vasopressin (USP) for Shock

INDICATIONS AND USAGE Vasostrict ® is indicated to increase blood pressure in adults with vasodilatory shock (e.g., post-cardiotomy or sepsis) who remain hypotensive despite fluids and catecholamines. Vasostrict ® is indicated to increase blood pressure in adults with vasodilatory shock (e.g., post-cardiotomy or sepsis) who remain hypotensive despite fluids and catecholamines. ( 1 )

DOSAGE AND ADMINISTRATION Dilute 20 units/mL single dose vial or 200 units/10 mL (20 units/mL) multiple dose vial contents with normal saline (0.9% sodium chloride) or 5% dextrose in water (D5W) to either 0.1 units/mL or 1 unit/mL for intravenous administration. Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration. ( 2.1 ) The 20 units/100 mL, 40 units/100 mL, 60 units/100 mL and 50 units/50 mL single dose vials do not require further dilution prior to administration. ( 2.1 ) Post-cardiotomy shock: 0.03 to 0.1 units/minute ( 2.2 ) Septic shock: 0.01 to 0.07 units/minute ( 2.2 ) 2.1 Preparation of Solution Inspect parenteral drug products for particulate matter and discoloration prior to use, whenever solution and container permit. Vasostrict ® Solution for Dilution, 20 units/mL and 200 units/10 mL (20 units/mL) Dilute Vasostrict ® in normal saline (0.9% sodium chloride) or 5% dextrose in water (D5W) prior to use for intravenous administration. Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration. Table 1 Preparation of diluted solutions Fluid restriction? Final concentration Mix Vasostrict ® Diluent No 0.1 units/mL 2.5 mL (50 units) 500 mL Yes 1 unit/mL 5 mL (100 units) 100 mL Vasostrict ® Premixed Solution, 20 units/100 mL (0.2 units/mL), 40 units/100 mL (0.4 units/mL), 60 units/100 mL (0.6 units/mL) and 50 units/50 mL (1 unit/mL) 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 Septic Shock: 0.01 units/minute 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 post-cardiotomy 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 injection by 0.005 units/minute every hour as tolerated to maintain target blood pressure.

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 Injection, USP. 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.

DRUG INTERACTIONS Pressor effects of catecholamines and vasopressin injection are expected to be additive. ( 7.1 ) Indomethacin may prolong effects of vasopressin injection. ( 7.2 ) Co-administration of ganglionic blockers or drugs causing SIADH (syndrome of inappropriate antidiuretic hormone secretion) 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 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 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 (Syndrome of Inappropriate Antidiuretic Hormone Secretion) 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 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 injection. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

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 Postmarketing Experience Reversible diabetes insipidus [ see Warnings and Precautions ( 5.2 ) ]. 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 Amphastar Pharmaceuticals, Inc. at 1-800-423-4136 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch