Vasostrict

1 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 )

2 DOSAGE AND ADMINISTRATION Dilute Vasostrict ® 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 ) 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 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.

4 CONTRAINDICATIONS Vasostrict ® is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol. Vasostrict ® is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol. ( 4 )

5 WARNINGS AND PRECAUTIONS Can worsen cardiac function. ( 5.1 ) 5.1 Worsening Cardiac Function Use in patients with impaired cardiac response may worsen cardiac output.

7 DRUG INTERACTIONS Pressor effects of catecholamines and Vasostrict ® are expected to be additive. ( 7.1 ) Indomethacin may prolong effects of Vasostrict ® . ( 7.2 ) Co-administration of ganglionic blockers or drugs causing SIADH may increase the pressor response. ( 7.3 , 7.5 ) Co-administration of drugs causing diabetes insipidus may decrease the pressor response. ( 7.6 ) 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 (12.3) ]. 7.3 Ganglionic Blocking Agents Use with ganglionic blocking agents may increase the effect of Vasostrict ® on mean arterial blood pressure [see Clinical Pharmacology (12.3) ]. 7.4 Furosemide Use with furosemide increases the effect of Vasostrict ® on osmolar clearance and urine flow [see Clinical Pharmacology (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 ® .

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 Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Pregnancy Category C Risk Summary: There are no adequate or well-controlled studies of Vasostrict ® in pregnant women. It is not known whether vasopressin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Animal reproduction studies have not been conducted with vasopressin [see Clinical Pharmacology (12.3) ]. Clinical Considerations: Because of increased clearance of vasopressin in the second and third trimester, the dose of Vasostrict ® may need to be up-titrated to doses exceeding 0.1 units/minute in post-cardiotomy shock and 0.07 units/minute in septic shock. Vasostrict ® may produce tonic uterine contractions that could threaten the continuation of pregnancy .