Intranasal corticosteroids (INCSs) are widely utilized for the treatment of allergic rhinitis. Epistaxis is a known adverse effect of INCSs, but it is not known if the risk of epistaxis differs among INCSs.
Data Sources
Systematic review of primary studies identified through Medline, Embase, Web of Science, PubMed Central, and Cochrane databases.
Review Methods
Systematic review was conducted according to the PRISMA standard. English-language studies were queried through February 1, 2018. The search identified randomized controlled trials of INCSs for treatment of allergic rhinitis that reported incidence of epistaxis. An itemized assessment of the risk of bias was conducted for each included study, and meta-analysis was performed of the relative risk of epistaxis for each INCS.
Results
Of 949 identified studies, 72 met the criteria for analysis. Meta-analysis demonstrated an overall relative risk of epistaxis of 1.48 (95% CI, 1.32-1.67) for all INCSs. The INCSs associated with the highest risk of epistaxis were beclomethasone hydrofluoroalkane, fluticasone furoate, mometasone furoate, and fluticasone propionate. Beclomethasone aqueous, ciclesonide hydrofluoroalkane, and ciclesonide aqueous were associated with the lowest risk of epistaxis. Conclusions about epistaxis with use of budesonide, triamcinolone, and flunisolide are limited due to the low number of studies and high heterogeneity.
Conclusions
While a differential effect on epistaxis among INCS agents is not clearly demonstrated, this meta-analysis does confirm an increased risk of epistaxis for patients using INCSs as compared with placebo for treatment of allergic rhinitis.
NathanRA.The burden of allergic rhinitis. Allergy Asthma Proc. 2007;28:3-9.
5.
CiprandiGKlersyCCirilloIMarsegliaGL.Quality of life in allergic rhinitis: relationship with clinical, immunological, and functional aspects. Clin Exp Allergy. 2007;37:1528-1535.
6.
BenningerMSAhmadNMarpleBF.The safety of intranasal steroids. Otolaryngol Head Neck Surg. 2003;129:739-750.
7.
PenagosMCompalatiETarantiniFBaena-CagnaniCEPassalacquaGCanonicaGW.Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis: meta-analysis of randomized, double-blind, placebo-controlled, clinical trials. Allergy. 2008;63:1280-1291.
8.
NaclerioR.Intranasal corticosteroids reduce ocular symptoms associated with allergic rhinitis. Otolaryngol Head Neck Surg. 2008;138:129-139.
9.
CorrenJ.Intranasal corticosteroids for allergic rhinitis: how do different agents compare?J Allergy Clin Immunol. 1999;104:s144-s149.
10.
ScaddingGErkanANChauHMaskellS.Audit of nasal steroid use and effectiveness in a rhinitis clinic. Expert Rev Pharmacoecon Outcomes Res. 2010;10:87-90.
11.
MinshallEGhaffarOCameronLet al. Assessment by nasal biopsy of long-term use of mometasone furoate aqueous nasal spray (Nasonex) in the treatment of perennial rhinitis. Otolaryngol Head Neck Surg. 1998;118:648-654.
12.
VerkerkMMBhatiaDRimmerJEarlsPSacksRHarveyRJ.Intranasal steroids and the myth of mucosal atrophy: a systematic review of original histological assessments. Am J Rhinol Allergy. 2015;29:3-18.
13.
BenningerMSHadleyJAOsguthorpeJDet al. Techniques of intranasal steroid use. Otolaryngol Head Neck Surg. 2004;130:5-24.
14.
GaneshVBanigoAMcMurranAELShakeelMRamB.Does intranasal steroid spray technique affect side effects and compliance? Results of a patient survey. J Laryngol Otol. 2017;131:991-996.
15.
HigginsJPTAltmanDGGøtzschePCet al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
16.
RatnerPHMillerSDHampelFCJMelchiorADunbarSATantrySK.Once-daily treatment with beclomethasone dipropionate nasal aerosol does not affect hypothalamic-pituitary-adrenal axis function. Ann Allergy Asthma Immunol. 2012;109:336-341.
17.
MeltzerEOJacobsRLLaForceCFKelleyCLDunbarSATantrySK.Safety and efficacy of once-daily treatment with beclomethasone dipropionate nasal aerosol in subjects with perennial allergic rhinitis. Allergy Asthma Proc. 2012;33:249-257.
18.
SmallPBarrettD.Effects of high doses of topical steroids on both ragweed and histamine-induced nasal provocation. Ann Allergy. 1991;67:520-524.
19.
RaphaelGDBergerWEPrennerBMFinnAFJrKelleyLTantrySK.Efficacy, safety, and optimal dose selection of beclomethasone dipropionate nasal aerosol for seasonal allergic rhinitis in adolescents and adults. Curr Med Res Opin. 2013;29:1329-1340.
20.
van BavelJHRatnerPHAmarNJet al. Efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol in subjects with seasonal allergic rhinitis. Allergy Asthma Proc. 2012;33:386-396.
21.
WeinsteinSFAndrewsCPShahSRet al. Long-term efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol. Allergy Asthma Proc. 2014;35:323-331.
22.
AndrewsCPMartinBGJacobsRLet al. Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy. Allergy Asthma Proc. 2009;30:128-138.
23.
FokkensWJJogiRReinartzSet al. Once daily fluticasone furoate nasal spray is effective in seasonal allergic rhinitis caused by grass pollen. Allergy Eur J Allergy Clin Immunol. 2007;62:1078-1084.
24.
GivenJCheemaADreykluftTet al. Fluticasone furoate nasal spray is effective and well tolerated for perennial allergic rhinitis in adolescents and adults. Am J Rhinol Allergy. 2010;24:444-450.
25.
GradmanJCaldwellMFWolthersOD.A 2-week, crossover study to investigate the effect of fluticasone furoate nasal spray on short-term growth in children with allergic rhinitis. Clin Ther. 2007;29:1738-1747.
26.
HanDLiuSZhangYet al. Efficacy and safety of fluticasone furoate nasal spray in Chinese adult and adolescent subjects with intermittent or persistent allergic rhinitis. Allergy Asthma Proc. 2011;32:472-481.
27.
JacobsRMartinBHampelFTolerWEllsworthAPhilpotE.Effectiveness of fluticasone furoate 110 microg 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;25:1393-1401.
28.
KaiserHBNaclerioRMGivenJTolerTNEllsworthAPhilpotEE.Fluticasone furoate nasal spray: a single treatment option for the symptoms of seasonal allergic rhinitis.[erratum appears in J Allergy Clin Immunol. 2010;125(5):1068]. J Allergy. 2007;119:1430-1437.
29.
LaforceCJourneayGEMillerSDet al. Ocular safety of fluticasone furoate nasal spray in patients with perennial allergic rhinitis: a 2-year study. Ann Allergy Asthma Immunol. 2013;111:45-50.
30.
MartinBGRatnerPHHampelFCet al. Optimal dose selection of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis in adults and adolescents. Allergy Asthma Proc. 2007;28:216-225.
31.
MeltzerEOLeeJTripathyILimJEllsworthAPhilpotE.Efficacy and safety of once-daily fluticasone furoate nasal spray in children with seasonal allergic rhinitis treated for 2 wk. Pediatr Allergy Immunol. 2009;20:279-286.
32.
NathanRABergerWYangWet al. 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.
33.
OkuboKNakashimaMMiyakeNUchidaJOkudaM.Dose-ranging study of fluticasone furoate nasal spray for Japanese patients with perennial allergic rhinitis. Curr Med Res Opin. 2008;24:3393-3403.
34.
OkuboKNakashimaMMiyakeNKomatsubaraMOkudaM.Comparison of fluticasone furoate and fluticasone propionate for the treatment of Japanese cedar pollinosis. Allergy Asthma Proc. 2009;30:84-94.
35.
PatelDRatnerPClementsDWuWFarisMPhilpotE.Lack of effect on adult and adolescent hypothalamic-pituitary-adrenal axis function with use of fluticasone furoate nasal spray. Ann Allergy Asthma Immunol. 2008;100:490-496.
36.
RosenblutABardinPGMullerBet al. Long-term safety of fluticasone furoate nasal spray in adults and adolescents with perennial allergic rhinitis. Allergy Eur J Allergy Clin Immunol. 2007;62:1071-1077.
37.
AnolikR.Clinical benefits of combination treatment with mometasone furoate nasal spray and loratadine vs monotherapy with mometasone furoate in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2008;100:264-271.
38.
AnolikRPearlmanDTeperAGatesD.Mometasone furoate improves nasal and ocular symptoms of seasonal allergic rhinitis in adolescents. Allergy Asthma Proc. 2009;30:406-412.
39.
BendeMCarrilloTVonaIda Castel-BrancoMGArhedenL.A randomized comparison of the effects of budesonide and mometasone furoate aqueous nasal sprays on nasal peak flow rate and symptoms in perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2002;88:617-623.
40.
BerkowitzRBBernsteinDILaForceCet al. Onset of action of mometasone furoate nasal spray (NASONEX) in seasonal allergic rhinitis. Allergy. 1999;54:64-69.
41.
BronskyEAAaronsonDWBerkowitzRBet al. Dose ranging study of mometasone furoate (Nasonex) in seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 1997;79:51-56.
42.
DrouinMYangWHBertrandBet al. Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients. Ann Allergy Asthma Immunol. 1996;77:153-160.
43.
GawchikSGoldsteinSPrennerBJohnA.Relief of cough and nasal symptoms associated with allergic rhinitis by mometasone furoate nasal spray. Ann Allergy Asthma Immunol. 2003;90:416-421.
44.
GraftDAaronsonDChervinskyPet al. A placebo- and active-controlled randomized trial of prophylactic treatment of seasonal allergic rhinitis with mometasone furoate aqueous nasal spray. J Allergy. 1996;98:724-731.
45.
HebertJRNolopKLutskyBN.Once-daily mometasone furoate aqueous nasal spray (Nasonex(TM)) in seasonal allergic rhinitis: an active- and placebo-controlled study. Allergy Eur J Allergy Clin Immunol. 1996;51:569-576.
46.
KunaPWasiakWJonesSKreftKZ.Comparative safety and efficacy of two formulations of mometasone nasal spray in adult seasonal allergic rhinitis. Allergy Asthma Proc. 2014;35:332-337.
47.
MakiharaSOkanoMFujiwaraTet al. Early interventional treatment with intranasal mometasone furoate in Japanese cedar/cypress pollinosis: a randomized placebo-controlled trial. Allergol Int. 2012;61:295-304.
48.
MandlMNolopKLutskyBN; 194-079 Study Group. Comparison of once daily mometasone furoate (Nasonex) and fluticasone propionate aqueous nasal sprays for the treatment of perennial rhinitis. Ann Allergy Asthma Immunol. 1997;79:370-378.
49.
MeltzerEOShekarTTeperAA.Mometasone furoate nasal spray for moderate-to-severe nasal congestion in subjects with seasonal allergic rhinitis. Allergy Asthma Proc. 2011;32:159-167.
50.
MeltzerEOBernsteinDIPrennerBMBergerWEShekarTTeperAA.Mometasone furoate nasal spray plus oxymetazoline nasal spray: short-term efficacy and safety in seasonal allergic rhinitis. Am J Rhinol Allergy. 2013;27:102-108.
51.
BanovCHWoehlerTRLaForceCFet al. Once daily intranasal fluticasone propionate is effective for perennial allergic rhinitis. Ann Allergy. 1994;73:240-246.
52.
BonerASetteLMartinatiLSharmaRRichardsD.The efficacy and tolerability of fluticasone propionate aqueous nasal spray in children with seasonal allergic rhinitis. Allergy. 1995;50:498-505.
53.
DayJCarrilloT.Comparison of the efficacy of budesonide and fluticasone propionate aqueous nasal spray for once daily treatment of perennial allergic rhinitis. J Allergy. 1998;1:902-908.
54.
DockhornRPaullBMeltzerEet al. Once- versus twice-daily fluticasone propionate aqueous nasal spray for seasonal allergic rhinitis. Am J Rhinol. 1993;7:77-83.
55.
DolovichJWongAGChodirkerWBet al. Multicenter trial of fluticasone propionate aqueous nasal spray in ragweed allergic rhinitis. Ann Allergy. 1994;73:147-153.
56.
GalantSMelamedINayakAet al. Lack of effect of fluticasone propionate aqueous nasal spray on the hypothalamic-pituitary-adrenal axis in 2- and 3-year-old patients. Pediatrics. 2003;112:96-100.
57.
GrossmanJBanovCBronskyEet al. Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis. Pediatrics. 1993;92:594-599.
58.
HampelFCRatnerPHVan BavelJet al. Double-blind, placebo-controlled study of azelastine and fluticasone in a single nasal spray delivery device. Ann Allergy Asthma Immunol. 2010;105:168-173.
59.
MunkZPearlmanDGraftDet al. Intranasal fluticasone propionate is effective and well-tolerated in adolescents with seasonal allergic rhinitis. Pediatr Asthma Allergy Immunol. 1994;8:39-46.
60.
NathanRABronskyEAFiremanPet al. Once daily fluticasone propionate aqueous nasal spray is an effective treatment for seasonal allergic rhinitis. Ann Allergy. 1991;67:332-338.
61.
PriceDBousquetJHellingsPet al. Short and long-term safety of MP29-02*: a new therapy for the treatment of allergic rhinitis. Clin Transl Allergy. 2013;3(suppl 2):O15.
62.
RatnerPHPaullBRFindlaySRet al. Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily. J Allergy. 1992;1:285-291.
63.
RatnerPHHowlandWC3rdJacobsRLet al. Relief of sinus pain and pressure with fluticasone propionate aqueous nasal spray: a placebo-controlled trial in patients with allergic rhinitis. Allergy Asthma Proc. 2002;23:259-263.
64.
RatnerPVan BavelJMoharDet al. Efficacy of daily intranasal fluticasone propionate on ocular symptoms associated with seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2015;114:141-147.
65.
van AsABronskyEADockhornRJet al. Once daily fluticasone propionate is as effective for perennial allergic rhinitis as twice daily beclomethasone diproprionate. J Allergy. 1993;91:1146-1154.
66.
BergerWEMoharDELaForceCet al. A 26-week tolerability study of ciclesonide nasal aerosol in patients with perennial allergic rhinitis. J Rhinol. 2012;26:302-307.
67.
MoharDBergerWELaForceCet al. Efficacy and tolerability study of ciclesonide nasal aerosol in patients with perennial allergic rhinitis. Allergy Asthma Proc. 2012;33:19-26.
68.
RatnerPJacobsRMoharDHuangHDesaiSYHinkleJ.Evaluation of the efficacy and safety of ciclesonide hydrofluoroalkane nasal aerosol, 80 or 160 mug once daily, for the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2010;105:471-479.
69.
RatnerPHAndrewsCMartinBet al. A study of the efficacy and safety of ciclesonide hydrofluoroalkane nasal aerosol in patients with seasonal allergic rhinitis from mountain cedar pollen. Allergy Asthma Proc. 2012;33:27-35.
70.
DaviesRJLundVJHarten-AshVJ.The effect of intranasal azelastine and beclomethasone on the symptoms and signs of nasal allergy in patients with perennial allergic rhinitis. Rhinology. 1993;31:159-164.
71.
Newson-SmithGPowellMBaehreMGarnhamSPMacMahonMT.A placebo controlled study comparing the efficacy of intranasal azelastine and beclomethasone in the treatment of seasonal allergic rhinitis. Eur Arch Otorhinolaryngol. 1997;254:236-241.
72.
PrennerBMChervinskyPHampelFCJret al. Double-strength beclomethasone dipropionate (84 μg/spray) aqueous nasal spray in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol. 1996;98:302-308.
73.
SkonerDPRachelefskyGSMeltzerEOet al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics. 2000;105:E23.
74.
BergerWENayakALanierBQet al. Efficacy and safety of once-daily ciclesonide nasal spray in children with allergic rhinitis. Pediatr Asthma Allergy Immunol. 2008;21:73-82.
75.
ChervinskyPKunjibettuSMillerDLet al. Long-term safety and efficacy of intranasal ciclesonide in adult and adolescent patients with perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2007;99:69-76.
76.
CourouxPKunjibettuSHallNWingertzahnMA.Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2009;102:62-68.
77.
KimKWeiswasserMNaveRet al. Safety of once-daily ciclesonide nasal spray in children 2 to 5 years of age with perennial allergic rhinitis. Pediatr Asthma Allergy Immunol. 2007;20:229-242.
78.
MeltzerEOKunjibettuSHallNet al. Efficacy and safety of ciclesonide, 200 μg once daily, for the treatment of perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2007;98:175-181.
79.
PatelPPatelDKunjibettuSHallNWingertzahnMA.Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis. Ear Nose Throat J. 2008;87:340-353.
80.
RatnerPHWingertzahnMAvan BavelJHet al. Effectiveness of ciclesonide nasal spray in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2006;97:657-663.
81.
RatnerPHWingertzahnMAvan BavelJHHampelFDarkenPFShahT.Efficacy and safety of ciclesonide nasal spray for the treatment of seasonal allergic rhinitis. J Allergy. 2006;118:1142-1148.
82.
DayJAlexanderMDrouinMet al. Budesonide aqueous nasal spray and pressurized metered dose inhaler in the treatment of adult patients with seasonal allergic rhinitis. J Rhinol. 1997;11:77-83.
83.
FokkensWJCserhatiEdos SantosJMLet al. Budesonide aqueous nasal spray is an effective treatment in children with perennial allergic rhinitis, with an onset of action within 12 hours. Ann Allergy Asthma Immunol. 2002;89:279-284.
84.
KobayashiRHBeaucherWNKoepkeJWet al. Triamcinolone acetonide aqueous nasal spray for the treatment of patients with perennial allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 1995;17:503-513.
85.
MunkZGrossGHampelFRatnerP.Preseasonal, once daily triamcinolone acetonide nasal aerosol for seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 1997;78:325-331.
86.
NayakASEllisMHGrossGNet al. The effects of triamcinolone acetonide aqueous nasal spray on adrenocortical function in children with allergic rhinitis. J Allergy. 1998;1:157-162.
WallaceDVDykewiczMSOppenheimerJPortnoyJMLangDM.Pharmacologic treatment of seasonal allergic rhinitis: synopsis of guidance from the 2017 Joint Task Force on Practice Parameters. Ann Intern Med. 2017;167:876-881.
89.
WaddellANPatelSKTomaAGMawAR.Intranasal steroid sprays in the treatment of rhinitis: is one better than another?J Laryngol Otol. 2003;117:843-845.
90.
BridgemanMB.Overcoming barriers to intranasal corticosteroid use in patients with uncontrolled allergic rhinitis. Integr Pharm Res Pract. 2017;6:109-119.
91.
EmanuelIABlaissMSMeltzerEOEvansPConnorA.Nasal deposition of ciclesonide nasal aerosol and mometasone aqueous nasal spray in allergic rhinitis patients. Am J Rhinol Allergy. 2014;28:117-121.
92.
BergerWEPrennerBTurnerRMeltzerEO.A patient preference and satisfaction study of ciclesonide nasal aerosol and mometasone furoate aqueous nasal spray in patients with perennial allergic rhinitis. Allergy Asthma Proc. 2013;34:542-550.
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