Vasopressin by Amphastar Pharmaceuticals, Inc. VASOPRESSIN injection

Vasopressin by

Drug Labeling and Warnings

Vasopressin by is a Prescription medication manufactured, distributed, or labeled by Amphastar Pharmaceuticals, Inc.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    Vasopressin Injection, USP is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 Preparation of Solution

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

    Dilute Vasopressin Injection, USP 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 
     Vasopressin
    Injection, USP    		 Diluent
     No0.1 units/mL 2.5 mL (50 units) 500 mL
     Yes 1 unit/mL 5 mL (100 units) 100 mL

    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

    Tritate 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.

  • 3 DOSAGE FORMS AND STRENGTHS

    Vasopressin Injection, USP is a clear, practically colorless solution for intravenous administration available as 20 units/mL in a single dose vial. To be used after dilution.

  • 4 CONTRAINDICATIONS

    Vasopressin Injection, USP 1 mL single dose vial is contraindicated in patients with known allergy or hypersensitivity to 8‑L-arginine vasopressin or chlorobutanol.

  • 5 WARNINGS AND PRECAUTIONS

    5.1 Worsening Cardiac Function

    A decrease in cardiac index may be observed with the use of Vasopressin Injection, USP.

    5.2 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.

  • 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

    Postmarketing Experience
    Reversible diabetes insipidus [see Warnings and Precautions (5.2)].

  • 7 DRUG INTERACTIONS

    7.1 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.

    7.2 Indomethacin

    Use with indomethacin may prolong the effect of Vasopressin Injection, USP on cardiac index and systemic vascular resistance. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed [see Clinical Pharmacology (12.3)].

    7.3 Ganglionic Blocking Agents

    Use with ganglionic blocking agents may increase the effect of Vasopressin Injection, USP on mean arterial blood pressure. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed [seeClinical 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 Vasopressin Injection, USP. 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 Vasopressin Injection, USP. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary
    There are no available data on Vasopressin Injection, USP 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 with vasopressin.

    Clinical Considerations
    Dose adjustments during pregnancy and the postpartum period: Because of increased clearance of vasopressin in the second and third trimester, the dose of Vasopressin Injection, USP may need to be increased [see Dosage and Administration(2.2) and Clinical Pharmacology (12.3)].

    Maternal adverse reactions: Vasopressin Injection, USP may produce tonic uterine contractions that could threaten the continuation of pregnancy.

    8.2 Lactation

    There are no data on the presence of vasopressin 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 Vasopressin Injection, USP 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)].

  • 10 OVERDOSAGE

    Overdosage with Vasopressin Injection, USP 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.

  • 11 DESCRIPTION

    Vasopressin is a polypeptide hormone. Vasopressin Injection, USP is a sterile, aqueous solution of synthetic arginine vasopressin for intravenous administration.

    The 1 mL solution contains vasopressin 20 units/mL, chlorobutanol, NF 0.5% as a preservative, and Water for Injection, USP adjusted with acetic acid to pH 3.4-3.6.

    The chemical name of vasopressin is Cyclo (1-6) L-Cysteinyl-L-Tyrosyl-L-Phenylalanyl-LGlutaminyl-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:

    structure

    Molecular Formula: C46H65N15O12S2      Molecular Weight: 1084.23

    One mg is equivalent to 530 units.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Vasopressin causes vasoconstriction by binding to V1 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 V2 receptors which are coupled to adenyl cyclase.

    12.2 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 V1-receptors and release of prolactin and ACTH via V3 receptors. At lower concentrations typical for the antidiuretic hormone vasopressin inhibits water diuresis via renal V2 receptors. In addition, vasopressin has been demonstrated to cause vasodilation in numerous vascular beds that are mediated by V2, V3, 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 t1/2 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.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 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.

    13.2 Animal Toxicology and/or Pharmacology

    No toxicology studies were conducted with vasopressin.

  • 14 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.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    Vasopressin Injection, USP is a clear, practically colorless solution for intravenous administration available as:

    A carton of 10 single dose vials. Each vial contains vasopressin 1 mL at 20 units/mL.

    NDC: 0548-9701-00 Stock No. 9701

    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 Vasopressin Injection, USP beyond the manufacturer’s expiration date stamped on the vial. 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

  • SPL UNCLASSIFIED SECTION

    Rx Only


    © 2021 Amphastar Pharmaceuticals, Inc.
    Amphastar Pharmaceuticals, Inc.
    Rancho Cucamonga, CA 91730 U.S.A.
    Rev. 07/21

    6997016F

  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL TEXT - CARTON

    NDC 0548-9701-00   Rx Only

    Vasopressin
    Injection, USP

    20 Units per mL

    For Intravenous Infusion
    Must be diluted prior to use

    10 x 1 mL Single Dose Vials

    5297016D/6-19

    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.

    Do not freeze.

    Usual Dosage: See full
    prescribing information.

    Stock No. 9701

    AMPHASTAR PHARMACEUTICALS, INC.
    Rancho Cucamonga, CA 91730 U.S.A.

    carton

  • INGREDIENTS AND APPEARANCE
    VASOPRESSIN 
    vasopressin injection
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0548-9701
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    VASOPRESSIN (UNII: Y4907O6MFD) (ARGIPRESSIN - UNII:Y4907O6MFD) VASOPRESSIN20 [USP'U]  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    CHLOROBUTANOL (UNII: HM4YQM8WRC)  
    WATER (UNII: 059QF0KO0R)  
    ACETIC ACID (UNII: Q40Q9N063P)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0548-9701-001 in 1 CARTON08/31/2022
    11 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA21185708/22/2022
    Labeler - Amphastar Pharmaceuticals, Inc. (024736733)
    Establishment
    NameAddressID/FEIBusiness Operations
    Amphastar Pharmaceuticals, Inc.024736733manufacture(0548-9701) , analysis(0548-9701)
    • © 2024 FDA.report
    This site is not affiliated with or endorsed by the FDA.