Get your patient on Vasopressin In 0.9% Sodium Chloride - Vasopressin solution (Vasopressin)
Vasopressin In 0.9% Sodium Chloride - Vasopressin solution prescribing information
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.
DOSAGE AND ADMINISTRATION
Preparation of Solution
Inspect parenteral drug products for particulate matter and discoloration prior to use, whenever solution and container permit.
This product does not require further dilution prior to administration.
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 postcardiotomy 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 in Sodium Chloride Injection by 0.005 units/minute every hour as tolerated to maintain target blood pressure.
DOSAGE FORMS AND STRENGTHS
Vasopressin in Sodium Chloride Injection is a clear, colorless premixed solution for intravenous administration in a single-dose, ready to use vial available as:
- 20 units/100 mL (0.2 units/mL) in 0.9% Sodium Chloride
- 40 units/100 mL (0.4 units/mL) in 0.9% Sodium Chloride
- 50 units/50 mL (1 unit/mL) in 0.9% Sodium Chloride
USE IN SPECIFIC POPULATIONS
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
Maternal adverse reactions: Vasopressin in Sodium Chloride Injection may produce tonic uterine contractions that could threaten the continuation of pregnancy.
Lactation
There are no data on the presence of Vasopressin in Sodium Chloride Injection in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.
Pediatric Use
Safety and effectiveness of Vasopressin in Sodium Chloride Injection in pediatric patients with vasodilatory shock have not been established.
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 ) ].
CONTRAINDICATIONS
Vasopressin in Sodium Chloride Injection is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol.
WARNINGS AND PRECAUTIONS
Worsening Cardiac Function
A decrease in cardiac index may be observed with the use of vasopressin.
Reversible Diabetes Insipidus
Patients may experience reversible diabetes insipidus, manifested by the development of polyuria, a dilute urine, and hypernatremia, after cessation of treatment with vasopressin. Monitor serum electrolytes, fluid status and urine output after vasopressin discontinuation. Some patients may require readministration of vasopressin or administration of desmopressin to correct fluid and electrolyte shifts.
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
Postmarketing Experience
Reversible diabetes insipidus [see Warnings and Precautions (5.2 )]
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 may increase the pressor response. (7.3 , 7.4 )
- Co-administration of drugs causing diabetes insipidus may decrease the pressor response. (7.5 )
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.
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 ) ].
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 ) ].
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.
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.
DESCRIPTION
Vasopressin is a polypeptide hormone. Vasopressin in Sodium Chloride Injection is a sterile, aqueous solution of synthetic arginine vasopressin for intravenous administration.
Each mL of the 0.2 unit/mL strength contains 0.2 units vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.05 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP. Each mL of the 0.4 unit/mL strength contains 0.4 units vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.10 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP. Each mL of the 1 unit/mL strength contains 1 unit vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.25 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP.
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
CLINICAL PHARMACOLOGY
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.
Pharmacodynamics
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 addition, vasopressin has been demonstrated to cause vasodilation in numerous vascular beds that are mediated by V 2 , 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.
Pharmacokinetics
Vasopressin plasma concentrations increase linearly with increasing infusion rates from 10 micro-units/kg/min to 200 micro-units /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 units/minute 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.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
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.
CLINICAL STUDIES
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.
HOW SUPPLIED/STORAGE AND HANDLING
Vasopressin in Sodium Chloride Injection is a clear, colorless solution for intravenous administration available as:
NDC 81298-8552-3: A carton of 10 single dose vials. Each vial contains vasopressin 20 units/100 mL (0.2 units/mL).
NDC 81298-8554-3: A carton of 10 single dose vials. Each vial contains vasopressin 40 units/100 mL (0.4 units/mL).
NDC 81298-8550-3: A carton of 10 single dose vials. Each vial contains vasopressin 50 units/50 mL (1 unit/mL).
Store unopened vials refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Keep vials in original carton to protect from light.
Vials may be held up to three (3) 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 three (3) months 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 Vasopressin in Sodium Chloride Injection beyond the manufacturer's expiration date stamped on the vial.
Manufactured for: Long Grove Pharmaceuticals, LLC Rosemont, IL 60018
Made in India
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.
