Ondansetron

Ondansetron acts both centrally and peripherally to prevent and treat nausea and vomiting. Central effects are mediated by the antagonism of 5-HT3 serotonin receptors in the area postrema. The area postrema, located on the floor of the 4th ventricle, contains the "chemoreceptor trigger zone." This zone detects neurotransmitters such as serotonin, toxins, and other signals and mediates the sensation of nausea and subsequent vomiting. Ondansetron also exerts peripheral effects by acting on the vagus nerve.

Ondansetron is as effective an anti-emetic as high-dose metoclopramide but does not have the extra-pyramidal side- effects.

Ondansetron is widely used in the management of acute emesis following cancer chemotherapy.

Currently, two other selective 5HT3-receptor antagonists are licensed for use in the UK - granisetron and palonosetron - and all work by the same mechanism and have high affinity and selectivity for the 5HT3 receptor.

Unwanted effects:

• most commonly reported unwanted effects of 5HT3-receptor antagonists are constipation and headache - constipation may be severe
• other unwanted effects are generally mild and transient, including light-headedness, abdominal discomfort, fatigue and asymptomatic rises in liver transaminases
• ECG changes, including prolongation of the QTC interval, have been reported with 5HT3-receptor antagonists - therefore caution is required before prescribing these drugs to patients with pre-existing cardiac conduction defects or a history of cardiac rhythm disturbance (2) Intravenous administration has a higher risk for arrhythmias; consequently, the FDA does not recommend a single dose greater than 16 mg intravenously (3)
• a possible association between first-trimester ondansetron use and cleft palate has been reported so pregnant patients should be monitored for adverse foetal outcomes (4)

The Summary of Product Characteristics must be consulted before prescribing this drug.

Reference:

1. Hesketh PJ et al. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020 Aug 20;38(24):2782-2797.
2. Patel E, Rosemond D, Afzal A. Ondansetron induced torsades de pointes. Clin Case Rep. 2019 Aug;7(8):1557-1558
3. Fernandes FM et al. Assessment of the risk of QT-interval prolongation associated with potential drug-drug interactions in patients admitted to Intensive Care Units. Saudi Pharm J. 2019 Feb;27(2):229-234.
4. Balayla J. Comment on: Ondansetron in Pregnancy and the Risk of Congenital Malformations: A Systematic Review. J Obstet Gynaecol Can. 2018 Dec;40(12):1567-1568.