Barhemsys

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) ] .

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

<table width="75%" ID="table1"><caption>Table 1. Common Adverse Reactions<footnote>Reported in at least 2% of patients treated with BARHEMSYS and at a higher rate than placebo</footnote> in Adult Patients in Studies 1 and 2 of BARHEMSYS for Prevention of PONV</caption><col width="33%" align="left" valign="top"/><col width="34%" align="center" valign="top"/><col width="33%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule" rowspan="2"/><th styleCode="Rrule">BARHEMSYS 5 mg</th><th styleCode="Rrule">Placebo</th></tr><tr><th styleCode="Rrule" align="center">N=748</th><th styleCode="Rrule">N=741</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Chills</td><td styleCode="Rrule">4%</td><td styleCode="Rrule">3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hypokalemia</td><td styleCode="Rrule">4%</td><td styleCode="Rrule">2%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Procedural hypotension</td><td styleCode="Rrule">3%</td><td styleCode="Rrule">2%</td></tr><tr><td styleCode="Lrule Rrule">Abdominal distension</td><td styleCode="Rrule">2%</td><td styleCode="Rrule">1%</td></tr></tbody></table>