5-Hydroxytryptamine3 receptor antagonists and cardiac side effects

Expert Opin Drug Saf. 2014 Oct;13(10):1407-22. doi: 10.1517/14740338.2014.954546. Epub 2014 Sep 6.


Introduction: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients.

Areas covered: The purpose of this article is to outline the risk of cardiac adverse events (AEs) from 5-HT3-RAs, with focus on the three most commonly used, ondansetron, granisetron and palonosetron.

Expert opinion: Most of the studies analyze electrocardiogram (ECG) changes after 5-HT3-RA administrations in healthy, young adults, or in noncancer patients to treat postoperative nausea and vomiting (PONV). Only a few studies have addressed ECG changes in cancer patients treated for chemotherapy-induced nausea and vomiting (CINV). Investigations in cancer patients are essential, because these patients are older and have a higher incidence of comorbidity, than those usually included in clinical trials. Furthermore, polypharmacy is frequent and drug-drug interactions between chemotherapy and other QTc-prolonging drugs may influence the pharmacokinetics and pharmacodynamics of the 5-HT3-RAs. During the next 10 - 15 years a huge increase in the number of cancer patients is expected, primarily in the group of 65-plus-year old. Therefore it will be crucial to address the incidence of cardiac AEs in cancer patients with known heart disease receiving chemotherapy and a 5-HT3 RA for the prophylaxis of CINV.

Keywords: 5-Hydroxytryptamine3-receptor antagonist; QT prolongation; cardiac adverse events; cardiac side effects; granisetron; ondansetron; palonosetron.

Publication types

  • Review

MeSH terms

  • Aged
  • Antiemetics / adverse effects*
  • Antiemetics / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology
  • Granisetron / adverse effects
  • Granisetron / therapeutic use
  • Humans
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use
  • Long QT Syndrome / chemically induced
  • Long QT Syndrome / epidemiology
  • Nausea / chemically induced
  • Nausea / prevention & control
  • Neoplasms / drug therapy
  • Ondansetron / adverse effects
  • Ondansetron / therapeutic use
  • Palonosetron
  • Quinuclidines / adverse effects
  • Quinuclidines / therapeutic use
  • Serotonin 5-HT3 Receptor Antagonists / adverse effects*
  • Serotonin 5-HT3 Receptor Antagonists / therapeutic use
  • Vomiting / chemically induced
  • Vomiting / prevention & control


  • Antiemetics
  • Antineoplastic Agents
  • Isoquinolines
  • Quinuclidines
  • Serotonin 5-HT3 Receptor Antagonists
  • Ondansetron
  • Palonosetron
  • Granisetron