Barhemsys Drug Information

® 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. Treatment of PONV in patients who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis.

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 . 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%).

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

Dopamine Agonists Reciprocal antagonism of effects occurs between dopamine agonists (e.g., levodopa)

and BARHEMSYS. Avoid using levodopa with BARHEMSYS.

Drugs Prolonging the QT Interval

BARHEMSYS causes dose- and concentration-dependent QT prolongation . 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) .

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.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

is contraindicated in patients with known hypersensitivity to amisulpride . Known hypersensitivity to amisulpride.

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) . 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.