General Information

Barhemsys (amisulpride) is a dopamine-2 (D2) antagonist.

Barhemsys is specifically indicated for use in adults for:

prevention of postoperative nausea and vomiting (PONV), either alone or in combination with an antiemetic of a different class

treatment of PONV in patients who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis

Barhemsys is supplied as an injection for intravenous administration. The recommended adult dosage of Barhemsys and infusion rate by indication is shown below:

Prevention of PONV 5 mg as a single intravenous injection infused over 1 to 2 minutes at the time of induction of anesthesia

Treatment of PONV 10 mg as a single intravenous injection infused over 1 to 2 minutes in the event of nausea and/or vomiting after a surgical procedure

Clinical Trials

FDA Approval

Prevention of Postoperative Nausea and Vomiting

The efficacy of Barhemsys for the prevention of PONV was evaluated in two randomized, double-blind, placebo-controlled, multi-center trials in patients undergoing general anesthesia and elective surgery (Study 1 and Study 2). In Study 1, patients received monotherapy with Barhemsys; while in Study 2, patients received Barhemsys in combination with one other intravenously administered, non-dopaminergic antiemetic (ondansetron, dexamethasone or betamethasone). In both trials, patients were administered Barhemsys at the induction of anesthesia. Study 1 was conducted in the United States in 342 patients. Study 2 was conducted in the United States and Europe in 1,147 patients. The primary efficacy endpoint in both trials was Complete Response, defined as absence of any episode of emesis or use of rescue medication within the first 24 hours postoperatively. In Study 1, complete response was reached by 44% of patients receiving Barhemsys versus 33% on placebo. In Study 2, complete response was reached by 58% of patients receiving Barhemsys with another antiemetic versus 47% on placebo plus another antiemetic.

Treatment of Postoperative Nausea and Vomiting

The efficacy of Barhemsys 10 mg as a single dose was evaluated in two randomized, double-blind, placebo-controlled, multi-center trials in patients experiencing PONV after general anesthesia and elective surgery (Study 3 and Study 4). Study 3 enrolled patients who had not received prior PONV prophylaxis, whereas Study 4 included patients who had received and failed PONV prophylaxis with an antiemetic of another class. Patients were excluded if they had received a D2 receptor antagonist antiemetic. Study 3 was conducted in 369 patients and Study 4 was conducted in 465 patients. For both trials, the primary efficacy endpoint was Complete Response defined as absence of any episode of emesis or use of rescue medication within the first 24 hours after treatment (excluding emesis within the first 30 minutes). In Study 3, complete response was reached by 31% of patients receiving Barhemsys versus 22% on placebo. In Study 4, complete response was reached by 42% of patients receiving Barhemsys versus 29% on placebo.

Side Effects

Adverse reactions associated with the use of Barhemsys for the prevention of PONV may include, but are not limited to, the following:

increased blood prolactin concentrations

chills

hypokalemia

procedural hypotension

abdominal distension

The most common adverse reaction associated with the use of Barhemsys for the treatment of PONV is infusion site pain.

Mechanism of Action

Barhemsys (amisulpride) is a selective dopamine-2 (D2) and dopamine-3 (D3) receptor antagonist. D2 receptors are located in the chemoreceptor trigger zone (CTZ) and respond to the dopamine released from the nerve endings. Activation of CTZ relays stimuli to the vomiting center which is involved in emesis. Studies in multiple species indicate that D3 receptors in the area postrema also play a role in emesis. Studies conducted in ferrets have shown that amisulpride inhibits emesis caused by apomorphine, with an estimated ED50 of less than 1 mcg/kg, subcutaneously; and inhibits cisplatin-induced emesis at 2 mg/kg and morphine-induced emesis at 3 to 6 mg/kg, when given intravenously. Amisulpride has no appreciable affinity for any other receptor types apart from low affinities for 5-HT2B and 5-HT7 receptors.