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Wise et al.

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of action, occurring as early as 15 minutes after administration. Azelastine and olopatadine were directly compared in 3 studies, with no significant difference in symptom relief between agents. 1208,1210,1211 In 2 additional studies, azelastine was compared with an experimental formulation of intranasal levocabastine, with either comparable or superior results for azelastine. 1200,1223 Intranasal antihistamine was compared to INCS in 12 studies, with the primary outcome favoring antihistamine in 2 studies, 1213,1214 corticosteroid in 3 studies, 1224,1227,1229 and showing equivalency in 7 studies. 1199,1203,1206,1233,1238,1239,1241 In 2 of the studies showing equivalency, antihistamine was superior for ocular symptoms. 1203,1239 The 3 studies showing superiority of corticosteroids were all conducted prior to 2000 and used heterogeneous nonvalidated symptom scores as primary outcomes. Intranasal antihistamine was compared to oral antihistamine monotherapy in 8 studies, with the primary outcome favoring intranasal antihistamine in 3 studies 1215,1217,1232 and showing equivalency in 5 studies. 1221,1234-1236,1240 One study included a treatment arm with oral chlorpheniramine as a positive control without intent to compare efficacy with azelastine. 1231 One study comparing azelastine spray with oral loratadine plus intranasal beclomethasone found that azelastine monotherapy was at least as effective as combination therapy. 1226 Two studies comparing intranasal azelastine plus oral antihistamine to intranasal azelastine monotherapy showed no additional benefit for combination therapy. 1220,1221 The minimum age of subjects in the included studies was generally 12 years or older. Children aged 6 to 12 years old were included in 3 studies, which in aggregate showed superiority of intranasal antihistamine to placebo in improving symptoms and QOL. 1202,1204,1228 Serious adverse effects were not reported in any study. Intranasal antihistamine was generally well tolerated, with the most commonly reported adverse effect of an unpleasant taste. One study that compared the commercially available form of azelastine with a reformulated vehicle found no difference in taste aversion. 1205 One study directly comparing olopatadine with azelastine reported better sensory attributes for olopatadine. 1210 Other reported adverse effects included somnolence, headache, epistaxis and nasal discomfort, all occurring in less than 10% of cases in any study. • Aggregate Grade of Evidence: A (Level 1b: 43 studies; Level 2b: 1 study; Table IX.B.1.c). Due to the large number of studies with high level of evidence, studies of lower evidence levels are not considered here. • Benefit: Intranasal antihistamines have a rapid onset, are more effective for nasal congestion than oral antihistamines, are more effective for ocular symptoms than INCS, and show consistent reduction in symptoms and improvement in QOL in RCTs compared to placebo. • Harm: Concerns for patient tolerance, especially due to taste. Intranasal antihistamines are less effective for congestion than INCS. • Costs: Low-to-moderate financial burden; available as prescription only.

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.