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Wise et al.

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are alpha-adrenergic stimulatory drugs which bind to precapillary and post-capillary blood vessels resulting in vasoconstriction of nasal mucosa. 1447 The unrelated biologic targets of these medications’ mechanisms of action has been shown in RCTs to result in synergistic improvement in AR symptoms. 1448,1449 The combination of an oral antihistamine along with an oral decongestant has been shown to be more effective than placebo in controlling sneezing, nasal itching, and reducing nasal congestion in patients with AR 1044,1050,1052,1167,1450-1456 (Table IX.B.10.a). Investigations by Kaiser et al. 1450 found that both once-daily or twice-daily loratadine-pseudoephedrine were consistently superior to placebo in reducing total nasal and non-nasal symptom scores with significantly higher risk of insomnia and dry mouth in both antihistamine-decongestant arms compared to placebo. Additionally, Nathan et al. 1451 reported in 2006 that cetirizine pseudoephedrine reduced AR total symptom severity scores, asthma symptom severity scores, and improved asthma QOL scores significantly vs placebo. However, they found no significant changes in pulmonary function testing in patients receiving cetirizine pseudoephedrine or placebo and they identified similar rates of discontinuation and adverse events in both treatment arms. Oral antihistamine and oral decongestant combinations have also been shown to be more effective in controlling AR symptoms when compared to INCS or compared to treatment with either oral antihistamines or oral decongestants alone. 1050,1455,1457-1460 In 2005, Zieglmayer et al. 1449 found that the combination of cetirizine with prolonged release pseudoephedrine was significantly superior to budesonide nasal spray for improving nasal congestion after exposure to HDM, as measured by anterior rhinomanometry and nasal imaging. The combination of second-generation oral antihistamines and pseudoephedrine has been shown to significantly reduce symptom scores in patients with SAR more than either drug alone. 1050,1455,1457-1462 Additionally, the type of second-generation antihistamine and medication dosing schedule does not seem to have a significant effect on efficacy. 1463,1464 Oral decongestants have the benefit of relieving the symptoms of nasal congestion through their ability to vasoconstrict capillaries within the nasal mucosa; however, their mechanism of action can also result in unfavorable systemic adverse effects such as hypertension and urinary retention. Oral decongestants have also been linked to an increased incidence of specific birth defects including pyloric stenosis and endocardial cushion defects when utilized by pregnant women. 1465 Furthermore, decongestants are not recommended for children under 4 years of age secondary to the high risk of adverse drug events associated with utilization in this age group. 1466 Finally, oral decongestants have OTC sales restrictions secondary to their potential utilization in the production of methamphetamines. Therefore, caution must be applied in the utilization of these medications, particularly in children under 4 years and patients who are pregnant or have a preexisting cardiovascular condition, hypertension, or benign prostatic hypertrophy. Oral antihistamines are well tolerated, with a favorable risk-benefit ratio. However, caution should still be exercised as antihistamines have cardiac side effects, alter the metabolism of other medicines, and have been linked to a higher incidence of adverse events and drug-drug interactions in the elderly. 216

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