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- 8-Arginine Vasopressin
- Antidiuretic Hormone
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Pitressin Synthetic: 20 units/mL (1 mL [DSC]) [contains chlorobutanol (chlorobutol)]
Generic: 20 units/mL (0.5 mL [DSC], 1 mL [DSC], 10 mL [DSC])
Vasostrict: 20 units/mL (1 mL)
Vasostrict: 20 units/mL (10 mL) [contains chlorobutanol (chlorobutol)]
Generic: 40 units/100 mL in NaCl 0.9% (100 mL); 50 units/50 mL in NaCl 0.9% (50 mL); 60 units/100 mL in NaCl 0.9% (100 mL)
Brand Names: U.S.
- Pitressin Synthetic [DSC]
- Antidiuretic Hormone Analog
- Hormone, Posterior Pituitary
Vasopressin stimulates a family of arginine vasopressin (AVP) receptors, oxytocin receptors, and purinergic receptors (Russell 2011). Vasopressin, at therapeutic doses used for vasodilatory shock, stimulates the AVPR1a (or V1) receptor and increases systemic vascular resistance and mean arterial blood pressure; in response to these effects, a decrease in heart rate and cardiac output may be seen. When the AVPR2 (or V2) receptor is stimulated, cyclic adenosine monophosphate (cAMP) increases which in turn increases water permeability at the renal tubule resulting in decreased urine volume and increased osmolality. Vasopressin, at pressor doses, also causes smooth muscle contraction in the GI tract by stimulating muscular V1 receptors and release of prolactin and ACTH via AVPR1b (or V3) receptors.
None from GI tract, destroyed by trypsin in GI tract, must be administered parenterally
Hepatic, renal (inactive metabolites)
Nasal: Urine; Parenteral: SubQ: Urine (5% as unchanged drug) after 4 hours; IV: Urine (~6% as unchanged drug)
Onset of Action
Nasal: 1 hour
IV: Vasopressor effect: Rapid with peak effect occurring within 15 minutes of initiation of continuous IV infusion
Duration of Action
Nasal: 3 to 8 hours; IM, SubQ: Antidiuretic: 2 to 8 hours; IV: Vasopressor effect: Within 20 minutes after IV infusion terminated
IM, IV, SubQ: 10 to 20 minutes (apparent half-life: ≤10 minutes)
Use: Labeled Indications
Diabetes insipidus (Pitressin Synthetic only): Treatment of central diabetes insipidus; differential diagnosis of diabetes insipidus
Vasodilatory shock (Vasostrict only): To increase blood pressure in adults with vasodilatory shock (eg, postcardiotomy or sepsis) who remain hypotensive despite fluids and catecholamines
Guideline recommendations: Septic shock: The Surviving Sepsis Campaign guidelines recommend vasopressin, if needed, be used in addition to norepinephrine (the preferred first-line, single-agent vasopressor) for the intent of raising mean arterial pressure (MAP) to target or to decrease norepinephrine dosage (Rhodes 2017).
Off Label Uses
Cadaveric organ recovery (hormonal resuscitation)
Data from two consecutive retrospective cohort studies of brain-dead donors who successfully donated organs suggests that the use of intravenous vasopressin given concomitantly with a continuous infusion of insulin (goal blood glucose: 120 to 180 mg/dL), liothyronine, and methylprednisolone may be beneficial for hemodynamically unstable brain-dead donors to increase the quantity and quality of organs available for transplantation [Rosendale 2003a], [Rosendale 2003b]. Additional data may be necessary to further define the role of levothyroxine in this setting.
Based on a consensus document sponsored by the American Society of Transplant Surgeons and the American Society of Transplantation, the use of vasopressin (in combination with liothyronine, methylprednisolone, and insulin) is effective and recommended for hormonal resuscitation in brain-dead donors [Rosengard 2002], [Zaroff 2002].
Gastroesophageal variceal hemorrhage
Based on older controlled trials and AASLD/ACG guidelines, vasopressin with nitroglycerin may effectively control acute variceal bleeding. The use of concomitant nitroglycerin may improve safety, but significant systemic adverse effects of the combination still limit the clinical use of vasopressin compared to other splanchnic vasoconstrictors.
In-hospital cardiac arrest (in combination with epinephrine and methylprednisolone)
Data from two randomized controlled trials in patients experiencing in-hospital cardiac arrest (IHCA) suggest that the combination of vasopressin, epinephrine (standard dose), and methylprednisolone administered during cardiac arrest followed by hydrocortisone given after return of spontaneous circulation may be beneficial for the treatment of patients in this setting [Mentzelopoulos 2009], [Mentzelopoulos 2013]. Additional trials are necessary to further define the role of vasopressin (in combination with epinephrine and methylprednisolone) for the treatment of patients experiencing IHCA.
Based on the 2015 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, the intra-arrest use of vasopressin (in combination with epinephrine and methylprednisolone) followed by hydrocortisone given after return of spontaneous circulation in patients with IHCA may be considered (based on limited evidence); however, further studies are warranted before routine administration of this combination can be recommended.
Hypersensitivity to vasopressin or any component of the formulation; hypersensitivity to chlorobutanol (Vasostrict only); uncorrected chronic nephritis with nitrogen retention (Pitressin Synthetic only)
Diabetes insipidus: Note: Dosage is highly variable; titrated based on serum and urine sodium and osmolality in addition to fluid balance and urine output. Use of vasopressin is impractical for chronic therapy.
IM, SubQ: 5 to 10 units 2 to 4 times daily as needed
Continuous IV infusion (off-label route): Continuous infusion has not been formally evaluated in the post-neurosurgical adult. However, some convert IM/SubQ requirement to an hourly continuous IV infusion rate.
Vasodilatory shock: IV: Note: Dosage provided is empirical; titrate to lowest dose compatible with an acceptable response.
Post-cardiotomy shock: Initial: 0.03 units per minute. If the target blood pressure response is not achieved, titrate up by 0.005 units per minute at 10- to 15-minute intervals (maximum dose: 0.1 units per minute). After target blood pressure has been maintained for 8 hours without the use of catecholamines, taper by 0.005 units per minute every hour as tolerated to maintain target blood pressure.
Surviving Sepsis Campaign recommendations: ≤0.03 units per minute added to norepinephrine to raise MAP to target or to decrease norepinephrine dose. Use with caution in patients who are not euvolemic or at doses >0.03 units/ minute (Rhodes 2017).
Manufacturer's labeling: Initial: 0.01 units per minute. If the target blood pressure response is not achieved, titrate up by 0.005 units per minute at 10- to 15-minute intervals. Maximum dose: 0.07 units per minute. After target blood pressure has been maintained for 8 hours without the use of catecholamines, taper by 0.005 units per minute every hour as tolerated to maintain target blood pressure.
Discontinuation (off-label): If vasopressin is used concurrently with other catecholamines (eg, norepinephrine), patients may experience hypotension if vasopressin is discontinued first (Bauer 2010). To prevent subsequent hypotension after withdrawal of vasopressors, some experts recommend slowly tapering vasopressin (eg, reducing by 0.01 units per minute every 30 minutes) after the catecholamine(s) are discontinued until no longer required.
Cadaveric organ donation (hormonal resuscitation) (off-label use): IV: Initial: 1 unit bolus followed by a continuous infusion of 0.5 to 4 units/hour administered to the brain-dead donor who is hemodynamically unstable requiring significant vasopressor support; titrate to SVR of 800 to 1200 dynes-sec/cm5; give concomitantly with levothyroxine or liothyronine (preferred), methylprednisolone, and continuous regular insulin infusion (Rosendale 2003a; Rosendale 2003b; Rosengard 2002; Zaroff 2002)
Central diabetes insipidus, post-traumatic (off-label use): IV: Initial: 2.5 units/hour; titrate to adequately reduce urine output (Levitt 1984)
Gastroesophageal variceal hemorrhage (off-label use): Note: Other therapies may be preferred.
Continuous IV infusion: Initial: 0.2 to 0.4 units per minute, may titrate dose as needed to a maximum dose of 0.8 units per minute; maximum duration: 24 hours at highest effective dose continuously (to reduce incidence of adverse effects). Patient should also receive IV nitroglycerin concurrently to prevent myocardial ischemic complications. Monitor closely for signs/symptoms of ischemia (myocardial, peripheral, bowel) (AASLD [Garcia-Tsao 2007]).
Refer to adult dosing.
Note: Units of measure vary by indication and age (ie, milliunits/kg/hour, units/kg/hour, milliunits/kg/minute, units/kg/minute; units/minute, units/hour); extra precautions should be taken.
Diabetes insipidus: Note: Highly variable dosage; titrate dosage based upon serum and urine sodium and osmolality in addition to fluid balance and urine output.
IM, SubQ: Children and Adolescents: 2.5 to 10 units 2 to 4 times daily (Kleigman 2007)
Continuous IV infusion (off-label route): Limited data available: Infants, Children, and Adolescents: Initial: 0.5 milliunits/kg/hour; titrate upward in 0.5 milliunits/kg/hour increments at approximately 10-minute intervals to target urine output (suggested output target: <2 mL/kg/hour) (Sperling 2014; Wise-Faberowski 2004); infusion rates up to 10 milliunits/kg/hour have been reported (Alharfi 2013). Note: Use in conjunction with fluid therapy, monitor urine output and specific gravity, serum and urine electrolytes (primarily Na), and plasma osmolality.
GI hemorrhage (off-label use): Continuous IV infusion: Limited data available: Children and Adolescents: Initial: 2 to 5 milliunits/kg/minute; titrate dose as needed; maximum dose: 10 milliunits/kg/minute (Kliegman 2007; Tuggle 1988); usual adult dosing range is 0.2 to 0.4 units/minute up to a maximum rate of 0.8 units/minute (AASLD [Garcia-Tsao 2007]). Note: Higher doses have not been associated with greater efficacy but have been associated with increased risk of complications (Tuggle 1988).
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer's labeling.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling.
Vasostrict: Note: Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration.
No fluid restriction: Final concentration 0.1 units/mL: Reconstitute vasopressin 50 units (2.5 mL) with 500 mL NS or D5W.
Fluid restriction: Final concentration 1 unit/mL: Reconstitute vasopressin 100 units (5 mL) with 100 mL NS or D5W.
IM or SubQ: Administer without further dilution.
Continuous IV infusion: Dilute prior to administration. Infusion through central line is recommended.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate topical nitroglycerin. Apply dry, warm compresses (based on mechanism of extravasation injury proximal to the injection site) (Reynolds 2014).
Nitroglycerin (topical): Nitroglycerin topical 2% ointment (based on mechanism of extravasation injury):
Adults: Apply a 1-inch strip to the site of ischemia; may repeat every 8 hours as necessary (Reynolds 2014).
Pediatrics: Apply 4 mm/kg as a thin ribbon to the site of ischemia; may repeat after 8 hours if needed (Wong 1992) or apply a 1-inch strip to the site of ischemia; may repeat every 8 hours as necessary (Denkler 1989; Reynolds 2014).
Intranasal (topical administration on nasal mucosa): For diabetes insipidus, may administer injectable vasopressin on cotton plugs, as nasal spray, or by dropper. Should not be inhaled.
Store intact vials between 2°C and 8°C (36°F and 46°F). Do not freeze.
Vasostrict: May also remove intact vials from refrigeration and store at 20°C to 25°C (68°F to 77°F) for up to 12 months or manufacturer expiration date, whichever is earlier (indicate date of removal on the vial or note the manufacturer expiration date, whichever is earlier). After initial entry into the 10 mL vial, opened vial must be refrigerated; discard 30 days after first puncture. Discard unused diluted solution (in D5W or NS) after 18 hours at room temperature or 24 hours under refrigeration.
There are no known significant interactions.
Frequency not defined.
Cardiovascular: Angina pectoris, atrial fibrillation, bradycardia, cardiac arrest, cardiac arrhythmia, ischemic heart disease, limb ischemia (distal), localized blanching, low cardiac output, myocardial infarction, right heart failure, shock, vasoconstriction (peripheral)
Central nervous system: Headache (pounding), vertigo
Dermatologic: Circumoral pallor, diaphoresis, gangrene of skin or other tissues, skin lesion (ischemic), urticaria
Endocrine & metabolic: Hyponatremia, hypovolemic shock, water intoxication
Gastrointestinal: Abdominal cramps, flatulence, mesenteric ischemia, nausea, vomiting
Hematologic & oncologic: Decreased platelet count, hemorrhage (intractable)
Hepatic: Increased serum bilirubin
Neuromuscular & skeletal: Tremor
Renal: Renal insufficiency
Concerns related to adverse effects:
• Extravasation: Vesicant; ensure proper needle or catheter placement prior to and during infusion. Extravasation may lead to severe vasoconstriction and localized tissue necrosis; also, gangrene of extremities, tongue, and ischemic colitis. Avoid extravasation.
• Water intoxication: May cause water intoxication; early signs include drowsiness, listlessness, and headache; these should be recognized to prevent coma and seizures.
• Asthma: Use with caution in patients with asthma.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, including arteriosclerosis; may worsen cardiac output.
• Goiter: Use with caution in patients with a goiter with cardiac complications.
• Migraine: Use with caution in patients with a history of migraines.
• Renal impairment: Use with caution in patients with renal disease.
• Seizures: Use with caution in patients with a history of seizure disorder.
• Vascular disease: Use with caution in patients with vascular disease.
• Elderly: Caution elderly patients not to increase their fluid intake beyond that sufficient to satisfy their thirst in order to avoid water intoxication and hyponatremia; under experimental conditions, the elderly have shown to have a decreased responsiveness to vasopressin with respect to its effects on water homeostasis.
Serum and urine sodium, urine specific gravity, urine and serum osmolality; urine output, fluid input and output, blood pressure, heart rate.
Consult individual institutional policies and procedures.
Pregnancy Risk Factor
Animal reproduction studies have not been conducted. Vasopressin may produce tonic uterine contractions; however, doses sufficient for diabetes insipidus are not likely to produce this effect.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, vomiting, pale skin, abdominal cramps, or flatulence. Have patient report immediately to prescriber signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), bruising, bleeding, angina, bradycardia, tachycardia, shortness of breath, excessive weight gain, swelling of arms or legs, urinary retention, change in amount of urine passed, skin sores, fatigue, headache, seizures, confusion, abnormal heartbeat, or skin discoloration (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: antidiuretic hormones