Cardiotoxicity of new antihistamines and cisapride

Toxicol Lett. 2002 Feb 28;127(1-3):279-84. doi: 10.1016/s0378-4274(01)00510-0.


Although the new second-generation nonsedative antihistamines terfenadine and astemizole were launched as highly selective and specific H(1)-receptor antagonists, they were later found to cause prolongation of the QT-interval and severe cardiac arrhythmias. The prolongation of the QT-interval is caused by the blockade of one or more of the cardiac potassium channels, among which the delayed rectifier I(Kr), encoded by the HERG-gene, appears to be the most significant. The potency of the prokinetic drug cisapride to block I(Kr) appears to be similar to that of terfenadine (IC(50) about 50 nmol/l). These drugs cause problems when overdosed, used in combination with inhibitors of their CYP3A4-mediated metabolism, or when given to individuals with altered drug kinetics (the aged) or patients with existing cardiac disease (congenitally long QT). Moreover, interactions with other QT-interval prolonging drugs require special attention. Active hydrophilic metabolites of the second-generation antihistaminic compounds (ebastine-carebastine, loratadine-desloratadine, terfenadine-fexofenadine, astemizole-norastemizole) are new compounds with probably reduced risk for drug interactions and cardiac toxicity.

Publication types

  • Review

MeSH terms

  • Arrhythmias, Cardiac / chemically induced
  • Astemizole / adverse effects
  • Benzimidazoles / adverse effects
  • Butyrophenones / adverse effects
  • Cetirizine / adverse effects
  • Cisapride / adverse effects*
  • Heart Diseases / chemically induced*
  • Heart Diseases / physiopathology
  • Histamine H1 Antagonists / adverse effects*
  • Humans
  • Loratadine / adverse effects
  • Piperidines / adverse effects
  • Serotonin Receptor Agonists / adverse effects*
  • Terfenadine / adverse effects
  • Triprolidine / adverse effects
  • Triprolidine / analogs & derivatives*


  • Benzimidazoles
  • Butyrophenones
  • Histamine H1 Antagonists
  • Piperidines
  • Serotonin Receptor Agonists
  • Triprolidine
  • carebastine
  • Loratadine
  • Terfenadine
  • Astemizole
  • acrivastine
  • ebastine
  • Cisapride
  • tecastemizole
  • Cetirizine