VASOPRESSIN

16 HOW SUPPLIED/STORAGE AND HANDELING VASOSTRICT(TM) (VASOPRESSIN INJECTION, USP) is supplied in the following dosage forms. NDC 51662-1314-1 VASOSTRICT(TM) (VASOPRESSIN INJECTION, USP) 20 UNITS PER mL 1mL VIAL NDC 51662-1314-2 VASOSTRICT(TM) (VASOPRESSIN INJECTION, USP) 20 UNITS PER mL 1mL VIAL in 1 pouch HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275 Also supplied in the following manufacture supplied dosage forms Vasostrict® (vasopressin injection, USP) is a clear, practically colorless solution for intravenous administration available as: NDC 42023-164-25: A carton of 25 single dose vials each containing vasopressin 1 mL at 20 units/mL. NDC 42023-190-01: A carton of 1 multiple dose vial containing vasopressin 10 mL at 200 units/10 mL (20 units/mL). Store between 2°C and 8°C (36°F and 46°F). Do not freeze. Vials may be held up to 12 months upon removal from refrigeration to room temperature storage conditions (20°C to 25°C [68°F to 77°F], USP Controlled Room Temperature), anytime within the labeled shelf life. Once removed from refrigeration, unopened vial should be marked to indicate the revised 12 month expiration date. If the manufacturer’s original expiration date is shorter than the revised expiration date, then the shorter date must be used. Do not use Vasostrict® beyond the manufacturer’s expiration date stamped on the vial. After initial entry into the 10 mL vial, the remaining contents must be refrigerated. Discard the refrigerated 10 mL vial after 30 days after first puncture. The storage conditions and expiration periods are summarized in the following table. HOW SUPPLIED-STORAGE

2 DOSAGE & ADMINISTRATION 2.1 Preparation of Diluted Solutions 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 Inspect parenteral drug products for particulate matter and discoloration prior to use, whenever solution and container permit. 2.2 Administration The goal of treatment is optimization of perfusion to critical organs, but aggressive treatment can compromise perfusion of organs, like the gastrointestinal tract, whose function is difficult to monitor. The following advice is empirical. In general, titrate to the lowest dose compatible with a clinically acceptable response. For post-cardiotomy shock, start with a dose of 0.03 units/minute. For septic shock, start with a dose of 0.01 units/minute. If the target blood pressure response is not achieved, titrate up by 0.005 units/minute at 10- to 15-minute intervals. The maximum dose for post-cardiotomy shock is 0.1 units/minute and for septic shock 0.07 units/minute. After target blood pressure has been maintained for 8 hours without the use of catecholamines, taper Vasostrict® by 0.005 units/minute every hour as tolerated to maintain target blood pressure.

Vasostrict® is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol.

7.1 Catecholamines Use with catecholamines is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters. 7.2 Indomethacin Use with indomethacin may prolong the effect of Vasostrict® on cardiac index and systemic vascular resistance [see Clinical Pharmacology ( 12- 12.3)]. 7.3 Ganglionic Blocking Agents Use with ganglionic blocking agents may increase the effect of Vasostrict® on mean arterial blood pressure [see Clinical Pharmacology ( 12- 12.3)]. 7.4 Furosemide Use with furosemide increases the effect of Vasostrict® on osmolar clearance and urine flow [see Clinical Pharmacology ( 12- 12.3)]. 7.5 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 Vasostrict®. 7.6 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 Vasostrict®.

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

Overdosage with Vasostrict® 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.