Amisulpride

Amisulpride is a Dopamine D2 receptor antagonist belonging to Antiemetic agent.

Amisulpride is a dopamine D2 receptor antagonist used in the treatment of acute and chronic schizophrenia, and in the prevention and treatment of postoperative nausea and vomiting in adults.

Following oral administration, amisulpride is rapidly absorbed with absolute bioavailability of 48%. The volume of distribution is 5.8 L/kg. Following intravenous infusion, the mean volume of distribution of amisulpride is estimated to be 127 to 144 L in surgical patients and 171 L in healthy subjects. Plasma protein binding ranges from 25% to 30% in the concentration range from 37 to 1850 ng/mL. Amisulpride undergoes minimal metabolism and its metabolites in plasma are largely undetectable. Metabolites remain largely uncharacterized. About 74% of amisulpride is excreted in urine, where 58% of the recovered dose was excreted as unchanged amisulpride. About 23% of the dose is excreted in feces, with 20% of the excreted dose as unchanged parent drug.

Amisulpride shows side effects like feeling cold or chills, injection site pain.

Amisulpride is available in the form of Intravenous solution.

Amisulpride is available in India, Canada, US, Spain, France, Malaysia, Italy, China, Germany, Japan, and Australia.

Amisulpride belongs to the Antiemetic agent acts as a Dopamine D2 receptor antagonist.

Amisulpride is an atypical antipsychotic with selective binding to D2 and D3 dopamine receptors. Antagonism of D2 receptors in the chemoreceptor trigger zone relays inhibitory stimuli to the vomiting center. Antagonism of D3 receptors in the area postrema also inhibits emesis. Has minimal affinity for 5-HT2B and 5-HT7 receptors, and no affinity for any other receptor types.

The Data of Onset and duration of action of Amisulpride is not clinically established.

Amisulpride is available in the form of Intravenous solution.

Amisulpride Intravenous solution is given single dose at the time of anesthesia induction or after surgery.

Amisulpride is an atypical anti-psychotic medicine that is used to treat symptoms like hallucinations, delusions, thought disturbances, lack of interest, apathy etc. that may be associated with mental disorders like psychoses and schizophrenia (acute and chronic).

Amisulpride is a Dopamine D2 receptor antagonist belonging to Antiemetic agent.

Amisulpride is an atypical antipsychotic with selective binding to D2 and D3 dopamine receptors. Antagonism of D2 receptors in the chemoreceptor trigger zone relays inhibitory stimuli to the vomiting center. Antagonism of D3 receptors in the area postrema also inhibits emesis. Has minimal affinity for 5-HT2B and 5-HT7 receptors, and no affinity for any other receptor types.

Amisulpride is approved for use in the following clinical indications.

• Postoperative nausea and vomiting

Amisulpride is used in the treatment of postoperative nausea and vomiting in adults.

• Postoperative nausea and vomiting

IV Dose

Prevention: 5 mg as a single dose, at the time of anesthesia induction.

Treatment: 10 mg as a single dose after surgery (in patients who did not receive prophylaxis or received an agent of a different class).

Amisulpride is available in various strengths as 5 mg/2 mL (2 mL); 10 mg/4 mL (4 mL).

Amisulpride is contraindicated in patients with

• Amisulpride is contraindicated in patients with known hypersensitivity to amisulpride.

• QT Prolongation

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.

Avoid or limit the uptake of alcohol while taking this medicine as the risk of adverse effects are increasingly high.

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.

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.

Common Adverse effects

• Insomnia, anxiety, agitation, drowsiness, weight gain, acute dystonia, parkinsonism, akathisia, tardive dyskinesia, QT prolongation, hypotension, bradycardia, GI disorders (e.g. constipation, nausea, vomiting, dry mouth), hyperglycaemia, breast pain, erectile dysfunction, amenorrhoea, gynaecomastia, galactorrhoea, allergic reactions, abnormal LFTs, seizures.

• Dopamine Agonists

Reciprocal antagonism of effects occurs between dopamine agonists (e.g., levodopa) and amisulpride. Avoid using levodopa with amisulpride.

• Drugs Prolonging the QT Interval

Amisulpride causes dose-and concentration-dependent QT prolongation. To avoid potential additive effects, avoid use of amisulpride in patients taking droperidol. ECG monitoring is recommended in patients taking other drugs known to prolong the QT interval (e.g., ondansetron).

The common side effect of Amisulpride include the following

Common

• Feeling cold or chills, Injection site pain.

Rare

• Fast, slow or irregular heartbeat, blurred vision or vision loss, Dizziness, light-headedness, or fainting, Rash, Hives, Itching, Swelling of the face, Eyes, or Mouth, Rash, Hives, Itching, Swelling of the face, Eyes, or Mouth, Wheezing, Shortness of breath.

• Pregnancy

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.

• Nursing Mothers

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.

• Pediatric Use

As FDA, the safety and effectiveness in pediatric patients have not been established.

• Geriatric Use

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.

Symptoms: Generalized convulsions, coma, motor restlessness, tachycardia, slight prolongation of the QT interval, drowsiness, sedation, hypotension, extrapyramidal symptoms.

Management: Symptomatic and supportive treatment. Institute close supervision of vital functions including continuous cardiac monitoring until patient recovers. Perform gastric lavage. In case severe extrapyramidal symptoms occur, administer anticholinergic agents.

Pharmacodynamic

Amisulpride is also an antiemetic agent that prevents and alleviates postoperative nausea and vomiting. It primarily works by blocking dopamine signaling in the chemoreceptor trigger zone, which is a brain area that relays stimuli to the vomiting center.

Pharmacokinetics

• Absorption

Following oral administration, amisulpride is rapidly absorbed with absolute bioavailability of 48%. Amisulpride has two absorption peaks, with one rapidly achieved within one-hour post-dose and a second peak occurring between three to four hours post-dose. Following oral administration of a 50 mg dose, two peak plasma concentrations were 39 ± 3 and 54 ± 4 ng/mL.

• Distribution

Following oral administration, the volume of distribution is 5.8 L/kg. Following intravenous infusion, the mean volume of distribution of amisulpride is estimated to be 127 to 144 L in surgical patients and 171 L in healthy subjects. Plasma protein binding ranges from 25% to 30% in the concentration range from 37 to 1850 ng/mL.

• Metabolism and Excretion

Amisulpride undergoes minimal metabolism and its metabolites in plasma are largely undetectable. Two identified metabolites, formed by de-ethylation and oxidation, are pharmacologically inactive and account for approximately 4% of the dose. Metabolites remain largely uncharacterized. About 74% of amisulpride is excreted in urine, where 58% of the recovered dose was excreted as unchanged amisulpride. About 23% of the dose is excreted in feces, with 20% of the excreted dose as unchanged parent drug.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209510s000lbl.pdf
• https://go.drugbank.com/drugs/DB06288
• https://www.drugs.com/pregnancy/amisulpride.html
• https://www.rxlist.com/barhemsys-drug.htm#warnings
• https://medlineplus.gov/druginfo/meds/a622062.html
• https://reference.medscape.com/drug/barhemsys-amisulpride-1000253
• https://www.mims.com/india/drug/info/amisulpride?type=full&mtype=generic