약물역학위해관리학회지 2017;9:11-17 ORIGINAL ARTICLE 계절성또는통년성알레르기비염을가진한국인에서시판후조사를통한플루티카손푸로에이트비강분무제 (Fluticasone Furoate Nasal Spray) 의안전성및유효성평가 글락소스미스클라인 조정은ㆍ민성준ㆍ이일섭 A Post-Marketing Surveillance to Evaluate the Safety and Effectiveness of Fluticasone Furoate Nasal Spray in Korean with Seasonal and Perennial Allergic Rhinitis Jung-Eun Cho, RN, BSN, Soung-Jun Min, MD and Yil-Seob Lee, MD, PhD GlaxoSmithKline, Seoul, Korea Objective: The aim of this study was to evaluate the safety and effectiveness of Fluticasone Furoate nasal spray in Korean patients with seasonal and perennial allergic rhinitis. Methods: A total of 3,244 patients were enrolled consecutively in 154 hospitals, by 179 physicians. Subjects who were administered Fluticasone Furoate nasal spray at least once and were monitored for safety, effectiveness were included in the analysis. Primary endpoint was the incidence of adverse events (AEs) among the Korean subjects administered Fluticasone Furoate nasal spray according to the prescribing information in real world practice. For the secondary end point, effectiveness was assessed through overall evaluation by physicians. Results: The safety assessment group was 3,218; male 1,721 (53.5%), female 1,497 (46.5%). The mean age of subjects was 32.5±20.1 years. The overall incidence of AEs was reported 2.3% (75 patients, 81 cases). The most frequent AEs reported were epistaxis (0.6%), followed by cough (0.6%) and headache (0.3%). Among 81 AE reports, 32 AEs (29 patients, 0.9%) were reported to be related with the use of Fluticasone Furoate nasal spray. There were 3 cases of serious AEs (SAEs). Most subjects (2,823 patients 92.6%) showed overall improvement of disease after treatment of Fluticasone Furoate nasal spray. Conclusion: The results suggest that Fluticasone Furoate nasal spray administered to Korean subjects according to the prescribing information was well tolerated. (JPERM 2017;9:11-17) Key Words: Fluticasone; Nasal Sprays; Drug-Related Side Effects and Adverse Reactions; Rhinitis, Allergic 서 알레르기비염은꽃가루나먼지, 동물의비듬 ( 털이나탈피 론 의일부 ) 과같은알레르기항원을흡입하였을때발생하며이러한개체에서알레르기항원은히스타민을가진비만세포와호염기성세포에결합하는면역글로불린 E 항체 접수 : 2015 년 10 월 26 일, 승인 : 2017 년 6 월 1 일연락처 : 이일섭, 04386, 서울시용산구한강대로 92 LS 용산타워글락소스미스클라인 Tel: (02) 709-4114, Fax: (02) 775-8758 E-mail: yil-seob.lee@gsk.com Correspondence to: Yil-Seob Lee, MD, PhD GlaxoSmithKline Korea, 9th Floor LS Yongsan Tower, 92 Hangang-daero, Yongsan-gu, Seoul 04386, Korea Tel: +82-2-709-4114, Fax: +82-2-775-8758 E-mail: yil-seob.lee@gsk.com
12 약물역학위해관리학회지제 9 권제 1 호, 2017 (Antibody immunoglobulin E, IgE) 의생산을유발한다. 1) 알레르기비염은전세계적으로 400만명에영향을미치고있으며산업화된국가와특히영어사용국가에서높은유병률을기록했다. 2) 알레르기비염은비교적가벼운질병으로여겨지지만삶의질에지대한영향을미치며, 건강과사회적기능간의불균형뿐아니라천식과같은동반질환의원인으로될수있다는것을고려해봤을때상당한경제적부담이발생한다. 3) 어린이의경우는학습부족, 주의력산만, 피로, 수면부족, 과민성으로수업에어려움을겪으며, 청소년알레르기질환유병률조사에서초등학생의 29.4%, 중학생의 19.8% 가지난 12개월동안알레르기비염치료력이있는것으로나타났다. 4) 알레르기비염치료의주요한목적은증상의완화이다. 비강투여스테로이드는알레르기반응초기와후기모두에항염증반응을보이는동시에콧물등코증상에효과를보이고비점막자체에직접전달되기때문에부작용의발생이적다. 5-7) 1990년대초반에소개된플루티카손푸로에이트 (fluticasone furoate) 는시장에도입될당시알레르기비염과천식에서주요한치료법으로사용되었다. 플루티카손푸로에이트는 Fluticasone Propionate의진화된형태의합성플루오르화코르티코스테로이드로세포내글루티코코르티코이드수용체와의상호작용으로항염증성반응을보인다. 8,9) In vitro에서플루티카손푸로에이트는 Fluticasone Propionate, Momentasone Furoate 등과비교하여인간글루코코르티코이드수용체에높은친화성을보였으며이는플루티카손푸로에이트가비교된다른약제들에비해세포손상에대한더효과적인보호효과를보여주고있음을의미한다. 10) 또한 In-vitro에서행한 Fluticasone Propionate와비교한전임상시험을보면 Fluticasone Propionate와는달리 30시간이상글루코코르티코이드수용체에결합되어있어장기간작용하는약제로서의가능성을보여주고있다. 11) 플루티카손푸로에이트는이중맹검통제임상연구에서위약보다어린이, 청소년, 성인모든연령층에서계절성및통년성알레르기비염증상완화효과가증명되었다. 12-20) 또한무작위, 이중맹검, 위약-통제임상연구에서계절성알레르기비염의눈증상에도플루티카손푸로에이트비강분무제가효과가있음이밝혀졌다. 21) 플루티카손푸로에이트비강분무제는성인과 2세이상의소아에서계절성알레르기성비염및통년성알레르기성비염증상에대한치료법으로허가를받았고그유효성과안전성이국외의많은임상시험에서증명되었지만, 실제임상하에서한국인알레르기비염환자를대상으로본제의사용경험은매우제한적이었기때문에한국인에게서의안전성과유효성을알아보기위해관찰적조사방법으로본연구가계획되었다. 대상및방법플루티카손푸로에이트비강분무제시판후조사는식품의약품안전처신약등의재심사규정을준수하여 2008년 5월부터 2014년 5월까지시행되었으며, 국내총 154개기관에서 179명의조사자가참여하였다. 본조사는실제치료상황에서진행된전향적, 다기관, 관찰연구로서, 신약등의재심사기준 규정에따라최종분석에 3,000명이포함될수있도록, 20% 의탈락률을고려하여총조사대상자수는 3,300명으로계획하였다. 총 3,244명의조사표가회수되었고탈락례를제외하고총 3,218명이안전성평가조사대상자로, 3,049명이유효성평가조사대상자로포함되었다. 조사대상은계절성혹은통년성알레르기비염을진단을받고허가된용법용량에따라플루티카손푸로에이트비강분무제를투여받은환자중본조사에동의한대상자로서, 본제성분에과민증의기왕력이있는환자, 최근에코수술을받았거나, 비궤양또는코외상이있는환자는조사에서제외되었다. 본조사에서는환자의인구학적정보, 과거병력, 본제처방내역, 병용약물을조사하였다. 그리고추적조사를통한유해사례의발생, 결과, 중증도및다른요인과의인과관계를조사하였다. 본제를투여후발생한모든유해사례는본제와의인과관계에상관없이기록하였고유해사례와약물과의인과관계, 중증도, 중대한유해사례여부는조사자에의학적판단에의해평가되었다. 수집된유해사례는세계보건기구유해사례용어집 (World Health Organization Adverse Reaction Terminology, WHOART 092) 에따라신체기관 (System Organ Class) 및선호단어 (Preferred Term) 로분류하여정리하였다. 본연구의일차결과변수는플루티카손푸로에이트비강분무제투여후유해사례발현율이며, 이차결과변수로플루티카손푸로에이트비강분무제투여후예상하지못한약물유해반응발현율, 중대한유해사례발현율및유효성을확인하였다. 본연구의유효성은개선, 불변, 악화, 평가불능으로평가하였으며, 재심사규정에따라조사자가대상환자의증상등을전반적으로고려하여조사자의의학적판단을기반으로평가하였으며평가시점은투여 2주후로계획되었다. 개선은증상등의호전또는유지효과등이판단되는경우, 불변은투약전과별다른변화를보이지않은경우로유지효과로도판단되지않는경우, 그리고악화는투약전보다증상이나빠지는경우로정의하였다. 중대한유해사례는사망을초래하거나생명을위협하는경우, 입원또는입원기간의연장이필요한경우, 지속적또는중대한불구나기능저하를초래하는경우, 선천적기형또는이상을초래
조정은외. 플루티카손프로에이트비강분무제의안전성및유효성평가 13 하는경우, 기타의학적으로중요한상황중어느하나에해당하는경우로정의하였다. 예상하지못한유해사례는당시허가사항과비교하여위해정도, 특이사항또는그결과등에차이가있는유해사례로정의하여분석하였다. 약물유해반응은의약품등을정상적으로투여 사용하여발생한유해하고의도하지아니한반응으로서해당의약품등과의인과관계를배제할수없는경우로정의하였다. 본조사의자료분석은 SAS 9.2 software를통해수행되었으며자료는관측수와발현율또는평균과표준편차로제시하였다. 결과 1. 조사대상자의특성본조사에참여한 3,244명의환자중계약일이전에약물을투여했거나추적조사가이루어지지않았거나본제를허가받은처방정보에따라투여받지않은등의사유로 26명을제외한 3,218명이분석의대상이되었다. 조사대상자는 남자 1,721명 (53.5%), 여자 1,497명 (46.5%), 평균나이는평균 32.5±20.1였으며, 12세를기준으로 12세미만 을소아군으로분류하여분석한결과, 조사대상자중 642명 (20.0%) 이소아군으로분류되었고, 65세를기준으로 65세이상 을노인군으로분류하여분석한결과, 216명 (6.7%) 이조사대상자에포함되어 10세미만부터 70세이상까지다양한연령이조사에포함되었다 ( 표 1). 이중알러지력이있는조사대상자는 436명 (13.5%) 이었으며, 약물투여기간은평균 32.7±26.9일로최소 1일부터최대 380일 ( 약 13개월 ) 이었으며 장기 (180일이상 ) 사용군은 19명 (0.6%) 으로조사되었다. 2. 안전성평가본조사에서확인된유해사례발현율은 2.3% 로 3,218명중 75명에게서 81건이보고되었으며, 이중본제와의인과관계를배제할수없는약물유해반응은 0.9% 로 29명에게서 32건이보고되었다. 유해사례로는비출혈 18건, 기침 17건, 두통 9건, 비염 7건, 코자극 5건, 발열 4건순이었다. 본제와의인과관계를배제할수없는약물유해반응의종류및발생률역시유해사례의내용과유사하였다. 예상하지못한유해사례는 28명에게서 30건이보고되었다. 이중 0.3%, 10 명에서보고된 12건은본제와의인과관계를배제할수없는약물유해반응이었다. 약물유해반응을세부적으로살펴본결과, 호흡기계질환 에서 비염 2건, 기침, 부비동염, 호흡곤란 각 1건, 위장관계장애 의 소화불량, 구토, 복통, 오심, 위궤양 각 1건, 방어기전장 의 모닐리아증 1건, 특수기관장애 의 미각도착증 1건이보고되었다. 본조사동안중대한유해사례는 3명에서 비염 3건이보고되었고진단받은 비염 치료를위한입원을사유로위의대상과방법에기술된정의에중대한유해사례로분류되었으며 3건모두본제와의인과관계가 가능성적음 으로평가되었다 ( 표 2). 3. 유효성평가 안전성평가대상 3,218 명중유효성평가불능, 본제 2 주 Table 1. Subject demographics Subjects, n (%) Sex Men 1,721 (53.5) Women 1,497 (46.5) Age Mean±std (year) 32.5±2.50 Median 31.0 Min-max 2.0-86.0 10 years 503 (15.6) 10-19 years 584 (18.1) 20-29 years 447 (13.9) 30-39 years 483 (15.0) 40-49 years 412 (12.8) 50-59 years 451 (14.0) 60-69 years 222 (6.9) Over 70 years 116 (3.6) Child Under 12 years 642 (20.0) Over 12 years 2,576 (80.0) Elderly Under 65 years 3,002 (93.3) Over 65 years 216 (6.7) Weight* n 2,737 Mean±std (kg) 54.3±4.3 Median 57.0 Min-max 11.5-130.0 Height* n 2,617 Mean±std (cm) 156.6±56.6 Median 162.0 Min-max 65.0-195.0 Pregnancy (only women) Yes 0 (0.0) No 1,497 (100.0) Total 1,497 (100.0) *No data: Weight 481 subjects (ND 82 subjects), Height 607 subjects (ND-no data 120 subjects, UK-unknown 120 subjects).
14 약물역학위해관리학회지제 9 권제 1 호, 2017 미만투여, 유효성평가일이본제투여 2주이전시점인조사대상자를제외한 3,049명에대하여유효성을분석하였다 ( 그림 1). 개선으로평가된조사대상자가 92.6% (2,823명 /3,049명), 불변으로평가된조사대상자는 7.3% (224명/3,049 명 ) 로조사되었고, 악화로평가된조사대상자는 0.1% (2명 /3,049명) 로조사되었다. 유효성평가기준가운데개선은유효로, 불변및악화는무효로재분류하여분석하였을때유효로평가된조사대상자는 92.6% (2,823명/3,049명) 로조사되었다. 고찰플루티카손푸로에이트비강분무제는광범위한연령층에서사용할수있으며정확한용량을제공해사용이편리한분무제이다. 약 112개국가에서이용가능하며다국가 3 상임상시험을통하여그유효성과안전성이입증되었다. 그러나국외정보에따르면전신및국소용코르티코스테로이드는투여시비출혈, 비궤양, 백색칸디다감염, 상처치유장애, 백내장과녹내장, 면역억제, 성장지연을포함한시상하부-뇌하수체-부신축에대한영향과같은이상반응을유발할가능성이있음이보고되었다. 이러한국외사례들을 Table 2. Adverse event and adverse drug reaction subjects n (%) Adverse event 95% confidence level (Lower bound, upper bound) occurrence subjects n n (%) Adverse drug reaction 95% confidence level (Lower bound, upper bound) occurrence Respiratory disease 57 (1.8) (1.3, 2.2) 58 22 (0.7) (0.4, 1.0) 23 Epitasis 18 (0.6) (0.3, 0.8) 18 11 (0.3) (0.1, 0.5) 11 Cough 17 (0.5) (0.3, 0.8) 17 1 (<0.1) (0.0, 0.1) 1 Rhinitis 7 (0.2) (0.1, 0.4) 7 2 (0.1) (0.0, 0.1) 2 Nasal irritation 5 (0.2) (0.0, 0.3) 5 4 (0.1) (0.0, 0.2) 4 Rhinopharygitis 3 (0.1) (0.0, 0.2) 3 0 (0.0) (0.0, 0.0) 0 Sore throat 2 (0.1) (0.0, 0.1) 2 0 (0.0) (0.0, 0.0) 0 Nasal pain 2 (0.1) (0.0, 0.1) 2 2 (0.1) (0.0, 0.1) 2 Sinusitis 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 URI 1 (<0.1) (0.0, 0.1) 1 0 (0.0) (0.0, 0.0) 0 Nose dryness 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Dyspnea 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Central and peripheral nervous disorder 9 (0.3) (0.1, 0.5) 9 2 (0.1) (0.0, 0.1) 2 Headache 9 (0.3) (0.1, 0.5) 9 2 (0.1) (0.0, 0.1) 2 Systemic disorder 5 (0.2) (0.0, 0.3) 5 0 (0.0) (0.0, 0.0) 0 Fever 4 (0.1) (0.0, 0.2) 4 0 (0.0) (0.0, 0.0) 0 Periorbital edema 1 (<0.1) (0.0, 0.1) 1 0 (0.0) (0.0, 0.0) 0 Gastrointestinal disorder 4 (0.1) (0.0, 0.2) 6 3 (0.1) (0.0, 0.2) 5 Dyspepsia 2 (0.1) (0.0, 0.1) 2 1 (<0.1) (0.0, 0.1) 1 Vomiting 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Abdominal pain 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Nausea 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Gastric ulcer 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Defensive mechanism disorder 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Monilasis 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Visual disorder 1 (<0.1) (0.0, 0.1) 1 0 (0.0) (0.0, 0.0) 0 Conjunctivitis 1 (<0.1) (0.0, 0.1) 1 0 (0.0) (0.0, 0.0) 0 Special sense disorder 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Taste perversion 1 (<0.1) (0.0, 0.1) 1 1 (<0.1) (0.0, 0.1) 1 Total 75 (2.3) (1.8, 2.9) 81 29 (0.9) (0.6, 1.2) 32 The incidence is 0.0000031075% in case the one subject who has adverse event is one person. Coding Dictionary: WHO-ART. n
조정은외. 플루티카손프로에이트비강분무제의안전성및유효성평가 15 Figure 1. Subjects disposition. Table 3. Adverse event categorized by age group Number and rate of occurrence, n (%) 95% confidence level (lower margin, upper margin) p-value 10 years 15 (3.0) (1.5, 4.5) 0.2789 10-19 years 10 (1.7) (0.7, 2.8) 20-29 years 11 (2.5) (1.0, 3.9) 30-39 years 12 (2.5) (1.1, 3.9) 40-49 years 4 (1.0) (0.0, 1.9) 50-59 years 12 (2.7) (1.2, 4.1) 60-69 years 9 (4.1) (1.5, 6.6) Over 70 years 2 (1.7) (0.0, 4.1) Total 75 (2.3) (1.8, 2.9) 통해유효성과이상반응가능성을확인하였지만국내다양한처방환경에서발생하는안전성자료와한국인을대상으로확인된유효성정보는제한적이어서, 안전성및유효성정보를능동적으로수집하고자본연구가계획되었다. 최소 2세부터최고 86세까지의조사대상자를대상으로한본연구에서확인된유해사례발현율은 2.3% 로, 비출혈, 기침, 비염등의호흡기계질환이가장많은비중을차지했다. 이러한양상은국외문헌및연구에서확인된유해사례와비슷하다. 중대한유해사례는 3건이보고되었는데모두비염이었으며본제와의인과관계는 가능성적음 으로나타났다. 본연구를통하여확인된유효성조사결과에서는본제투여 2주후조사자의평가결과알레르기비염증상치료는 개선 ( 차후 유효 로통합 ) 이전체의 92.6% 를차지하였다. 성별과연령모두유효성에서유의한차이를보이지않 았으며본제를투여한기간이 2개월이상일때유효성이가장높았다. 본연구는실제진료환경에서수집한정보를토대로진행되었다. 각연령대별유해사례발현율을분석한결과, 60-69세 가 9명 (4.1%) 으로가장높았으며, 해당내용은표 3 에기술하였다. 전연령층에서고르게낮은비율로유해사례가보고되었으며연령에따른유해사례발현율의차이는통계적으로유의하지않아 (p=0.2789) 특정연령층에한정된유해사례가없었다는점에서약제안전성을확인할수있다. 유효성평가측면에서는약제투여후 개선 으로평가된환자가전연령층, 성별에서 90% 이상임을확인할수있다. 다만이평가는개별진료의사의판단에근거한것으로, 진료의사의판단근거자료와각연구자간판단기준을통일시킬만할근거자료가없다는한계점이있다. 그러나이러한한계점에도본연구는플루티카손푸로에이트비강
16 약물역학위해관리학회지제 9 권제 1 호, 2017 분무제의사용후안전성및유효성에대한국내첫연구로서플루티카손푸로에이트비강분무제의단기사용의안전성및유효성평가에도움이되는자료가될것이다. ACKNOWLEDGEMENTS Funding for this study was provided by GlaxoSmithKline (113596). All listed authors are the GSK employees. CONFLICT OF INTEREST All listed authors are holding GSK stock except Jung-Eun Cho. REFERENCES 1. Hall M. Lectures on the theory and practice of medicine:now in course of delivery at the thratre of anatomy and medicine, webb-street, southwark. Lancet 1838;30:244-5. 2. Wilson AM, O Byrne PM, Parameswaran K. Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis. Am J Med 2004;116:338-44. 3. Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc 2007;28:3-9. 4. Arrighi HM, Cook CK, Redding GJ. The prevalence and impact of allergic rhinitis among teenagers. Journal of Allergy and Clinical Immunology 1996;971:430. 5. Dykewicz MS, Fineman S. Executive summary of joint task force practice parameters on diagnosis and management of rhinitis. Ann Allergy Asthma Immunol 1998;81:463-8. 6. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: Systematic review of randomised controlled trials. BMJ 1998;317:1624-9. 7. Stempel DA, Thomas M. Treatment of allergic rhinitis: an evidence-based evaluation of nasal corticosteroids versus nonsedating antihistamines. Am J Manag Care 1998;4:89-96. 8. Kariyawasam H, Scadding G. Seasonal allergic rhinitis: fluticasone propionate and fluticasone furoate therapy evaluated. J Asthma Allergy 2010;3:19-28. 9. Giavina-Bianchi P, Agondi R, Stelmach R, Cukier A, Kalil J. Fluticasone furoate nasal spray in the treatment of allergic rhinitis. Ther Clin Risk Manag 2008;4:465-72. 10. Salter M, Biggadike K, Matthews JL, West MR, Haase MV, Farrow SN, Uings IJ, Gray DW. Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease. Am J Physiol Lung Cell Mol Physiol 2007;293: L660-7. 11. Rossios C, To Y, To M, Ito M, Barnes PJ, Adcock IM, Johnson M, Ito K. Long-acting fluticasone furoate has a superior pharmacological profile to fluticasone propionate in human respiratory cells. Eur J Pharmacol 2011;670:244-51. 12. Okubo K, Nakashima M, Miyake N, Komatsubara M, Okuda M. Comparison of fluticasone furoate and fluticasone propionate for the treatment of Japanese cedar pollinosis. Allergy Asthma Proc 2009;30:84-94. 13. Fokkens WJ, Jogi R, Reinartz S, Sidorenko I, Sitkauskiene B, van Oene C, Faris MA, Ellsworth A, Caldwell MF. Once daily fluticasone furoate nasal spray is effective in seasonal allergic rhinitis caused by grass pollen. Allergy 2007;62:1078-84. 14. Martin BG, Ratner PH, Hampel FC, Andrews CP, Toler T, Wu W, Faris MA, Philpot EE. Optimal dose selection of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis in adults and adolescents. Allergy Asthma Proc 2007;28:216-25. 15. Kaiser HB, Naclerio RM, Given J, Toler TN, Ellsworth A, Philpot EE. Fluticasone furoate nasal spray: a single treatment option for the symptoms of seasonal allergic rhinitis. J Allergy Clin Immunol 2007;119:1430-7. 16. Jacobs R, Martin B, Hampel F, Toler TN, Ellsworth A, Philpot EE. Effectiveness of fluticasone furoate 110 mcg once daily in the treatment of nasal and ocular symptoms of seasonal allergic rhinitis in adults and adolescents sensitized to mountain cedar pollen. Curr Med Res Opin 2009;25:1393-401. 17. Nathan RA, Berger W, Yang W, Cheema A, Silvey M, Wu W, Philpot E. Effect of once-daily fluticasone furoate nasal spray on nasal symptoms in adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2008; 100:497-505. 18. Vasar M, Houle PA, Douglass JA, Meltzer EO, Silvey M, Wu W, Caldwell M, Philpot E. Fluticasone furoate nasal spray:effective monotherapy for symptoms of perennial allergic rhinitis in adults/adolescents. Allergy Asthma Proc 2008; 29:313-21. 19. Andrews CP, Martin BG, Jacobs RL, Mohar DE, Diaz JD, Amar NJ, Kaiser HB, Vandewalker ML, Bernstein J, Toler WT, Prillaman BA, Dalal AA, Lee LA, Philpot EE. Fluticasone furoatenasal spray is more effective than fexofenadine for nighttimesymptoms of seasonal allergy. Allergy Asthma Proc 2009;30:128-38.
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