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Wise et al.

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IX.B. Pharmacotherapy

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Whether selected by patients themselves or prescribed by medical personnel, medications are the primary modality for control of allergic symptoms. There are numerous options for oral or systemic use, topical intranasal application, and alternative therapies that can be considered. It is, therefore, imperative to understand the data supporting the efficacy and appropriate use of these pharmacotherapy options. IX.B.1. Antihistamines IX.B.1.a. Oral H 1 antihistamines.: Histamine is a major mediator associated with the symptomatology of AR. Oral H 1 antihistamines block the action of histamine by binding the histamine H 1 receptor, thereby inhibiting the proinflammatory effects of histamine. Antihistamines are typically categorized by generation, such as first or second-generation agents. The older first-generation agents (ie, diphenhydramine, chlorpheniramine, brompheniramine) were lipophilic and readily crossed the blood-brain barrier. This caused unwanted side effects such as sedation, drowsiness, fatigue, and impaired concentration, and memory as well as anti-muscarinic effects. First-generation antihistamines are also inhibitors of the CYP2D6 hepatic enzymes. They may, therefore, alter the metabolism of other medicines dependent upon CYP2D6 metabolism, such as tricyclic antidepressants, some antipsychotics, β -blockers, anti-arrhythmics, and tramadol. Because of these significant side effects, in previously published guidelines and other papers, first-generation antihistamines have not been recommended for the treatment of AR. 218,1166,1167 The newer-generation agents (ie, loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine) were developed to minimize the adverse effects of earlier drugs. They are highly selective for the H 1 receptor, lipophobic, and have limited penetration across the blood-brain barrier. Practitioners should be cognizant that the concurrent use of other medicines (eg, macrolides, antifungals, or calcium-channel blockers) that inhibit CYP3A4 can result in accumulation of drug concentrations and increase the risk for side effects and toxicity. Furthermore, adverse cardiac effects (torsades de pointes, arrhythmia, and prolongation of the QT interval) were reported with astemizole and terfenadine, leading to their ultimate withdrawal from the market. 1168,1169 RCTs have established the long-term safety and efficacy of the newer generation H 1 antihistamines cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine (Table IX.B.1.a-1). Because oral antihistamines have been in use since the early 1940s, there have been many RCTs establishing oral antihistamines as an appropriate pharmacotherapy for AR. 218 As such, this section does not list every published study but summarizes the highest-grade evidence that has been published. Guidelines on AR have been published, including those by the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) 761 and the ARIA group. 1167 The AAO-HNS concluded, based upon RCTs and a preponderance of benefit over harm, a “strong recommendation” for the use of newer-generation oral H 1 antihistamines for patients with AR. 218 Similar consensus came from ARIA where a “strong recommendation” was given for oral H 1 antihistamines for AR. 1167 Furthermore, ARIA and Newer-generation antihistamines, except for cetirizine, levocetirizine, bilastine, and fexofenadine, are metabolized by the hepatic cytochrome P450 CYP3A4 system.

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