Cardiovascular safety of antihistamines

Abstract

Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and stimulates mucous glands in the nasal cavity. Antihistamines are the basis of symptomatic treatment in the majority of allergic diseases, especially allergic rhinitis, allergic conjunctivitis, urticaria and anaphylaxis. The cardiotoxic effects of the two withdrawn drugs, terfenadine and astemizole, were manifested by prolonged QT intervals and triggering torsades de pointes (TdP) caused by blockade of the ‘rapid’ IKr potassium channels. These phenomena, however, are not a class effect. This review deals with a new generation of antihistamine drugs in the context of QT interval prolongation risk.

A Simple ImageJ-Based Method to Measure Cardiac Rhythm in Zebrafish Embryos

“…However, it has already been withdrawn from the market due to the cardiotoxicity effect [21]. During electrocardiogram (ECG) detection in human patients, astemizole displayed long QT intervals, arrhythmia that triggered torsades de pointes, and caused sudden death [22]. We observed that embryonic zebrafish changed the cardiac rhythm within 1 hour after being treated with 5 µM astemizole by an endpoint evaluation method (see Video S1 for wild-type and Video S2 for astemizole-treated embryos).…”

BSACI guideline for the diagnosis and management of allergic and non‐allergic rhinitis (Revised Edition 2017; First edition 2007)

“…174 Ebastine and mizolastine also need to be used with caution in those with cardiac risk factors, 175 but even cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine were possibly associated with cardiac arrhythmias in a single large European pharmacovigilance study. 174 Ebastine and mizolastine also need to be used with caution in those with cardiac risk factors, 175 but even cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine were possibly associated with cardiac arrhythmias in a single large European pharmacovigilance study.…”

“…Terfenadine and astemizole were implicated in deaths from ventricular fibrillation via QT interval prolongation. 174 Ebastine and mizolastine also need to be used with caution in those with cardiac risk factors, 175 but even cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine were possibly associated with cardiac arrhythmias in a single large European pharmacovigilance study. 176 Interaction with other medications is rare other than for mizolastine with certain anti-arrhythmics, antibiotics and beta-blockers leading to an increased risk of arrhythmia.…”

Comprehensive review of cardiovascular toxicity of drugs and related agents

“…In some cases, in particular the mentioned antihistamines, inhibition of their CYP3A4‐mediated metabolism by several drugs (e.g., macrolides like erythromycin, azole antimycotics such as itrakonazole and ketokonazole) increased the plasma concentration of them with subsequent blockade of the I Kr current and markedly increased risk of torsade de pointes. A similar situation is encountered in persons with reduced metabolic capacity due to liver diseases …”

“…A similar situation is encountered in persons with reduced metabolic capacity due to liver diseases. [265][266][267][268] The relationship between QT interval prolongation and the incidence of torsade de pointes is not direct. 261,262,269 Also, QT prolongation is not a uniform condition (see Fig.…”