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Fluticasone Propionate And Salmeterol Xinafoate
FDA Drug Information • Also known as: Advair Hfa, Fluticasone Propionate And Salmeterol Hfa
- Brand Names
- Advair Hfa, Fluticasone Propionate And Salmeterol Hfa
- Route
- RESPIRATORY (INHALATION)
- Dosage Form
- AEROSOL, METERED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION ADVAIR HFA 45 mcg/21 mcg, ADVAIR HFA 115 mcg/21 mcg, and ADVAIR HFA 230 mcg/21 mcg are combinations of fluticasone propionate and salmeterol xinafoate. One active component of ADVAIR HFA is fluticasone propionate, a corticosteroid having the chemical name S- (fluoromethyl) 6α,9-difluoro-11β,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-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. The other active component of ADVAIR HFA 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 1 -[[[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. ADVAIR HFA is a purple plastic inhaler with a light purple cap containing a pressurized metered-dose aerosol canister fitted with a counter. Each canister contains a microcrystalline suspension of micronized fluticasone propionate and micronized salmeterol xinafoate in propellant HFA-134a (1,1,1,2-tetrafluoroethane). It contains no other excipients. After priming, each actuation of the inhaler delivers 50, 125, or 250 mcg of fluticasone propionate and 25 mcg of salmeterol in 75 mg of suspension from the valve. Each actuation delivers 45, 115, or 230 mcg of fluticasone propionate and 21 mcg of salmeterol from the actuator. Twenty-one micrograms (21 mcg) of...What Is Fluticasone Propionate And Salmeterol Xinafoate Used For?
1 INDICATIONS AND USAGE ADVAIR HFA is indicated for treatment of asthma in adult and adolescent patients aged 12 years and older. ADVAIR HFA should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ICS) or whose disease warrants initiation of treatment with both an ICS and long-acting beta 2 -adrenergic agonist (LABA). Limitations of Use ADVAIR HFA is not indicated for the relief of acute bronchospasm. ADVAIR HFA is a combination of fluticasone propionate, an inhaled corticosteroid, and salmeterol, a long-acting beta 2 ‑adrenergic agonist (LABA), indicated for treatment of asthma in adult and adolescent patients aged 12 years and older. ( 1 ) Limitations of use: Not indicated for relief of acute bronchospasm. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION
For oral inhalation only. ( 2.1 ) Adult and adolescent patients aged 12 years and older: 2 inhalations of ADVAIR HFA 45 mcg/21 mcg, ADVAIR HFA 115 mcg/21 mcg, or ADVAIR HFA 230 mcg/21 mcg twice daily. ( 2.2 ) Starting dosage is based on asthma severity. ( 2.2 ) 2.1 Administration Information ADVAIR HFA should be administered by the orally inhaled route only. After inhalation, rinse mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis. Priming Prime ADVAIR HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 4 weeks or when it has been dropped, prime the inhaler again by releasing 2 sprays into the air away from the face, shaking well for 5 seconds before each spray. Avoid spraying in eyes. 2.2 Recommended Dosage Adult and adolescent patients aged 12 years and older: 2 oral inhalations twice daily, approximately 12 hours apart. The maximum recommended dosage is 2 inhalations of ADVAIR HFA 230 mcg/21 mcg twice daily. General Dosing Recommendation When choosing the starting dosage strength of ADVAIR HFA, consider the patients’ disease severity, based on their previous asthma therapy, including the ICS dosage, as well as the patients’ current control of asthma symptoms and risk of future exacerbation. If asthma symptoms arise in the period between doses, an inhaled, short-acting beta 2 -agonist should be used for immediate relief. Improvement in asthma control following inhaled administration of ADVAIR HFA can occur within 30 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 dosage after 2 weeks of therapy, replacing the current strength of ADVAIR HFA with a higher strength may provide additional improvement in asthma control. If a previously effective dosage regimen fails to provide adequate improvement in asthma control, the therapeutic regimen should be reevaluated and additional therapeutic options (e.g., replacing the current strength of ADVAIR HFA with a higher strength, adding additional ICS, initiating oral corticosteroids) should be considered. More frequent administration or a greater number of inhalations (more than 2 inhalations twice daily) of the prescribed strength of ADVAIR HFA is not recommended as some patients are more likely to experience adverse effects with higher doses of salmeterol. Patients using ADVAIR HFA should not use additional LABA for any reason. [See Warnings and Precautions ( 5.3 , 5.12 ).]Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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)] Pneumonia in patients with COPD [see Warnings and Precautions (5.5)] Immunosuppression and risk of infections [see Warnings and Precautions (5.6)] Hypercorticism and adrenal suppression [see Warnings and Precautions (5.8)] Cardiovascular and central nervous system effects [see Warnings and Precautions (5.12)] Reduction in bone mineral density [see Warnings and Precautions (5.13)] Growth effects [see Warnings and Precautions (5.14)] Glaucoma and cataracts [see Warnings and Precautions (5.15)] Most common adverse reactions (incidence ≥3%) include: upper respiratory tract infection or inflammation, throat irritation, dysphonia, headache, dizziness, nausea and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult and Adolescent Subjects Aged 12 Years and Older The incidence of adverse reactions associated with ADVAIR HFA in Table 2 is based upon two 12-week, placebo-controlled, U.S. clinical trials (Trials 1 and 3) and 1 active-controlled 12-week U.S. clinical trial (Trial 2). A total of 1,008 adult and adolescent subjects with asthma (556 females and 452 males) previously treated with albuterol alone, salmeterol, or ICS were treated twice daily with 2 inhalations of ADVAIR HFA 45 mcg/21 mcg or ADVAIR HFA 115 mcg/21 mcg, fluticasone propionate CFC inhalation aerosol (44- or 110-mcg doses), salmeterol CFC inhalation aerosol 21 mcg, or placebo HFA inhalation aerosol. The average duration of exposure was 71 to 81 days in the active treatment groups compared with 51 days in the placebo group. Table 2. Adverse Reactions with ADVAIR HFA with ≥3% Incidence in Adult and Adolescent Subjects with Asthma Adverse Event ADVAIR HFA Fluticasone Propionate CFC Inhalation Aerosol Salmeterol CFC Inhalation Aerosol Placebo HFA Inhalation Aerosol 45 mcg/21 mcg (n = 187) % 115 mcg/21 mcg (n = 94) % 44 mcg (n = 186) % 110 mcg (n = 91) % 21 mcg (n = 274) % (n = 176) % Ear, nose, and throat Upper respiratory tract infection 16 24 13 15 17 13 Throat irritation 9 7 12 13 9 7 Upper respiratory inflammation 4 4 3 7 5 3 Hoarseness/dysphonia 3 1 2 0 1 0 Lower respiratory Viral respiratory infection 3 5 4 5 3 4 Neurology Headache 21 15 24 16 20 11 Dizziness 4 1 1 0 <1 0 Gastrointestinal Nausea and vomiting 5 3 4 2 2 3 Viral gastrointestinal infection 4 2 2 0 1 2 Gastrointestinal signs and symptoms 3 2 2 1 1 1 Musculoskeletal Musculoskeletal pain 5 7 8 2 4 4 Muscle pain 4 1 1 1 3 <1 The incidence of common adverse reactions reported in Trial 4, a 12-week non-U.S. clinical trial in 509 subjects previously treated with ICS who were treated twice daily with 2 inhalations of ADVAIR HFA 230 mcg/21 mcg, fluticasone propionate CFC inhalation aerosol 220 mcg, or 1 inhalation of ADVAIR DISKUS 500 mcg/50 mcg was similar to the incidences reported in Table 2. Additional Adverse Reactions Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that occurred in the groups receiving ADVAIR HFA with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo include the following: tachycardia, arrhythmias, myocardial infarction, postoperative complications, wounds and lacerations, soft tissue injuries, ear signs and symptoms, rhinorrhea/postnasal drip, epistaxis, nasal congestion/blockage, laryngitis, unspecified...Drug Interactions
7 DRUG INTERACTIONS ADVAIR HFA has been used concomitantly with other drugs, including short-acting beta 2 -agonists, methylxanthines, and nasal 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 ADVAIR HFA.
Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. 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 ADVAIR HFA, are substrates of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with ADVAIR HFA 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....Contraindications
4 CONTRAINDICATIONS ADVAIR HFA is contraindicated in the following conditions:
Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required [see Warnings and Precautions ( 5.2 )] . Hypersensitivity to any of the ingredients [see Warnings and Precautions ( 5.11 ), Adverse Reactions ( 6.2 ), Description ( 11 )] . Primary treatment of status asthmaticus or acute episodes of asthma requiring intensive measures. ( 4 ) Hypersensitivity to any ingredient. (4)Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are insufficient data on the use of ADVAIR HFA or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. There are clinical considerations with the use of ADVAIR HFA in pregnant women. (See Clinical Considerations.) In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits, was 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 25 times the MRHDID on an AUC 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 10 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 Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant...
Overdosage
10 OVERDOSAGE No human overdosage data has been reported for ADVAIR HFA. ADVAIR HFA contains both fluticasone propionate and salmeterol; therefore, the risks associated with overdosage for the individual components described below apply to ADVAIR HFA. Treatment of overdosage consists of discontinuation of ADVAIR HFA 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 (5.8)] . 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-3672 NDC: 50090-3672-0 120 AEROSOL, METERED in a INHALER / 1 in a CARTON
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.