VASOPRESSIN injection

VASOPRESSIN injection, for intravenous use

VASOPRESSIN

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, 1.36 mg sodium acetate buffer and Water for Injection, USP.  Sodium hydroxide and hydrochloric acid are included to adjust 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:

Molecular Formula: C46H65N15O12S2

Molecular Weight: 1084.23

One mg is equivalent to 530 units.

INDICATIONS AND USAGE

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

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 V 2 receptors which are coupled to adenyl cyclase.

DOSAGE AND ADMINISTRATION

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

Vasopressin Injection Solution for Dilution, 20 units/mL: Dilute vasopressin injection 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.

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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.

CONTRAINDICATIONS

Vasopressin injection 1 mL single dose vial does not contain chlorobutanol and is therefore contraindicated only in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin.

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 re-administration 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

DRUG INTERACTIONS

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 injection on cardiac index and  vascular resistance.  Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed 

Ganglionic Blocking Agents: Use with ganglionic blocking agents may increase the effect of vasopressin injection on mean arterial blood pressure.  Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed 

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.  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 injection. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

USE IN SPECIFIC POPULATIONS

Pregnancy: There are no available data on vasopressin 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.

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 may need to be increased

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

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.

Pediatric Use: Safety and effectiveness of vasopressin 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

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OVERDOSAGE

Overdosage with vasopressin injection 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.

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