Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Vasostrict: 20 units/mL (10 mL) [contains chlorobutanol (chlorobutol)]
Solution, Intravenous [preservative free]:
Vasostrict: 20 units/mL (1 mL)
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
Absorption
None from GI tract, destroyed by trypsin in GI tract, must be administered parenterally
Metabolism
Hepatic, renal (inactive metabolites)
Excretion
Parenteral: SubQ: Urine (5% as unchanged drug) after 4 hours; IV: Urine (~6% as unchanged drug).
Onset of Action
Antidiuretic: Peak effect: 1 to 2 hours (Murphy-Human 2010).
Vasopressor effect: IV: Rapid with peak effect occurring within 15 minutes of initiation of continuous IV infusion.
Duration of Action
SubQ: Antidiuretic: 2 to 8 hours; IV: Vasopressor effect: Within 20 minutes after IV infusion terminated.
Half-Life Elimination
IV, SubQ: 10 to 20 minutes (apparent half-life: ≤10 minutes).
Use: Labeled Indications
Shock, vasodilatory: To increase blood pressure in adults with vasodilatory shock (eg, postcardiotomy or sepsis) who remain hypotensive despite fluid resuscitation and catecholamines.
Use: Off Label
Cadaveric organ recovery (hormone replacement therapy)cyes
Data from four consecutive retrospective cohort studies of brain-dead donors who successfully donated organs suggests that the use of intravenous vasopressin given concomitantly with levothyroxine, methylprednisolone, and a continuous infusion of insulin (goal blood glucose: 120 to 180 mg/dL) may be beneficial for hemodynamically unstable brain-dead donors to increase the quantity and quality of organs available for transplantation Callahan 2014, Plurad 2012, Rosendale 2003a, Rosendale 2003b.
Based on a consensus statement by Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations, the use of vasopressin (in combination with liothyronine [or levothyroxine], methylprednisolone, and insulin) should be considered for hemodynamically unstable donors or potential cardiac donors with reduced left ventricular ejection fraction (<45%) Kotloff 2015. In addition, a consensus document by the American Society of Transplant Surgeons and the American Society of Transplantation recommends the use of vasopressin (in combination with liothyronine, methylprednisolone, and insulin) for hormone replacement therapy in brain-dead donors Rosengard 2002, Zaroff 2002.
Diabetes insipidus, central (acute)cyes
Based on the 2016 Endocrine Society guidelines for hormonal replacement in hypopituitarism in adults, vasopressin may be used as initial short-term treatment of diabetes insipidus in ICU patients following pituitary surgery.
In addition, clinical experience suggests that vasopressin may also be useful for initial short-term control of acute central/neurogenic diabetes insipidus in the neurocritical care setting Murphy-Human 2010.
Gastroesophageal variceal hemorrhageyes
Based on the 2016 American Association for the Study of Liver Diseases practice guidelines, vasopressin (with nitroglycerin) may effectively reduce portal pressure and 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 (eg, octreotide) Garcia-Tsao 2017.
Contraindications
Hypersensitivity to vasopressin or any component of the formulation; hypersensitivity to chlorobutanol (Vasostrict 10 mL vial only).
Dosage and Administration
Dosing: Adult
Diabetes insipidus, central (acute) (off-label use): Note: Dosage is highly variable; titrated based on serum and urine sodium and osmolality in addition to fluid balance and urine output. Vasopressin may be considered for short-term use in some neurocritical care settings due to its short duration of action (ES [Fleseriu 2016]; Murphy-Human 2010; Prete 2017). Use in neurosurgical patients is generally limited to the early postoperative period (eg, days 1 to 4); use caution in this setting to avoid overtreatment, as diabetes insipidus may spontaneously resolve or revert to syndrome of inappropriate antidiuretic hormone secretion/hyponatremia (ES [Fleseriu 2016]; Prete 2017).
SubQ (off-label route): 5 to 10 units 2 to 3 times daily as needed (Prete 2017).
Continuous IV infusion: Continuous infusion has not been formally evaluated in the post-neurosurgical adult. However, some clinicians may convert SubQ requirement to an hourly continuous IV infusion rate with careful titration based on urine output (Murphy-Human 2010). Specific protocols may vary.
Shock, vasodilatory: Note: Vasopressors should be used if patient is hypotensive during or after fluid resuscitation to maintain mean arterial pressure (MAP) ≥65 mm Hg (Levy 2018). Use in addition to norepinephrine (preferred single-agent vasopressor) for raising MAP to target or to decrease norepinephrine dosage (Dellinger 2013; Rhodes 2017). Titrate to lowest effective dose.
Shock, post-cardiotomy: IV: Initial: 0.03 units/minute. If the target blood pressure response is not achieved, titrate up by 0.005 units/minute at 10- to 15-minute intervals (maximum dose: 0.1 units/minute). After target blood pressure has been maintained for 8 hours without the use of catecholamines, taper by 0.005 units/minute every hour as tolerated to maintain target blood pressure.
Shock, sepsis: IV:
Initial: ≤0.03 units/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 (Dellinger 2013; Rhodes 2017).
Discontinuation in septic shock: Multiple studies describe clinically significant hypotension when vasopressin is discontinued prior to norepinephrine. When discontinuing therapy, consider slowly tapering by 0.01 units/minute every 30 to 60 minutes to reduce the risk of hypotension (Bauer 2010; Bissell 2017; Hammond 2017; Jeon 2018; Manaker 2018; Musallam 2018; Sacha 2018); cautiously monitor MAP when discontinuing vasopressin.
Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. Initial: 0.01 units/minute. Maximum dose: 0.07 units/minute.
Cadaveric organ recovery (hormone replacement therapy) (off-label use): Based on limited data: Note: Use if hypotensive despite adequate fluid resuscitation, left ventricular ejection fraction <45%, low systemic vascular resistance (SVR), or if diabetes insipidus is present. Use in combination with levothyroxine (or liothyronine), methylprednisolone, and continuous insulin infusion (goal blood glucose: 120 to 180 mg/dL) (Kotloff 2015; Zaroff 2002).
IV: Initial: 0.01 to 0.04 units/minute (Kotloff 2015); some experts recommend a bolus of 1 unit followed by 0.01 to 0.1 units/minute titrated to a SVR of 800 to 1,200 dynes-sec/cm5 (usual dose: 0.01 to 0.04 units/minute) (Garrity 2019).
Gastroesophageal variceal hemorrhage (alternative agent) (off-label use): Note: Other therapies (eg, octreotide) may be preferred (AASLD [Garcia-Tsao 2017]).
Continuous IV infusion: Initial: 0.2 to 0.4 units/minute, may titrate dose as needed to a maximum dose of 0.8 units/minute; maximum duration is 24 hours at highest effective dose (to reduce incidence of adverse effects). Administer IV nitroglycerin concurrently to prevent ischemic complications; monitor closely for signs/symptoms of ischemia (myocardial, peripheral, bowel) (AASLD [Garcia-Tsao 2017]).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
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. Children and Adolescents: IM, SubQ: 2.5 to 10 units 2 to 4 times daily (Kliegman 2007)
Central diabetes insipidus: Limited data available: Infants, Children, and Adolescents: Continuous IV infusion: 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.
Cadaveric organ donations (hormone replacement therapy): Limited data available (Nakagawa/NATCO Guidelines 2008): Infants, Children, and Adolescents: Continuous IV infusion: Initial: 0.5 to 1 milliunits/kg/hour; titrate dose to maintain targeted urine output. In a retrospective case-controlled study (n=34, age: 8.2 ± 6.2 years), a mean dose of 41 milliunits/kg/hour was reported with a range of 0.2 milliunits/kg/hour to 150 milliunits/kg/hour (Katz 2000).
GI hemorrhage: Limited data available: Children and Adolescents: Continuous IV infusion: 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).
Pulseless arrest, ventricular fibrillation, ventricular tachycardia: Limited data available: Infants, Children, and Adolescents: IV: 0.4 units/kg as a single dose after traditional resuscitation methods and at least two doses of epinephrine have been administered. Note: Due to insufficient evidence, no formal recommendations for or against the routine use of vasopressin during pediatric cardiac arrest are provided (Duncan 2009; Mann 2002; PALS 2010).
Vasodilatory shock with hypotension unresponsive to fluid resuscitation and exogenous catecholamines: Limited data available; efficacy results have varied (SCCM [Dellinger 2013]): Infants, Children, and Adolescents: Continuous IV infusion: 0.17 to 8 milliunits/kg/minute (0.01 to 0.48 units/kg/hour) has been used; dosing based on retrospective reviews and case reports that have shown increases in arterial blood pressure and urine output and also allowed for dosage reductions of additional vasopressors (Brierley 2009; Choong 2008; Meyer 2008). The only double-blind, placebo-controlled trial (n=65, age: 3 to 14 years) evaluated a dose of 0.5 to 2 milliunits/kg/minute (0.03 to 0.12 units/kg/hour) at multiple centers and found no significant difference in the time to reach hemodynamic stability and a trend toward increased mortality in the vasopressin group was noted. Based on these findings, the authors did not recommend routine use of vasopressin (Choong 2009). Note: Abrupt discontinuation of infusion may result in hypotension; to discontinue, gradually taper infusion.
Reconstitution
Note: Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration.
For IV administration:
No fluid restriction:
Final concentration 0.1 units/mL: Dilute vasopressin 50 units (2.5 mL) with 500 mL NS or D5W.
Final concentration 0.2 units/mL: Dilute vasopressin 20 units (1 mL) with 100 mL D5W (Ali 2018).
Final concentration 0.4 units/mL: Dilute vasopressin 40 units (2 mL) with 100 mL NS (Van Matre 2019).
Fluid restriction: Final concentration 1 unit/mL: Dilute vasopressin 100 units (5 mL) with 100 mL NS or D5W.
Administration
SubQ (off-label route): 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): Apply a 1-inch strip to the site of ischemia; may repeat every 8 hours as necessary (Reynolds 2014).
Storage
Store intact vials between 2°C and 8°C (36°F and 46°F). Do not freeze.
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.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
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
Hypersensitivity: Anaphylaxis
Neuromuscular & skeletal: Tremor
Renal: Renal insufficiency
Respiratory: Bronchoconstriction
Warnings/Precautions
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.
Disease-related concerns:
- Cardiovascular disease: Use with caution in patients with cardiovascular disease, including arteriosclerosis; may worsen cardiac output.
- Migraine: Use with caution in patients with a history of migraines.
- Renal impairment: Use with caution in patients with renal disease.
- Vascular disease: Use with caution in patients with vascular disease.
Monitoring Parameters
Serum and urine sodium, urine specific gravity, urine and serum osmolality; urine output, fluid input and output, blood pressure, heart rate, digital/extremity perfusion.
Consult individual institutional policies and procedures.
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
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.
Patient Education
What is this drug used for?
- It is used to treat low blood pressure and diabetes insipidus. It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Nausea
- Vomiting
- Pale skin
- Abdominal cramps
- Passing gas
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Low sodium like headache, difficulty focusing, trouble with memory, confusion, weakness, seizures, or change in balance
- Bruising
- Bleeding
- Vomiting blood
- Black, tarry or bloody stools
- Severe abdominal pain
- Chest pain
- Slow heartbeat
- Fast heartbeat
- Shortness of breath
- Excessive weight gain
- Swelling of arms or legs
- Unable to pass urine
- Change in amount of urine passed
- Skin sores
- Fatigue
- Headache
- Abnormal heartbeat
- Skin discoloration
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
