Brand name: Vasostrict
Drug class: Pituitary

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Exogenous antidiuretic hormone (ADH); maintains serum osmolality in normal range and acts as a vasopressor.

Uses for Vasopressin

Vasodilatory Shock

Used to increase BP in patients with vasodilatory shock (e.g., postcardiotomy shock, septic shock) who remain hypotensive despite adequate fluid resuscitation and catecholamines (e.g., norepinephrine).

Appears to have a catecholamine-sparing effect; however, effect on mortality remains unclear.

The Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock recommend norepinephrine as the first-line vasopressor of choice in adults with septic shock; may add vasopressin if further increase in mean arterial pressure (MAP) required or to reduce dosage requirements of norepinephrine.

Advanced Cardiovascular Life Support

Used for its vasopressor effects in patients with cardiac arrest^{† [off-label]}.

Previously recommended in ACLS guidelines as a substitute for epinephrine in adults with cardiac arrest since both drugs comparably effective. However, vasopressin has been removed from the current ACLS guideline in an effort to simplify the management approach when therapies are found to be equivalent.

High-quality CPR and defibrillation are the only proven interventions to increase survival to hospital discharge in ACLS. Other resuscitative efforts, including drug therapy, are considered secondary and should be performed without compromising the quality and timely delivery of chest compressions and defibrillation.

Diabetes Insipidus

Has been used to control polydypsia, polyuria, and dehydration in patients with central diabetes insipidus^{† [off-label]}; however, desmopressin is considered drug of choice for this use.

Impractical for chronic therapy because of its short duration of action.

Not effective in controlling polyuria caused by renal disease, nephrogenic diabetes insipidus, hypokalemia or hypercalcemia, or polyuria secondary to the administration of demeclocycline or lithium carbonate.

Abdominal Distention

Has been used to stimulate peristalsis in the management of intestinal paresis^{† [off-label]}, postoperative abdominal distention^{† [off-label]}, and distention complicating pneumonias or toxemias^{† [off-label]}.

Abdominal Radiographic Procedures

Has been used prior to abdominal radiographic procedures^† to dispel interfering gas shadows and/or to concentrate the contrast media.

Diagnostic Uses

Has been used as a provocative test for pituitary release of growth hormone and corticotropin^†; however, other diagnostic tests (e.g., insulin tolerance test) are considered more reliable diagnostic indicators of growth hormone reserve.

GI Hemorrhage

Has been administered IV or intra-arterially^† into the superior mesenteric artery as an adjunct in the treatment of acute and life-threatening, massive GI hemorrhage^† caused by various conditions (e.g., esophageal varices, inflammatory bowel disease, peptic ulcer disease, esophagogastritis, esophageal laceration, acute gastritis, colitis associated with Behcet’s disease, colonic diverticulosis, Mallory-Weiss syndrome, intestinal perforation).

May provide effective control of bleeding, but there is no evidence that the drug improves overall survival. In addition, there is a high recurrence of bleeding when discontinued.

Clinical usefulness also limited by adverse effects. Other vasoactive agents with fewer adverse effects (e.g., octreotide) preferred.

Vasopressin Dosage and Administration

Administration

Administer by IV infusion for vasodilatory shock.

Also has been administered by IM^† or sub-Q injection^† for other uses (e.g., postoperative abdominal distention, diabetes insipidus).

Also has been applied topically^† (e.g., with a cotton pledget, nasal spray, or dropper) to nasal mucosa in patients with diabetes insipidus.

Has been administered by intraosseous (IO) injection^† in the ACLS setting, generally when IV access not readily available; onset of action and systemic concentrations are comparable to those achieved with venous administration.

Also has been administered via endotracheal tube^† if vascular access (IV or IO) cannot be established during cardiac arrest.

Has been administered by intra-arterial^† infusion in patients with GI hemorrhage; requires specialized techniques and should only be performed by clinicians familiar with this method of administration. (See Risks of Intra-arterial Administration under Cautions.)

IV Administration

Dilution

Must dilute the commercially available 20-units/mL injection with 0.9% sodium chloride or 5% dextrose injection prior to IV administration. Manufacturer recommends dilution to the following final concentrations depending on patient's fluid status:

Patients who are not fluid restricted: Prepare concentration of 0.1 units/mL by mixing 50 units (2.5 mL) of vasopressin injection with 500 mL of diluent.

Patients who are fluid restricted: Prepare concentration of 1 unit/mL by mixing 100 units (5 mL) of vasopressin injection with 100 mL of diluent.

Discard unused portions of the diluted solution after 18 hours at room temperature or 24 hours under refrigeration.

Rate of Administration

Individualize IV infusion rates based on response.

Standardize 4 Safety

Standardized concentrations for vasopressin have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].

The S4S panel recommends trying to standardize dosing units but understands that some protocols may use “flat” dosing while others may require weight-based dosing.

dosing units differ from concentration units

Dosage

Potency of vasopressin is standardized according to pressor activity in rats and is expressed in USP posterior pituitary (pressor) units.

Pediatric Patients

Diabetes Insipidus†

IM or Sub-Q

Usually has been given in proportionately reduced dosage (from adult dosage).

Dosage of 2.5–10 units 2–4 times daily has been given.

Abdominal Distention†

IM

Usually has been given in proportionately reduced dosage (from adult dosage).

Abdominal Radiographic Procedures†

IM or Sub-Q

Usually has been given in proportionately reduced dosage (from adult dosage).

Diagnostic Uses

Provocative Testing for Growth Hormone and Corticotropin Release†

IM

0.3 units/kg has been given.

Adults

Vasodilatory Shock

IV Infusion

Individualize dosage; in general, titrate to lowest dose compatible with a clinically acceptable response. Goal of therapy is to optimize and maintain perfusion to critical organs without causing ischemic complications.

Patients with postcardiotomy shock: Manufacturer recommends initial dosage of 0.03 units/minute. If target BP response not achieved, may increase infusion rate by 0.005 units/minute at intervals of 10–15 minutes to a maximum of 0.1 units/minute.

Patients with septic shock: Manufacturer recommends initial dosage of 0.01 units/minute. If target BP response not achieved, may increase infusion rate by 0.005 units/minute at intervals of 10–15 minutes to a maximum of 0.07 units/minute.

After target BP has been maintained for 8 hours without use of catecholamines, taper vasopressin infusion rate by 0.005 units/minute every hour as tolerated to maintain target BP.

ACLS†

IV/IO†

40 units (given as a single dose) has been used to replace first or second dose of epinephrine in the treatment of cardiac arrest.

Diabetes Insipidus†

IM or Sub-Q

Has been given in a dosage of 5–10 units 2–3 times daily as needed; dosage range of 5–60 units daily.

Abdominal Distention†

IM

Initial dose of 5 units has been given with subsequent doses every 3–4 hours and doses increased to 10 units if necessary.

Abdominal Radiographic Procedures†

IM or Sub-Q

Usually, two 10-unit injections have been given (the first injection at 2 hours and the second injection at 30 minutes) prior to exposure of the radiographs.

Diagnostic Uses

Provocative Testing for Growth Hormone and Corticotropin Release†

IM

Dose of 10 units has been given.

GI Hemorrhage†

Has been administered by continuous IV or intra-arterial infusion after dilution with 0.9% sodium chloride or 5% dextrose injection to a concentration of 0.1–1 unit/mL. Continuous IV infusion is preferred. (See Risks of Intra-arterial Administration under Cautions.)

Dosage is empiric and must be individualized according to response and tolerance. Because many of the adverse effects are dose related, the lowest possible effective dosage should be used.

IV Infusion

Has been initiated at 0.2–0.4 units/minute and progressively increased to maximum of 0.6–0.9 units/minute based on individual patient response.

To minimize adverse effects, some experts recommend concomitant use of IV nitroglycerin (initiated at 40 mcg/minute, increased to a maximum of 400 mcg/minute).

Some experts recommend continuous use for no longer than 24 hours.

Intra-arterial Infusion†

Dosage of 0.1–0.5 units/minute has been used.

Special Populations

Hepatic Impairment

No specific dosage recommendations; titrate to effect.

Renal Impairment

No specific dosage recommendations; titrate to effect.

Geriatric Patients

Select dosage with caution, usually starting at the low end of the dosage range, because of possible age-related decreases in hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Cautions for Vasopressin

Contraindications

• Known allergy or hypersensitivity (e.g., anaphylaxis) to synthetic vasopressin or chlorobutanol (a preservative in the formulation).

• Some manufacturers state that drug is also contraindicated in patients with chronic nephritis accompanied by nitrogen retention, until reasonable nitrogen concentrations are attained.

Warnings/Precautions

Warnings

Cardiovascular Effects

In large doses, may cause increased BP, bradycardia, arrhythmias, heart block, peripheral vascular constriction or collapse, coronary insufficiency, decreased cardiac output, myocardial ischemia, or MI.

Patients with impaired cardiac response may experience worsening cardiac output. Use with caution in patients with vascular disease (especially of the coronary arteries) since even small doses can precipitate angina.

Aggressive treatment in patients with vasodilatory shock can compromise perfusion of organs, including those of the GI tract.

Diseases in Which Rapid Addition to Extracellular Fluids May Be Hazardous

Use cautiously in patients with seizure disorders, migraine, asthma, heart failure, vascular disease (especially of the coronary arteries), angina pectoris, coronary thrombosis, renal disease, goiter with cardiac complications, arteriosclerosis, or any other disease in which rapid addition to extracellular fluids may be hazardous.

Water Intoxication

May produce water intoxication.

Observe closely for signs of possible development (see Monitoring under Cautions) to prevent ensuing seizures, coma, and death.

Water intoxication may be treated with water restriction and temporary withdrawal of vasopressin until polyuria occurs.

Severe water intoxication may require osmotic diuresis (e.g., with mannitol, hypertonic dextrose, or urea alone or with furosemide).

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions characterized by urticaria, angioedema, bronchoconstriction, fever, rash, wheezing, dyspnea, circulatory collapse, cardiac arrest, and anaphylaxis, reported.

Appropriate agents for the treatment of hypersensitivity reactions should be readily available.

General Precautions

Polyuria

Caution in preoperative and postoperative polyuric patients, since vasopressin requirements may be considerably less than normal.

Monitoring

Monitor fluid intake and output closely, especially in comatose or semicomatose patients.

Monitor electrolyte balance periodically.

Perform ECGs periodically during therapy.

Observe for early signs of water intoxication (e.g., drowsiness, listlessness, headache, confusion, anuria, weight gain). (See Water Intoxication under Cautions.)

Risks of Intra-arterial Administration

Risk of coronary thrombosis, mesenteric infarction, venous thrombosis, infarction and necrosis of the small bowel, and peripheral emboli resulting from intra-arterial catheterization and infusion into the superior mesenteric artery.

Specific Populations

Pregnancy

Category C.

Not known whether vasopressin can cause fetal harm when administered to pregnant women or affect reproduction capacity; use only if potential benefit justifies potential risk to fetus.

May produce tonic uterine contractions that could threaten the continuation of pregnancy.

Clearance increased in second or third trimester of pregnancy; dosage >0.1 units/minute may be required in patients with postcardiotomy shock and dosage >0.07 units/minute may be required in patients with septic shock.

Lactation

Not known whether vasopressin is distributed into human milk. Some manufacturers recommend use with caution. Oral absorption in nursing infants considered unlikely since drug is rapidly destroyed in the GI tract.

Consider advising a lactating woman to pump and discard breast milk for 1.5 hours after receiving drug to minimize potential exposure to the infant.

Pediatric Use

Children are particularly sensitive to vasopressin’s effects (e.g., volume/hydration disturbances); exercise caution.

Safety and efficacy in pediatric patients with vasodilatory shock not established.

Geriatric Use

Geriatric patients are particularly sensitive to vasopressin’s effects; exercise caution.

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Adverse effects associated with low doses are infrequent and mild, but increase in frequency and severity with high doses.

Adverse effects reported with IV vasopressin for the treatment of vasodilatory shock include hemorrhagic shock, decreased platelets, intractable bleeding, right heart failure, atrial fibrillation, bradycardia, myocardial ischemia, mesenteric ischemia, increased bilirubin levels, acute renal insufficiency, distal limb ischemia, hyponatremia, and ischemic lesions.

Other adverse effects include circumoral pallor, sweating, tremor, pounding in the head, abdominal cramps, passage of gas, vertigo, nausea, vomiting, and eructation. In addition, diarrhea, intestinal hyperactivity, and uterine cramps may occur.

Drug Interactions

Specific Drugs

Vasopressin Pharmacokinetics

Absorption

Destroyed by trypsin which is found in the GI tract and, therefore, must be administered parenterally or intranasally.

Absorption of vasopressin through the nasal mucosa is relatively poor.

Onset

Following IV administration, onset of pressor effect is rapid, with peak effect occurring within 15 minutes.

Duration

Following sub-Q or IM administration, duration of antidiuretic activity is variable, but effects are usually maintained for 2–8 hours.

Pressor effects fade within 20 minutes after discontinuance of IV infusion.

Plasma Concentrations

Urine isotonicity is maintained when plasma concentrations of vasopressin are approximately 1 microunit/mL, while plasma concentrations of 4.5–6 microunits/mL produce maximum concentration of urine.

Distribution

Extent

Distributed throughout the extracellular fluid.

Not known whether vasopressin is distributed into human milk.

Plasma Protein Binding

No evidence of plasma protein binding.

Elimination

Metabolism

Predominantly metabolized by liver and kidneys.

At sites relevant for pharmacologic activity, drug is cleaved by serine protease, carboxipeptidase, and disulfide oxidoreductase; metabolites not expected to be pharmacologically active.

Elimination Route

Sub-Q: Approximately 5% of a dose is excreted in urine unchanged after 4 hours.

IV: 5–15% of the total dosage appears in urine.

Half-life

About 10–20 minutes.

Apparent half-life is ≤10 minutes when administered by IV infusion at usual dosage for vasodilatory shock.

Special Populations

Oxytocinase, a circulating enzyme produced early in pregnancy, is capable of cleaving the polypeptide; otherwise, plasma inactivation of vasopressin is negligible.

Stability

Storage

Parenteral

Injection for IV Infusion

Store between 2–8°C; do not freeze.

May store unopened vials at room temperature (20–25°C) for up to 12 months; once removed from the refrigerator, indicate revised 12-month expiration date on vial (unless manufacturer's original expiration date is sooner).

Following dilution, solution is stable for 18 hours at room temperature or 24 hours under refrigeration.

Actions

• Exogenous vasopressin elicits all the pharmacologic responses usually produced by endogenous vasopressin (antidiuretic hormone); primary physiologic role of vasopressin is to maintain serum osmolality within a normal range.

• The vasoconstrictive action of vasopressin is mediated by vascular V₁ receptors; the vascular receptors are coupled to phospholipase C, resulting in release of calcium from sarcoplasmic reticulum in smooth muscle cells, leading to vasoconstriction.

• Causes vasoconstriction, particularly of capillaries and of small arterioles, resulting in decreased blood flow to the splanchnic, coronary, GI, pancreatic, skin, and muscular systems.

• When administered in therapeutic doses to patients with vasodilatory shock, increases systemic vascular resistance and MAP (with pressor effect proportional to infusion rate); also tends to decrease heart rate and cardiac output. No evidence of tachyphylaxis or tolerance to pressor effect.

• Produces relatively concentrated urine by increasing reabsorption of water by the renal tubules. Its action in regulating body fluid balance is mediated by renal vasopressin V₂ receptors, which are coupled to adenyl cyclase and the generation of cyclic AMP. At the tubular level, vasopressin stimulates adenyl cyclase activity, leading to increases in cyclic adenosine monophosphate (AMP). Cyclic AMP increases water permeability at the luminal surface of the distal convoluted tubule and collecting duct, resulting in increased urine osmolality and decreased urinary flow rate.

• Conserves up to 90% of the water that might otherwise be excreted in the urine. Vasopressin also increases reabsorption of urea by the collecting ducts.

• Increases coronary blood flow and the availability of oxygen to the myocardium.

• When administered into the celiac or superior mesenteric arteries, vasopressin constricts gastroduodenal, left gastric, superior mesenteric, and splenic arteries; however, hepatic arteries are not constricted and, instead, hepatic blood flow often increases.

• At pressor doses, triggers contraction of smooth muscles in the GI tract mediated by muscular V₁ receptors and release of prolactin and ACTH via V₃ receptors.

• In the intestinal tract, increases peristaltic activity, particularly of the large bowel; also causes an increase in GI sphincter pressure and a decrease in gastric secretion but has no effect on gastric acid concentration.

• Oxytocic properties of vasopressin are minimal, but in large doses the drug may stimulate uterine contraction. The hormone also possesses slight milk ejecting properties but its role during lactation is negligible.

• In addition to its peripheral effects, vasopressin causes release of corticotropin, growth hormone, and follicle-stimulating hormone.

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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