The current cardiac safety situation with antihistamines

Antihistamines (H-1-receptor antagonists) are amongst the most frequently p rescribed drugs worldwide for the treatment of allergic conditions. The cli nical interest of classical 'first generation' antihistamines is currently rather limited by their anticholinergic and sedative properties. The second generation of antihistamines, so-called non-sedating antihistamines, are f ree of these side-effects. However, since the 1990s, there have been report s that certain non-sedating antihistamines, mainly terfenadine and astemizo le, might be associated with the risk of rare but severe dysrhythmias. Thes e drugs prolong the monophasic action potential and surface electrocardiogr aphic QT interval and may lead to the development of early after-depolariza tion and possibly torsades de pointes through an inhibition of potassium ch annel repolarization. Concomitant administration with drugs that inhibit th e hepatic cytochrome P-450 (imidazole antifungals, macrolide antibiotics) o r those that prolong the QT interval by the same or other mechanism (e.g. a ntiarrhythmics, antipsychotics, tricyclic antidepressants) increases their effect on the cardiac repolarization. The cardiac safety profile of newer non-sedating antihistamines requires co nfirmation. Drugs with low or no potential to block the K+ rectification ch annel (e.g. IKr channels) are likely to possess cardiac safety advantages. Other drug-related factors such as the physico-chemical properties of the a ntihistamines and its metabolic profile may also contribute to the cardiac response. Mizolastine is a new non-sedating antihistamine with antiallergic propertie s. It has a good bioavailability and a metabolism via the cytochrome P-450 oxidation accounting for only 35% of its hepatic clearance. In addition, mi zolastine displays low lipophilicity and consequently low cardiac tissue fi xation. In clinical studies, mizolastine has not shown any dose-related inc rease in QT intervals. Its clinical use has not been associated with ventri cular dysrhythmias. Thus, although the post-marketing experience with mizol astine is still limited, mizolastine offers a safe alternative for the ther apeutic management of allergic rhinitis and urticaria. However, more data a re still needed on the cardiac safety of this and other non-sedating antihi stamines.