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Vasopressin

Pronunciation

Pronunciation

(vay soe PRES in)

Index Terms

  • 8-Arginine Vasopressin
  • ADH
  • Antidiuretic Hormone
  • AVP

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

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])

Solution, Intravenous:

Vasostrict: 20 units/mL (1 mL)

Brand Names: U.S.

  • Pitressin Synthetic [DSC]
  • Vasostrict

Pharmacologic Category

  • Antidiuretic Hormone Analog
  • Hormone, Posterior Pituitary

Pharmacology

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.

Absorption

None from GI tract, destroyed by trypsin in GI tract, must be administered parenterally

Metabolism

Hepatic, renal (inactive metabolites)

Excretion

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

Half-Life Elimination

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

Use: Unlabeled

ACLS guidelines: Pulseless arrest (ventricular tachycardia [VT]/ventricular fibrillation [VF], asystole/pulseless electrical activity [PEA]); cardiac arrest secondary to anaphylaxis (unresponsive to epinephrine)

Adjunct in the treatment of GI hemorrhage and esophageal varices; adjunct in the treatment of vasodilatory shock (septic shock); donor management in brain-dead patients (hormone replacement therapy)

Contraindications

Hypersensitivity to vasopressin or any component of the formulation; hypersensitivity to chlorobutanol (Vasostrict only); uncorrected chronic nephritis with nitrogen retention (Pitressin Synthetic only)

Dosing: Adult

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.

Septic shock:

Surviving Sepsis Campaign recommendations: 0.03 units per minute added to norepinephrine to raise MAP to target or to decrease norepinephrine dose. Doses >0.03 units per minute may have more cardiovascular side effects and should only be reserved for salvage therapy (ie, failure to achieve MAP goal with other vasopressors) (SCCM [Dellinger 2013]). 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.

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.

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]).

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.

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.

Reconstitution

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.

Administration

IM or SubQ: Administer without further dilution.

Continuous IV infusion: Dilute prior to administration. Infusion through central line is strongly recommended (SCCM [Dellinger 2013]).

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 phentolamine (or alternative antidote).

Phentolamine: Dilute 5 to 10 mg in 10 to 15 mL NS and administer into extravasation site as soon as possible after extravasation (Peberdy 2010).

Alternatives to phentolamine:

Nitroglycerin topical 2% ointment (based on limited case reports in neonates/infants): Apply 4 mm/kg as a thin ribbon to the affected areas; may repeat after 8 hours if needed (Wong 1992) or apply a 1-inch strip on the affected site (Denkler 1989).

Terbutaline (based on limited case reports): Infiltrate extravasation area using a solution of terbutaline 1 mg diluted to 10 mL in NS (large extravasation site; administration volume varied from 3 to 10 mL) or 1 mg diluted in 1 mL NS (small/distal extravasation site; administration volume varied from 0.5 to 1 mL) (Stier 1999).

Intranasal (topical administration on nasal mucosa; off-label route): For diabetes insipidus, may administer injectable vasopressin on cotton plugs, as nasal spray, or by dropper. Should not be inhaled.

Compatibility

Stable in D5W, NS.

Y-site administration: Incompatible with phenytoin.

Storage

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). 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:

• 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.

Special populations:

• 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.

Monitoring Parameters

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

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

• 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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