VASOPRESSIN: 1,953 Adverse Event Reports & Safety Profile

Vasopressin is a polypeptide hormone. Vasopressin injection, USP is a sterile, aqueous solution of synthetic arginine vasopressin for intravenous administration.

The

1 mL solution contains vasopressin 20 units/mL, 1.36 mg sodium acetate buffer and Water for Injection, USP. Sodium hydroxide and hydrochloric acid are included to adjust to a pH of 3.3 to 3.6.

The

100 mL solution contains vasopressin 0.4 units/mL. Each mL of the 0.4 unit/mL strength also contains dextrose anhydrous, 0.0546 mg glacial acetic acid, 0.012 mg sodium acetate and Water for Injection, USP. Sodium hydroxide and hydrochloric acid are included to adjust to a pH of 3.3 to 3.6. Each vial of the vasopressin injection premixed solutions contains 5% Dextrose in approximately 100 mL Water for Injection. The chemical name of vasopressin is Cyclo (1-6) L-Cysteinyl-L-Tyrosyl-L-Phenylalanyl-L-Glutaminyl-L-Asparaginyl-L-Cysteinyl-L-Prolyl-L-Arginyl-L-Glycinamide. It is a white to off-white powder or flakes, very soluble in water. The structural formula is: Molecular Formula: C 46 H 65 N 15 O 12 S 2 Molecular Weight:

1084.24 One mg is equivalent to 530 units. structure.jpg

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 )

AND ADMINISTRATION Dilute 20 units/mL single 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

40 units/100 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.

Vasopressin Injection

Solution for Dilution, 20 units/mL Dilute vasopressin injection 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 Vasopressin Injection Diluent No 0.1 units/mL 2.5 mL (50 units) 500 mL Yes 1 unit/mL 5 mL (100 units) 100 mL Vasopressin Injection Premixed Solution, 40 units/100 mL (0.4 units/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.

Vasopressin injection 10 mL multiple dose vial is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol.

The

1 mL single-dose vial does not contain chlorobutanol and is therefore contraindicated only in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin. Vasopressin injection 10 mL multiple dose vial is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol.

The

1 mL single-dose vial does not contain chlorobutanol and is therefore contraindicated only in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin. (4)

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

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.

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 (syndrome of inappropriate antiduretic 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 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.