amisulpride (Rx)

1-10%

Prevention of PONV

• Increased blood prolactin (5%)
• Chills (4%)
• Hypokalemia (4%)
• Procedural hypotension (3%)
• Abdominal distension (2%)

Treatment of PONV

• Infusion site pain (6%)

Postmarketing Reports

Blood and lymphatic system disorders: Agranulocytosis

Cardiac disorders: Bradycardia, torsades de pointes, ventricular tachycardia, prolonged QT by ECG

General disorders: Neuroleptic malignant syndrome

Immune system disorders: Angioedema, hypersensitivity, urticaria

Hepatic disorders: Increased hepatic enzymes

Nervous system disorders: Agitation, anxiety, dystonia, extrapyramidal disorder, seizure

Psychiatric disorders: Confusional state, insomnia, somnolence

Vascular disorders: Hypotension

Contraindications

Hypersensitivity

Cautions

QT prolongation

• May causes dose- and concentration-dependent prolongation of the QT interval
• Avoid in patients with congenital long QT syndrome and in patients taking droperidol
• ECG monitoring recommended with preexisting arrhythmias/cardiac conduction disorders, electrolyte abnormalities (eg, hypokalemia, hypomagnesemia), congestive heart failure, and in patients taking other drugs (eg, ondansetron) or with other medical conditions known to prolong the QT interval

Drug interactions overview

• Amisulpride inhibits MATE1 and MATE2-K transporters
• Amisulpride is a substrate for P-gp, BCRP, OCT1, MATE1, and MATE2-K

• Dopamine agonists

  • Reciprocal antagonism of effects occurs between dopamine agonists (eg, levodopa)
  • Avoid use

• Drugs prolonging the QT interval

  • Amisulpride causes dose- and concentration-dependent QT prolongation
  • Avoid use with droperidol
  • ECG monitoring recommended if coadministered with other drugs known to prolong QT interval (eg, ondansetron)

Pregnancy

Insufficient data available regarding use in pregnant women to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Infertility

• In animal fertility studies, administration of repeated doses of amisulpride over a 10­-day period to female rats resulted in infertility that was reversible

Lactation

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 (200-400 mg/day)

There are no reports of adverse effects on breastfed children and no information on effects of amisulpride on milk production

May consider interrupting breastfeeding and pumping and discarding breast milk for 48 hr after administration to minimize drug exposure to a breastfed infant

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

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

Absorption

Peak plasma concentration

• Healthy subjects: 200 ng/mL (5 mg); 451 ng/mL (10 mg)
• Patients: 58-64 ng/mL (5 mg); 446 ng/mL (10 mg)

AUC

• Healthy subjects: 154 ng⋅hr/mL (5 mg); 136 ng⋅hr/mL (10 mg)
• Patients: 204-260 ng⋅hr/mL (5 mg); 401 ng⋅hr/mL (10 mg)

Distribution

Vd: 127-144 L (surgical patients); 171 L (healthy subjects)

Protein bound: 25-30%

Metabolism

No metabolites were detectable in plasma while 4 metabolites were identified in urine and feces

Each metabolite accounts for <7% of the dose

In vitro amisulpride is not metabolized by major cytochrome P450 enzymes

Elimination

Half-life: ~ 4-5 hr

Clearance: 20.6 hr (surgical patients); 24.1 L/hr (healthy subjects)

Renal clearance: 20.5 L/hr (healthy subjects)

Excretion: Urine (74% [58% unchanged]), feces (23% [20% unchanged])

IV Compatibilities

Sterile water for injection

Dextrose 5% (D5W)

0.9% NaCl

IV Administration

Dilution not required

Infuse over 1-2 min

May flush IV line before or after administration with sterile water for injection, D5W, or 0.9% NaCl

Storage

Protect from light

Unopened vials: Store at 20-25ºC (68-77ºF)

Open vials: Administer within 12 hr of removal of the vial from the protective carton