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Are All 5-HT3 Receptor Antagonists the Same?

Robert McNulty

The 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have become the cornerstone for preventing and treating chemotherapy-induced nausea and vomiting. Four 5-HT3 antagonists are commercially available in the United States, and numerous reports have been published comparing 2 or more agents. The studies ranged from randomized, double-blinded to open-label or retrospective trials; included chemotherapy-naïve and –non-naïve patients; and covered a range of doses and routes of administration with and without concomitant steroids, for preventing and treating nausea and vomiting after highly and moderately high emetogenic chemotherapy. With few exceptions, the studies uniformly show an equivalent efficacy rate and side effect profile among the various agents at equivalent doses. This article reviews the pharmacology of the class for insight into minor differences among the agents that could possibly influence drug selection for certain patients, and considers data on the absorption, half-life, metabolism, and receptor activity. Clinical trials support the claim of various guidelines that the 5-HT3 receptor antagonists are therapeutically similar in safety and efficacy, particularly because the current best practice for preventing nausea and vomiting after highly and moderately high emetogenic chemotherapy is a combination of a 5-HT3 antagonist, steroids, and aprepitant.