Barhemsys Drug Information

• 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.

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. 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.

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.

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. Table 1. 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 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.

BARHEMSYS 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.