Fluticasone Propionate

Pronunciation

Class: Adrenals
VA Class: RE101
Molecular Formula: C25H31F3O5S
CAS Number: 80474-14-2
Brands: Advair Diskus, Advair HFA (combination), Flovent HFA

Introduction

Synthetic trifluorinated glucocorticoid.2 3 35

Uses for Fluticasone Propionate

Asthma

Fluticasone used for long-term prevention of bronchospasm in patients with asthma.2 18 23 35

In corticosteroid-dependent patients, fluticasone may permit a substantial reduction in the daily maintenance dosage of the systemic corticosteroid and gradual discontinuance of corticosteroid maintenance dosages.2 5 35

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Fluticasone/salmeterol fixed combination is used only in patients with asthma not responding adequately to long-term asthma controller therapy (e.g., inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a long-acting β2-adrenergic agonist.18 51

Once asthma control achieved and maintained, assess patient at regular intervals and step down therapy (e.g., discontinue fluticasone/salmeterol), if possible without loss of asthma control, and maintain patient on long-term asthma controller therapy (e.g., inhaled corticosteroids).18 51

Do not use fluticasone/salmeterol in patients with asthma adequately controlled on low or medium dosage of inhaled corticosteroids.18 51

COPD

Fixed combination with salmeterol as the oral inhalation powder (Advair Diskus) is used for maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema; also used to reduce exacerbations of COPD in patients with a history of exacerbations.18

Fluticasone/salmeterol is not indicated for relief of acute bronchospasm.18

Fluticasone Propionate Dosage and Administration

General

  • Adjust dosage carefully according to individual requirements and response.18 23

  • After a satisfactory response is obtained, decrease dosage gradually to the lowest dosage that maintains an adequate clinical response.23 35 Achieve the lowest effective dosage, particularly in children, since inhaled corticosteroids have the potential to affect growth.23 35

Asthma

  • Recommended initial and maximum dosages of fluticasone oral inhalation are based on previous asthma therapy.2 35

  • Recommended initial dosage of fluticasone in fixed combination with salmeterol (Advair Diskus) oral inhalation powder based on patient’s asthma severity.18

  • Recommended initial dosage of fluticasone in fixed combination with salmeterol (Advair HFA) oral inhalation aerosol based on patient’s current asthma therapy.51

  • After 2 weeks of fluticasone therapy alone or in fixed combination with salmeterol at the initial dosage, if asthma is inadequately controlled, replace the current strength with a higher strength.35 51

Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

  • When switching from systemic corticosteroids to orally inhaled fluticasone, asthma should be reasonably stable before initiating treatment with the oral inhalation.5 28

  • Initially, administer fluticasone oral inhalation concurrently with the maintenance dosage of the systemic corticosteroid.35 After at least 1 week, gradually withdraw the systemic corticosteroid.2 35

  • Decrements of the systemic corticosteroid usually should not exceed 2.5–5 mg of prednisone (or its equivalent) each week in patients receiving fluticasone oral inhalation.2 35 Once oral corticosteroids are discontinued and symptoms of asthma have been controlled, titrate fluticasone dosage to the lowest effective level.2 17 18 35

  • Slowly withdraw patients requiring oral corticosteroids from systemic corticosteroid use after transferring to fluticasone/salmeterol (Advair Diskus) oral inhalation powder.18 Prednisone dosage reduction may be accomplished by reducing daily dosage of prednisone by 2.5 mg weekly during therapy with fluticasone/salmeterol oral inhalation powder.18

  • Do not use fluticasone/salmeterol (Advair HFA) oral inhalation aerosol for transferring patients from systemic corticosteroid therapy.51

  • Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.23 35 (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)

Administration

Administer by oral inhalation.23 35

Oral Inhalation

Administer fluticasone alone or in fixed combination with salmeterol (Advair HFA) as a microcrystalline suspension by oral inhalation using an oral aerosol inhaler with hydrofluoroalkane (HFA; non-chlorofluorocarbon) propellant.35 51

Administer inhalation powder in fixed combination with salmeterol using a special oral inhaler (Advair Diskus) that delivers the drug from foil-wrapped blisters.2 18 23

Following each treatment, rinse the mouth thoroughly with water without swallowing.17 18 23 36 51 55

Inhalation Powder

Administer fluticasone in fixed combination with salmeterol using a special oral inhaler (Advair Diskus).18 43 Administer twice daily (morning and evening), about 12 hours apart.23 43

Hold the Diskus device in one hand, put the thumb of the other hand on the thumbgrip, and push the thumbgrip until the mouthpiece appears and snaps into position.26 43

Depress the lever away from the body until a click is heard; the lever pierces the foil blister and releases the powdered drug into an exit port.26 43 Do not tilt or close the Diskus device, play with the lever, or advance the lever more than once at this point.26 43 A dose counter will advance each time the lever is depressed.26 43

Exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with lips closed around it.26 43 After inhaling dose through the mouth, hold the breath for 10 seconds, and exhale slowly.26 43

Do not exhale into the Diskus device.43 Do not use an extra dose from the Diskus device if patient does not feel or taste the drug.43

Rinse the mouth after inhalation of fluticasone/salmeterol.18 23 43 Slide the thumbgrip toward the body to close the Diskus device and reset the device for the next dose.26 43 Do not wash the inhaler or take it apart.26 43

Do not use fluticasone/salmeterol with a spacer device.43

Inhalation Aerosol

Shake well (5 seconds) immediately prior to initial use.36 51 55 Actuate fluticasone aerosol inhaler 4 times prior to initial use.35 36 Test spray the aerosol inhaler containing fluticasone in fixed combination with salmeterol (Advair HFA) 4 times into the air (away from face) before initial use, and shake well for 5 seconds before each spray.51 55

Actuate fluticasone inhaler once prior to use if it has not been used for >1 week or if inhaler was dropped.35 36 If Advair HFA aerosol inhaler not used for >4 weeks or if inhaler was dropped, test spray inhaler twice into the air (away from face) and shake well for 5 seconds before each spray.51 55

Exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with lips closed around it.36 55 Inhale slowly and deeply through the mouth while actuating the inhaler.36 55 Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.36 55

Allow 30 seconds to elapse between subsequent inhalations from aerosol inhaler.36 55

Following each treatment, rinse the mouth thoroughly.36 51 55

Clean fluticasone inhaler at least once a week after the evening dose by removing the mouthpiece cap from the inhaler and washing the mouthpiece with moistened cotton; allow the actuator to air-dry overnight.36

Clean Advair HFA aerosol inhaler by wiping the opening where medicine sprays out of metal canister and mouthpiece with a dry cotton swab and dampened tissue, respectively, at least once a week after evening dose; allow actuator to air-dry overnight.51 55

When dose counter on the aerosol inhaler for fluticasone alone or in fixed combination with salmeterol (Advair HFA) reads “020”, recommend that the patient contact the pharmacy for a refill or consult clinician to determine need for a refill.35 51 Discard aerosol inhaler when the dose counter reads “000”.35 51 Never alter or remove dose counter from canister.35 51

Dosage

Unless otherwise stated, the dose of fluticasone propionate administered as an aerosol via metered-dose inhaler is expressed as the amount delivered from the actuator of the inhaler per metered spray.35

Fluticasone propionate oral inhalation aerosol delivers 50, 125, or 250 mcg from the valve, and 44, 110, or 220 mcg, respectively, from the actuator per metered spray.35 The 10.6- or 12-g canister delivers 120 metered sprays.35

Doses of fluticasone propionate and salmeterol in the fixed combination oral inhalation powder (Advair Diskus) are expressed as the nominal (labeled) doses contained in each foil-wrapped blister.18 23 The amount of drug powder delivered to the lungs depends on factors such as the patient’s inspiratory flow.2 18

Each actuation of the Advair HFA oral aerosol inhaler delivers 50, 125, or 250 mcg of fluticasone propionate and 25 mcg of salmeterol from the valve.51 Dosages of Advair HFA are expressed in terms of drug delivered from the mouthpiece; each actuation of the inhaler delivers 45, 115, or 230 mcg of fluticasone propionate and 21 mcg of salmeterol from the mouthpiece.51

Commercially available Advair HFA inhalation aerosol delivers 60 or 120 metered sprays per 8- or 12-g canister, respectively.51 55

Pediatric Patients

Asthma
Fluticasone
Oral Inhalation Aerosol

Children 4–11 years of age: Initial and maximal dosage is 88 mcg twice daily.35

Children ≥12 years of age previously receiving bronchodilators alone: Initially, 88 mcg twice daily.35 If control of asthma is inadequate after 2 weeks of therapy at the initial dosage, a higher strength may provide additional asthma control.35 If required, dosage may be increased to a maximum of 440 mcg twice daily.35 Consider initial dosages >88 mcg twice daily in children with inadequate asthma control.17 35

Children ≥12 years of age previously receiving inhaled corticosteroids: Initially, 88–220 mcg twice daily.35 If required, dosage may be increased to a maximum of 440 mcg twice daily.35 Consider initial dosages >88 mcg twice daily in those receiving inhaled corticosteroids at higher end of dosage range.17 35

Children ≥12 years of age previously receiving oral corticosteroids: Initially, 440 mcg twice daily; maximum dosage is 880 mcg twice daily.35

Fluticasone/Salmeterol Fixed Combination
Oral Inhalation Aerosol

Children ≥12 years of age: 90, 230, or 460 mcg of fluticasone propionate and 42 mcg of salmeterol (2 inhalations) twice daily, given approximately 12 hours apart (morning and evening);17 51 55 recommended initial dosage is based on patient’s current asthma therapy.51

If control of asthma is inadequate after 2 weeks of therapy at the initial dosage, replacing the current strength of the fixed combination with a higher strength (higher strengths contain higher dosages of fluticasone only) may provide additional asthma control.51

Oral Inhalation Powder

Children 4–11 years of age: 100 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily, given approximately 12 hours apart (morning and evening).18

Children ≥12 years of age: 100, 250, or 500 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily, given approximately 12 hours apart (morning and evening);17 18 recommended initial dosage is based on patient’s asthma severity.18

If control of asthma is inadequate after 2 weeks of therapy at the initial dosage, replacing the current strength with a higher strength (higher strengths contain higher dosages of fluticasone only) may provide additional asthma control.18

Adults

Asthma
Fluticasone
Oral Inhalation Aerosol

Previously receiving bronchodilators alone: Initially, 88 mcg twice daily.35 If required, dosage may be increased to a maximum of 440 mcg twice daily.35 Consider initial dosages >88 mcg twice daily in adults with inadequate asthma control.17 35

Previously receiving inhaled corticosteroids: Initially, 88–220 mcg twice daily.35 If required, dosage may be increased to a maximum of 440 mcg twice daily.35 Consider initial dosages >88 mcg twice daily in those receiving inhaled corticosteroids at higher end of dosage range.17 35

Previously receiving oral corticosteroids: Initial and maximum dosage is 880 mcg twice daily.35

If control of asthma is inadequate after 2 weeks of therapy at the initial dosage, a higher strength may provide additional asthma control.35

Fluticasone/Salmeterol Fixed Combination
Oral Inhalation Aerosol

90, 230, or 460 mcg of fluticasone propionate and 42 mcg of salmeterol (2 inhalations) twice daily, given approximately 12 hours apart (morning and evening);17 51 55 recommended initial dosage is based on patient’s current asthma therapy.51

If control of asthma is inadequate after 2 weeks of therapy at the initial dosage, replacing the current strength with a higher strength (higher strengths contain higher dosages of fluticasone only) may provide additional asthma control.51

Oral Inhalation Powder

100, 250, or 500 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily, given approximately 12 hours apart (morning and evening);17 18 recommended initial dosage is based on patient’s asthma severity.18

If control of asthma is inadequate after 2 weeks of therapy at the initial dosage, replacing the current strength with a higher strength (higher strengths contain higher dosages of fluticasone only) may provide additional asthma control.18

COPD
Fluticasone/Salmeterol Fixed Combination
Oral Inhalation Powder

250 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily, given approximately every 12 hours (morning and evening).18

Prescribing Limits

Pediatric Patients

Asthma
Fluticasone
Oral Inhalation Aerosol

Children 4–11 years of age: Maximum 88 mcg twice daily.35

Children ≥12 years of age previously receiving bronchodilators alone or inhaled corticosteroids: Maximum 440 mcg twice daily.35

Children ≥12 years of age previously receiving oral corticosteroids: Maximum 880 mcg twice daily.35

Fluticasone/Salmeterol Fixed Combination
Oral Inhalation Aerosol

Children ≥12 years of age: Maximum 460 mcg of fluticasone propionate and 42 mcg of salmeterol (2 inhalations) twice daily.51

Oral Inhalation Powder

Children 4–11 years of age: Maximum 100 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily.18

Children ≥12 years of age: Maximum 500 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily.18

Adults

Asthma
Fluticasone
Oral Inhalation Aerosol

Previously receiving bronchodilators alone or inhaled corticosteroids: Maximum 440 mcg twice daily.35

Previously receiving oral corticosteroids: Maximum 880 mcg twice daily.35

Fluticasone/Salmeterol Fixed Combination
Oral Inhalation Aerosol

Maximum 460 mcg of fluticasone propionate and 42 mcg of salmeterol (2 inhalations) twice daily.51

Oral Inhalation Powder

Maximum 500 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily.18

COPD
Fluticasone/Salmeterol Fixed Combination
Oral Inhalation Powder

Maximum 250 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily.18 Use of higher than recommended dosages does not improve lung function.18

Special Populations

The following information addresses dosage of fluticasone propionate in special populations. When fluticasone propionate is used in fixed combination with salmeterol, dosage requirements for salmeterol should be considered.18 51

Geriatric Patients

Inhalation aerosol: Select dosage with caution, reflecting the greater frequency of decreased hepatic function, presence of coexisting conditions, or other drug therapies.35

Fluticasone/salmeterol: Dosage adjustments not recommended solely because of age.18 51

Cautions for Fluticasone Propionate

Contraindications

  • Primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures2 22 25 35 (e.g., oxygen, parenteral bronchodilators, IV corticosteroids)25 are required.

  • Fluticasone in fixed combination with salmeterol: primary treatment of status asthmaticus or other acute episodes of asthma or COPD when intensive measures are required.18 51

  • Known hypersensitivity to fluticasone or any ingredient (e.g., milk protein) in the formulation.18 23 35 51

Warnings/Precautions

Warnings

Use of Fixed Combinations

When used in fixed combination with salmeterol, consider cautions, precautions, contraindications, and interactions associated with each drug.18 51

Acute Exacerbations of Asthma or COPD

Do not initiate therapy with the fixed combination of fluticasone and salmeterol in patients with substantially worsening or acutely deteriorating asthma or acute symptoms of COPD.18

Failure to respond to a previously effective dosage of fluticasone in fixed combination with salmeterol may indicate substantially worsening asthma or COPD that requires reevaluation.18

Do not initiate fluticasone in fixed combination with salmeterol therapy in patients with acute symptoms of asthma (e.g., unresponsive to usual medications, increasing need for inhaled short-acting β-agonists, marked increase in symptoms, recent emergency room visits, sudden or progressive deterioration in pulmonary function).18

If inadequate control of symptoms persists with supplemental β2-agonist bronchodilator therapy or lung function (e.g., PEF) decreases appreciably, reevaluate asthma therapy promptly.18 Extra/increased doses of salmeterol or other long-acting inhaled β2-agonists (e.g., formoterol) should not be used in such situations.18 Such reevaluation may include increasing the strength of the fixed combination (higher strengths contain higher dosages of fluticasone only), adding additional inhaled corticosteroids, or initiating systemic corticosteroids.18 Do not increase the frequency of administration of the fixed combination.18

Withdrawal of Systemic Corticosteroid Therapy

Possible life-threatening exacerbation of asthma or adrenal insufficiency in patients being switched from systemic corticosteroids to orally inhaled fluticasone.23 35

Withdraw systemic corticosteroid therapy gradually and monitor for objective signs of adrenal insufficiency (e.g., fatigue, lassitude, weakness, nausea, vomiting, hypotension) during withdrawal of systemic therapy.18 23 35 Also carefully monitor lung function (FEV1 or morning PEF), adjunctive β2-adrenergic agonist use, and asthma symptoms.23 35 Patients who have been maintained on ≥20 mg of prednisone (or its equivalent) daily may be most susceptible to such adverse events, particularly during the later part of the transfer.18 35

Corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, fatigue, lassitude, depression) may occur.18 23 35

Monitor carefully for acute adrenal insufficiency during exposure to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with acute electrolyte loss.18 23 35

Monitor carefully for eosinophilia, vasculitic rash, worsening of pulmonary symptoms, cardiac complications, and/or neuropathy consistent with Churg-Strauss syndrome.23 35

Monitor carefully for unmasking of conditions previously controlled by systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).2 35

Do not use the fixed combination of fluticasone and salmeterol as the oral inhalation aerosol (Advair HFA) for transferring patients from systemic corticosteroid therapy.51

Immunosuppressed Patients

Increased susceptibility to infections in patients who are taking immunosuppressant drugs compared with healthy individuals.2 35 Certain infections (e.g., chickenpox, measles) can have a more serious or even fatal outcome in such patients, particularly in children.2 35

Take particular care to avoid exposure in susceptible patients.23 35 If exposure to chickenpox or measles occurs in susceptible patients, consider administering varicella zoster immune globulin (VZIG) or pooled immune globulin (IG), respectively.23 35 Consider treatment with an antiviral agent if chickenpox develops.23 35

Respiratory Effects

Bronchospasm and/or wheezing may occur.23 35

If bronchospasm occurs, treat immediately (e.g., with a short-acting β-adrenergic agonist), and discontinue treatment with fluticasone.23 35

General Precautions

Ocular Effects

Glaucoma, increased intraocular pressure, and cataracts reported rarely.23 35 Consider regular eye examinations.18 43

Systemic Corticosteroid Effects

Administration of higher than recommended dosages of orally inhaled fluticasone may result in manifestations of hypercorticism and suppression of HPA function.2 15 16 35 If such changes occur, reduce the dosage of fluticasone slowly, consistent with accepted procedures for reducing corticosteroid dosage and management of asthma symptoms.18

Take particular care in monitoring patients postoperatively or during periods of stress for evidence of inadequate adrenal response.18

Musculoskeletal Effects

Long-term use may affect normal bone metabolism, resulting in a loss of bone mineral density (BMD).

Use of fluticasone in fixed combination with salmeterol can pose additional risks in patients with major risk factors for decreased BMD, such as tobacco use, advanced age, sedentary life-style, poor nutrition, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, corticosteroids).18

Since patients with COPD often have multiple risk factors for reduced BMD, assess BMD prior to initiation of therapy and periodically thereafter.18 Consider use of agents to treat or prevent osteoporosis if appreciable reductions in BMD are seen and use of fluticasone and salmeterol in fixed combination is considered to be important for treatment of COPD.18

Infections

Localized candidal infections of the pharynx reported.23 35 If infection occurs, appropriate local or systemic treatment and/or discontinuance of therapy may be required.23 35

Use with extreme caution, if at all, in patients with clinical or asymptomatic Mycobacterium tuberculosis infections of the respiratory tract; untreated fungal, bacterial, or parasitic infections; or ocular herpes simplex or untreated, systemic viral infections.23 35

Remain vigilant for possible development of pneumonia in patients with COPD receiving fluticasone in fixed combination with salmeterol (Advair Diskus) oral inhalation powder, since clinical features of pneumonia and COPD exacerbations frequently overlap.18

Lower respiratory tract infections, (e.g., pneumonia) reported in patients with COPD receiving inhaled corticosteroids, including fluticasone alone or in fixed combination with salmeterol (Advair Diskus) oral inhalation powder.18 51

Other Effects

Unknown long-term, systemic, and local effects of the drug in humans, particularly developmental or immunologic processes in the mouth, pharynx, trachea, and lung.23

Specific Populations

Pregnancy

Category C.18 23 35 51

Lactation

Distributed into milk in rats; not known whether distributed into human milk.2 18 23 35 51

Use not studied in nursing women.18 23 35 51 Discontinue nursing or the drug.18 23 35 51

Pediatric Use

Safety and efficacy of fluticasone oral inhalation aerosol or the oral inhalation powder via the Diskus containing fluticasone in fixed combination with salmeterol not established in children <4 years of age.18 23 35

Safety and efficacy of the oral inhalation aerosol containing fluticasone in fixed combination with salmeterol (Advair HFA) not established in children <12 years of age.51 Adverse effect profile of Flovent HFA in pediatric patients (4–11 years of age) generally is similar to that observed in adolescents and adults.35

With long-term use, slows growth rate in children and adolescents;2 18 18 35 Monitor routinely (e.g., via stadiometry) the growth and development of children receiving prolonged corticosteroid therapy.2 18 35 43 Weigh benefits of corticosteroid therapy versus possibility of growth suppression and the risks associated with alternative therapies.18 23 35 Use the lowest possible dosage that effectively controls asthma.18 23 35

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.2 35 51

Insufficient experience with fluticasone in fixed combination with salmeterol oral inhalation powder in patients ≥65 years of age with asthma to determine whether geriatric patients respond differently than younger patients.18

Increased incidence of serious adverse effects reported in patients ≥65 years of age with COPD receiving fluticasone in fixed combination with salmeterol oral inhalation powder compared with younger adults; however, distribution of adverse effects similar in the two groups.18 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Plasma concentrations may be increased.23 35 Monitor patient closely.23 35

Common Adverse Effects

Fluticasone oral inhalation aerosol: Upper respiratory tract infection, upper respiratory inflammation, sinusitis, sinus infection, dysphonia, throat irritation, candidiasis, cough, bronchitis, headache.35

Interactions for Fluticasone Propionate

The following information addresses potential interactions with fluticasone. When used in fixed combination with salmeterol, consider interactions associated with salmeterol.18 51 No formal drug interaction studies performed to date with the fixed combinations.18 51

Metabolized by CYP3A4 isoenzyme.23

Drugs Affecting Hepatic Microsomal Enzymes

Potent inhibitors of CYP3A4: potential pharmacokinetic interaction (increased fluticasone propionate plasma concentrations).23 35

Specific Drugs

Drug

Interaction

Comments

Erythromycin

No effect on fluticasone pharmacokinetics23

Ketoconazole

Increased plasma fluticasone concentrations resulting in reduced plasma cortisol AUC23

Use concomitantly with caution23 35

Ritonavir

Increased plasma fluticasone concentrations and AUC, resulting in systemic corticosteroid effects (e.g., Cushing’s syndrome, adrenal suppression)23 35

Concomitant use not recommended unless the potential benefit outweighs the risk of systemic corticosteroid adverse effects23 35

Fluticasone Propionate Pharmacokinetics

Absorption

Bioavailability

Efficacy of orally inhaled fluticasone appears to result from local action rather than systemic absorption.2 4 23 35 Drug plasma concentrations do not predict therapeutic effect.18 23 35

Onset

Fluticasone: Substantial relief usually is evident within 1–2 days; however, may require ≥1–2 weeks of continuous therapy for optimum effectiveness.9 23 26 35

Fluticasone in fixed combination with salmeterol: Initial improvement in asthma control may occur within 30 minutes following oral inhalation; optimal benefit occurs ≥1 week of continuous therapy.18 51

Duration

When corticosteroids are discontinued, asthma control remains stable for several days or longer.23 35

Special Populations

Gender does not affect the systemic exposure of fluticasone in patients with asthma.23 35

Distribution

Extent

Glucocorticoids, including fluticasone, cross the placenta and may be distributed into milk.18 g 35

Binds weakly to erythrocytes.23

Plasma Protein Binding

Averages 91%; little or no binding to transcortin.23

Elimination

Metabolism

Metabolized to an inactive metabolite via CYP3A4.2 3 35

Elimination Route

Excreted in feces (approximately 95%) as unchanged drug and metabolites and in urine (<5%) as metabolites.17 23 35

Half-Life

Following IV administration, approximately 7.8 hours.23 35

Special Populations

In patients with hepatic impairment, plasma concentrations of the drug may be increased.23 35

Stability

Storage

Oral Inhalation

Aerosol

Fluticasone: 25°C (may be exposed to 15–30°C).35 Protect from excessive heat.35 Store metered-dose inhaler with the mouthpiece down.35

Fixed combination with salmeterol: 25°C (may be exposed to 15–30°C) with mouthpiece down.51 55 Contents under pressure; do not puncture, use or store near heat or open flame, or place into fire or incinerator.51 55 Exposure to temperatures >49°C may cause canister to burst.51 55 Discard when dose counter reads “000”.51

Powder

Fixed combination with salmeterol: 20–25°C.18 43 Protect from light and excessive heat.18 Discard Advair Diskus 1 month after removal from the foil pouch or when every blister used, whichever comes first.43

Actions

  • Potent glucocorticoid activity and minimal mineralocorticoid activity.g

  • Reduces the inflammatory asthmatic response by inhibiting multiple cell types (e.g., mast cells, eosinophils, basophils, lymphocytes, neutrophils).18 23 35

  • Inhibits macrophage accumulation in inflamed areas.g

  • Inhibits mediator production or secretion (e.g., eicosanoids, leukotrienes, cytokines, histamine) involved in the asthmatic response.18 23 35

  • Improves lung function (e.g., FEV1, morning peak expiratory flow).2 5 14 18 19 20 21 22 23 24 25

Advice to Patients

  • When used in fixed combination with salmeterol, importance of informing patients of important cautionary information about salmeterol.18 51

  • Provide a copy of the manufacturer's patient information (medication guide) for fluticasone in fixed combination with salmeterol with each prescription.39 45 Importance of instructing patients to read the medication guide prior to initiation of therapy and each time prescription is refilled.43 55

  • Importance of informing patients receiving the fixed combination of fluticasone and salmeterol that long-acting β2-adrenergic agonists (e.g., salmeterol) increase the risk of asthma-related death and may increase the risk of asthma-related hospitalization in children and adolescents.18 51

  • Importance of instructing patients in the use of the oral inhaler and Diskus devices and providing a copy of the manufacturer’s information for patients.23 26 35

  • Importance of children receiving fluticasone oral inhalation therapy under adult supervision.36

  • Importance of adequate understanding of proper storage, disposal, preparation, and inhalation techniques, including use of the inhalation delivery systems.2 23 26 35

  • Importance of rinsing the mouth after oral inhalation.23 43 51

  • Importance of advising patients that fluticasone oral inhalation must be used at regular intervals to be therapeutically effective.2 35

  • Importance of not exceeding the recommended dosage and of contacting a clinician immediately if symptoms of asthma or COPD occur that are not responsive to bronchodilators.18 23 26 35 43 51

  • Importance of advising patient that if a dose of fluticasone alone or in fixed combination with salmeterol is missed, the next dose should be taken at the regularly scheduled time; the dose should not be doubled.36 43 55

  • Importance of not discontinuing therapy with fluticasone in fixed combination with salmeterol without clinician’s guidance, as symptoms may recur.18 43 51

  • Importance of discontinuing regular use of short-acting, oral or inhaled β2-adrenergic agonists when initiating therapy with fluticasone in fixed combination with salmeterol and using short-acting, inhaled β2-adrenergic agonists only for relief of acute symptoms (e.g., shortness of breath).18 43 51

  • Importance of availability of a short-acting, inhaled β2-adrenergic agonist for acute asthma symptoms.43 55 Importance of informing a clinician if a short-acting, inhaled β2-adrenergic agonist is not available for use.43 55

  • Importance of contacting a clinician if decreased effectiveness of a short-acting β2-adrenergic agonist (requiring use of ≥4 inhalations for ≥2 consecutive days or 1 canister in 8 weeks) for acute symptoms occurs.43 55

  • Importance of advising patients that although substantial improvement may occur within the first day of therapy with fluticasone propionate, ≥1–2 weeks of continuous therapy may be required for optimum effects to be achieved.23 26 35 36

  • Importance of advising patients using fixed combination of fluticasone with salmeterol that ≥1 week of therapy may be required for optimum effects to be achieved.18 51 Importance of contacting a clinician if asthma symptoms do not improve after 1 week of regular use of the fixed combination.43 55

  • Importance of informing patients receiving therapy with fixed combination of fluticasone and salmeterol regarding common adverse effects associated with β2-adrenergic agonists such as palpitations, chest pain, rapid heart rate, tremor, or nervousness.18 51

  • Importance of informing patients that corticosteroids may decrease BMD.18 43

  • Importance of informing patients that long-term use of inhaled corticosteroids may increase the risk for development of cataracts or glaucoma.18 43 51

  • Importance of informing clinician of heart problems, hypertension, seizures, thyroid disorders, diabetes mellitus, liver disorders, osteoporosis, or immune disorders prior to initiation of therapy.43 55

  • Importance of advising patients that orally inhaled fluticasone should not be used as a bronchodilator and that the drug is not indicated for emergency use (e.g., relief of acute bronchospasm).18 35 51

  • Importance of obtaining emergency medical care if breathing problems worsen quickly.43 55

  • Importance of advising patients that additional salmeterol or other long-acting inhaled β2-adrenergic agonists should not be used for prevention of exercise-induced bronchospasm, treatment of asthma or COPD, or any other reason when the fixed combination is used.18 51

  • Importance of advising patients being transferred from systemic corticosteroid to fluticasone oral inhalation therapy to carry special identification (e.g., card, bracelet) indicating the need for supplementary systemic corticosteroids during periods of stress.18 23 35 Importance of advising such patients to immediately resume full therapeutic dosages of systemic corticosteroids and contact their clinician for further instructions during stressful periods (e.g., severe infection, severe asthmatic attack).18 23 35

  • Importance of avoiding exposure to chickenpox or measles, and, if exposed, of immediately consulting their clinician.2 35 43 51

  • Importance of informing patients with COPD receiving fluticasone in fixed combination with salmeterol oral inhalation powder (Advair Diskus) that they have an increased risk of pneumonia and to contact their clinician if they develop symptoms of pneumonia.18

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including therapy with prescription drugs, particularly other orally inhaled corticosteroids or ritonavir, and OTC drugs, vitamins, or herbal supplements.35 36 43 55

  • Importance of informing clinicians of allergies to fluticasone, salmeterol (in fixed combination), other drugs, or food.43 55

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.18 35 43 51 55

  • Importance of informing patients of other important precautionary information.18 23 35 51 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Fluticasone Propionate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Aerosol

44 mcg/metered spray

Flovent HFA (with tetrafluoroethane propellant)

GlaxoSmithKline

110 mcg/metered spray

Flovent HFA (with tetrafluoroethane propellant)

GlaxoSmithKline

220 mcg/metered spray

Flovent HFA (with tetrafluoroethane propellant)

GlaxoSmithKline

Fluticasone Propionate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Aerosol

45 mcg with Salmeterol Xinafoate 21 mcg (of salmeterol) per metered spray (from the actuator)

Advair HFA (combination) (with hydrofluoroalkane propellant)

GlaxoSmithKline

115 mcg with Salmeterol Xinafoate 21 mcg (of salmeterol) per metered spray (from the actuator)

Advair HFA (combination) (with hydrofluoroalkane propellant)

GlaxoSmithKline

230 mcg with Salmeterol Xinafoate 21 mcg (of salmeterol) per metered spray (from the actuator)

Advair HFA (combination) (with hydrofluoroalkane propellant)

GlaxoSmithKline

Powder for oral inhalation only

100 mcg with Salmeterol Xinafoate 50 mcg (of salmeterol) per inhalation

Advair Diskus

GlaxoSmithKline

250 mcg with Salmeterol Xinafoate 50 mcg (of salmeterol) per inhalation

Advair Diskus

GlaxoSmithKline

500 mcg with Salmeterol Xinafoate 50 mcg (of salmeterol) per inhalation

Advair Diskus

GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Advair Diskus 100-50MCG/DOSE Aerosol (GLAXO SMITH KLINE): 60/$189.99 or 120/$369.97

Advair Diskus 250-50MCG/DOSE Aerosol (GLAXO SMITH KLINE): 60/$232.99 or 180/$679.97

Advair Diskus 500-50MCG/DOSE Aerosol (GLAXO SMITH KLINE): 60/$304.99 or 120/$599.98

Advair HFA 115-21MCG/ACT Aerosol (GLAXO SMITH KLINE): 12/$248.99 or 36/$719.94

Advair HFA 230-21MCG/ACT Aerosol (GLAXO SMITH KLINE): 12/$320.99 or 36/$929.99

Advair HFA 45-21MCG/ACT Aerosol (GLAXO SMITH KLINE): 12/$209.00 or 24/$403.96

Flovent Diskus 100MCG/BLIST Aerosol (GLAXO SMITH KLINE): 60/$119.99 or 180/$349.97

Flovent Diskus 250MCG/BLIST Aerosol (GLAXO SMITH KLINE): 60/$166.99 or 180/$468.98

Flovent Diskus 50MCG/BLIST Aerosol (GLAXO SMITH KLINE): 60/$114.99 or 180/$323.97

Flovent HFA 110MCG/ACT Aerosol (GLAXO SMITH KLINE): 12/$162.98 or 36/$461.96

Flovent HFA 220MCG/ACT Aerosol (GLAXO SMITH KLINE): 12/$246.99 or 36/$695.98

Flovent HFA 44MCG/ACT Aerosol (GLAXO SMITH KLINE): 11/$119.99 or 32/$339.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 28, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

2. GlaxoSmithKline. Flovent Rotadisk (fluticasone propionate) inhalation powder prescribing information. Research Triangle Park, NC; 2004 Mar.

3. Jarvis B, Faulds D. Inhaled fluticasone propionate: a review of its therapeutic efficacy at dosages # 500 mcg/day in adults and adolescents with mild to moderate asthma. Drugs. 1999; 57:769-803. [PubMed 10353302]

4. Lawrence M, Wolfe J, Webb DR et al. Efficacy of inhaled fluticasone propionate in asthma results from topical and not from systemic activity. Am J Respir Crit Care Med. 1997; 156(3 Part 1):744-51. [IDIS 393535] [PubMed 9309988]

5. Nelson HS, Busse WW, deBoisblanc BP et al. Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma. J Allergy Clin Immunol. 1999; 103(2 Part 1):267-75. [IDIS 424760] [PubMed 9949318]

6. Noonan MJ, Chervinsky P, Wolfe J et al. Dose-related response to inhaled fluticasone propionate in patients with methacholine-induced bronchial hyperresponsiveness: a double-blind, placebo-controlled study. J Asthma. 1998; 35:153-64. [PubMed 9576141]

7. Chervinsky P, van As A, Bronsky EA et al. (The Fluticasone Propionate Asthma Study Group). Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. J Allergy Clin Immunol. 1994; 94:676-83. [IDIS 336954] [PubMed 7930300]

8. Pearlman DS, Noonan MJ, Tashkin DP et al. Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma. Ann Allergy Asthma Immunol. 1997; 78:356-62. [IDIS 383607] [PubMed 9109702]

9. Sheffer AL, LaForce C, Chervinsky P et al. Fluticasone propionate aerosol: efficacy in patients with mild to moderate asthma: Fluticasone Propionate Asthma Study Group. J Fam Pract. 1996; 42:369-75. [PubMed 8627205]

10. Galant SP, Lawrence M, Meltzer EO et al. Fluticasone propionate compared with theophylline for mild-to-moderate asthma. Ann Allergy Asthma Immunol. 1996; 77:112-8. [IDIS 371950] [PubMed 8760776]

11. Leblanc P, Mink S, Keistinen T et al. A comparison of fluticasone propionate 200 micrograms/day with beclomethasone dipropionate 400 micrograms/day in adult asthma [published erratum appears in Allergy. 1994; 49:908]. Allergy. 1994; 49:380-5. [PubMed 8092438]

12. Lundback B, Alexander M, Day J et al. Evaluation of fluticasone propionate (500 mcg day-1) administered either as dry powder via a Diskhaler inhaler or pressurized inhaler and compared with beclomethasone dipropionate (1000 mcg day-1) administered by pressurized inhaler. Respir Med. 1993; 87:609-20. [PubMed 8290745]

13. Condemi JJ, Chervinsky P, Goldstein MF et al. Fluticasone propionate powder administered through Diskhaler versus triamcinolone acetonide aerosol administered through metered-dose inhaler in patients with persistent asthma. J Allergy Clin Immunol. 1997; 100:467-74. [PubMed 9338539]

14. Peden DB, Berger WE, Noonan MJ et al. Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma. J Allergy Clin Immunol. 1998; 102:32-8. [PubMed 9679845]

15. Wilson AM, Clark DJ, McFarlane L et al. Adrenal suppression with high doses of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers. Eur J Clin Pharmacol. 1997; 53:33-7. [PubMed 9349927]

16. Wilson AM, Sims EJ, Lipworth BJ et al. Dose response with fluticasone propionate on adrenocortical activity and recovery of basal and stimulated responses after stopping treatment. Clin Endocrinol (Oxf). 1999; 50:329-35. [PubMed 10435058]

17. GlaxoSmithKline, Research Triangle Park, NC: Personal communication.

18. GlaxoSmithKline. Advair Diskus (fluticasone propionate/salmeterol xinafoate) inhalation powder prescribing information. Research Triangle Park, NC; 2010 Jun.

19. Kavuru M, Melamed J, Gross G et al. Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized. double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2000; 105:1108-16. [IDIS 448987] [PubMed 10856143]

20. Shapiro G, Lumry W, Wolfe J et al. Combined salmeterol 50 mcg and fluticasone propionate 250 mcg in the diskus device for the treatment of asthma. Am J Respir Crit Care Med. 2000; 161:527-34. [IDIS 443727] [PubMed 10673196]

21. Aubier M, Pieters WR, Schlosser NJ et al. Salmeterol/fluticasone propionate (50/500 mcg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma. Respir Med. 1999; 93:876-84. [PubMed 10653049]

22. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 2002 Feb. NIH/NHLBI Publication No. 02-3659. Available at NIH website. Accessed Sep. 26, 2002.

23. GlaxoSmithKline. Flovent Diskus (fluticasone propionate) inhalation powder prescribing information. Research Triangle Park, NC; 2005 Jul.

24. LaForce CF, Pearlman DS, Ruff ME et al. Efficacy and safety of dry powder fluticasone propionate in children with persistent asthma. Ann Allergy Asthma Immunol. 2000; 85:407-15. [IDIS 455895] [PubMed 11101186]

25. National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma update on selected topics—2002. J Allergy Clin Immunol. 2002; 110(Suppl.5):S141-219.

26. GlaxoSmithKline. Flovent Diskus (fluticasone propionate) inhalation powder patient instructions for use. Research Triangle Park, NC; 2000 Sep.

28. 3M Pharmaceuticals. Qvar (beclomethasone dipropronate) inhalation aerosol prescribing information. Northridge, CA; 2002 May.

29. Hawthorne AB, Record CO, Holdsworth CD et al. Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis. Gut. 1993; 34:125-8. [IDIS 308470] [PubMed 8432442]

30. Angus P, Snook JA, Reid M et al. Oral fluticasone propionate in active distal ulcerative colitis. Gut. 1992; 33:711-4. [IDIS 297298] [PubMed 1612492]

31. Mitchison HC, Al Mardini H, Gillespie S et al. A pilot study of fluticasone propionate in untreated coeliac disease. Gut. 1991; 32:260-5. [IDIS 279109] [PubMed 1901562]

32. de Kaski M, Peters AM, Lavender JP et al. Fluticasone propionate in Crohn’s disease. Gut. 1991; 32:657-61. [IDIS 284152] [PubMed 2060874]

33. Hanania NA, Darken P, Horstman D et al. The efficacy and safety of fluticasone propionate (250 mcg)/salmeterol (50 mcg) combined in the diskus inhaler for the treatment of COPD. Chest. 2003; 124:834-43. [IDIS 503620] [PubMed 12970006]

34. Clevenbergh P, Corostegul M, Gerard D et al. Iatrogenic Cushing’s syndrome in an HIV-infected patient treated with inhaled corticosteroids (fluticasone propionate) and low dose ritonavir enhanced PI containing regimen. J Infect. 2002; 44:194-5. [IDIS 484667] [PubMed 12099750]

35. GlaxoSmithKline. Flovent HFA (fluticasone propionate) inhalation aerosol prescribing information. Research Triangle Park, NC; 2006 Feb.

36. GlaxoSmithKline. Flovent HFA (fluticasone propionate) inhalation aerosol patient instructions for use. Research Triangle Park, NC; 2005 Dec.

37. GlaxoWellcome, Research Triangle Park, NC: Personal communication on salmeterol monograph.

38. Food and Drug Administration. FDA drug safety communication: New safety requirements for long-acting inhaled asthma medications called long-acting beta-agonists (LABAs). Rockville, MD; 2010 Feb 18. Available from FDA website. Accessed 2010 Jul 7.

39. Advair HFA (salmeterol and fluticasone propionate) risk evaluation and mitigation strategy (REMS). Initial approval 2008 Jul. Revised 2011 Jan. Reference ID: 2886411. Available from FDA website. Accessed 2011 Apr 20.

40. Food and Drug Administration. Study of asthma-drug halted. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 2003 Jan 23. Available at FDA website. Accessed Apr 26, 2006.

41. Lurie P, Wolfe SM. Misleading data analyses in salmeterol (SMART) study. Lancet. 2005; 366:1261-2. [IDIS 541200] [PubMed 16214589]

42. GlaxoSmith Kline. GlaxoSmithKline clinical trial register: salmeterol studies. SLGA5011: a double-blind, randomized, placebo-controlled surveillance study of asthma event outcomes in subjects receiving either usual pharmacolotherapy of asthma or usual pharmacotherapy plus salmeterol 42 mcg twice daily. Research Triangle Park, NC. Available at GSK website. Accessed Apr 26, 2006.

43. GlaxoSmithKline. Advair Diskus (fluticasone propionate and salmeterol xinafoate) inhalation powder medication guide. Research Triangle Park, NC; 2011 Jan.

44. Rickard KA. Dear healthcare professional letter regarding important revisions to prescribing information for Serevent (salmeterol xinafoate) and Advair Diskus (fluticasone propionate and salmeterol) inhalation powder. Rockville, MD: US Food and Drug Administration; 2003 Aug. From FDA web site.

45. Advair Diskus (salmeterol and fluticasone propionate) risk evaluation and mitigation strategy (REMS). Initial approval 2008 Jul. Revised 2011 Jan. Reference ID: 2886407. Available from FDA website. Accessed 2011 Apr 20.

46. Fontana PG, LeClerc JM. Dear healthcare professional letter regarding Foradil (formoterol fumurate) Aerolizer dry powder capsules for inhalation safety update. Dorval, QC: Novartis Pharmaceuticals Canada; 2005 Sep. 7. Available at Novartis Canada website. Accessed Apr. 26, 2006.

47. Food and Drug Administration. Approved risk evaluation and mitigation strategies (REMS). Available from FDA website. Accessed 2011 Apr 20.

49. National Asthma Education and Prevention Program. Expert panel report III: guidelines for the diagnosis and management of asthma. 2007 Jul. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. Available at NIH website. Accessed Jul 27, 2008.

51. GlaxoSmithKline. Advair HFA (fluticasone propionate and salmeterol) inhalation aerosol prescribing information. Research Triangle Park, NC; 2010 Jun.

52. Nelson HS, Wolfe JD, Gross G et al. Efficacy and safety of fluticasone propionate 44 mcg/salmeterol 21 mcg administered in a hydrofuoroalkane metered-dose inhaler as an initial asthma maintenance treatment. Ann Allergy Asthma Immunol. 2003; 91:263-9. [PubMed 14533658]

53. Nathan RA, Rooklin A, Schoaf L et al. Efficacy and tolerability of fluticasone propionate/salmeterol administered twice daily via hydrofluoroalkane 134a metered-dose inhaler in adolescent and adult patients with persistent asthma: a randomized, double-blind, placebo-controlled, 12-week study. Clin Ther. 2006; 28:73-85. [PubMed 16490581]

54. Pearlman DS, Peden D, Condemi JJ et al. Efficacy and safety of fluticasone propionate/salmeterol HFA 134A MDI in patients with mild-to-moderate persistent asthma. J Asthma. 2004; 41:797-806. [PubMed 15641629]

55. GlaxoSmithKline. Advair HFA (fluticasone propionate and salmeterol) inhalation aerosol medication guide. Research Triangle Park, NC; 2011 Jan.

56. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention. Bethesda, MD: National Institutes of Health. 2009 Dec. Available at NIH website. Accessed 2010 Sep 23.

g. AHFS drug information 2004. McEvoy GK, ed. Corticosteroids general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2886-98.

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