Vasostrict Injection
FDA Label NDC 71872-7014

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.

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.

Inspect parenteral drug products for particulate matter and discoloration prior to use, whenever solution and container permit.

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 ^® (vasopressin injection, USP) is a clear, practically colorless solution for intravenous administration available as 20 units/mL in a single dose vial and 200 units/10 mL (20 units/mL) in a multiple dose vial.

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

Use in patients with impaired cardiac response may worsen cardiac output.

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

Use with catecholamines is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters.

Use with indomethacin may prolong the effect of Vasostrict ^® on cardiac index and systemic vascular resistance [see Clinical Pharmacology (12.3)].

Use with ganglionic blocking agents may increase the effect of Vasostrict ^® on mean arterial blood pressure [see Clinical Pharmacology (12.3)].

Use with furosemide increases the effect of Vasostrict ^® on osmolar clearance and urine flow [see Clinical Pharmacology (12.3)].

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 ^®.

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 ^®.

It is not known whether vasopressin is present in human milk. However, oral absorption by a nursing infant is unlikely because vasopressin is rapidly destroyed in the gastrointestinal tract. Consider advising a lactating woman to pump and discard breast milk for 1.5 hours after receiving vasopressin to minimize potential exposure to the breastfed infant.

Safety and effectiveness of Vasostrict ^® in pediatric patients with vasodilatory shock have not been established.

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)] .

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.

Vasopressin is a polypeptide hormone that causes contraction of vascular and other smooth muscles and antidiuresis. Vasostrict ^® is a sterile, aqueous solution of synthetic arginine vasopressin for intravenous administration. The 1 mL solution contains vasopressin 20 units/mL, Water for Injection, USP, and sodium acetate buffer adjusted to a pH of 3.8.  The 10 mL solution contains vasopressin 20 units/mL, chlorobutanol, NF 0.5% as a preservative, and Water for Injection, USP and, sodium acetate buffer adjusted to a pH of 3.8.

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:

Chemical Structure (Vasostrict 1)

Molecular Formula: C ₄₆H ₆₅N ₁₅O ₁₂S ₂                 Molecular Weight: 1084.23

One mg is equivalent to 530 units.

The vasoconstrictive effects of vasopressin are mediated by vascular V ₁ receptors. Vascular V ₁ receptors are directly coupled to phopholipase C, resulting in release of calcium, leading to vasoconstriction. In addition, vasopressin stimulates antidiuresis via stimulation of V ₂ receptors which are coupled to adenyl cyclase.

At therapeutic doses exogenous vasopressin elicits a vasoconstrictive effect in most vascular beds including the splanchnic, renal and cutaneous circulation. In addition, vasopressin at pressor doses triggers contractions of smooth muscles in the gastrointestinal tract mediated by muscular V ₁-receptors and release of prolactin and ACTH via V ₃ receptors. At lower concentrations typical for the antidiuretic hormone vasopressin inhibits water diuresis via renal V ₂ 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. Onset of the pressor effect of vasopressin is rapid, and the peak effect occurs 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.

At infusion rates used in vasodilatory shock (0.01-0.1 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. Vasopressin is predominantly metabolized and only about 6% of the dose is excreted unchanged in urine. Animal experiments suggest that the metabolism of vasopressin is primarily by liver and kidney. 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.

No formal carcinogenicity or fertility studies with vasopressin have been conducted in animals. Vasopressin was found to be negative in the in vitro bacterial mutagenicity (Ames) test and the in vitro Chinese hamster ovary (CHO) cell chromosome aberration test. In mice, vasopressin has been reported to have an effect on function and fertilizing ability of spermatozoa.

Increases in systolic and mean blood pressure following administration of vasopressin were observed in 7 studies in septic shock and 8 in post-cardiotomy vasodilatory shock.

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).

NDC 71872-7014-1

Rx Only

Vasostrict^®

(Vasopressin Injection, USP)

20 Units per mL

For Intravenous Infusion

Must be diluted prior to use

Store between 2°C and 8°C (36°F and 46°F).

Do not store above 25°C (77°F).

Vials may be held at 20°C to 25°C (68°F to 77°F) for up to 12 months.

1 mL Single Dose Vial

Pdp (7014)