Epistaxis Risk Associated with Intranasal Corticosteroid Sprays: A Systematic Review and Meta‐analysis

Abstract

Objective 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.

Intranasal Corticosteroid Therapy: Systematic Review and Meta‐analysis of Reported Safety and Adverse Effects in Adults

“…Their meta-analysis showed that the risk of epistaxis was higher in the INCS group (RR 2.74; 95% CI, 1.88-4.00; n = 2508) as compared with placebo and no intervention. 65 The increased risk of epistaxis with the use of INCS versus placebo is also consistent with findings from Wu et al, 66 who performed a systematic review of the literature related to epistaxis and the use of INCS in patients with AR. The authors performed a meta-analysis of 72 articles, for which the overall RR was 1.48 (95% CI, 1.32-1.67; I 2 0%).…”

“…68,69 Ciclesonide hydrofluoroalkane, mometasone furoate, and fluticasone propionate have been shown to have very low systemic bioavailability, reducing the total amount of systemic corticosteroids when used in combination with inhaled steroids. 66,69 In fact, Sheth et al 70 performed 2 parallel-group double-blind RCTs comparing oral inhaled fluticasone propionate alone with oral inhaled fluticasone propionate and intranasal fluticasone propionate and did not find an increased risk of adrenal suppression. Based on this information, we suggest that thoughtful discretion be exercised in the use of concomitant nasal and inhaled corticosteroid agents.…”

Allergic rhinitis

“…INCS are not systemically absorbed; therefore, there are no systemic adverse effects. The most common INCS adverse effects are local, including nasal irritation, stinging and epistaxis 111 , and can usually be prevented by aiming the spray slightly away from the nasal septum. Long-term INCS use does not damage nasal mucosa or induce glaucoma 112 , and growth effects in children seem to be minimal 78 .…”

Pharmacology, particle deposition and drug administration techniques of intranasal corticosteroids for treating allergic rhinitis

“…Local irritation and dryness of the nose and throat and sneezing after administration are common local side effects of INCs 24,25 . All INC sprays are associated with a significantly increased risk of epistaxis compared with placebo or no intervention, according to two reviews with relative risk 1.48 (95% CI: 1.32–1.67, 72 studies) and risk ratio 2.74 (95% CI: 1.88–4.00, 2508 participants, 13 studies), respectively 26,27 . In the Cochrane review, the number needed to harm (NNH) can be extracted (NNH = 20 [95% CI: 12–49]) 27 .…”