numbers for the dose counter.
Discard the inhaler when the counter displays 0, 30 days after opening the foil pouch or after the expiration date on the product, whichever comes first.
The labeled amount of medication in each actuation cannot be assured after the counter displays 0, even though the inhaler is not completely empty and will continue to operate [see Patient Counseling Information (17)].
Storage and Handling
Store at room temperature (between 15ºC and 25ºC; 59ºF and 77ºF) in a dry place; excursions permitted from 59º F to 86º F (15ºC to 30ºC).
Avoid exposure to extreme heat, cold, or humidity.
Store Fluticasone Propionate/Salmeterol MDPI inside the unopened moisture‑protective foil pouch until initial use.
Discard the product 30 days after opening the foil pouch or when the counter reads 0, whichever comes first.
The inhaler is not reusable.
Do not attempt to take the inhaler apart.
Repackaged/Relabeled by: Bryant Ranch Prepack, Inc.
Burbank, CA 91504

Quoted from the official label, section “How Supplied”.

What is in it

Fluticasone Propionate/Salmeterol MDPI 55 mcg/14 mcg, 113 mcg/14 mcg and 232 mcg/14 mcg are combinations of fluticasone propionate and salmeterol. Fluticasone Propionate One active component of this product is fluticasone propionate, a corticosteroid having the chemical name S -(fluoromethyl) 6α,9-difluoro-11ß,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17ß-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. Salmeterol Xinafoate The other active component of this product 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 -[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol, 1-hydroxy-2-naphthalenecarboxylate and the following chemical structure:
Salmeterol xinafoate is a white powder with a molecular weight of 603.8, and the empirical formula is C 25 H 37 NO 4
C 11 H 8 O 3 . It is freely soluble in methanol; slightly soluble in ethanol, chloroform, and isopropanol; and sparingly soluble in water. Fluticasone Propionate/Salmeterol MDPI Fluticasone Propionate/Salmeterol MDPI is a multidose dry powder inhaler (MDPI) for oral inhalation only. It contains fluticasone propionate, salmeterol xinafoate, and lactose monohydrate (which may contain milk proteins). The opening of the mouthpiece cover meters 5.5 mg of the formulation from the device reservoir, which contains 55 mcg, 113 mcg, or 232 mcg of fluticasone propionate, and 14 mcg of salmeterol base (equivalent to 20.3 mcg of salmeterol xinafoate). Patient inhalation through the mouthpiece causes the deagglomeration and aerosolization of the drug particles as the formulation moves through the cyclone component of the device. This is followed by dispersion into the airstream. Under standardized in vitro test conditions, the Fluticasone Propionate/Salmeterol MDPI delivers 49 mcg, 100 mcg, or 202 mcg of fluticasone propionate and 12.75 mcg of salmeterol base (equivalent to 18.5 mcg of salmeterol xinafoate), with lactose from the mouthpiece when tested at a flow rate of 85 L/min for 1.4 seconds. The amount of drug delivered to the lung will depend on patient factors such as inspiratory flow profiles. In adult subjects (N=50, aged 18 to 45 years) with asthma, mean peak inspiratory flow (PIF) through the Fluticasone Propionate/Salmeterol MDPI was 108.28 L/min (range:
70.37 to 129.24 L/min). In adolescent subjects (N=50, aged 12 to 17 years) with asthma, mean peak inspiratory flow (PIF) through the Fluticasone Propionate/Salmeterol MDPI was 106.72 L/min (range:
73.64 to 125.51 L/min).

Quoted from the official label, section “Description”.

Ingredients people check for

Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.

The stored label for this product has no list of inactive ingredients. The list on the pack is the one to check.

Quoted from the FDA label. A label that does not name an ingredient is not a guarantee that the product is free of it, and formulations change. With an allergy, check the pack and ask a pharmacist.

Every version of this medicine (4)

The same active substance, strength and kind of form, from every company that sells it — with what each label lists.

Showing 4 of 4

Same active substance, strength and form in other countries

Matched on active substance, strength and kind of form only. This is not a statement that the products are equivalent or interchangeable: other ingredients, release and approved uses can differ — ask a pharmacist before swapping.

Medicine passport: one printable page to show a pharmacist abroad

European UnionNo exact match for this strength and form

Every strength and form (3)

Details

Made by	Bryant Ranch Prepack
Active substance	Fluticasone Propionate and Salmeterol
Used in	Breathing, airways, allergies and cough
Strength	113 ug + 14 ug
Form	Powder, Metered
Route	Respiratory (inhalation)
Packs	1 POUCH in 1 CARTON / 1 INHALER in 1 POUCH / 60 POWDER, METERED in 1 INHALER
NDC	63629-8809

Source: NDC Directory · 2026-09-13 · not reviewed by a clinician

Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).

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Other strengths and forms

24 products are sold under this name. Grouped by form; a number on a strength means several companies make it.

Powder15 products
- 50 ug + 100 ug4
  50 ug + 100 ug · 4 companies
- 50 ug + 250 ug4
  50 ug + 250 ug · 4 companies
- 50 ug + 500 ug
- 100 ug + 50 ug2
  100 ug + 50 ug · 2 companies
  - Cipla USA Inc.
  - Teva Pharmaceuticals USA, Inc.
- 250 ug + 50 ug2
  250 ug + 50 ug · 2 companies
  - Cipla USA Inc.
  - Teva Pharmaceuticals USA, Inc.
- 500 ug + 50 ug2
  500 ug + 50 ug · 2 companies
  - Cipla USA Inc.
  - Teva Pharmaceuticals USA, Inc.
Powder, Metered9 products
- 55 ug + 14 ug3
  55 ug + 14 ug · 3 companies
- 113 ug + 14 ug3
  113 ug + 14 ug · 3 companies
  - A-S Medication Solutions
  - Bryant Ranch Prepack · this page
  - Teva Pharmaceuticals USA, Inc.
- 232 ug + 14 ug3
  232 ug + 14 ug · 3 companies

Same active substance

These contain the same substance. That does not mean one can replace another — ask a pharmacist.

Advair Diskus50 ug + 100 ugPrescription onlyPowder GlaxoSmithKline LLC · Fluticasone Propionate and Salmeterol Advair Diskus50 ug + 250 ugPrescription onlyPowder GlaxoSmithKline LLC · Fluticasone Propionate and Salmeterol Advair Diskus50 ug + 500 ugPrescription onlyPowder GlaxoSmithKline LLC · Fluticasone Propionate and Salmeterol Advair Diskus50 ug + 100 ugPrescription onlyPowder A-S Medication Solutions · Fluticasone Propionate and Salmeterol Advair Diskus50 ug + 250 ugPrescription onlyPowder A-S Medication Solutions · Fluticasone Propionate and Salmeterol Advair Diskus50 ug + 500 ugPrescription onlyPowder A-S Medication Solutions · Fluticasone Propionate and Salmeterol

See every product with Fluticasone Propionate and Salmeterol