Introduction

Amisulpride is an intravenously administered dopamine receptor 2 antagonist used for the prevention and therapy of postoperative nausea and vomiting. Amisulpride when given in single doses intravenously has not been associated with serum aminotransferase elevations or with instances of clinically apparent liver.

Background

Amisulpride (a” mi sul’ pride) is a dopamine receptor type 2 (DR2) antagonist used for the prevention and therapy of postoperative nausea and vomiting. Amisulpride blocks dopamine receptors found in the chemoreceptor trigger zone in the hypothalamus that relays stimuli to the vomiting center. In several controlled trials, administration of a single intravenous dose of amisulpride at the time of induction of anesthesia for surgery reduced nausea and vomiting during the 24 to 48 hours thereafter. Similarly, administration of a single intravenous dose after onset of nausea reduced the frequency and severity of subsequent nausea and vomiting. Amisulpride can be given orally and is approved as an oral antipsychotic medication in Europe, but not in the United States. Intravenously administered amisulpride was approved in the United States in 2020 for prevention of postoperative nausea and vomiting either alone or in combination with an antiemetic of a different class or for treatment of postoperative nausea and vomiting in patients who did not receive preventive therapy or received another class of antiemetics. Amisulpride is available in solution for intravenous administration in vials of 2 and 4 mL (2.5 mg/mL) under the brand name Barhemsys. The recommended dose for prevention is 5 mg (2 mL) and for therapy of nausea and vomiting is 10 mg (4 mL). Amisulpride given in a single intravenous dose has few adverse events. While oral amisulpride, like other dopamine receptor antagonists, has been linked to rare instances of extrapyramidal side effects and neuroleptic malignant syndrome, these severe adverse events have not been found to be associated with its use in single doses given intravenously. Amisulpride has been linked to prolongation of the QTc interval and should be avoided in patients with known prolonged QTc intervals or in patients receiving other agents that can prolong the QTc interval as well as other dopamine antagonists.

Hepatotoxicity

Intravenous single doses of amisulpride are generally well tolerated, and in multiple randomized controlled trials were not associated with rates of serum aminotransferase or bilirubin elevations above those that occurred in placebo treated subjects. While oral amisulpride has been linked to transient serum aminotransferase elevations during therapy, single intravenous doses of amisulpride have not been linked to liver enzyme elevations in excess of rates found postoperatively. Since its approval and more widespread use, amisulpride has not been implicated in cases of clinically apparent liver injury.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

The possible mechanism of liver injury from amisulpride is not known, but liver test abnormalities can occur with prolonged oral dosing. Oral amisulpride can also cause extrapyramidal symptoms and neuroleptic malignant syndrome, probably due to excessive dopamine receptor antagonism. Amisulpride is not metabolized to a great extent by the liver, is not a substrate of the P450 system, and has no interaction with CYP enzyme activities.

Drug Class: Gastrointestinal Agents, Antiemetic Agents