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Wise et al.

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• Value Judgments: Combination therapy of oral antihistamine and INCS can be helpful when managing the symptoms of nasal congestion. • Policy Level: Option. • Intervention: Combination therapy of INCS and oral antihistamine does not improve symptoms of nasal congestion over INCS use alone, and does risk the adverse effects of systemic antihistamine use. IX.B.10.c. Oral antihistamine and LTRA.: Combination therapy with LTRA and oral antihistamines in the treatment of AR has been studied in a single systematic review 1300 and multiple RCTs 1467,1472,1475-1483 (Table IX.B.10.c). Combination therapy generally improved symptoms and QOL compared to placebo in multiple RCTs. 1472,1475,1479,1482,1483 The efficacy of combination therapy compared to monotherapy with either LTRA or oral antihistamine is less clear. In the systematic review by Wilson et al., 1300 combination therapy improved patient symptoms compared to either agent as monotherapy, but there were no differences in standardized QOL measures. An RCT by Cingi et al. 1477 indicated that montelukast and fexofenadine combination therapy was superior at reducing symptoms and nasal resistance measured by rhinomanometry, compared to either fexofenadine alone or fexofenadine administered concomitantly with placebo. Several other RCTs, however, did not demonstrate a difference in symptom reduction between combination therapy and oral antihistamine monotherapy. 1475,1479,1482 Several studies also examined the relative effectiveness of combination LTRA and oral antihistamine therapy compared to INCS. Combination therapy was generally less effective than INCS monotherapy, 1472,1479,1481 although some studies did not detect a statistically significant difference. 1300,1484 The systematic review by Wilson et al. 1300 did not discern a difference in symptom reduction between LTRA and oral antihistamine combination therapy and INCS. In contrast, 3 RCTs showed that INCS resulted in improved nasal symptoms compared to treatment with the combination, 1472,1479,1481 in addition to decreased nasal mucosa eosinophil counts. 1472,1481 There is conflicting evidence on whether combination therapy is more effective than oral antihistamine alone, and there appears to be relatively consistent evidence that INCS monotherapy is more effective at nasal symptom reduction than LTRA and oral antihistamine combination therapy. Therefore, combination therapy may be an option in patients whose symptoms are incompletely controlled with oral antihistamine monotherapy, and in whom INCS are not tolerated or contraindicated. This may be particularly useful in a subset of these patients with concurrent asthma. Montelukast may be effective at simultaneously reducing AR symptoms and improving asthma control. 1341 Drug interaction and safety are an important consideration when using combination therapies. Reported adverse events for montelukast and loratadine in combination were similar to montelukast and loratadine monotherapy and placebo. 1485 The most common reported adverse events were headache (4.5%), fatigue (1.2%), and pharyngolaryngeal pain (1.2%). There were no changes of vital signs, electrocardiogram, or physical exam findings during the monitoring period. 1485 Combination LTRA and oral antihistamine therapy can be

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