ABSTRACT
Antihistamines are among the most frequently prescribed drugs worldwide for the treatment of allergic disorders, particularly in developed countries (1). The use of first-generation antihistamines, such as diphenhydramine, hydroxyzine, chlorpheniramine, brompheniramine, and cyproheptadine, is limited by their sedative and anticholinergic properties. The second-generation, nonsedating antihistamines (e.g., terfenadine, astemizole, loratadine, cetirizine, acrivastine, mizolastine) are relatively free of these side effects; however, since the 1990s there have been some reports of syncope, torsade de pointes (TdP), and sudden death in patients taking the nonsedating antihistamines terfenadine and astemizole. As a result of these reports, regulatory approval for terfenadine and astemizole has since been suspended in many countries. The cardiac safety profile of the H1antihistamines is now being monitored by regulatory agencies in many countries. Although the occurrence of cardiotoxic effects in some patients taking terfenadine and astemizole (1-12) has led to the speculation that other nonsedating antihistamines may induce similar cardiotoxic effects, these potential adverse effects are not a class property of antihistamines, as will be discussed below.
