Class: Antiemetics, Miscellaneous
Chemical Name: 4-amino-N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-ethylsulfonyl-2-methoxybenzamide;4-amino-N-[[(2R)-1-ethylpyrrolidin-2-yl]methyl]-5-ethylsulfonyl-2-methoxybenzamide
Molecular Formula: C34H54N6O8S2
Amisulpride, a dopamine-2 (D2) antagonist, is an antiemetic.
Uses for Amisulpride
Amisulpride has the following uses:
Amisulpride is indicated in adults for prevention of postoperative nausea and vomiting (PONV), either alone or in combination with an antiemetic of a different class.
Amisulpride is indicated in adults for treatment of PONV in patients who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis.
Amisulpride Dosage and Administration
Amisulpride is available in the following dosage form(s) and strength(s):
Injection: 5 mg/2 mL (2.5 mg/mL) in a single-dose vial.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
The recommended dosage of amisulpride:
Prevention of PONV, either alone or in combination with another antiemetic: 5 mg as a single intravenous dose infused over 1 to 2 minutes at the time of induction of anesthesia.
Treatment of PONV: 10 mg as a single intravenous dose infused over 1 to 2 minutes in the event of nausea and/or vomiting after a surgical procedure.
Cautions for Amisulpride
Known hypersensitivity to amisulpride.
Amisulpride causes dose- and concentration-dependent prolongation of the QT interval. The recommended dosage is 5 or 10 mg as a single intravenous dose infused over 1 to 2 minutes.
Avoid amisulpride in patients with congenital long QT syndrome and in patients taking droperidol.
Electrocardiogram (ECG) monitoring is recommended in patients with pre-existing arrhythmias/cardiac conduction disorders; electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia); congestive heart failure; and in patients taking other medicinal products (e.g., ondansetron) or with other medical conditions known to prolong the QT interval.
Risk Summary: Available data with amisulpride use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, there were no adverse developmental effects observed with oral administration of amisulpride in rats and rabbits during the period of organogenesis at exposures about 43 and 645 times, respectively, the exposure delivered by the highest recommended human dose.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Animal Data: Reproduction studies of amisulpride were conducted in pregnant rats administered oral doses up to 160 mg/kg/day (43 times the exposure based on area under the curve (AUC) at the highest recommended dose of 10 mg) throughout the period of organogenesis. No adverse embryo-fetal developmental effects were observed at any dose level. Maternal animals exhibited a dose-related decrease in overall mean body weight gain. In rabbits administered amisulpride throughout the period of organogenesis, oral doses up to 210 mg/kg/day (645 times the exposure based on AUC at the highest recommended dose of 10 mg) had no adverse developmental effects on the fetus. Maternal animals exhibited reduced mean body weight gain at doses of 100 and 210 mg/kg/day and reduced food intake was observed at 210 mg/kg/day.
The pre- and post-natal developmental effects of amisulpride were assessed in rats administered oral doses of 60, 100 or 160 mg/kg/day during the periods of organogenesis and lactation. At 160 mg/kg/day (43 times the exposure based on AUC at the highest recommended dose of 10 mg), maternal animals exhibited a reduction in mean body weight gain and decrease in food intake during lactation. Amisulpride had no effect on maternal pregnancy parameters, litter survival or pup growth, development or maturation at any dose tested.
Risk Summary: Based on case reports in published literature, amisulpride is present in human milk at concentrations that are 11- to 20-fold higher than human plasma in patients taking multiple oral doses of amisulpride (200 to 400 mg/day). The estimated infant daily dose ranged from 5% to 11% of the maternal dose. There are ways to minimize drug exposure to a breastfed infant. There are no reports of adverse effects on the breastfed child and no information on the effects of amisulpride on milk production. The pharmacological action of amisulpride, a dopamine-2 (D2) receptor antagonist, may result in an increase in serum prolactin levels, which may lead to a reversible increase in maternal milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for amisulpride and any potential adverse effects on the breastfed child from amisulpride or from the underlying maternal condition.
Clinical Considerations: A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 48 hours after amisulpride administration to minimize drug exposure to a breastfed infant.
Females and Males of Reproductive Potential
In animal fertility studies, administration of repeated doses of amisulpride over a 10-day period to female rats resulted in infertility that was reversible.
Safety and effectiveness in pediatric patients have not been established.
Of the total number of patients enrolled in controlled clinical trials who received amisulpride 5 mg for prevention of PONV or 10 mg for treatment of PONV, 235 (17%) were 65 years of age and older, while 59 (4%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Amisulpride is known to be substantially excreted by the kidneys, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.
Avoid amisulpride in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m 2). The pharmacokinetics of amisulpride in patients with severe renal impairment have not been adequately studied in clinical trials. Amisulpride is known to be substantially excreted by the kidneys and patients with severe renal impairment may have increased systemic exposure and an increased risk of adverse reactions.
No dosage adjustment is necessary in patients with mild to moderate renal impairment (eGFR 30 mL/min/1.73 m 2 and above).
Common Adverse Effects
Most common adverse reactions (≥ 2%) are:
Prevention of PONV: increased blood prolactin concentrations, chills, hypokalemia, procedural hypotension, and abdominal distension.
Treatment of PONV: infusion site pain.
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Mechanism of Action
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.
Advice to Patients
Instruct patients to contact their healthcare provider immediately if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode.
Advise patients to report to their healthcare provider if they are taking drugs which prolong the QT interval.
Women may consider reducing infant exposure through pumping and discarding breastmilk for 48 hours after amisulpride administration.
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Injection, solution, for IV infusion
AHFS Drug Information. © Copyright 2021, Selected Revisions August 3, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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