Toxicity and side effects of ondansetron

Area of Science:

• Pharmacology
• Clinical Safety
• Oncology Supportive Care

Background:

• Ondansetron is a 5-HT3 receptor antagonist used to prevent nausea and vomiting.
• Chemotherapy-induced nausea and vomiting (CINV) is a significant challenge for cancer patients.
• Evaluating the safety profile of ondansetron in diverse patient populations is crucial.

Purpose of the Study:

• To assess the preclinical and clinical safety of ondansetron.
• To compare the safety and tolerability of ondansetron with metoclopramide in cancer patients undergoing chemotherapy.
• To investigate the safety of intravenous ondansetron in both adult and pediatric populations.

Main Methods:

• Preclinical safety evaluation in rats and dogs at high doses.
• Clinical trials involving over 2,500 adult cancer patients receiving intravenous ondansetron.
• A subgroup analysis of 209 pediatric patients receiving chemotherapy.

Main Results:

• Preclinical studies showed no end-organ toxicity; high doses caused transient subdued activity, ataxia, and convulsions.
• In adults, ondansetron (36%) had a lower incidence of adverse events than metoclopramide (50%), with less diarrhea and no extra-pyramidal symptoms.
• Pediatric patients showed a 19% incidence of adverse events; transient transaminase increases were observed in 6-8% of patients, unrelated to ondansetron dose but potentially related to cisplatin.
• Vascular occlusive events and seizure disorders were similar between ondansetron and metoclopramide.

Conclusions:

• Ondansetron demonstrates a favorable safety profile in preclinical and clinical settings.
• Ondansetron is better tolerated than metoclopramide for managing CINV in adult and pediatric cancer patients.
• Intravenous ondansetron is safe for administration to pediatric and adult patients receiving chemotherapy.