Amisulpride (Monograph)

Brand name: Barhemsys
Drug class: Dopamine Receptor Antagonists

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

Antiemetic; selective dopamine (D)₂ and D₃ antagonist.

Uses for Amisulpride

Postoperative Nausea and Vomiting

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.

Experts state amisulpride may be included in the multimodal drug therapy approach to PONV prevention and treatment.

Amisulpride Dosage and Administration

General

Patient Monitoring

ECG monitoring is recommended in patients with pre-existing arrhythmias or cardiac conduction disorders, electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, and in patients taking other drugs (e.g., ondansetron) or with other medical conditions known to prolong the QT interval.

Administration

IV Administration

Administer undiluted by IV injection.

Inspect visually for particulate matter and discoloration prior to administration; discard if particulate matter and discoloration observed.

May flush IV line before or after with water for injection, dextrose 5% injection, 0.9% sodium chloride injection, lactated Ringer’s solution, compound sodium lactate solution, or Hartmann's solution.

For prevention of PONV, administer at the time of induction of anestheia.

For treatment of PONV, administer in the event of nausea and/or vomiting after surgical procedure.

Rate of Administration

Inject over 1–2 minutes.

Dosage

Adults

Postoperative Nausea and Vomiting

Prevention

5 mg as a single IV injection over 1–2 minutes at the time of induction of anesthesia.

Treatment

10 mg as a single IV injection over 1–2 minutes in the event of nausea and/or vomiting after a surgical procedure.

Special Populations

Hepatic Impairment

No dosage recommendations at this time.

Renal Impairment

No dosage recommendations at this time.

Geriatric Patients

No dosage recommendations at this time.

Cautions for Amisulpride

Contraindications

Known hypersensitivity to amisulpride.

Warnings/Precautions

QT Prolongation

Causes dose- and concentration-dependent QT interval prolongation.

Avoid use in patients with congenital long QT syndrome and patients taking droperidol.

ECG monitoring recommended in patients with pre-existing arrhythmias or cardiac conduction disorders, electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, and in patients taking other QT-prolonging drugs (e.g., ondansetron) or with other medical conditions known to prolong the QT interval.

Specific Populations

Pregnancy

No data in pregnant women. No adverse developmental effects observed with oral administration in rats and rabbits at exposures significantly exceeding the highest recommended human dose of 10 mg.

Lactation

Present in human milk at concentrations higher than human plasma in patients taking multiple oral doses (200 to 400 mg/day, not available in the United States). Dopamine-2 receptor antagonists may increase serum prolactin levels; may lead to reversible increased maternal milk production.

Consider developmental and health benefits of breast-feeding along with mother's clinical need for amisulpride and any potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.

Consider interrupting breastfeeding and pumping and discarding breast milk for 48 hours after amisulpride administration to minimize breastfed infant drug exposure.

Females and Males of Reproductive Potential

Reversible infertility observed in female rats at exposures significantly exceeding the highest recommended human dose of 10 mg.

Pediatrics

Safety and effectiveness not established in pediatric patients.

Geriatric Use

No overall differences in safety or effectiveness observed in a limited number of elderly patients compared to younger patients.

Hepatic Impairment

Not studied in patients with hepatic impairment.

Not expected to significantly affect amisulpride systemic exposure; not metabolized by major CYP enzymes.

Renal Impairment

Severe renal impairment (eGFR < 30 mL/minute per 1.73 m² not requiring dialysis): AUC increased approximately 2-fold; peak plasma concentration not changed.

Mild or moderate renal impairment (eGFR 30–89 mL/minute per 1.73 m²): AUC increased approximately 1.3-fold; peak plasma concentration not changed.

Pharmacokinetic changes with mild, moderate, or severe renal impairment not considered clinically meaningful.

Common Adverse Effects

Common adverse reactions (≥2%) in patients receiving amisulpride for prevention of PONV: increased blood prolactin concentrations, chills, hypokalemia, procedural hypotension, and abdominal distension.

Common adverse reactions (≥2%) in patients receiving amisulpride for treatment of PONV: infusion site pain.

Drug Interactions

Clinical drug interaction studies not conducted.

Does not inhibit or induce CYP enzymes or the transporters P-gp, BCRP, OCT1, OCT2, OAT1, OAT3, OATP1B1, OATP1B3.

Not a substrate of CYP enzymes or transporters OATP1B1, OATP1B3, OAT1, OAT3 and OCT2.

Inhibits MATE1 and MATE2-K transporters.

Substrate of P-gp, BCRP, OCT1, MATE1 and MATE2-K transporters.

Drugs Affecting or Affected by Transport Systems

Substrate of and inhibits MATE1 and MATE2-K at therapeutic concentrations. Clinically significant drug interaction not expected.

Dopamine Agonists

Avoid concomitant use of levodopa with amisulpride. Reciprocal antagonism between dopamine agonists (e.g., levodopa) and dopamine-2 antagonists (e.g., amisulpride) can occur.

Drugs that Prolong QT Interval

Amisulpride causes dose- and concentration-dependent QT interval prolongation. Avoid use of amisulpride in patients taking droperidol due to risk of additive effects. ECG monitoring recommended in patients taking drugs known to prolong QT interval (e.g., ondansetron).

Amisulpride Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentration achieved at end of infusion.

Plasma concentration decreases to about 50% of peak within approximately 15 minutes.

Distribution

Protein Binding

25–30%.

Elimination

Metabolism

Metabolites not detectable in plasma; 4 metabolites (<7% of dose) identified in urine and feces.

Elimination Route

Urine: 74%; 58% unchanged.

Feces: 23%; 20% unchanged.

Half-life

Mean elimination: 4–5 hours.

Clearance

Active renal secretion via MATE1 and MATE2-K suspected.

Special Populations

Exposure increased in patients with mild, moderate, and severe renal impairment not requiring dialysis; not considered to be clinically meaningful.

No clinically significant differences observed based on age (18–90 years of age), sex, or race.

Stability

Storage

Parenteral

Injection

20–25°C; protect from light.

Once removed from carton, administer in <12 hours.

Actions

Binds to D₂/D₃ receptors; antiemetic.
No binding affinity for D₁, D₄, alpha-adrenergic, histaminergic, muscarinic, gamma-aminobutyric acid (GABA) type A, GABA type B or n-methyl-D-aspartic acid (NMDA) receptors; little or no affinity for 5-HT_2B and 5-HT₇receptors.
Inhibits hERG potassium ion channels (IC₅₀approximately 100 μM); exhibits dose- and concentration-dependent QT interval prolongation.

Advice to Patients

Advise patients to contact their healthcare provider immediately if they perceive a change in their heart rate, feel lightheaded, or have a syncopal episode.
Advise patients to report to their healthcare provider if they are taking drugs which prolong the QT interval.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Women may consider reducing infant exposure through pumping and discarding breastmilk for 48 hours after amisulpride administration.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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.