Class: Adrenals
VA Class: RE101
Molecular Formula: C25H31F3O5S
CAS Number: 80474-14-2
Brands: Advair, Flovent
Special Alerts:
[Posted 02/18/2010] FDA notified healthcare professionals and consumers that, due to safety concerns, FDA is requiring a risk management strategy (REMS) and class-labeling changes for all Long-Acting Beta-Agonists (LABAs). The REMS will require a revised Medication Guide written specifically for patients, and a plan to educate healthcare professionals about the appropriate use of LABAs. These changes are based on FDA's analyses of studies showing an increased risk of severe exacerbation of asthma symptoms, leading to hospitalizations in pediatric and adult patients as well as death in some patients using LABAs for the treatment of asthma.
Healthcare professionals are reminded that to ensure the safe use of these products:
Single-ingredient LABAs should only be used in combination with an asthma controller medication; they should not be used alone.
LABAs should only be used long-term in patients whose asthma cannot be adequately controlled on asthma controller medications.
LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved. Patients should then be maintained on an asthma controller medication.
Pediatric and adolescent patients who require the addition of a LABA to an inhaled corticosteroid should use a combination product containing both an inhaled corticosteroid and a LABA, to ensure compliance with both medications.
FDA has determined that the benefits of LABAs in improving asthma symptoms outweigh the potential risks when used appropriately with an asthma controller medication in patients who need the addition of LABAs. FDA believes the safety measures recommended will improve the safe use of these drugs. For more information visit the FDA website at: and .
- Fluticasone Propionate in Fixed Combination with Salmeterol
Possible increase in asthma-related death in patients receiving long-acting β2-adrenergic bronchodilators, including salmeterol, in addition to usual asthma therapy.18 38 40 41 42
Reserve use of fixed combination with salmeterol for patients with asthma whose disease is inadequately controlled with other asthma controller therapy (e.g., low to medium dosage of inhaled corticosteroids) or whose disease severity warrants treatment with 2 maintenance therapies.18 39 (See Acute Exacerbations of Asthma or COPD under Cautions).
Introduction
Synthetic trifluorinated glucocorticoid.2 3 35
Uses for Fluticasone Propionate
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Asthma
Long-term prevention of bronchospasm in patients with asthma.2 18 23 35
In corticosteroid-dependent patients, may permit a substantial reduction in the daily maintenance dosage of the systemic corticosteroid and gradual discontinuance of corticosteroid maintenance dosages.2 5 35
Used in fixed combination with salmeterol in asthmatic patients whose disease is inadequately controlled with other anti-asthma therapy (e.g., low to medium dosage of inhaled corticosteroids) or whose disease severity warrants treatment with 2 maintenance therapies.18
Fixed combination with salmeterol should not be used in patients whose asthma can be successfully managed with inhaled corticosteroids and occasional use of inhaled short-acting β2 adrenergic agonists.18 43
COPD
Fixed combination of salmeterol and fluticasone propionate used for maintenance treatment of airflow obstruction in patients with COPD associated with chronic bronchitis.18
Reevaluate patients receiving long-term therapy (>6 months) periodically to assess continuing benefits and risks.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 oral inhalation are based on previous asthma therapy.2 18 35 After 2 weeks of therapy at the initial dosage, if asthma is inadequately controlled, replace the current strength with a higher strength.18 35
Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids
When switching from systemic corticosteroids to orally inhaled fluticasone propionate, asthma should be reasonably stable before initiating treatment with the oral inhalation.5 28
Initially, administer 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 usually should not exceed 2.5–5 mg of prednisone (or its equivalent) each week in patients receiving the oral inhalation.2 35 Once oral corticosteroids are discontinued and symptoms of asthma have been controlled, titrate the dosage to the lowest effective level.2 17 18 35
Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.23 35 (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)
Chronic Obstructive Pulmonary Disease
In patients receiving long-term therapy (>6 months) for chronic bronchitis, reevaluate periodically to assess continuing benefits and risks.18
Administration
Administer by oral inhalation.23 35
Oral Inhalation
Administer microcrystalline suspension by oral inhalation using a metered-dose inhaler.35 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
Inhalation Powder
Administer fluticasone propionate 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 breathe out into the Diskus device.43
Rinse the mouth after inhalation of fluticasone propionate in fixed combination with 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.26 43 Do not take apart the inhaler.26 43
Do not use fluticasone propionate in fixed combination with salmeterol xinafoate with a spacer device.43
Inhalation Aerosol
Shake well (5 seconds) immediately prior to use.36 Actuate aerosol inhaler 4 times prior to the initial use.35 36 Actuate inhaler once prior to use if it has not been used for >1 week or if the inhaler has been dropped.35 36
Exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with lips closed around it.36 Inhale slowly and deeply through the mouth while actuating the inhaler.36 Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.36
Allow 30 seconds to elapse between subsequent inhalations from the aerosol inhaler.36
Following each treatment, rinse the mouth thoroughly.36
Clean inhaler at least once a week by removing canister from the inhaler and washing plastic cap and case in warm water; allow the actuator to air-dry.36
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
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
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 (labeled as containing 44, 110, or 220 mcg of fluticasone propionate) delivers 120 metered sprays of fluticasone propionate.35
Doses of fluticasone propionate and salmeterol in the combination preparation (Advair inhalation powder) 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
Pediatric Patients
Asthma
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 who were receiving inhaled corticosteroids at the higher end of the dosage range.17 35
Children ≥12 years of age previously receiving oral corticosteroids: Initially, 440 mcg twice daily and maximum dosage is 880 mcg twice daily.35
Inhalation Powder
Fixed combination of fluticasone propionate and salmeterol in children 4–11 years of age inadequately controlled with an inhaled corticosteroid: Initial and maintenance dosage is 100 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily.18
Fixed combination of fluticasone propionate and salmeterol in children ≥12 years of age not currently receiving an orally inhaled corticosteroid: Initially, 100 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily.18
The dosage of fluticasone propionate and salmeterol in fixed combination in adolescents receiving inhaled corticosteroids depends on the dosage of the inhaled corticosteroid currently in use.18
Current Daily Dosage of Inhaled Corticosteroid (mcg) | Recommended Strength of Fluticasone Propionate Contained in Advair Diskus (with 50 mcg of Salmeterol) at Twice-Daily Dosage (mcg) | |
|---|---|---|
Beclomethasone Dipropionate HFA Inhalation Aerosol | ≤160 | 100 |
320 | 250 | |
640 | 500 | |
Budesonide Inhalation Aerosol | ≤400 | 100 |
800–1200 | 250 | |
1600 | 500 | |
Flunisolide Inhalation Aerosol | ≤1000 | 100 |
1250–2000 | 250 | |
Flunisolide HFA Inhalation Aerosol | ≤320 | 100 |
640 | 250 | |
Fluticasone Propionate HFA Inhalation Aerosol | ≤176 | 100 |
440 | 250 | |
660–880 | 500 | |
Fluticasone Propionate Inhalation Powder | ≤200 | 100 |
500 | 250 | |
1000 | 500 | |
Mometasone Furoate Inhalation Powder | 220 | 100 |
440 | 250 | |
880 | 500 | |
Triamcinolone Acetonide Inhalation Aerosol | ≤1000 | 100 |
1100–1600 | 250 |
Adults
Asthma
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 who were receiving inhaled corticosteroids at the higher end of the 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
Inhalation Powder
Fixed combination of fluticasone propionate and salmeterol in patients not currently receiving an orally inhaled corticosteroid: Initially, 100 or 250 mcg of fluticasone propionate and 50 mcg of salmeterol (1 inhalation) twice daily.18
The dosage of fluticasone propionate and salmeterol in fixed combination in patients currently receiving inhaled corticosteroids depends on the dosage of the inhaled corticosteroid currently in use.18
Current Daily Dosage of Inhaled Corticosteroid (mcg) | Recommended Strength of Fluticasone Propionate Contained in Advair Diskus (with 50 mcg of Salmeterol) at Twice-Daily Dosage (mcg) | |
|---|---|---|
Beclomethasone Dipropionate HFA Inhalation Aerosol | ≤160 | 100 |
320 | 250 | |
640 | 500 | |
Budesonide Inhalation Aerosol | ≤400 | 100 |
800–1200 | 250 | |
1600 | 500 | |
Flunisolide Inhalation Aerosol | ≤1000 | 100 |
1250–2000 | 250 | |
Flunisolide HFA Inhalation Aerosol | ≤320 | 100 |
640 | 250 | |
Fluticasone Propionate HFA Inhalation Aerosol | ≤176 | 100 |
440 | 250 | |
660–880 | 500 | |
Fluticasone Propionate Inhalation Powder | ≤200 | 100 |
500 | 250 | |
1000 | 500 | |
Mometasone Furoate Inhalation Powder | 220 | 100 |
440 | 250 | |
880 | 500 | |
Triamcinolone Acetonide Inhalation Aerosol | ≤1000 | 100 |
1100–1600 | 250 |
If control of asthma is inadequate 2 weeks after initiation of therapy at the initial dosage, a higher strength may provide additional asthma control.18
COPD
Oral Inhalation
Fixed combination of fluticasone propionate and salmeterol: Initial and maintenance dosage is 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
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
Inhalation Powder
Fixed combination of fluticasone propionate and salmeterol in children 4–11 years of age: Maximum 100 mcg of fluticasone propionate and 50 mcg salmeterol (1 inhalation) twice daily.18
Fixed combination of fluticasone propionate and salmeterol in children ≥12 years of age: Maximum 500 mcg of fluticasone propionate and 50 mcg salmeterol (1 inhalation) twice daily.18
Adults
Asthma
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
Inhalation Powder
Fixed combination of fluticasone propionate and salmeterol: Maximum 500 mcg of fluticasone propionate and 50 mcg salmeterol (1 inhalation) twice daily.18 Use of higher than recommended dosage (500 mcg of fluticasone propionate and 50 mcg of salmeterol twice daily) does not improve lung function compared with recommended dosages.18
COPD
Oral Inhalation
Fixed combination of fluticasone propionate and salmeterol: Maximum 250 mcg fluticasone propionate and 50 mcg salmeterol (1 inhalation) twice daily.18 Use of higher than recommended dosage (250 mcg of fluticasone propionate and 50 mcg of salmeterol twice daily) does not improve lung function compared with the recommended dosage.18
Special Populations
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
Inhalation powder of fluticasone propionate in fixed combination with salmeterol: Dosage adjustments not recommended solely because of age.18 23
Cautions for Fluticasone Propionate
Contraindications
Primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures2 18 22 25 35 (e.g., oxygen, parenteral bronchodilators, IV corticosteroids)25 are required.
Known hypersensitivity to fluticasone propionate or any ingredient in the formulation.18 23 35
Warnings/Precautions
Warnings
Acute Exacerbations of Asthma or COPD
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Long-acting β2-adrenergic agonists such as salmeterol, a component of Advair Diskus, may increase the risk of asthma-related life-threatening events and death.18 38 39 40 41 42 44 45 In a large (>26,000 patients), placebo-controlled safety study, interim analysis on approximately 50% of the intended enrollment revealed an overall higher rate of asthma-related death with add-on salmeterol therapy in addition to usual asthma therapy compared with add-on placebo therapy.18 38 39 40 45 In addition, subgroup analyses revealed a higher rate of asthma death with add-on salmeterol therapy in African-American patients18 38 39 40 45 and in patients not receiving concomitant inhaled corticosteroid therapy compared with add-on placebo.39 40 46 Data currently are insufficient to determine whether concurrent use of inhaled corticosteroids provides protection from or modifies the risk of asthma-related death associated with salmeterol.18 38 44
Do not initiate therapy with the fixed combination of fluticasone propionate 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 propionate in fixed combination with salmeterol xinafoate may indicate substantially worsening asthma or COPD that requires reevaluation.18
Do not initiate fluticasone propionate 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 propionate 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 propionate.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 Lung function (FEV1 or morning PEF), adjunctive β2-adrenergic agonist use, and asthma symptoms should also be carefully monitored.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
The fixed combination of fluticasone propionate and salmeterol should not be used for the purpose of transferring a patient’s therapy from systemic to inhaled corticosteroids.18
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 propionate.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 propionate may result in manifestations of hypercorticism and suppression of HPA function.2 15 16 35 If such changes occur, reduce the dosage of fluticasone propionate 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 propionate 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 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 propionate 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
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
Use of Fixed Combination
When fluticasone propionate is used in fixed combination with salmeterol, consider the cautions, precautions, and contraindications associated with salmeterol therapy.18
Specific Populations
Pregnancy
Category C.23 35
Lactation
Distributed into milk in rats; not known whether distributed into human milk.2 18 23 35
Use not studied in nursing women.23 35 Discontinue nursing or the drug.23 35
Pediatric Use
Safety and efficacy of fluticasone propionate inhalation aerosol or the inhalation powder via the Diskus containing fluticasone in fixed-combination with salmeterol not established in children <4 years of age.18 23 35 The 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 pediatric patients 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 18 35 (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 propionate inhalation aerosol: Upper respiratory tract infection, upper respiratory inflammation, sinusitis, sinus infection, dysphonia, throat irritation, candidiasis, cough, bronchitis, headache.35
Fixed combination of fluticasone propionate and salmeterol in the treatment of COPD: Headache, candidiasis, musculoskeletal pain, throat irritation, viral respiratory infections, hoarseness/dysphonia, dizziness, fever, sinusitis, malaise/fatigue, muscle cramps/spasms.18
Fixed combination of fluticasone propionate and salmeterol in the treatment of asthma: Upper respiratory tract infection, pharyngitis, headaches, upper respiratory inflammation, hoarseness/dysphonia, sinusitis, viral respiratory infections, nausea/vomiting, GI discomfort and pain, diarrhea, musculoskeletal pain, candidiasis, bronchitis, viral GI infections, cough.18
Interactions for Fluticasone Propionate
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 propionate pharmacokinetics23 | |
Ketoconazole | Increased plasma fluticasone propionate concentrations resulting in reduced plasma cortisol AUC23 | Use concomitantly with caution23 35 |
Ritonavir | Increased plasma fluticasone propionate 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 the orally inhaled drug 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 propionate alone: 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 within 30 minutes following oral inhalation; optimal benefit occurs ≥1 week of continuous therapy.18
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 in patients with asthma.23 35
Distribution
Extent
Glucocorticoids, including fluticasone propionate, 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
25°C (may be exposed to 15–30°C).35 Protect from excessive heat.35 Store metered-dose inhaler with the mouthpiece down.35
Powder
Fluticasone propionate in fixed combination with salmeterol: 20–25°C.18 43 Protect from light and excessive heat.18 Discard the Advair Diskus 1 month after removal from the foil pouch or when every blister has been used, whichever comes first.43
ActionsActions
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., forced expiratory volume in 1 second [FEV1], morning peak expiratory flow).2 5 14 18 19 20 21 22 23 24 25
Reduces the inflammatory response in COPD18 possibly by inhibiting certain cell types including neutrophils, T-lymphocytes, and macrophages.18
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Importance of instructing patient in the use of the oral inhaler and Diskus devices and providing a copy of the manufacturer’s information and/or medication guide for patients.18 23 26 35 43
Importance of advising patients of the potential risk of asthma-related death with salmeterol alone and that data are not adequate to determine whether concurrent use of fluticasone or other anti-asthma agents with salmeterol modifies this risk.18 43
Importance of pediatric patients receiving fluticasone propionate 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
Importance of advising patients that fluticasone propionate 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
Importance of advising patient that if a dose of fluticasone propionate 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
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