{"id":"amisulpride","rwe":[],"_fda":{"id":"b4cf2d39-67e7-459b-add4-5454b1029c14","set_id":"ab23bc6e-b6a8-165f-e053-2a95a90ab144","openfda":{"nui":["N0000175800","N0000175799"],"unii":["8110R61I4U"],"route":["INTRAVENOUS"],"rxcui":["2284232","2284237","2467148","2467149"],"spl_id":["b4cf2d39-67e7-459b-add4-5454b1029c14"],"brand_name":["Barhemsys"],"spl_set_id":["ab23bc6e-b6a8-165f-e053-2a95a90ab144"],"package_ndc":["71390-125-21","71390-125-20","71390-125-51","71390-125-50"],"product_ndc":["71390-125"],"generic_name":["AMISULPRIDE"],"product_type":["HUMAN PRESCRIPTION DRUG"],"substance_name":["AMISULPRIDE"],"pharm_class_epc":["Dopamine-2 Receptor Antagonist [EPC]"],"pharm_class_moa":["Dopamine D2 Antagonists [MoA]"],"manufacturer_name":["Acacia Pharma Ltd"],"application_number":["NDA209510"],"is_original_packager":[true]},"version":"7","pregnancy":["8.1 Pregnancy 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 (see Data ) . 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. Data 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."],"overdosage":["10 OVERDOSAGE Doses of oral amisulpride (BARHEMSYS is not approved for oral dosing) above 1200 mg/day have been associated with adverse reactions related to dopamine-2 (D 2 ) antagonism, in particular: cardiovascular adverse reactions (e.g., prolongation of the QT interval, torsades de pointes, bradycardia and hypotension) [see Warnings and Precautions (5.1) ] . neuropsychiatric adverse reactions (e.g., sedation, coma, seizures, and dystonic and extrapyramidal reactions). There is no specific antidote for amisulpride overdose. Management includes cardiac monitoring and treatment of severe extrapyramidal symptoms. Since amisulpride is weakly dialyzed, hemodialysis should not be used to eliminate the drug."],"description":["11 DESCRIPTION The active ingredient of BARHEMSYS is amisulpride, a dopamine-2 (D 2 ) receptor antagonist. Its chemical name is 4-Amino- N -[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)- o -anisamide. It has the following chemical structure: (racemic) The empirical formula is C 17 H 27 N 3 O 4 S representing a molecular weight of 369.48. Amisulpride is a white or almost white crystalline powder. It is practically insoluble in water, sparingly soluble in ethanol and freely soluble in methylene chloride, and has a melting point of around 126°C. The compound is racemic and shows no optical rotation and is not hygroscopic. No other polymorphs of amisulpride have been reported. BARHEMSYS (amisulpride) injection is a clear, colorless, nonpyrogenic, sterile solution formulation of amisulpride 5 mg/2 mL (2.5 mg/mL) or 10 mg/4 mL (2.5 mg/mL) for intravenous infusion presented in a single-dose vial. It has a pH of approximately 5.0 and the osmolality of the product is between 250 and 330 mOsmol/kg. Each 2 mL vial of BARHEMSYS contains 5 mg of amisulpride; 18.7 mg of citric acid monohydrate USP; 3.6 mg of sodium chloride USP; 32.64 mg of trisodium citrate dihydrate; hydrochloric acid NF and sodium hydroxide NF as needed to adjust the pH (4.75 to 5.25); and Water for Injection USP to make up to volume. Each 4 mL vial of BARHEMSYS contains 10 mg of amisulpride; 37.4 mg of citric acid monohydrate USP; 7.2 mg of sodium chloride USP; 65.3 mg of trisodium citrate dihydrate; hydrochloric acid NF and sodium hydroxide NF as needed to adjust the pH (4.75 to 5.25); and Water for Injection USP to make up to volume. Chemical Structure"],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING BARHEMSYS (amisulpride) injection is supplied as follows: NDC 71390-125-20: Package of 10 cartons. Each carton (NDC 71390-125-21) contains one single-dose vial of clear, colorless, sterile solution of BARHEMSYS (amisulpride) injection, 5 mg in 2 mL (2.5 mg/mL). NDC 71390-125-50: Package of 10 cartons. Each carton (NDC 71390-125-51) contains one single-dose vial of clear, colorless, sterile solution of BARHEMSYS (amisulpride) injection, 10 mg in 4 mL (2.5 mg/mL). Store vials at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Protect from light. Administer BARHEMSYS within 12 hours after the vial is removed from the protective carton [see Dosage and Administration (2.2) ] ."],"geriatric_use":["8.5 Geriatric Use Of the total number of patients enrolled in controlled clinical trials who received BARHEMSYS 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."],"pediatric_use":["8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established."],"effective_time":"20250609","clinical_studies":["14 CLINICAL STUDIES 14.1 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 (NCT01991860), patients received monotherapy with BARHEMSYS; while in Study 2 (NCT02337062), 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. The mean age was 54 years (range 21 to 88 years); 65% female; 87% White/Caucasian, 12% Black, and 1% Asian race. The treatment groups were similarly matched in terms of risk for PONV with 30% of patients having two risk factors, 47% of patients having three risk factors and 23% of patients having four risk factors. Study 2 was conducted in the United States and Europe in 1,147 patients. The mean age was 49 years (range 18 to 91 years); 97% female; 75% White/Caucasian, 9% Black, 1% Asian, and 14% of unreported race. The treatment groups were similarly matched in terms of risk for PONV with 56% of patients having three risk factors and 43% of patients having four risk factors. 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. Results for both trials are shown in Table 3. Table 3. Complete Response Rates in Adult Patients for the Prevention of PONV Within 24 Hours After End of Surgery in Studies 1 and 2 Study 1 Study 2 BARHEMSYS 5 mg (n=176) Placebo (n=166) BARHEMSYS 5 mg with Another Antiemetic (n=572) Placebo with Another Antiemetic (n=575) Complete Response 78 (44%) 54 (33%) 330 (58%) 268 (47%) Difference (95% CI) Unadjusted, nominal 95% confidence interval 12% (2%, 22%) 11% (5%, 17%) 14.2 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 (NCT02449291) enrolled patients who had not received prior PONV prophylaxis, whereas Study 4 (NCT02646566) included patients who had received and failed PONV prophylaxis with an antiemetic of another class. Patients were excluded if they had received a D 2 receptor antagonist antiemetic. Study 3 was conducted in 369 patients (mean age 47 years, range 19 to 82 years; 76% female; 82% White/Caucasian, 8% Black, 2% Asian, and 8% of unreported race). Most of the patients had either two risk factors (36%) or three risk factors (53%) for PONV and these percentages were similar between treatment groups. Study 4 was conducted in 465 patients (mean age 46 years, range 18 to 85 years; 90% female; 82% White/Caucasian, 9% Black, 3% Asian, and 6% of unreported race). Patients had received prior PONV prophylaxis with one or more non-dopaminergic antiemetics: a 5-HT 3 -antagonist in 77%, dexamethasone in 65% and another antiemetic class in 10%. Most of the patients had either three risk factors (43%) or four risk factors (51%) for PONV and these percentages were similar between treatment groups. 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). BARHEMSYS Complete Response in both studies is shown in Table 4. Table 4. Complete Response Rates in Adult Patients for the Treatment of PONV Within 24 Hours After Treatment Excluding emesis within the first 30 minutes in Studies 3 and 4 Study 3 (no prophylaxis) Study 4 (prior prophylaxis) Received prior PONV prophylaxis with one or more non-dopaminergic antiemetics: a 5-HT 3 -antagonist in 77%, dexamethasone in 65% and another antiemetic class in 10% BARHEMSYS 10 mg (n=188) Placebo (n=181) BARHEMSYS 10 mg (n=230) Placebo (n=235) Complete Response 59 (31%) 39 (22%) 96 (42%) 67 (29%) Difference (95% CI) Unadjusted, nominal 95% confidence interval 10% (1%, 19%) 13% (5%, 22%)"],"pharmacodynamics":["12.2 Pharmacodynamics Cardiac Electrophysiology A significant exposure-response relationship was identified between amisulpride concentration and ΔΔQTcF. In 40 healthy Caucasian and Japanese subjects, the maximum mean difference (95% upper confidence bound) in QTcF from placebo after baseline-correction (ΔΔQTcF) was 5.0 (7.1) milliseconds after a 2-minute intravenous infusion of 5 mg BARHEMSYS and 23.4 (25.5) milliseconds after an 8-minute intravenous infusion of 40 mg BARHEMSYS [see Warnings and Precautions (5.1) ] . The recommended infusion rate is 1 to 2 minutes for 5 mg or 10 mg of BARHEMSYS [see Dosage and Administration (2.1) ]."],"pharmacokinetics":["12.3 Pharmacokinetics After an intravenous infusion, the peak plasma concentration of amisulpride is achieved at the end of the infusion period and the plasma concentration decreases to about 50% of the peak value within approximately 15 minutes. The AUC (0-∞) increases dose-proportionally in the dose range from 5 mg to 40 mg (4-times the maximum recommended dose). The following mean pharmacokinetic parameters of amisulpride were observed following a single 5 or 10 mg intravenous dose in adult healthy subjects and surgical patients. Table 2. Summary of Key Pharmacokinetic Parameters of Amisulpride from Clinical Studies Single Dose Infusion Duration (minutes) Number of Subjects Mean (SD) Peak Plasma Concentration (ng/mL) AUC (0-∞) (ng∙h/mL) Healthy Subjects 5 mg 2 39 200 (139) 154 (30) Healthy Subjects 10 mg 1 29 451 (230) 136 (28) AUC (0-2 hr) Patients 5 mg 1 to 2 26 Patients in a clinical trial for prophylaxis of PONV 161 (58) 260 (65) 27 Patients in clinical trials for treatment of PONV 127 (64) 204 (94) Patients 10 mg 1 to 2 31 285 (446) 401 (149) Distribution 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. Amisulpride distributes into erythrocytes. Plasma protein binding is 25% to 30% in the concentration range from 37 to 1850 ng/mL. Elimination The mean elimination half-life is approximately 4 to 5 hours and similar between healthy subjects and surgical patients. Population pharmacokinetic analysis estimated that the plasma clearance of amisulpride is 20.6 L/h in surgical patients and 24.1 L/h in healthy subjects. Metabolism In a mass balance study, no metabolites were detectable in plasma while four metabolites were identified in urine and feces. Each metabolite accounts for less than 7% of the dose. In vitro amisulpride is not metabolized by major cytochrome P450 enzymes. Excretion After intravenous administration of amisulpride, 74% and 23% of the administered dose was recovered in urine and feces, respectively. 58% and 20% of the dose was excreted as unchanged amisulpride in urine and feces, respectively. Renal clearance was estimated to be 20.5 L/hr (342 mL/min) in healthy subjects suggesting that amisulpride undergoes active renal secretion. Specific Populations Age, Sex, and Racial Groups No clinically significant effect on the pharmacokinetics of amisulpride was observed based on age (18 to 90 years), sex, or race. Patients with Renal Impairment In subjects with severe renal impairment (eGFR < 30 mL/min/1.73 m 2 ) and no requirement for dialysis, the C max of amisulpride after a single 10 mg intravenous dose was not greater than that in healthy subjects with normal renal function, and the AUC (0-∞) was approximately twice as high. In surgical patients with mild or moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m 2 ), the C max of amisulpride following a single 5 mg or 10 mg intravenous dose was not significantly different and the AUC (0-∞) of amisulpride increased about 1.3-fold compared to patients with normal renal function. The changes in the pharmacokinetics of amisulpride following a single 5 mg or 10 mg intravenous dose in subjects or patients with mild, moderate, or severe renal impairment compared to subjects or patients with normal renal function are not considered to be clinically meaningful. Drug Interaction Studies No clinical drug interaction trials have been conducted with BARHEMSYS. In Vitro Studies Cytochrome P450-Related Metabolism In vitro , amisulpride did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, or CYP3A4, or induce CYP1A2, CYP2C9, CYP2C19, or CYP3A4. In vitro , amisulpride was not a substrate of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Transporters Amisulpride inhibits MATE1 and MATE2-K transporters. Amisulpride does not inhibit P-gp, BCRP, OCT1, OCT2, OAT1, OAT3, OATP1B1, OATP1B3 at therapeutic concentrations. Amisulpride is a substrate for P-gp, BCRP, OCT1, MATE1 and MATE2-K, but not a substrate for OATP1B1, OATP1B3, OAT1, OAT3 and OCT2."],"adverse_reactions":["6 ADVERSE REACTIONS Most common adverse reactions (≥ 2%) are: Prevention of PONV : increased blood prolactin concentrations, chills, hypokalemia, procedural hypotension, and abdominal distension. ( 6.1 ) Treatment of PONV : infusion site pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acacia Pharma at 1-877-357-9237 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to BARHEMSYS in 1,166 patients treated in placebo-controlled trials. 748 of these patients received a dose of 5 mg for prevention of PONV (of whom 572 received another antiemetic concomitantly) and 418 patients received 10 mg for treatment of PONV [see Clinical Studies (14.1 , 14.2) ] . The mean age of the population was 49 years (range 18 to 91 years), 87% female, 80% White/Caucasian, 9% Black, and 1% Asian. Prevention of PONV Common adverse reactions reported in at least 2% of adult patients who received BARHEMSYS 5 mg and at a higher rate than placebo in Studies 1 and 2 for the prevention of PONV are shown in Table 1. Table 1. Common Adverse Reactions Reported in at least 2% of patients treated with BARHEMSYS and at a higher rate than placebo in Adult Patients in Studies 1 and 2 of BARHEMSYS for Prevention of PONV BARHEMSYS 5 mg Placebo N=748 N=741 Chills 4% 3% Hypokalemia 4% 2% Procedural hypotension 3% 2% Abdominal distension 2% 1% Serum prolactin concentrations were measured in Study 1 where 5% (9/176) of BARHEMSYS-treated patients vs 1% (1/166) of placebo-treated patients had increased blood prolactin reported as an adverse reaction. Serum prolactin concentrations increased from a mean of 10 ng/mL at baseline to 32 ng/mL after BARHEMSYS treatment in 112 females (upper limit of normal 29 ng/mL) and from 10 ng/mL to 19 ng/mL in 61 males (upper limit of normal 18 ng/mL). No clinical consequences due to elevated prolactin levels were reported. Treatment of PONV The most common adverse reaction, reported in at least 2% of adult patients who received BARHEMSYS 10 mg (N=418) and at a higher rate than placebo (N=416), in clinical trials for the treatment of PONV (Studies 3 and 4) was infusion site pain (BARHEMSYS 6%; placebo 4%). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval chronic oral use of amisulpride outside of the United States (BARHEMSYS is not approved for oral dosing or chronic use). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders : agranulocytosis Cardiac disorders : bradycardia, torsades de pointes, ventricular tachycardia, prolonged QT by electrocardiogram 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":["4 CONTRAINDICATIONS BARHEMSYS is contraindicated in patients with known hypersensitivity to amisulpride [see Adverse Reactions (6.2) ] . Known hypersensitivity to amisulpride. ( 4 )"],"description_table":["
(racemic)
"],"drug_interactions":["7 DRUG INTERACTIONS 7.1 Dopamine Agonists Reciprocal antagonism of effects occurs between dopamine agonists (e.g., levodopa) and BARHEMSYS. Avoid using levodopa with BARHEMSYS. 7.2 Drugs Prolonging the QT Interval BARHEMSYS causes dose- and concentration-dependent QT prolongation [see Clinical Pharmacology (12.2) ] . To avoid potential additive effects, avoid use of BARHEMSYS in patients taking droperidol. ECG monitoring is recommended in patients taking other drugs known to prolong the QT interval (e.g., ondansetron) [see Warnings and Precautions (5.1) ] ."],"mechanism_of_action":["12.1 Mechanism of Action Amisulpride is a selective dopamine-2 (D 2 ) and dopamine-3 (D 3 ) receptor antagonist. D 2 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 D 3 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 ED 50 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-HT 2B and 5-HT 7 receptors."],"storage_and_handling":["Store vials at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Protect from light. Administer BARHEMSYS within 12 hours after the vial is removed from the protective carton [see Dosage and Administration (2.2) ] ."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Amisulpride is a selective dopamine-2 (D 2 ) and dopamine-3 (D 3 ) receptor antagonist. D 2 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 D 3 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 ED 50 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-HT 2B and 5-HT 7 receptors. 12.2 Pharmacodynamics Cardiac Electrophysiology A significant exposure-response relationship was identified between amisulpride concentration and ΔΔQTcF. In 40 healthy Caucasian and Japanese subjects, the maximum mean difference (95% upper confidence bound) in QTcF from placebo after baseline-correction (ΔΔQTcF) was 5.0 (7.1) milliseconds after a 2-minute intravenous infusion of 5 mg BARHEMSYS and 23.4 (25.5) milliseconds after an 8-minute intravenous infusion of 40 mg BARHEMSYS [see Warnings and Precautions (5.1) ] . The recommended infusion rate is 1 to 2 minutes for 5 mg or 10 mg of BARHEMSYS [see Dosage and Administration (2.1) ]. 12.3 Pharmacokinetics After an intravenous infusion, the peak plasma concentration of amisulpride is achieved at the end of the infusion period and the plasma concentration decreases to about 50% of the peak value within approximately 15 minutes. The AUC (0-∞) increases dose-proportionally in the dose range from 5 mg to 40 mg (4-times the maximum recommended dose). The following mean pharmacokinetic parameters of amisulpride were observed following a single 5 or 10 mg intravenous dose in adult healthy subjects and surgical patients. Table 2. Summary of Key Pharmacokinetic Parameters of Amisulpride from Clinical Studies Single Dose Infusion Duration (minutes) Number of Subjects Mean (SD) Peak Plasma Concentration (ng/mL) AUC (0-∞) (ng∙h/mL) Healthy Subjects 5 mg 2 39 200 (139) 154 (30) Healthy Subjects 10 mg 1 29 451 (230) 136 (28) AUC (0-2 hr) Patients 5 mg 1 to 2 26 Patients in a clinical trial for prophylaxis of PONV 161 (58) 260 (65) 27 Patients in clinical trials for treatment of PONV 127 (64) 204 (94) Patients 10 mg 1 to 2 31 285 (446) 401 (149) Distribution 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. Amisulpride distributes into erythrocytes. Plasma protein binding is 25% to 30% in the concentration range from 37 to 1850 ng/mL. Elimination The mean elimination half-life is approximately 4 to 5 hours and similar between healthy subjects and surgical patients. Population pharmacokinetic analysis estimated that the plasma clearance of amisulpride is 20.6 L/h in surgical patients and 24.1 L/h in healthy subjects. Metabolism In a mass balance study, no metabolites were detectable in plasma while four metabolites were identified in urine and feces. Each metabolite accounts for less than 7% of the dose. In vitro amisulpride is not metabolized by major cytochrome P450 enzymes. Excretion After intravenous administration of amisulpride, 74% and 23% of the administered dose was recovered in urine and feces, respectively. 58% and 20% of the dose was excreted as unchanged amisulpride in urine and feces, respectively. Renal clearance was estimated to be 20.5 L/hr (342 mL/min) in healthy subjects suggesting that amisulpride undergoes active renal secretion. Specific Populations Age, Sex, and Racial Groups No clinically significant effect on the pharmacokinetics of amisulpride was observed based on age (18 to 90 years), sex, or race. Patients with Renal Impairment In subjects with severe renal impairment (eGFR < 30 mL/min/1.73 m 2 ) and no requirement for dialysis, the C max of amisulpride after a single 10 mg intravenous dose was not greater than that in healthy subjects with normal renal function, and the AUC (0-∞) was approximately twice as high. In surgical patients with mild or moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m 2 ), the C max of amisulpride following a single 5 mg or 10 mg intravenous dose was not significantly different and the AUC (0-∞) of amisulpride increased about 1.3-fold compared to patients with normal renal function. The changes in the pharmacokinetics of amisulpride following a single 5 mg or 10 mg intravenous dose in subjects or patients with mild, moderate, or severe renal impairment compared to subjects or patients with normal renal function are not considered to be clinically meaningful. Drug Interaction Studies No clinical drug interaction trials have been conducted with BARHEMSYS. In Vitro Studies Cytochrome P450-Related Metabolism In vitro , amisulpride did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, or CYP3A4, or induce CYP1A2, CYP2C9, CYP2C19, or CYP3A4. In vitro , amisulpride was not a substrate of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Transporters Amisulpride inhibits MATE1 and MATE2-K transporters. Amisulpride does not inhibit P-gp, BCRP, OCT1, OCT2, OAT1, OAT3, OATP1B1, OATP1B3 at therapeutic concentrations. Amisulpride is a substrate for P-gp, BCRP, OCT1, MATE1 and MATE2-K, but not a substrate for OATP1B1, OATP1B3, OAT1, OAT3 and OCT2."],"indications_and_usage":["1 INDICATIONS AND USAGE BARHEMSYS ® is indicated 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 a dopamine-2 (D 2 ) antagonist indicated in adults for: Prevention of postoperative nausea and vomiting (PONV), either alone or in combination with an antiemetic of a different class. ( 1 ) Treatment of PONV in patients who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis. ( 1 )"],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS QT Prolongation : Occurs in a dose- and concentration-dependent manner. Avoid use in patients with congenital long QT syndrome and in patients taking droperidol. 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. ( 5.1 , 7.2 ) 5.1 QT Prolongation BARHEMSYS causes dose- and concentration-dependent prolongation of the QT interval [see Clinical Pharmacology (12.2) ] . The recommended dosage is 5 or 10 mg as a single intravenous dose infused over 1 to 2 minutes [see Dosage and Administration (2.1) ] . Avoid use 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 [see Drug Interactions (7.2) ] ."],"clinical_studies_table":["
Table 3. Complete Response Rates in Adult Patients for the Prevention of PONV Within 24 Hours After End of Surgery in Studies 1 and 2
Study 1Study 2
BARHEMSYS 5 mg (n=176)Placebo (n=166)BARHEMSYS 5 mg with Another Antiemetic (n=572)Placebo with Another Antiemetic (n=575)
Complete Response78 (44%)54 (33%)330 (58%)268 (47%)
Difference (95% CI)Unadjusted, nominal 95% confidence interval12% (2%, 22%)11% (5%, 17%)
","
Table 4. Complete Response Rates in Adult Patients for the Treatment of PONV Within 24 Hours After TreatmentExcluding emesis within the first 30 minutes in Studies 3 and 4
Study 3 (no prophylaxis)Study 4 (prior prophylaxis)Received prior PONV prophylaxis with one or more non-dopaminergic antiemetics: a 5-HT3-antagonist in 77%, dexamethasone in 65% and another antiemetic class in 10%
BARHEMSYS 10 mg (n=188)Placebo (n=181)BARHEMSYS 10 mg (n=230)Placebo (n=235)
Complete Response59 (31%)39 (22%)96 (42%)67 (29%)
Difference (95% CI)Unadjusted, nominal 95% confidence interval10% (1%, 19%)13% (5%, 22%)
"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to assess the carcinogenic potential of amisulpride have not been conducted. Amisulpride was not genotoxic in the bacterial reverse mutation assay, the in vitro human peripheral blood lymphocytes assay, and the in vivo rat bone marrow micronucleus assay. The effect of amisulpride on fertility was studied in rats at oral doses up to 160 mg/kg/day (43 times the exposure based on AUC at the highest recommended dose of 10 mg). Most female animals (90% to 95%) at each dose level remained in diestrus and failed to mate. However, this effect on mating reversed following cessation of treatment. No treatment-related effects were observed on uterine/implantation parameters or sperm counts, sperm motility or sperm morphology."],"pharmacokinetics_table":["
Table 2. Summary of Key Pharmacokinetic Parameters of Amisulpride from Clinical Studies
Single DoseInfusion Duration (minutes)Number of SubjectsMean (SD)
Peak Plasma Concentration (ng/mL)AUC(0-∞) (ng∙h/mL)
Healthy Subjects5 mg239200 (139)154 (30)
Healthy Subjects10 mg129451 (230)136 (28)AUC(0-2 hr)
Patients5 mg1 to 226Patients in a clinical trial for prophylaxis of PONV161 (58)260 (65)
27Patients in clinical trials for treatment of PONV127 (64)204 (94)
Patients10 mg1 to 231285 (446)401 (149)
"],"adverse_reactions_table":["
Table 1. Common Adverse ReactionsReported in at least 2% of patients treated with BARHEMSYS and at a higher rate than placebo in Adult Patients in Studies 1 and 2 of BARHEMSYS for Prevention of PONV
BARHEMSYS 5 mgPlacebo
N=748N=741
Chills4%3%
Hypokalemia4%2%
Procedural hypotension3%2%
Abdominal distension2%1%
"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION QT Prolongation 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 [see Warnings and Precautions (5.1) ] . Drug Interactions Advise patients to report to their healthcare provider if they are taking drugs which prolong the QT interval [see Warnings and Precautions (5.1) ]. Lactation Women may consider reducing infant exposure through pumping and discarding breastmilk for 48 hours after BARHEMSYS administration [see Use in Specific Populations (8.2) ] ."],"spl_unclassified_section":["Distributed by Acacia Pharma Inc. 8440 Allison Pointe Blvd, Suite 100 Indianapolis, IN 46250 USA © 2022 Acacia Pharma Inc. All rights reserved. BAR-0005-USPI-09/2022"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION The recommended dosage of BARHEMSYS: 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. ( 2.1 ) 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. ( 2.1 ) See full prescribing information for preparation and administration instructions . ( 2.2 ) 2.1 Recommended Dosage The recommended adult dosage of BARHEMSYS and infusion rate by indication is shown in the table below: Indication Adult Dosage Regimen Prevention of PONV 5 mg as a single intravenous injection infused over 1 to 2 minutes at the time of induction of anesthesia [see Dosage and Administration (2.2) ] . 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 [see Dosage and Administration (2.2) ] . 2.2 Preparation and Administration Dilution of BARHEMSYS is not required before administration. BARHEMSYS is chemically and physically compatible with Water for Injection, 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer's Solution (also known as Ringer's Lactate Solution, Compound Sodium Lactate Solution, and Hartmann's Solution), any of which may be used to flush an intravenous line before or after administration of BARHEMSYS. Protect from light. BARHEMSYS is subject to photodegradation. Administer BARHEMSYS within 12 hours of removal of the vial from the protective carton. Prior to administration, inspect the BARHEMSYS solution visually for particulate matter and discoloration. Discard if particulate matter or discoloration is observed."],"spl_product_data_elements":["Barhemsys Amisulpride Amisulpride Amisulpride Citric Acid Monohydrate Sodium Chloride Trisodium Citrate Dihydrate Hydrochloric Acid Sodium Hydroxide"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Injection: 5 mg/2 mL (2.5 mg/mL) or 10 mg/4 mL (2.5 mg/mL) as a clear, colorless sterile solution in a single-dose vial. Injection: 5 mg/2 mL (2.5 mg/mL) or 10 mg/4 mL (2.5 mg/mL) in a single-dose vial. ( 3 )"],"clinical_pharmacology_table":["
Table 2. Summary of Key Pharmacokinetic Parameters of Amisulpride from Clinical Studies
Single DoseInfusion Duration (minutes)Number of SubjectsMean (SD)
Peak Plasma Concentration (ng/mL)AUC(0-∞) (ng∙h/mL)
Healthy Subjects5 mg239200 (139)154 (30)
Healthy Subjects10 mg129451 (230)136 (28)AUC(0-2 hr)
Patients5 mg1 to 226Patients in a clinical trial for prophylaxis of PONV161 (58)260 (65)
27Patients in clinical trials for treatment of PONV127 (64)204 (94)
Patients10 mg1 to 231285 (446)401 (149)
"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS Lactation : A lactating woman may pump and discard breast milk for 48 hours after BARHEMSYS administration. ( 8.2 ) 8.1 Pregnancy 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 (see Data ) . 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. Data 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. 8.2 Lactation 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 (see Clinical Considerations ). 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 (D 2 ) receptor antagonist, may result in an increase in serum prolactin levels, which may lead to a reversible increase in maternal milk production [see Adverse Reactions (6.1) ]. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for BARHEMSYS and any potential adverse effects on the breastfed child from BARHEMSYS 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 BARHEMSYS administration to minimize drug exposure to a breastfed infant. 8.3 Females and Males of Reproductive Potential 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 [see Nonclinical Toxicology (13.1) ]. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of patients enrolled in controlled clinical trials who received BARHEMSYS 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."],"dosage_and_administration_table":["
IndicationAdult Dosage Regimen
Prevention of PONV5 mg as a single intravenous injection infused over 1 to 2 minutes at the time of induction of anesthesia [see Dosage and Administration (2.2)].
Treatment of PONV10 mg as a single intravenous injection infused over 1 to 2 minutes in the event of nausea and/or vomiting after a surgical procedure [see Dosage and Administration (2.2)].
"],"package_label_principal_display_panel":["PRINCIPAL DISPLAY PANEL - 2 mL Vial Label NDC 71390-125-21 Rx ONLY Barhemsys ® (amisulpride) injection 5 mg | 2 mL (2.5 mg/mL) Single-dose sterile vial, discard unused portion. For Intravenous Infusion Only. PRINCIPAL DISPLAY PANEL - 2 mL Vial Label","PRINCIPAL DISPLAY PANEL - 2 mL Vial Carton NDC 71390-125-21 Barhemsys ® (amisulpride) injection 5 mg | 2 mL (2.5 mg/mL) Single-dose sterile vial. For Intravenous Infusion Only. Discard Unused Portion. Rx ONLY PRINCIPAL DISPLAY PANEL - 2 mL Vial Carton","PRINCIPAL DISPLAY PANEL - 4 mL Vial Label NDC 71390-125-51 Rx ONLY Barhemsys ® (amisulpride) injection 10 mg | 4 mL (2.5 mg/mL) Single-dose sterile vial, discard unused portion. For Intravenous Infusion Only. PRINCIPAL DISPLAY PANEL - 4 mL Vial Label","PRINCIPAL DISPLAY PANEL - 4 mL Vial Carton NDC 71390-125-51 Barhemsys ® (amisulpride) injection 10 mg | 4 mL (2.5 mg/mL) Single-dose sterile vial. For Intravenous Infusion Only. Discard Unused Portion. Rx ONLY PRINCIPAL DISPLAY PANEL - 4 mL Vial Carton"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to assess the carcinogenic potential of amisulpride have not been conducted. Amisulpride was not genotoxic in the bacterial reverse mutation assay, the in vitro human peripheral blood lymphocytes assay, and the in vivo rat bone marrow micronucleus assay. The effect of amisulpride on fertility was studied in rats at oral doses up to 160 mg/kg/day (43 times the exposure based on AUC at the highest recommended dose of 10 mg). Most female animals (90% to 95%) at each dose level remained in diestrus and failed to mate. However, this effect on mating reversed following cessation of treatment. No treatment-related effects were observed on uterine/implantation parameters or sperm counts, sperm motility or sperm morphology."]},"tags":[{"label":"Dopamine-2 Receptor Antagonist","category":"class"},{"label":"Small Molecule","category":"modality"},{"label":"D(2) dopamine receptor","category":"target"},{"label":"DRD2","category":"gene"},{"label":"DRD3","category":"gene"},{"label":"HTR7","category":"gene"},{"label":"N05AL05","category":"atc"},{"label":"Intravenous","category":"route"},{"label":"Injection","category":"form"},{"label":"Active","category":"status"},{"label":"Chronic schizophrenia","category":"indication"},{"label":"Postoperative nausea and vomiting","category":"indication"},{"label":"Acacia","category":"company"},{"label":"Approved 2020s","category":"decade"},{"label":"Antidepressive Agents","category":"pharmacology"},{"label":"Antidepressive Agents, Second-Generation","category":"pharmacology"},{"label":"Antipsychotic Agents","category":"pharmacology"},{"label":"Central Nervous System Agents","category":"pharmacology"},{"label":"Central Nervous System Depressants","category":"pharmacology"},{"label":"Dopamine Agents","category":"pharmacology"},{"label":"Dopamine Antagonists","category":"pharmacology"},{"label":"Neurotransmitter Agents","category":"pharmacology"},{"label":"Psychotropic Drugs","category":"pharmacology"},{"label":"Tranquilizing Agents","category":"pharmacology"}],"phase":"marketed","safety":{"boxedWarnings":[],"safetySignals":[{"date":"","signal":"DRUG INEFFECTIVE","source":"FDA FAERS","actionTaken":"825 reports"},{"date":"","signal":"DRUG INTERACTION","source":"FDA FAERS","actionTaken":"442 reports"},{"date":"","signal":"WEIGHT INCREASED","source":"FDA FAERS","actionTaken":"426 reports"},{"date":"","signal":"TOXICITY TO VARIOUS AGENTS","source":"FDA FAERS","actionTaken":"382 reports"},{"date":"","signal":"NEUTROPENIA","source":"FDA FAERS","actionTaken":"379 reports"},{"date":"","signal":"SCHIZOPHRENIA","source":"FDA FAERS","actionTaken":"320 reports"},{"date":"","signal":"LEUKOPENIA","source":"FDA FAERS","actionTaken":"311 reports"},{"date":"","signal":"OFF LABEL USE","source":"FDA FAERS","actionTaken":"305 reports"},{"date":"","signal":"AKATHISIA","source":"FDA FAERS","actionTaken":"299 reports"},{"date":"","signal":"EXTRAPYRAMIDAL DISORDER","source":"FDA FAERS","actionTaken":"278 reports"}],"drugInteractions":[{"url":"/drug/high-risk-qt-prolonging-agents","drug":"High Risk QT Prolonging Agents","action":"Avoid combination","effect":"Moderate Risk QTc-Prolonging Agents may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents","source":"DrugCentral","drugSlug":"high-risk-qt-prolonging-agents"}],"commonSideEffects":[{"effect":"Chills","drugRate":"4%","severity":"common","_validated":true},{"effect":"Hypokalemia","drugRate":"4%","severity":"common","_validated":true},{"effect":"Procedural hypotension","drugRate":"3%","severity":"common","_validated":true},{"effect":"Abdominal distension","drugRate":"2%","severity":"common","_validated":true},{"effect":"Infusion site pain","drugRate":"6%","severity":"common","_validated":true},{"effect":"Increased blood prolactin concentrations","drugRate":"5%","severity":"common","_validated":true},{"effect":"Agranulocytosis","drugRate":"reported","severity":"serious"},{"effect":"Bradycardia","drugRate":"reported","severity":"serious"},{"effect":"Torsades de pointes","drugRate":"reported","severity":"serious"},{"effect":"Ventricular tachycardia","drugRate":"reported","severity":"serious"},{"effect":"Prolonged QT by electrocardiogram","drugRate":"reported","severity":"serious"},{"effect":"Neuroleptic malignant syndrome","drugRate":"reported","severity":"serious"},{"effect":"Angioedema","drugRate":"reported","severity":"serious"},{"effect":"Hypersensitivity","drugRate":"reported","severity":"serious"},{"effect":"Urticaria","drugRate":"reported","severity":"serious"},{"effect":"Increased hepatic enzymes","drugRate":"reported","severity":"serious"},{"effect":"Agitation","drugRate":"reported","severity":"serious"},{"effect":"Anxiety","drugRate":"reported","severity":"serious"},{"effect":"Dystonia","drugRate":"reported","severity":"serious"},{"effect":"Extrapyramidal disorder","drugRate":"reported","severity":"serious"},{"effect":"Seizure","drugRate":"reported","severity":"serious"},{"effect":"Confusional state","drugRate":"reported","severity":"serious"},{"effect":"Insomnia","drugRate":"reported","severity":"serious"},{"effect":"Somnolence","drugRate":"reported","severity":"serious"},{"effect":"Hypotension","drugRate":"reported","severity":"serious"}],"specialPopulations":{"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 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 breastfed infant (see Clinical Considerations). There are no reports of adverse effects on the breastfed child and no informati","Pregnancy":"Available data with amisulpride use in pregnant women are insufficient to establish 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 (see Data).The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have 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.","Geriatric use":"Of the total number of patients enrolled in controlled clinical trials who received BARHEMSYS 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 gre","Paediatric use":"Safety and effectiveness in pediatric patients have not been established."}},"trials":[],"aliases":[],"company":"Acacia","patents":[{"applNo":"N209510","source":"FDA Orange Book","status":"Active","expires":"Mar 10, 2031","useCode":"U-1744","territory":"US","drugProduct":false,"patentNumber":"9545426","drugSubstance":false},{"applNo":"N209510","source":"FDA Orange Book","status":"Active","expires":"Feb 26, 2034","useCode":"U-1744","territory":"US","drugProduct":false,"patentNumber":"9084765","drugSubstance":false},{"applNo":"N209510","source":"FDA Orange Book","status":"Active","expires":"Mar 10, 2031","useCode":"U-2754","territory":"US","drugProduct":false,"patentNumber":"9889118","drugSubstance":false},{"applNo":"N209510","source":"FDA Orange Book","status":"Active","expires":"Feb 9, 2038","useCode":"U-1744","territory":"US","drugProduct":false,"patentNumber":"12005042","drugSubstance":false},{"applNo":"N209510","source":"FDA Orange Book","status":"Active","expires":"Feb 9, 2038","useCode":"U-2754","territory":"US","drugProduct":false,"patentNumber":"11357753","drugSubstance":false},{"applNo":"N209510","source":"FDA Orange Book","status":"Active","expires":"Feb 9, 2038","useCode":"U-2754","territory":"US","drugProduct":false,"patentNumber":"12329740","drugSubstance":false},{"applNo":"N209510","source":"FDA Orange Book","status":"Active","expires":"Mar 10, 2031","useCode":"U-1744","territory":"US","drugProduct":false,"patentNumber":"12194022","drugSubstance":false},{"applNo":"N209510","source":"FDA Orange Book","status":"Active","expires":"Mar 10, 2031","useCode":"","territory":"US","drugProduct":true,"patentNumber":"10525033","drugSubstance":false}],"pricing":[],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=AMISULPRIDE","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-20T00:44:22.756630+00:00"},"patents":{"url":"","method":"deterministic","source":"FDA Orange Book","rawText":"","confidence":1,"sourceType":"fda_orange_book","retrievedAt":"2026-04-20T00:44:16.832046+00:00"},"aiSummary":{"url":"","method":"ai_extraction","source":"AI Strategic Summary","aiModel":"featherless","rawText":"","confidence":0.9,"sourceType":"ai_extraction","retrievedAt":"2026-04-20T00:44:54.489166+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-20T00:44:29.590002+00:00"},"regulatory.us":{"url":"","method":"api_direct","source":"FDA Drugs@FDA","rawText":"","confidence":1,"sourceType":"fda_drugsfda","retrievedAt":"2026-04-20T00:44:15.280790+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=AMISULPRIDE","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-20T00:44:30.337260+00:00"},"mechanism.drugClass":{"url":"https://api.fda.gov/drug/label.json","method":"deterministic","source":"FDA Label (EPC)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T00:44:14.284711+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T00:44:14.284745+00:00"},"indications.approved":{"url":"","method":"ai_extraction","source":"FDA Label + AI","aiModel":"featherless","rawText":"","confidence":0.9,"sourceType":"fda_label","retrievedAt":"2026-04-20T00:44:45.695416+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T00:44:14.284755+00:00"},"safety.safetySignals":{"url":"https://api.fda.gov/drug/event.json","method":"api_direct","source":"FDA FAERS","rawText":"","confidence":1,"sourceType":"fda_faers","retrievedAt":"2026-04-20T00:44:31.834756+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Dopamine receptors; D2 & D3 antagonist","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T00:44:30.918088+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL243712/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T00:44:30.814670+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"NDA209510","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T00:44:14.284762+00:00"}},"allNames":"barhemsys","offLabel":[],"synonyms":["barhemsys","amisulpride","aminosultopride","deniban","solian"],"timeline":[{"date":"1986-01-01","type":"positive","source":"DrugCentral","milestone":"YEAR INTRODUCED approval"},{"date":"2020-01-01","type":"neutral","source":"FDA Orange Book","milestone":"Rights transferred from ACACIA PHARMA LTD to Acacia"},{"date":"2020-02-26","type":"positive","source":"DrugCentral","milestone":"FDA approval (Acacia Pharma Ltd)"}],"aiSummary":"Amisulpride (Barhemsys), marketed by Acacia, is positioned as a preventive treatment for postoperative nausea and vomiting (PONV) with a key composition patent expiring in 2028. Its mechanism of action, which involves blocking dopamine receptors, provides a targeted approach to managing PONV, distinguishing it from broader-spectrum competitors. The primary risk to Barhemsys is the competitive landscape, including drugs like apomorphine, aripiprazole, cariprazine, and clozapine, all of which are patent-protected and target the same receptor, potentially limiting market share.","brandName":"Barhemsys","ecosystem":[{"indication":"Chronic schizophrenia","otherDrugs":[{"name":"carfenazine","slug":"carfenazine","company":"Wyeth Ayerst"},{"name":"haloperidol","slug":"haloperidol","company":"Ortho Mcneil"},{"name":"haloperidol decanoate","slug":"haloperidol-decanoate","company":"Janssen Pharms"}],"globalPrevalence":24000000},{"indication":"Postoperative nausea and vomiting","otherDrugs":[{"name":"benzquinamide","slug":"benzquinamide","company":""}],"globalPrevalence":null}],"mechanism":{"target":"D(2) dopamine receptor","novelty":"Follow-on","targets":[{"gene":"DRD2","source":"DrugCentral","target":"D(2) dopamine receptor","protein":"D(2) dopamine receptor"},{"gene":"DRD3","source":"DrugCentral","target":"D(3) dopamine receptor","protein":"D(3) dopamine receptor"},{"gene":"HTR7","source":"DrugCentral","target":"5-hydroxytryptamine receptor 7","protein":"5-hydroxytryptamine receptor 7"},{"gene":"HTR2B","source":"DrugCentral","target":"5-hydroxytryptamine receptor 2B","protein":"5-hydroxytryptamine receptor 2B"},{"gene":"ADRA2A","source":"DrugCentral","target":"Alpha-2A adrenergic receptor","protein":"Alpha-2A adrenergic receptor"},{"gene":"HTR1D","source":"DrugCentral","target":"5-hydroxytryptamine receptor 1D","protein":"5-hydroxytryptamine receptor 1D"},{"gene":"ADRA2C","source":"DrugCentral","target":"Alpha-2C adrenergic receptor","protein":"Alpha-2C adrenergic receptor"},{"gene":"HTR1B","source":"DrugCentral","target":"5-hydroxytryptamine receptor 1B","protein":"5-hydroxytryptamine receptor 1B"},{"gene":"DRD4","source":"DrugCentral","target":"D(4) dopamine receptor","protein":"D(4) dopamine receptor"},{"gene":"HTR6","source":"DrugCentral","target":"5-hydroxytryptamine receptor 6","protein":"5-hydroxytryptamine receptor 6"}],"moaClass":"Dopamine D2 Antagonists","modality":"Small Molecule","drugClass":"Dopamine-2 Receptor Antagonist [EPC]","explanation":"Amisulpride is 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 role in emesis. Studies conducted in ferrets have shown that amisulpride inhibits emesis caused by apomorphine, with an estimated ED50 of less than mcg/kg, subcutaneously; and inhibits cisplatin-induced emesis at mg/kg and morphine-induced emesis at to 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.","oneSentence":"Barhemsys works by blocking dopamine receptors in the brain.","technicalDetail":"Barhemsys (amisulpride) is a selective dopamine D(2) receptor antagonist that exerts its effects by competitively inhibiting the action of dopamine at the D(2) receptor, thereby modulating neurotransmission and alleviating symptoms of chronic schizophrenia and postoperative nausea and vomiting."},"commercial":{"launchDate":"2020","_launchSource":"DrugCentral (FDA 2020-02-26, ACACIA PHARMA LTD)"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/179","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=AMISULPRIDE","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=AMISULPRIDE","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files","fields":["patents","exclusivity","genericManufacturers"],"source":"FDA Orange Book"}],"_enrichedAt":"2026-03-30T08:43:54.023980","_validation":{"fieldsValidated":2,"lastValidatedAt":"2026-04-20T00:44:54.489863+00:00","fieldsConflicting":0,"overallConfidence":0.95},"biosimilars":[],"competitors":[{"drugName":"apomorphine","drugSlug":"apomorphine","fdaApproval":"2004-04-20","patentExpiry":"Jun 11, 2030","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"aripiprazole","drugSlug":"aripiprazole","fdaApproval":"2002-11-15","patentExpiry":"Sep 24, 2033","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"cariprazine","drugSlug":"cariprazine","fdaApproval":"2015-09-17","patentExpiry":"Sep 17, 2029","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"clozapine","drugSlug":"clozapine","fdaApproval":"1989-09-26","patentExpiry":"May 1, 2028","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"dopamine","drugSlug":"dopamine","fdaApproval":"1974-02-25","genericCount":9,"patentStatus":"Off-patent — generic available","relationship":"same-target"},{"drugName":"haloperidol","drugSlug":"haloperidol","fdaApproval":"1967-04-12","genericCount":20,"patentStatus":"Off-patent — generic available","relationship":"same-target"},{"drugName":"metoclopramide","drugSlug":"metoclopramide","fdaApproval":"1979-02-07","patentExpiry":"Nov 17, 2038","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"olanzapine","drugSlug":"olanzapine","fdaApproval":"1996-09-30","genericCount":34,"patentStatus":"Off-patent — generic available","relationship":"same-target"},{"drugName":"pergolide","drugSlug":"pergolide","fdaApproval":"1988-12-30","genericCount":2,"patentStatus":"Off-patent — generic available","relationship":"same-target"},{"drugName":"pramipexole","drugSlug":"pramipexole","fdaApproval":"1997-07-01","patentExpiry":"Sep 8, 2029","patentStatus":"Patent protected","relationship":"same-target"}],"genericName":"amisulpride","indications":{"approved":[{"id":"amisulpride-prevention-of-ponv","name":"Prevention of PONV","dosing":null,"approvals":[],"diseaseId":"","eligibility":"Adults","pivotalTrial":null,"restrictions":[],"patientPopulation":"Adults","diagnosticRequired":null,"brandNameForIndication":"Barhemsys"},{"id":"amisulpride-treatment-of-ponv","name":"Treatment of PONV","dosing":null,"approvals":[],"diseaseId":"","eligibility":"Adults","pivotalTrial":null,"restrictions":[],"patientPopulation":"Adults","diagnosticRequired":null,"brandNameForIndication":"Barhemsys"}],"offLabel":[{"name":"Dysthymia","source":"DrugCentral","drugName":"AMISULPRIDE","evidenceCount":35,"evidenceLevel":"moderate"}],"pipeline":[]},"currentOwner":"Acacia","drugCategory":"active","labelChanges":[],"relatedDrugs":[{"drugId":"apomorphine","brandName":"apomorphine","genericName":"apomorphine","approvalYear":"2004","relationship":"same-target"},{"drugId":"aripiprazole","brandName":"aripiprazole","genericName":"aripiprazole","approvalYear":"2002","relationship":"same-target"},{"drugId":"cariprazine","brandName":"cariprazine","genericName":"cariprazine","approvalYear":"2015","relationship":"same-target"},{"drugId":"clozapine","brandName":"clozapine","genericName":"clozapine","approvalYear":"1989","relationship":"same-target"},{"drugId":"dopamine","brandName":"dopamine","genericName":"dopamine","approvalYear":"1974","relationship":"same-target"},{"drugId":"haloperidol","brandName":"haloperidol","genericName":"haloperidol","approvalYear":"1967","relationship":"same-target"},{"drugId":"metoclopramide","brandName":"metoclopramide","genericName":"metoclopramide","approvalYear":"1979","relationship":"same-target"},{"drugId":"olanzapine","brandName":"olanzapine","genericName":"olanzapine","approvalYear":"1996","relationship":"same-target"},{"drugId":"pergolide","brandName":"pergolide","genericName":"pergolide","approvalYear":"1988","relationship":"same-target"},{"drugId":"pramipexole","brandName":"pramipexole","genericName":"pramipexole","approvalYear":"1997","relationship":"same-target"}],"trialDetails":[{"nctId":"NCT07494305","phase":"PHASE2","title":"Multicenter Study to Assess the Efficacy and Safety of LB-102 in the Treatment of Adult Patients With BP1MDE.","status":"RECRUITING","sponsor":"LB Pharmaceuticals Inc.","startDate":"2026-01-23","conditions":["Bipolar I Disorder"],"enrollment":320,"completionDate":"2028-02"},{"nctId":"NCT02926859","phase":"PHASE2","title":"Enhancing Recovery in Early Schizophrenia","status":"ACTIVE_NOT_RECRUITING","sponsor":"Central Institute of Mental Health, Mannheim","startDate":"2017-04-08","conditions":["Schizophrenia"],"enrollment":180,"completionDate":"2027-12"},{"nctId":"NCT07348172","phase":"EARLY_PHASE1","title":"Characterizing Drug Liking During Drug Administration in Peri-procedural Clinical Settings","status":"NOT_YET_RECRUITING","sponsor":"Stanford University","startDate":"2026-03-01","conditions":["Drug Liking"],"enrollment":100,"completionDate":"2028-03-31"},{"nctId":"NCT06581302","phase":"NA","title":"Magnetic Seizure Therapy for Psychotic Disorders","status":"RECRUITING","sponsor":"Shanghai Jiao Tong University School of Medicine","startDate":"2024-09-01","conditions":["Psychotic Disorders"],"enrollment":50,"completionDate":"2025-12-30"},{"nctId":"NCT05546359","phase":"PHASE2,PHASE3","title":"Study of Intravenous Amisulpride for Prophylaxis of Post-operative Nausea and Vomiting (PONV) in Pediatric Patients","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","startDate":"2024-01-18","conditions":["Nausea and Vomiting, Postoperative"],"enrollment":453,"completionDate":"2025-06-03"},{"nctId":"NCT01701258","phase":"PHASE1","title":"An Investigation of Early Life Stress and Depression","status":"COMPLETED","sponsor":"Mclean Hospital","startDate":"2013-08","conditions":["Major Depressive Disorder (MDD)","History of Childhood Sexual Abuse (CSA)"],"enrollment":153,"completionDate":"2017-05"},{"nctId":"NCT06887621","phase":"PHASE2","title":"Efficacy of Adding Oral Amisulpride to Dual Prophylaxis for Postoperative Nausea and Vomiting in Patients at High Risk for Nausea and Vomiting Undergoing Gynecological Surgery","status":"RECRUITING","sponsor":"Instituto do Cancer do Estado de São Paulo","startDate":"2025-04-10","conditions":["Post Operative Nausea and Vomiting (PONV)"],"enrollment":276,"completionDate":"2027-03-31"},{"nctId":"NCT04128683","phase":"EARLY_PHASE1","title":"Dopamine Receptor Contributions to Prediction Error and Reversal Learning in Anorexia Nervosa","status":"COMPLETED","sponsor":"University of California, San Diego","startDate":"2020-10-20","conditions":["Anorexia Nervosa"],"enrollment":31,"completionDate":"2025-01-01"},{"nctId":"NCT03510325","phase":"PHASE3","title":"Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments(SMART-CAT)","status":"COMPLETED","sponsor":"Shanghai Mental Health Center","startDate":"2019-02-12","conditions":["Schizophrenia"],"enrollment":762,"completionDate":"2023-09-27"},{"nctId":"NCT01029769","phase":"NA","title":"Efficacy of an Early Antipsychotic Switch in Case of Poor Initial Response to the Treatment of Schizophrenia","status":"COMPLETED","sponsor":"Technical University of Munich","startDate":"2009-12","conditions":["Schizophrenia","Schizoaffective Disorder","Schizophreniform Disorder"],"enrollment":350,"completionDate":"2015-03"},{"nctId":"NCT06585540","phase":"PHASE3","title":"A Pilot Study to Evaluate Barhemsys for the Prevention of Postoperative Nausea and Vomiting in the Bariatric Surgery Population","status":"RECRUITING","sponsor":"Benaroya Research Institute","startDate":"2024-09-13","conditions":["Post Operative Nausea and Vomiting"],"enrollment":100,"completionDate":"2026-01"},{"nctId":"NCT04876521","phase":"PHASE4","title":"Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in Post-Schizophrenic Depression","status":"COMPLETED","sponsor":"All India Institute of Medical Sciences, Bhubaneswar","startDate":"2019-10-14","conditions":["Post-Schizophrenic Depression"],"enrollment":60,"completionDate":"2021-06-30"},{"nctId":"NCT04218981","phase":"NA","title":"Definitive Selection of Neuroimaging Biomarkers for the Diagnosis and Treatment to Common Mental Disorders","status":"COMPLETED","sponsor":"Central South University","startDate":"2020-01-15","conditions":["Common Mental Disorder"],"enrollment":200,"completionDate":"2023-12-31"},{"nctId":"NCT01972711","phase":"PHASE1","title":"Study Assessing SEP-363856 in Male and Female Volunteers With High or Low Schizotype Characteristics","status":"COMPLETED","sponsor":"Otsuka Pharmaceutical Development & Commercialization, Inc.","startDate":"2014-03","conditions":["Schizophrenia"],"enrollment":105,"completionDate":"2015-07"},{"nctId":"NCT05956600","phase":"NA","title":"An Open-Label, Single-Arm Clinical Trial Evaluating the Safety and Efficacy of Amisulpride in Treating Patients With Schizophrenia and Schizoaffective Disorder Who Have Treatment-Resistant Positive Symptoms","status":"WITHDRAWN","sponsor":"University of California, Los Angeles","startDate":"2023-11","conditions":["Schizophrenia, Treatment-Resistant"],"enrollment":0,"completionDate":"2026-01"},{"nctId":"NCT04529226","phase":"PHASE2","title":"Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis","status":"ACTIVE_NOT_RECRUITING","sponsor":"Fundación Pública Andaluza para la gestión de la Investigación en Sevilla","startDate":"2020-11-26","conditions":["Psychosis","Intellectual Disability"],"enrollment":75,"completionDate":"2025-12-30"},{"nctId":"NCT05347199","phase":"PHASE1","title":"Effects of a Single Dose of Amisulpride on Functional Brain Changes","status":"COMPLETED","sponsor":"Simone Grimm","startDate":"2022-05-17","conditions":["Major Depressive Disorder"],"enrollment":127,"completionDate":"2023-09-25"},{"nctId":"NCT06066112","phase":"PHASE1","title":"Study on the Bioequivalence of Amisulpride Orally Disintegrating Tablets in Human Body","status":"UNKNOWN","sponsor":"The Affiliated Hospital of Qingdao University","startDate":"2023-09-20","conditions":["Bioequivalence","Schizophrenia"],"enrollment":100,"completionDate":"2024-03-31"},{"nctId":"NCT06040944","phase":"","title":"Antipsychotic Induced Hyperprolactinemaia as Risk Factor for Periodontitis in Schizophrenic Patients","status":"COMPLETED","sponsor":"Fayoum University","startDate":"2022-09-01","conditions":["Schizophrenia Spectrum and Other Psychotic Disorders","Periodontal Diseases"],"enrollment":64,"completionDate":"2022-11-01"},{"nctId":"NCT04674670","phase":"NA","title":"Psychobiological Mechanisms Underlying Chronic Pain","status":"COMPLETED","sponsor":"susanne becker","startDate":"2021-11-01","conditions":["Fibromyalgia","Pain, Chronic","Chronic Pain, Widespread"],"enrollment":48,"completionDate":"2023-07-31"},{"nctId":"NCT05822713","phase":"PHASE3","title":"A Comparison of the Efficacy of Amisulpride and Placebo in the Prevention of PONV in Patients at Moderate-to-high Risk of PONV.","status":"UNKNOWN","sponsor":"Qilu Pharmaceutical (Hainan) Co., Ltd.","startDate":"2023-04-29","conditions":["PONV"],"enrollment":516,"completionDate":"2023-12-31"},{"nctId":"NCT04954365","phase":"","title":"Post Operative Nausea and Vomiting (PONV) Rescue Outcomes After Amisulpride Treatment","status":"WITHDRAWN","sponsor":"Acacia Pharma Ltd","startDate":"2022-11-01","conditions":["Nausea and Vomiting, Postoperative"],"enrollment":0,"completionDate":"2024-12"},{"nctId":"NCT04341467","phase":"NA","title":"Amisulpride Treatment for BPSD in AD Patients","status":"UNKNOWN","sponsor":"Tianjin Anding Hospital","startDate":"2019-12-01","conditions":["BPSD","Amisulpride","Olanzapine","Dementia of the Alzheimer Type"],"enrollment":76,"completionDate":"2024-05"},{"nctId":"NCT04002258","phase":"","title":"Prolactin Change in Chinese Patients With Schizophrenia After Antipsychotics Treatment","status":"COMPLETED","sponsor":"Shanghai Mental Health Center","startDate":"2019-06-06","conditions":["Schizophrenia","Antipyretics Toxicity","Prolactin Excess"],"enrollment":10363,"completionDate":"2022-10-25"},{"nctId":"NCT03652974","phase":"PHASE4","title":"Disturbance of Plasma Cytokine Parameters in Clozapine-Resistant Treatment-Refractory Schizophrenia (CTRS) and Their Association With Combination Therapy","status":"COMPLETED","sponsor":"Shanghai Mental Health Center","startDate":"2018-09-06","conditions":["Schizophrenia"],"enrollment":145,"completionDate":"2021-08-30"},{"nctId":"NCT04588129","phase":"PHASE1","title":"Receptor Occupancy of LB-102 Using Positron Emission Tomography (PET) in Healthy Volunteers","status":"COMPLETED","sponsor":"LB Pharmaceuticals Inc.","startDate":"2021-01-05","conditions":["Schizophrenia"],"enrollment":16,"completionDate":"2021-11-15"},{"nctId":"NCT00448630","phase":"","title":"An Observational Study On Metabolic Syndrome Parameters In Schizophrenia Patients Treated With Atypical Antipsychotics","status":"COMPLETED","sponsor":"Pfizer's Upjohn has merged with Mylan to form Viatris Inc.","startDate":"2007-10-23","conditions":["Schizophrenia","Metabolic Syndrome X"],"enrollment":328,"completionDate":"2008-07-30"},{"nctId":"NCT01498770","phase":"","title":"An Observational Drug Utilization Study of Asenapine in the United Kingdom (P08308)","status":"COMPLETED","sponsor":"Organon and Co","startDate":"2013-04-01","conditions":["Bipolar Disorder"],"enrollment":42,"completionDate":"2017-12-21"},{"nctId":"NCT04849650","phase":"PHASE1","title":"PK Study of IV and Oral Amisulpride in Subjects With Severe Renal Impairment","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","startDate":"2021-06-03","conditions":["Renal Disease, End Stage"],"enrollment":12,"completionDate":"2021-10-30"},{"nctId":"NCT03451734","phase":"","title":"Optimizing and Individualizing the Pharmacological Treatment of First-episode Schizophrenic Patients","status":"COMPLETED","sponsor":"Central South University","startDate":"2018-01-23","conditions":["Schizophrenia","Metabolic Syndrome"],"enrollment":2000,"completionDate":"2021-06-30"},{"nctId":"NCT04187560","phase":"PHASE1","title":"Safety and Tolerability of Single and Multiple Doses of LB-102 in Healthy Adults","status":"COMPLETED","sponsor":"LB Pharmaceuticals Inc.","startDate":"2020-01-22","conditions":["Schizophrenia"],"enrollment":64,"completionDate":"2020-11-09"},{"nctId":"NCT02435095","phase":"PHASE4","title":"Antipsychotic Induced Structural and Functional Brain Changes","status":"TERMINATED","sponsor":"RWTH Aachen University","startDate":"2015-05","conditions":["Schizophrenia"],"enrollment":174,"completionDate":"2020-08"},{"nctId":"NCT01857232","phase":"PHASE2","title":"Dose-finding Study of APD403 to Prevent Nausea and Vomiting After Chemotherapy","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","startDate":"2013-10","conditions":["CINV"],"enrollment":342,"completionDate":"2015-02"},{"nctId":"NCT03863691","phase":"NA","title":"Influence of Dopaminergic Blockade on Stress Responses, Motivation and Emotional Reactivity in Humans.","status":"COMPLETED","sponsor":"Philipps University Marburg","startDate":"2019-04-15","conditions":["Healthy Participants"],"enrollment":85,"completionDate":"2020-07-15"},{"nctId":"NCT04533724","phase":"EARLY_PHASE1","title":"Study on the Gut Microbial Mechanism of Negative Symptoms of Schizophrenia","status":"UNKNOWN","sponsor":"Shanghai Mental Health Center","startDate":"2020-10-01","conditions":["Negative Symptom","Schizophrenia","Amisulpride","Gut Microbiomes"],"enrollment":6,"completionDate":"2022-09-30"},{"nctId":"NCT04528095","phase":"PHASE3","title":"SMART Design to Compare Antipsychotic Treatments in Treatment-Resistant Schizophrenia","status":"UNKNOWN","sponsor":"Shanghai Mental Health Center","startDate":"2020-12","conditions":["Treatment-resistant Schizophrenia"],"enrollment":162,"completionDate":"2022-12"},{"nctId":"NCT04446234","phase":"PHASE4","title":"Atypical Antipsychotics Influence on the Safety of the Heart and Monitoring Indicators Model Building","status":"UNKNOWN","sponsor":"Shanghai Mental Health Center","startDate":"2021-05","conditions":["Schizophrenia"],"enrollment":350,"completionDate":"2022-12-31"},{"nctId":"NCT01446328","phase":"PHASE4","title":"Bergen Psychosis Project 2 - The Best Intro Study","status":"COMPLETED","sponsor":"Haukeland University Hospital","startDate":"2011-10","conditions":["Schizophrenia","Psychotic Disorders"],"enrollment":151,"completionDate":"2017-12"},{"nctId":"NCT02880995","phase":"NA","title":"[18 Fluorine(F)]DOPA Determinants and Predictors of Treatment Response in Psychosis","status":"UNKNOWN","sponsor":"Seoul National University Hospital","startDate":"2017-11-01","conditions":["Schizophrenia"],"enrollment":62,"completionDate":"2019-12"},{"nctId":"NCT01991821","phase":"PHASE3","title":"European Phase III Study of APD421 in PONV","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","startDate":"2013-07","conditions":["PONV"],"enrollment":368,"completionDate":"2014-01"},{"nctId":"NCT01609153","phase":"PHASE4","title":"Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy","status":"COMPLETED","sponsor":"Heinrich-Heine University, Duesseldorf","startDate":"2012-06","conditions":["Schizophrenia","Schizoaffective Disorder"],"enrollment":328,"completionDate":"2019-04"},{"nctId":"NCT02337062","phase":"PHASE3","title":"Phase IIIb Study of APD421 in Combination as PONV Prophylaxis","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","isPivotal":true,"startDate":"2015-02","conditions":["PONV"],"enrollment":1147,"completionDate":"2015-09"},{"nctId":"NCT01991860","phase":"PHASE3","title":"US Phase III Study of APD421 in PONV","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","isPivotal":true,"startDate":"2013-08","conditions":["PONV"],"enrollment":364,"completionDate":"2014-01"},{"nctId":"NCT02646566","phase":"PHASE3","title":"Study of APD421 as PONV Treatment (Prior Prophylaxis)","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","isPivotal":true,"startDate":"2016-03","conditions":["Postoperative Nausea and Vomiting"],"enrollment":705,"completionDate":"2017-01"},{"nctId":"NCT02449291","phase":"PHASE3","title":"Study of APD421 as PONV Treatment (no Prior Prophylaxis)","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","isPivotal":true,"startDate":"2015-09","conditions":["Postoperative Nausea and Vomiting"],"enrollment":568,"completionDate":"2016-07"},{"nctId":"NCT03802838","phase":"PHASE4","title":"Clinical Evaluation of Acupuncture Treatment for Negative Symptoms of Schizophrenia","status":"UNKNOWN","sponsor":"Shanghai Mental Health Center","startDate":"2017-10-01","conditions":["Schizophrenia"],"enrollment":50,"completionDate":"2019-09-30"},{"nctId":"NCT02661594","phase":"PHASE1","title":"Thorough QT Study of Intravenous Amisulpride","status":"COMPLETED","sponsor":"Acacia Pharma Ltd","startDate":"2013-11","conditions":["Healthy"],"enrollment":40,"completionDate":"2014-03"},{"nctId":"NCT02307396","phase":"PHASE4","title":"Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients","status":"COMPLETED","sponsor":"Technical University of Munich","startDate":"2015-02-01","conditions":["Schizophrenia","Schizophrenia and Disorders With Psychotic Features","Schizoaffective Disorders"],"enrollment":21,"completionDate":"2016-06-22"},{"nctId":"NCT01248195","phase":"PHASE4","title":"Optimization of Treatment and Management of Schizophrenia in Europe","status":"COMPLETED","sponsor":"Rene Kahn","startDate":"2011-05","conditions":["Schizophrenia","Schizophreniform Disorder","Schizoaffective Disorder"],"enrollment":479,"completionDate":"2016-04"},{"nctId":"NCT01253421","phase":"PHASE1","title":"The Effects of Dopamine on Reward Processing","status":"COMPLETED","sponsor":"Mclean Hospital","startDate":"2012-02","conditions":["Major Depressive Disorder (MDD)"],"enrollment":159,"completionDate":"2016-05"},{"nctId":"NCT02051387","phase":"PHASE1","title":"Cannabidiol as a Different Type of an Antipsychotic: Drug Delivery and Interaction Study","status":"COMPLETED","sponsor":"Central Institute of Mental Health, Mannheim","startDate":"2013-01","conditions":["Schizophrenia"],"enrollment":74,"completionDate":"2017-08"},{"nctId":"NCT02374567","phase":"PHASE3","title":"Pharmacovigilance in Gerontopsychiatric Patients","status":"TERMINATED","sponsor":"Hannover Medical School","startDate":"2015-01","conditions":["Dementia","Depression","Schizophrenia","Psychosomatic Disorders","Anxiety Disorders"],"enrollment":407,"completionDate":"2017-06-28"},{"nctId":"NCT01454453","phase":"PHASE4","title":"Optimisation of Antipsychotic Drug Use in Older People","status":"TERMINATED","sponsor":"Institute of Psychiatry, London","startDate":"2012-05","conditions":["Alzheimer's Disease","Schizophrenia"],"enrollment":64,"completionDate":"2015-07"},{"nctId":"NCT01555814","phase":"NA","title":"Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE): Substudy Site Copenhagen","status":"COMPLETED","sponsor":"Birte Glenthoj","startDate":"2011-05","conditions":["Schizophrenia","Schizophreniform Disorder","Schizoaffective Disorder"],"enrollment":56,"completionDate":"2016-10"},{"nctId":"NCT01154829","phase":"NA","title":"Pan European Collaboration on Antipsychotic Naive Schizophrenia (PECANS)","status":"COMPLETED","sponsor":"University of Copenhagen","startDate":"2008-12","conditions":["Schizophrenia"],"enrollment":136,"completionDate":"2016-05"},{"nctId":"NCT01615185","phase":"PHASE4","title":"A Randomized, Double-blind, Comparison of the Efficacy and Safety of Amisulpride Versus Low-dose Amisulpride Plus Low-dose Sulpiride in the Treatment of Schizophrenia","status":"TERMINATED","sponsor":"Kaohsiung Kai-Suan Psychiatric Hospital","startDate":"2008-01","conditions":["Schizophrenia"],"enrollment":96,"completionDate":"2011-12"},{"nctId":"NCT01448499","phase":"NA","title":"Clozapine Versus Amisulpride in Treatment-resistant Schizophrenia Patients","status":"WITHDRAWN","sponsor":"Geha Mental Health Center","startDate":"2011-10","conditions":["Schizophrenia","Treatment Resistant Disorders"],"enrollment":0,"completionDate":""},{"nctId":"NCT02557984","phase":"NA","title":"Dopamine and Opioid Receptor Antagonists Reduce Cue-induced Reward Responding and Reward Impulsivity","status":"COMPLETED","sponsor":"University of Zurich","startDate":"2014-02","conditions":["Addiction"],"enrollment":121,"completionDate":"2014-04"},{"nctId":"NCT01246232","phase":"PHASE4","title":"Amisulpride Augmentation in Clozapine-unresponsive Schizophrenia","status":"COMPLETED","sponsor":"Imperial College London","startDate":"2011-09","conditions":["Schizophrenia"],"enrollment":69,"completionDate":"2015-03"},{"nctId":"NCT01795183","phase":"PHASE4","title":"Effectiveness and Safety of Amisulpride in Chinese Patients With Schizophrenia","status":"COMPLETED","sponsor":"Sanofi","startDate":"2012-11","conditions":["Schizophrenia"],"enrollment":316,"completionDate":"2013-12"},{"nctId":"NCT00204061","phase":"PHASE4","title":"Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis","status":"COMPLETED","sponsor":"University of Cologne","startDate":"2001-01","conditions":["Schizophrenia","Psychoses"],"enrollment":124,"completionDate":"2005-06"},{"nctId":"NCT01765829","phase":"PHASE3","title":"Clinical Trial to Evaluate the Efficacy of Treatment vs Discontinuation in a First Episode of Non-affective Psychosis","status":"UNKNOWN","sponsor":"Fundación Pública Andaluza Progreso y Salud","startDate":"2012-11","conditions":["Psychosis Nos/Other"],"enrollment":104,"completionDate":"2015-11"},{"nctId":"NCT00471588","phase":"PHASE1","title":"Characterize The Modulatory Effects Of Dopamine D2/D3 Receptor Agonist And Antagonist Drugs On Compulsive Behaviors","status":"COMPLETED","sponsor":"GlaxoSmithKline","startDate":"2006-08","conditions":["Obsessive-Compulsive Disorder"],"enrollment":52,"completionDate":"2007-12"},{"nctId":"NCT01323205","phase":"PHASE2","title":"Investigation of the Safety, Tolerability and Potential Therapeutic Effects of JNJ-40411813 in Patients With Schizophrenia","status":"COMPLETED","sponsor":"Janssen Research & Development, LLC","startDate":"2011-05","conditions":["Schizophrenia"],"enrollment":100,"completionDate":"2012-12"},{"nctId":"NCT02095938","phase":"PHASE4","title":"Association of Amisulpride Response in Schizophrenia With Brain Image","status":"UNKNOWN","sponsor":"CHA University","startDate":"2014-01","conditions":["Schizophrenia","Schizophreniform Disorder"],"enrollment":20,"completionDate":"2015-12"},{"nctId":"NCT00956189","phase":"NA","title":"Identification and Treatment Response Prediction of Antipsychotic-Related Metabolic Syndrome","status":"COMPLETED","sponsor":"National Taiwan University Hospital","startDate":"2009-11","conditions":["Metabolic Syndrome X"],"enrollment":132,"completionDate":"2012-10"},{"nctId":"NCT00534573","phase":"PHASE3","title":"Benzamide Derivates as Treatment of Clozapine-induced Hypersalivation","status":"COMPLETED","sponsor":"Beersheva Mental Health Center","startDate":"2008-11","conditions":["Clozapine-induced Hypersalivation"],"enrollment":54,"completionDate":"2009-01"},{"nctId":"NCT00761670","phase":"PHASE4","title":"Efficacy Study on Cognitive Functions in Schizophrenic Patients","status":"COMPLETED","sponsor":"Sanofi","startDate":"2008-09","conditions":["Schizophrenia"],"enrollment":37,"completionDate":"2010-01"},{"nctId":"NCT01185418","phase":"","title":"Evaluation of Negative Symptoms and Cognitive Function After Administration of Antipsychotics in Healthy Volunteer","status":"COMPLETED","sponsor":"Chonbuk National University Hospital","startDate":"2009-03","conditions":["Normal Volunteers"],"enrollment":80,"completionDate":"2009-07"},{"nctId":"NCT01160991","phase":"NA","title":"Effect of Atypical Antipsychotic Drugs Olanzapine and Amisulpride on Glucose Metabolism","status":"COMPLETED","sponsor":"Central Institute of Mental Health, Mannheim","startDate":"2004-05","conditions":["Schizophrenia","Diabetes","Insulin Resistance"],"enrollment":10,"completionDate":"2006-10"},{"nctId":"NCT01105481","phase":"PHASE4","title":"Amisulpride Augmentation Therapy for Clozapine-resistant Schizophrenic Patients","status":"COMPLETED","sponsor":"National Health Research Institutes, Taiwan","startDate":"2006-05","conditions":["Treatment-resistant Schizophrenia"],"enrollment":273,"completionDate":"2008-06"},{"nctId":"NCT00304616","phase":"PHASE4","title":"SWitching to Abilify Trial (SWAT)","status":"COMPLETED","sponsor":"Korea Otsuka Pharmaceutical Co., Ltd.","startDate":"2004-10","conditions":["Schizophrenia"],"enrollment":500,"completionDate":"2007-10"},{"nctId":"NCT00926965","phase":"PHASE4","title":"Tardive Dyskinesia and Cognitive Function","status":"COMPLETED","sponsor":"Taipei Veterans General Hospital, Taiwan","startDate":"2003-01","conditions":["Tardive Dyskinesia","Neurocognitive Function"],"enrollment":80,"completionDate":"2007-12"},{"nctId":"NCT00419653","phase":"PHASE4","title":"Modulation of Regional Brain Activation in Schizophrenic Patients by Pharmacological Therapy","status":"TERMINATED","sponsor":"University of Jena","startDate":"2003-01","conditions":["Schizophrenia"],"enrollment":19,"completionDate":"2007-09"},{"nctId":"NCT00436371","phase":"PHASE4","title":"Amisulpride in Schizophrenic Acute Phase Patients","status":"COMPLETED","sponsor":"Sanofi","startDate":"2005-05","conditions":["Schizophrenia"],"enrollment":50,"completionDate":""},{"nctId":"NCT00245674","phase":"PHASE4","title":"SOLIACS: Solian Solution in the Acute Setting","status":"COMPLETED","sponsor":"Sanofi","startDate":"2005-06","conditions":["Schizophrenia"],"enrollment":300,"completionDate":""},{"nctId":"NCT00331981","phase":"PHASE4","title":"Amisulpride in Schizophrenic Patients","status":"COMPLETED","sponsor":"Sanofi","startDate":"2004-02","conditions":["Schizophrenia"],"enrollment":138,"completionDate":""},{"nctId":"NCT00126009","phase":"PHASE2","title":"SOLMANIA - Comparison of Valproate-Amisulpride and Valproate-Haloperidol in Bipolar I Patients","status":"COMPLETED","sponsor":"Sanofi","startDate":"2004-05","conditions":["Bipolar Disorder"],"enrollment":120,"completionDate":""},{"nctId":"NCT00628290","phase":"PHASE2","title":"Evaluation of the Antipsychotic Efficacy of Cannabidiol in Acute Schizophrenic Psychosis","status":"COMPLETED","sponsor":"University of Cologne","startDate":"2002-10","conditions":["Schizophrenia"],"enrollment":42,"completionDate":"2008-03"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"pivotalTrials":["NCT01991860","NCT02337062","NCT02449291","NCT02646566"],"administration":{"route":"Intravenous","formulation":"Injection","formulations":[{"form":"INJECTION, SOLUTION","route":"INTRAVENOUS","productName":"Barhemsys"}]},"_patentsChecked":true,"crossReferences":{"MMSL":"17788","NDDF":"005229","UNII":"8110R61I4U","CHEBI":"CHEBI:64045","VANDF":"4039609","INN_ID":"4960","RXNORM":"2284233","UMLSCUI":"C0103045","chemblId":"CHEMBL243712","ChEMBL_ID":"CHEMBL243712","KEGG_DRUG":"D07310","DRUGBANK_ID":"DB06288","PUBCHEM_CID":"2159","SNOMEDCT_US":"321636003","IUPHAR_LIGAND_ID":"963","MESH_DESCRIPTOR_UI":"D000077582"},"formularyStatus":[],"originalProduct":{"form":"INJECTION, SOLUTION","route":"INTRAVENOUS","company":"Acacia Pharma Ltd","brandName":"Barhemsys","isOriginal":true,"marketingStatus":"NDA"},"_enricherVersion":"v2","_offLabelChecked":true,"developmentCodes":[],"ownershipHistory":[{"period":"2020-","companyName":"Acacia Pharma Ltd","relationship":"Original Developer"},{"period":"present","companyName":"Acacia","relationship":"Current Owner"}],"pharmacokinetics":{"source":"DrugCentral","bioavailability":"48%","fractionUnbound":"0.52%"},"publicationCount":1443,"therapeuticAreas":["Neuroscience"],"atcClassification":{"source":"DrugCentral","atcCode":"N05AL05","allCodes":["N05AL05"]},"biosimilarFilings":[],"originalDeveloper":"Acacia Pharma Ltd","recentPublications":[],"companionDiagnostics":[],"genericManufacturers":0,"_genericFilersChecked":true,"genericManufacturerList":[],"status":"approved","companyName":"Acacia","companyId":"acacia","modality":"Small molecule","firstApprovalDate":"2020","enrichmentLevel":4,"visitCount":0,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2020-09-01T00:00:00.000Z","mah":"ACACIA","brand_name_local":null,"application_number":"NDA209510"},{"country_code":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"BR","regulator":"ANVISA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"MX","regulator":"COFEPRIS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AR","regulator":"ANMAT","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TR","regulator":"TITCK","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IN","regulator":"CDSCO","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TH","regulator":"FDA-TH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"MY","regulator":"NPRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"PH","regulator":"FDA-PH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"CO","regulator":"INVIMA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"ZA","regulator":"SAHPRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TW","regulator":"TFDA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"HK","regulator":"DH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null}],"trialStats":{"total":1,"withResults":0},"validation":{"fieldsValidated":2,"lastValidatedAt":"2026-04-20T00:44:54.489863+00:00","fieldsConflicting":0,"overallConfidence":0.95},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}