| Revision as of 01:12, 30 August 2011 editBoghog (talk | contribs)Autopatrolled, Extended confirmed users, IP block exemptions, New page reviewers, Pending changes reviewers, Rollbackers, Template editors137,907 edits added missing parameters to drugbox template; ref reformatting; removed now redundant external links← Previous edit |
Latest revision as of 03:58, 8 September 2024 edit undoWhywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers49,218 edits infobox, rank, description, uses, refs |
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{{Short description|Formulation used in the management of asthma and chronic obstructive pulmonary disease}} |
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{{Cleanup|date=January 2009}} |
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{{Use dmy dates|date=October 2022}} |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 400094990 |
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| verifiedrevid = 447411501 |
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| type = combo |
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| image = Fluticasone propionate.svg |
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| image = Fluticasone propionate and salmeterol.svg |
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| image2 = Salmeterol.png |
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| width = 225 |
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| alt = |
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| caption = Fluticasone propionate (top) and salmeterol (bottom) |
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<!--Combo data--> |
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<!--Combo data--> |
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| component1 = Fluticasone propionate |
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| type = combo |
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| class1 = ] |
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| component1 = Fluticasone |
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| component2 = Salmeterol |
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| class1 = ] |
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| class2 = ] |
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| component2 = Salmeterol |
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| class2 = ] |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = Advair |
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| tradename = Advair, Seretide, Cyplos, others |
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| Drugs.com = {{drugs.com|parent|advair}} |
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| Drugs.com = {{drugs.com|pro|fluticasone-and-salmeterol-inhalation}} |
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| MedlinePlus = a699063 |
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| MedlinePlus = a699063 |
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| DailyMedID = Fluticasone and salmeterol |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU = B3 |
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| pregnancy_US = C |
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| pregnancy_category = |
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| pregnancy_category = |
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| routes_of_administration = ] |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| ATC_prefix = R03 |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| ATC_suffix = AK06 |
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| legal_UK = POM |
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| legal_US = Rx-only |
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| legal_status = |
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| routes_of_administration = Inhaled |
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| legal_AU = S4 |
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<!--Identifiers--> |
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| legal_AU_comment = <ref>{{cite web|url=https://www.tga.gov.au/resources/prescription-medicines-registrations/seroflo-multihaler-cipla-australia-pty-ltd |access-date=1 April 2023|website=Department of Health and Ages Care|title=Seroflo Multihaler (Cipla Australia Pty Ltd)}}</ref> |
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| CAS_number = |
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| legal_CA = Rx-only |
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| ATC_prefix = R03 |
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| legal_UK = POM |
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| ATC_suffix = AK06 |
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| legal_US = Rx-only |
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| PubChem = 9811567 |
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| legal_US_comment = <ref name="Advair Diskus FDA label">{{cite web | title=Advair Diskus- fluticasone propionate and salmeterol powder | website=DailyMed | date=30 June 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4eeb5f6a-593f-4a9e-9692-adefa2caf8fc | access-date=8 September 2024}}</ref><ref name="Advair HFA FDA label">{{cite web | title=Advair HFA- fluticasone propionate and salmeterol xinafoate aerosol, metered | website=DailyMed | date=23 May 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dfaca6f9-3277-47b2-319d-1377917cb54c | access-date=8 September 2024}}</ref> |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| legal_EU = Rx-only |
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| DrugBank = |
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| legal_status = Rx-only |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 7987322 |
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<!--Chemical data--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| smiles = O=C(SCF)3(OC(=O)CC)2(C(O)4(F)/1(\C(=C/C(=O)\C=C\1)(F)C42C3C)C)C.O(CCCCc1ccccc1)CCCCCCNCC(O)c2ccc(O)c(c2)CO |
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| CAS_number = 136112-01-1 |
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| InChI = 1/C25H31F3O5S.C25H37NO4/c1-5-20(31)33-25(21(32)34-12-26)13(2)8-15-16-10-18(27)17-9-14(29)6-7-22(17,3)24(16,28)19(30)11-23(15,25)4;27-20-23-18-22(13-14-24(23)28)25(29)19-26-15-7-1-2-8-16-30-17-9-6-12-21-10-4-3-5-11-21/h6-7,9,13,15-16,18-19,30H,5,8,10-12H2,1-4H3;3-5,10-11,13-14,18,25-29H,1-2,6-9,12,15-17,19-20H2/t13-,15+,16+,18+,19+,22+,23+,24+,25+;/m1./s1 |
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| PubChem = 9811567 |
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| InChIKey = YYAZJTUGSQOFHG-RZFXJYHSBR |
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| DrugBank_Ref = |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| DrugBank = |
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| StdInChI = 1S/C25H31F3O5S.C25H37NO4/c1-5-20(31)33-25(21(32)34-12-26)13(2)8-15-16-10-18(27)17-9-14(29)6-7-22(17,3)24(16,28)19(30)11-23(15,25)4;27-20-23-18-22(13-14-24(23)28)25(29)19-26-15-7-1-2-8-16-30-17-9-6-12-21-10-4-3-5-11-21/h6-7,9,13,15-16,18-19,30H,5,8,10-12H2,1-4H3;3-5,10-11,13-14,18,25-29H,1-2,6-9,12,15-17,19-20H2/t13-,15+,16+,18+,19+,22+,23+,24+,25+;/m1./s1 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 7987322 |
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| StdInChIKey = YYAZJTUGSQOFHG-RZFXJYHSSA-N |
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| KEGG = D08699 |
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}} |
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}} |
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The combination preparation '''fluticasone/salmeterol''' is a formulation containing ] and ] used in the management of ] and ] (COPD). It is marketed by ] under various trade names including '''Advair''' (US, CA), '''Seretide''' (Australia, Colombia, EU, México, New Zealand, South Africa, South Korea), '''Viani''' (Germany), '''Adoair''' (Japan), '''ForAir''' (India) and '''Foxair''' (South Africa). Annual worldwide sales approx $7B in 2009. Its US patent expires in 2010 and European patent in 2013. The availability of a generic form of Advair in the United States may be significantly delayed after the expiration of the patent because the Food and Drug Administration has not determined a standard for the bioequivalence for inhaled steroids in multi-dose inhalers or dry powder inhalers.<ref>{{cite web|last=Medco Health Solutions|title=Estimated Dates of Generic Availablity|url=http://www.medcohealth.com/art/corporate/anticipatedfirsttime_generics.pdf|accessdate=1 August 2011}}</ref> |
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<!-- Definition and medical uses --> |
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Fluticasone, a ], is the anti-inflammatory component of the combination, while salmeterol treats constriction of the airways. Together, they relieve the symptoms of coughing, wheezing and shortness of breath. |
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'''Fluticasone/salmeterol''', sold under the brand name '''Advair''' among others, is a ] medication containing ], an inhaled corticosteroid; and ], a long-acting beta2‑adrenergic agonist.<ref name="Advair Diskus FDA label" /><ref name="Advair HFA FDA label" /><ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=263–264|edition=76}}</ref> It is used in the management of ] and ] (COPD).<ref name=BNF76/> It is used by inhaling the medication into the lungs.<ref name=BNF76/> |
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<!-- Side effects and mechanisms --> |
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==Formulations== |
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Common side effects include ], headache, and cough.<ref name=FDA2018PI/> Serious side effects may include worsening asthma, ], ]s, and heart problems.<ref name=FDA2018PI/> Safety in pregnancy and breastfeeding is unclear.<ref name=Preg2019>{{cite web |title=Fluticasone / salmeterol Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/fluticasone-salmeterol.html |website=Drugs.com |access-date=3 March 2019 }}</ref> Fluticasone, a ], works by decreasing inflammation while salmeterol, a ] (LABA), works by activating ]s.<ref name=FDA2018PI/> |
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Advair is available in several dosage strengths, depending on the patient's country, as a '''DPI''' (]). The smallest dosage is 100mcg/50mcg, the intermediate dosage is 250mcg/50mcg and the highest dosage is 500mcg/50mcg (mcg refers to micrograms). |
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<!-- Society and culture --> |
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Advair HFA inhalation aerosol as a MDI (]) is available in Canada and the US and now in Australia and New Zealand as Advair HFA 45mcg/21mcg, Advair HFA 115mcg/21mcg, and Advair HFA 230mcg/21mcg. These contain 60 inhalations and are generally prescribed as a 30 day supply. (1 inhalation twice a day) |
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The combination was approved for medical use in the United States in 2000.<ref name=FDA2018PI>{{cite web |title=Fluticasone and Salmeterol inhalation - FDA prescribing information, side effects and uses |url=https://www.drugs.com/pro/fluticasone-and-salmeterol-inhalation.html |website=Drugs.com |access-date=4 March 2019 }}</ref> A ] version was approved in the United States in 2019.<ref name="FDA PR 20190130">{{cite press release |title=FDA approves first generic Advair Diskus |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-advair-diskus |website=U.S. ] (FDA) |access-date=30 January 2019 }}</ref> In 2022, it was the 59th most commonly prescribed medication in the United States, with more than 11{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Fluticasone; Salmeterol Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/FluticasoneSalmeterol | access-date = 30 August 2024 }}</ref> |
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==Medical uses== |
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Internationally the fluticasone/salmeterol combination is delivered by a number of devices, including standard aerosol metered dose inhalers (brand name "Evohaler" in México and UK) or dry-powder devices termed "Accuhaler" in Australia and the UK, and "Diskus" in France and the US. These purple disk-shaped containers are about 3.5 inches (8.9 cm) across and about 1 inch thick (2.5 cm). The discus container utilizes a machined 2 piece long foil ribbon with each unit dose held in small caplet-shaped depressions along the entire dose-count-length. Once the lever is actuated the dose is advanced by peeling away the flat outer most layer exposing the medication that is ready to be breathed in. |
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Fluticasone/salmeterol is ] for the treatment of asthma.<ref name="Advair Diskus FDA label" /><ref name="Advair HFA FDA label" /> |
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Fluticasone, a corticosteroid, is the ] component of the combination which decreases inflammation in the lungs. This leads to improvement in breathing. Salmeterol, a long-acting beta-adrenoceptor agonist, treats constriction of the airways. The combination of both is meant to be used as maintenance therapy and not as a rescue therapy for sudden symptoms. |
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On August 8, 2007 the FDA issued a "not approvable" letter to GlaxoSmithKline (GSK) on the 500/50 strength for the treatment of patients with chronic obstructive pulmonary disease (]). |
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==Side effects== |
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==Side effects== |
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The common side effects of this combination are those of its individual drugs. For instance, the use of inhaled corticosteroids is associated with ], commonly known as yeast infection or thrush. Rinsing the mouth with water after inhaling the medication decreases the risk of developing this condition. |
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{{Main|Salmeterol}} |
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The common and minor side effects of this combination are those of its individual drugs. For instance, the use of inhaled corticosteroids is associated with oral ]. |
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Whilst the use of inhaled steroids and ] (LABA) are recommended in asthma guidelines for the resulting improved symptom control,<ref name=SIGN>{{cite web | url = http://www.sign.ac.uk/guidelines/fulltext/101/index.html | title = Guideline 101: British Guideline on the Management of Asthma | publisher = British Thoracic Society & Scottish Intercollegiate Guidelines Network (SIGN) | work = | accessdate = }}</ref> concerns have been raised that salmeterol may increase the small risks of asthma deaths and this additional risk is not reduced with the additional use of inhaled steroids.<ref name="pmid16754916">{{cite journal | author = Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE | title = Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths | journal = Ann. Intern. Med. | volume = 144 | issue = 12 | pages = 904–12 | year = 2006 | month = June | pmid = 16754916 | doi = }}</ref> This seems to occur because although LABAs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.<ref name="urlAsthma deaths">{{cite web | url = http://www.news.cornell.edu/stories/June06/AsthmaDeaths.kr.html | title = Common asthma inhalers cause up to 80 percent of asthma-related deaths, Cornell and Stanford researchers assert | author = Ramanujan K | date = 2006-06-09 | format = | work = Chronicle Online | publisher = Cornell University | accessdate = 2011-08-30 }}</ref> Other side effects may include increased blood pressure, change in heart rate, an irregular heartbeat, increased risk of osteoporosis, cataracts, and glaucoma.<ref name="urlAsthma Treatment and COPD. Treatment with ADVAIR - ADVAIR.com">{{cite web | url = http://www.advair.com/ | title = Asthma Treatment and COPD. Treatment with ADVAIR | author = | work = | publisher = GlaxoSmithKline | accessdate = 2011-08-30 }}</ref> |
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While the use of inhaled steroids and long-acting beta2‑adrenergic agonists are recommended for the resulting improvement in control of symptoms of asthma,<ref name=SIGN>{{cite web | url = http://www.sign.ac.uk/guidelines/fulltext/101/index.html | title = Guideline 101: British Guideline on the Management of Asthma | publisher = British Thoracic Society & Scottish Intercollegiate Guidelines Network (SIGN) | archive-url = https://web.archive.org/web/20150418153117/http://sign.ac.uk/guidelines/fulltext/101/index.html | archive-date = 18 April 2015 | url-status = dead }}</ref> concerns have been raised that salmeterol may increase the risk of death due to asthma, and this additional risk is not reduced by the addition of inhaled steroids.<ref name="pmid16754916">{{cite journal |vauthors=Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE | title = Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths | journal = Ann. Intern. Med. | volume = 144 | issue = 12 | pages = 904–12 |date=June 2006 | pmid = 16754916 | doi = 10.7326/0003-4819-144-12-200606200-00126| doi-access = free }}</ref> Other side effects from this drug combination may include increased blood pressure, change in heart rate, an irregular heartbeat, increased risk of osteoporosis, cataracts, and glaucoma.<ref name="Advair Diskus FDA label" /> Studies have demonstrated the safety of inhaled fluticasone propionate in children. A systematic review published in 2013 found no significant adverse effect on the function of the ], growth, and bone mineral density in asthmatic children when inhaled fluticasone is used for up to three months.<ref>{{cite journal | vauthors = Muley P, Shah M, Muley A | title = Safety of inhaled fluticasone propionate therapy for pediatric asthma - a systematic review | journal = Current Drug Safety | volume = 8 | issue = 3 | pages = 186–194 | date = July 2013 | pmid = 23859431 | doi = 10.2174/15748863113089990038 }}</ref> |
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==Mechanism of action== |
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== References == |
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Fluticasone/salmeterol contains ], a synthetic corticosteroid, and ], a selective long-acting ] receptor agonist. Fluticasone works as a potent anti-inflammatory agent, inhibiting multiple cell types such as ]s, ]s, ]s, ]s, ]s, and ]s all of which contribute to inflammation, a large component in the pathogenesis of asthma. Salmeterol works by stimulating intracellular ], which acts as a ] in the production of ]. Increased cyclic AMP levels lead to a relaxation of bronchial smooth muscles. Additionally, cyclic AMP inhibits the release of mediators of immediate hypersensitivity.<ref name="Advair Diskus FDA label" /> |
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{{reflist}} |
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==Society and culture== |
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=== Legal status === |
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In January 2021, the ] (CHMP) of the ] (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Seffalair Spiromax, intended for the treatment of asthma.<ref name="Seffalair Spiromax: Pending EC decision" /> The applicant for this medicinal product is Teva B.V.<ref name="Seffalair Spiromax: Pending EC decision">{{cite web | title=Seffalair Spiromax: Pending EC decision | website=] (EMA) | date=1 February 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/seffalair-spiromax | access-date=1 February 2021 | archive-date=10 February 2021 | archive-url=https://web.archive.org/web/20210210112559/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/seffalair-spiromax | url-status=dead }}</ref> The CHMP also recommended the granting of a marketing authorization for the duplicate product BroPair Spiromax.<ref name="BroPair Spiromax: Pending EC decision">{{cite web | title=BroPair Spiromax: Pending EC decision | website=] (EMA) | date=1 February 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/bropair-spiromax | access-date=1 February 2021 | archive-date=13 April 2021 | archive-url=https://web.archive.org/web/20210413214625/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/bropair-spiromax | url-status=dead }}</ref> Seffalair Spiromax and BroPair Spiromax were both approved for medical use in the European Union in March 2021.<ref name="Seffalair Spiromax EPAR">{{cite web | title=Seffalair Spiromax EPAR | website=] (EMA) | date=25 January 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/seffalair-spiromax | access-date=23 August 2021}}</ref><ref name="BroPair Spiromax EPAR">{{cite web | title=BroPair Spiromax EPAR | website=] (EMA) | date=25 January 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/bropair-spiromax | access-date=23 August 2021}}</ref><ref>{{cite web | title=Seffalair Spiromax Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1533.htm | access-date=3 March 2023}}</ref><ref>{{cite web | title=BroPair Spiromax Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1534.htm | access-date=3 March 2023}}</ref> |
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===Generic equivalents=== |
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In January 2019, the FDA granted ] the first generic approval for Advair Diskus.<ref name="FDA PR 20190130" /> |
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===Civil settlements=== |
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In 2012, Advair was part of a larger civil settlement agreement between ] (GSK) and the United States, in which GSK agreed to pay $1.043 billion; the United States said that GSK promoted off-label uses of Advair and paid kickbacks to healthcare professionals to sell this drug, among others.<ref name=DOJ>{{cite web|title=GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data|url=https://www.justice.gov/opa/pr/glaxosmithkline-plead-guilty-and-pay-3-billion-resolve-fraud-allegations-and-failure-report|publisher=Department of Justice: Office of Public Affairs|date=2 July 2012}}</ref> |
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==References== |
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{{Reflist}} |
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{{Asthma and copd_rx}} |
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{{Asthma and copd_rx}} |
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{{GlaxoSmithKline}} |
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{{Portal bar | Medicine}} |
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{{Authority control}} |
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{{DEFAULTSORT:Fluticasone/Salmeterol}} |
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{{DEFAULTSORT:Fluticasone Salmeterol}} |
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