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 • Post-cardiotomy shock: 0.03 units/minute to 0.1 units/minute by intravenous infusion. ( 2.1 ) • Septic shock: 0.01 units/minute to 0.07 units/minute by intravenous infusion. ( 2.1 ) 2.1 Administration This product does not require dilution prior to 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 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. Inspect visually for any particulate matter and discoloration prior to administration. Discard Unused Portion Do not add supplemental medication or additive

3 DOSAGE FORMS AND STRENGTHS Injection: a clear, practically colorless solution for intravenous infusion, supplied in 100-mL single dose ready-to-use containers as: • 20 units vasopressin (0.2 units/mL) in 0.9% sodium chloride • 40 units vasopressin (0.4 units/mL) in 0.9% sodium chloride Injection: 100-mL single dose, ready-to-use containers with ( 3 ) • 20 units vasopressin (0.2 units/mL) in 0.9% sodium chloride. • 40 units vasopressin (0.4 units/mL) in 0.9% sodium chloride.

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

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 reliably their frequency or 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 Baxter Healthcare at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 (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.

8 USE IN SPECIFIC POPULATIONS • Pregnancy: May induce tonic uterine contractions. ( 8.1 ) • Pediatric Use: Safety and effectiveness have not been established. ( 8.4 ) • Geriatric Use: No safety issues have not been identified in older patients. ( 8.5 ) 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 (2.1) 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. 8.2 Lactation There are no data on the presence of vasopressin injection in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. 8.4 Pediatric Use Safety and effectiveness of Vasopressin in Sodium Chloride Injection in pediatric patients with vasodilatory shock have not been established. 8.5 Geriatric Use Clinical studies of vasopressin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [ see Warnings and Precautions (5) , Adverse Reactions (6) , and Clinical Pharmacology (12.3) ].

12.1 Mechanism of Action Vasopressin causes vasoconstriction by binding to V 1 receptors on vascular smooth muscle coupled to the Gq/11-phospholipase C-phosphatidyl-inositol-triphosphate pathway, resulting in the release of intracellular calcium. In addition, vasopressin stimulates antidiuresis via stimulation of V 2 receptors which are coupled to adenyl cyclase.

11 DESCRIPTION Vasopressin in Sodium Chloride Injection contains vasopressin, a polypeptide hormone. 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 amorphous powder, freely soluble in water. The structural formula is: Molecular Formula: C 46 H 65 N 15 O 12 S 2 Molecular Weight: 1084.23 Vasopressin in Sodium Chloride Injection is a sterile, aqueous solution of synthetic arginine vasopressin for intravenous administration. Each 100 mL contains 20 units (0.2 units/mL) or 40 units (0.4 units/mL) of vasopressin. Each 100mL also contains 900 mg Sodium Chloride, 33.6 mg Sodium DL-Lactate, and Water for Injection. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid. It has a pH of 3.6 – 4.0. Vasopressin Structural Formula

10 OVERDOSAGE Overdosage with Vasopressin in Sodium Chloride Injection can be expected to manifest as consequences of vasoconstriction of various vascular beds (peripheral, mesenteric, and coronary) and as hyponatremia. In addition, overdosage may lead less commonly to ventricular tachyarrhythmias (including Torsade de Pointes), rhabdomyolysis, and non-specific gastrointestinal symptoms. Direct effects will resolve within minutes of withdrawal of treatment.

16 HOW SUPPLIED/STORAGE AND HANDLING Vasopressin in Sodium Chloride Injection is supplied as a clear, practically colorless solution for intravenous administration in single-dose 100 mL ready-to-use containers available as: Product Code Product Description NDC Number 2G3498 20 units vasopressin (0.2 units/mL) Supplied as 12 bags per carton 0338-9640-12 2G3499 40 units vasopressin (0.4 units/mL) Supplied as 12 bags per carton 0338-9647-12 Store in the refrigerator (2°C to 8°C [36°F to 46°F]). Protect from freezing. If needed, Vasopressin in Sodium Chloride Injection may be stored at room temperature up to 25°C (77°F) for up to 6 months. Discard after 6 months if stored at room temperature or until the expiration date printed on the carton and container label, whichever is earlier. Once stored at room temperature, do not place back in the refrigerator. The drug product must be stored in its light protective carton during storage. Manufactured by, Packed by, Distributed by: Baxter Healthcare Corporation Deerfield, IL 60015 USA Printed in USA 07-19-06-884 Baxter and Galaxy are trademarks of Baxter International Inc.