Vasopressin in 0.9% Sodium Chloride

1 INDICATIONS AND USAGE Vasopressin in Sodium Chloride Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. Vasopressin in Sodium Chloride Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. ( 1 )

2 DOSAGE AND ADMINISTRATION This product does not require further dilution prior to administration. ( 2.1 ) Post-cardiotomy shock: 0.03 units/minute to 0.1 units/minute by intravenous infusion ( 2.2 ) Septic shock: 0.01 units/minute to 0.07 units/minute by intravenous infusion ( 2.2 ) 2.1 Preparation of Solution Inspect parenteral drug products for particulate matter and discoloration prior to use, whenever solution and container permit. This product does not require further dilution prior to administration. 2.2 Administration In general, titrate to the lowest dose compatible with a clinically acceptable response. The recommended starting dose is: Post-cardiotomy shock: 0.03 units/minute by intravenous infusion Septic Shock: 0.01 units/minute by intravenous infusion Titrate up by 0.005 units/minute at 10- to 15-minute intervals until the target blood pressure is reached. There are limited data for doses above 0.1 units/minute for postcardiotomy shock and 0.07 units/minute for septic shock. Adverse reactions are expected to increase with higher doses. After target blood pressure has been maintained for 8 hours without the use of catecholamines, taper Vasopressin in Sodium Chloride Injection by 0.005 units/minute every hour as tolerated to maintain target blood pressure.

5 WARNINGS AND PRECAUTIONS Can worsen cardiac function. ( 5.1 ) Reversible diabetes insipidus ( 5.2 ) 5.1 Worsening Cardiac Function A decrease in cardiac index may be observed with the use of vasopressin. 5.2 Reversible Diabetes Insipidus Patients may experience reversible diabetes insipidus, manifested by the development of polyuria, a dilute urine, and hypernatremia, after cessation of treatment with vasopressin. Monitor serum electrolytes, fluid status and urine output after vasopressin discontinuation. Some patients may require readministration of vasopressin or administration of desmopressin to correct fluid and electrolyte shifts.

4 CONTRAINDICATIONS Vasopressin in Sodium Chloride Injection is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol. Vasopressin in Sodium Chloride Injection is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol. ( 4 )

7 DRUG INTERACTIONS Pressor effects of catecholamines and Vasopressin in Sodium Chloride Injection are expected to be additive. ( 7.1 ) Indomethacin may prolong effects of Vasopressin in Sodium Chloride Injection. ( 7.2 ) Co-administration of ganglionic blockers or drugs causing SIADH may increase the pressor response. ( 7.3 , 7.4 ) Co-administration of drugs causing diabetes insipidus may decrease the pressor response. ( 7.5 ) 7.1 Catecholamines Use with catecholamines is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed. 7.2 Indomethacin Use with indomethacin may prolong the effect of Vasopressin in Sodium Chloride Injection on cardiac index and systemic vascular resistance. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed [ see Clinical Pharmacology ( 12.3 ) ]. 7.3 Ganglionic Blocking Agents Use with ganglionic blocking agents may increase the effect of Vasopressin in Sodium Chloride Injection on mean arterial blood pressure. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed [ see Clinical Pharmacology ( 12.3 ) ]. 7.4 Drugs Suspected of Causing SIADH Use with drugs suspected of causing SIADH (e.g., SSRIs, tricyclic antidepressants, haloperidol, chlorpropamide, enalapril, methyldopa, pentamidine, vincristine, cyclophosphamide, ifosfamide, felbamate) may increase the pressor effect in addition to the antidiuretic effect of Vasopressin in Sodium Chloride Injection. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed. 7.5 Drugs Suspected of Causing Diabetes Insipidus Use with drugs suspected of causing diabetes insipidus (e.g., demeclocycline, lithium, foscarnet, clozapine) may decrease the pressor effect in addition to the antidiuretic effect of Vasopressin in Sodium Chloride Injection. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

8.1 Pregnancy Risk Summary There are no available data on Vasopressin in Sodium Chloride Injection use in pregnant women to inform a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted. Clinical Considerations Dose adjustments during pregnancy and the postpartum period: Because of increased clearance of vasopressin in the second and third trimester, the dose of Vasopressin in Sodium Chloride Injection may need to be increased [ see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 ) ]. Maternal adverse reactions: Vasopressin in Sodium Chloride Injection may produce tonic uterine contractions that could threaten the continuation of pregnancy.

6 ADVERSE REACTIONS The following adverse reactions associated with the use of vasopressin were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Bleeding/lymphatic system disorders: Hemorrhagic shock, decreased platelets, intractable bleeding Cardiac disorders: Right heart failure, atrial fibrillation, bradycardia, myocardial ischemia Gastrointestinal disorders: Mesenteric ischemia Hepatobiliary: Increased bilirubin levels Renal/urinary disorders: Acute renal insufficiency Vascular disorders: Distal limb ischemia Metabolic: Hyponatremia Skin: Ischemic lesions The most common adverse reactions include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia and ischemia (coronary, mesenteric, skin, digital). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Long Grove Pharmaceuticals LLC at 1-855-642-2594 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Postmarketing Experience Reversible diabetes insipidus [see Warnings and Precautions ( 5.2 )]