ressure. 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 vasostrict ® . 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 vasostrict ® . hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

ard 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), and 60 units/100 ml (0.6 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.

. ( 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.

ressure. 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 vasostrict ® . 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 vasostrict ® . hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

n 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 vasostrict ® 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) ] .

iated by v2, v 3 , oxytocin and purinergic p2 receptors. in patients with vasodilatory shock vasopressin in therapeutic doses increases systemic vascular resistance and mean arterial blood pressure and reduces the dose requirements for norepinephrine. vasopressin tends to decrease heart rate and cardiac output. the pressor effect is proportional to the infusion rate of exogenous vasopressin. the pressor effect reaches its peak within 15 minutes. after stopping the infusion the pressor effect fades within 20 minutes. there is no evidence for tachyphylaxis or tolerance to the pressor effect of vasopressin in patients. 12.3 pharmacokinetics vasopressin plasma concentrations increase linearly with increasing infusion rates from 10 to 200 μu/kg/min. steady state plasma concentrations are achieved after 30 minutes of continuous intravenous infusion. distribution vasopressin does not appear to bind plasma protein. the volume of distribution is 140 ml/kg. elimination at infusion rates used in vasodilatory shock (0.01 to 0.1 units/minute), the clearance of vasopressin is 9 to 25 ml/min/kg in patients with vasodilatory shock. the apparent t 1/2 of vasopressin at these levels is ≤10 minutes. metabolism serine protease, carboxipeptidase and disulfide oxido-reductase cleave vasopressin at sites relevant for the pharmacological activity of the hormone. thus, the generated metabolites are not expected to retain important pharmacological activity. excretion vasopressin is predominantly metabolized and only about 6% of the dose is excreted unchanged into urine. specific populations pregnancy: because of a spillover into blood of placental vasopressinase, the clearance of exogenous and endogenous vasopressin increases gradually over the course of a pregnancy. during the first trimester of pregnancy, the clearance is only slightly increased. however, by the third trimester the clearance of vasopressin is increased about 4-fold and at term up to 5-fold. after delivery, the clearance of vasopressin returns to preconception baseline within two weeks. drug interactions indomethacin more than doubles the time to offset for vasopressin’s effect on peripheral vascular resistance and cardiac output in healthy subjects [ see drug interactions (7.2) ] . the ganglionic blocking agent tetra-ethylammonium increases the pressor effect of vasopressin by 20% in healthy subjects [ see drug interactions (7.3) ] . halothane, morphine, fentanyl, alfentanyl and sufentanyl do not impact exposure to endogenous vasopressin.

spillover into blood of placental vasopressinase, the clearance of exogenous and endogenous vasopressin increases gradually over the course of a pregnancy. during the first trimester of pregnancy, the clearance is only slightly increased. however, by the third trimester the clearance of vasopressin is increased about 4-fold and at term up to 5-fold. after delivery, the clearance of vasopressin returns to preconception baseline within two weeks. drug interactions indomethacin more than doubles the time to offset for vasopressin’s effect on peripheral vascular resistance and cardiac output in healthy subjects [ see drug interactions (7.2) ] . the ganglionic blocking agent tetra-ethylammonium increases the pressor effect of vasopressin by 20% in healthy subjects [ see drug interactions (7.3) ] . halothane, morphine, fentanyl, alfentanyl and sufentanyl do not impact exposure to endogenous vasopressin.

frigeration 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. unopened refrigerated 2°c to 8°c (36°f to 46°f) unopened room temperature 20°c to 25°c (68°f to 77°f) do not store above 25°c (77°f) opened (after first puncture) 1 ml vial until manufacturer expiration date 12 months or until manufacturer expiration date, whichever is earlier n/a 10 ml vial until manufacturer expiration date 12 months or until manufacturer expiration date, whichever is earlier 30 days 100 ml vial until manufacturer expiration date 12 months or until manufacturer expiration date, whichever is earlier n/a