The changing face of antihistamines and cardiac adverse drug reactions: a clinical perspective.
Recent times have witnessed a qualitative shift in the recognition and management of adverse drug effects. Many of them occur in organs that are unconnected to the primary target of pharmacological action. Out of these, cardiac side-effects have drawn particular attention because of their potential to cause death. Starting with the early observations on antibiotics such as macrolides, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever increasing levels of environmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban the use of this drug. Alerted by these developments, studies on a new member, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban use of this drug. Alerted by these developments, studies on a new member of non-sedating antihistamine class viz, fexofenadine, have been reviewed especially because of the structural similarity between terfenadine and fexofenadine. It is now clear that despite the closeness of its chemical structure to terfenadine fexofenadine behaves in a different manner and does not affect the electrophysiology of the heart muscle tissue, as proved by data from extensive clinical trials as well as membrane models in vitro. Interestingly, the solitary false alarm that was sounded on the drug by a group of workers in the Netherlands was later rectified by the same group. Clinically speaking, the cardiovascular safety of fexofenadine has been convincingly demonstrated at various dose levels and various time intervals, alone and together with other drugs of potential toxigenicity. All things put together, it appears reasonable to conclude that fexofenadine is free from cardiovascular ADRs of clinical significance. It could also be concluded that cardiac side-effects of antihistamines is not a class effect.
Shaikh
W A
WA
Hony Allergist, Bombay Hospital & Medical Research Centre, Mumbai 400020.
D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis; D004347:Drug Interactions; D004562:Electrocardiography; D004917:Erythromycin / Q000008:administration & dosage; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*; D016593:Terfenadine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D016171:Torsades de Pointes / Q000139:chemically induced
D006634:Histamine H1 Antagonists; D004917:Erythromycin; D016593:Terfenadine; C093230:fexofenadine