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  • CLASSES

    Antidiuretic Hormones
    Vasopressin (ADH) and Analogs

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral exogenous antidiuretic hormone (ADH)
    Used for prevention and treatment of postoperative abdominal distention, diabetes insipidus, and in gastrointestinal radiography to dispel interfering gas shadows as well as to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines
    Desmopressin (DDAVP) preferred for central diabetes insipidus due to longer duration of action and more favorable adverse effect profile

    COMMON BRAND NAMES

    Pitressin, Vasostrict

    HOW SUPPLIED

    Pitressin/Vasopressin/Vasostrict Intramuscular Inj Sol: 1mL, 20U
    Pitressin/Vasopressin/Vasostrict Subcutaneous Inj Sol: 1mL, 20U
    Vasostrict Intravenous Inj Sol: 1mL, 20U

    DOSAGE & INDICATIONS

    For the treatment of central diabetes insipidus.
    Intramuscular or Subcutaneous dosage
    Adults

    5 to 10 units IM or subcutaneously every 3 to 4 hours or 2 to 3 times per day as needed.

    Infants, Children, and Adolescents

    2.5 to 10 units IM or subcutaneously 2 to 4 times per day. The FDA-approved adult dosage is 5 to 10 units IM or subcutaneously every 3 to 4 hours or 2 to 3 times per day as needed with recommendation to reduce the dose proportionately for pediatric patients.

    Intranasal dosage
    Adults

    Intranasal dosages (on cotton pledgets or topically as a spray) must be determined for each patient individually.

    Children and Adolescents

    Intranasal dosages (on cotton pledgets or topically as a spray) must be determined for each patient individually.

    Intravenous dosage (continuous infusion)†
    Adults

    0.0005 unit/kg/hour (0.5 milliunit/kg/hour) by continuous IV infusion; titrate by 0.0005 unit/kg/hour (0.5 milliunit/kg/hour) every 5 to 10 minutes to achieve a urine output of approximately 100 mL/hour. Infusion rates more than 0.01 unit/kg/hour (10 milliunits/kg/hour) are rarely required. However, reported doses are variable; weight-based infusion rates ranging from 0.00025 to 0.04 unit/kg/hour (0.25 to 4 milliunits/kg/hour) have been recommended and standard infusions of 2.5 units/hour (0.0025 milliunit/hour) have been used.

    Infants, Children, and Adolescents

    0.0005 unit/kg/hour (0.5 milliunit/kg/hour) by continuous IV infusion; titrate by 0.0005 unit/kg/hour (0.5 milliunit/kg/hour) every 5 to 10 minutes until urine output is decreased to less than 2 mL/kg/hour. Infusion rates more than 0.01 unit/kg/hour (10 milliunits/kg/hour) are rarely required.

    For the treatment of hypotension in patients with post-cardiotomy shock or septic shock in patients who remain hypotensive despite fluids and catecholamines.
    For patients with post-cardiotomy shock.
    Intravenous dosage
    Adults

    0.03 units/minute continuous IV infusion initially. Titrate by 0.005 units/minute every 10 to 15 minutes until target blood pressure is achieved. Max: 0.1 units/minute. After target blood pressure is maintained for 8 hours without the use of catecholamines, taper by 0.005 units/minute every hour as tolerated to maintain target blood pressure.

    For patients with septic shock.
    Intravenous dosage
    Adults

    0.01 units/minute continuous IV infusion initially. Titrate by 0.005 units/minute every 10 to 15 minutes until target blood pressure is achieved. Max: 0.07 units/minute. After target blood pressure is maintained for 8 hours without the use of catecholamines, taper by 0.005 units/minute every hour as tolerated to maintain target blood pressure. Guidelines recommend adding vasopressin (up to 0.03 units/minute) to norepinephrine to raise mean arterial pressure (MAP) to target or to decrease norepinephrine dosage. Target a MAP of 65 mmHg initially. Titrate to an endpoint reflecting perfusion; reduce rate or discontinue the vasopressor if worsening hypotension or arrhythmias occur. Vasopressin is not recommended as single initial vasopressor. Reserve vasopressin rates higher than 0.03 to 0.04 units/minute for salvage therapy (i.e., failure to achieve adequate MAP with other vasopressors).

    For postoperative abdominal distention (e.g., ileus).
    Intramuscular dosage
    Adults

    5 units IM every 3 to 4 hours as needed. May increase dose to 10 units, if necessary.

    For use in gastrointestinal radiography.
    Intramuscular or Subcutaneous dosage
    Adults

    10 units IM or subcutaneously for 2 doses given 2.5 and 0.5 hours before film exposure.

    For the treatment of variceal bleeding† or nonvariceal upper GI bleeding†.
    For the treatment of variceal bleeding† or nonvariceal upper GI bleeding† in pediatric patients.
    Intravenous dosage
    Children and Adolescents

    0.3 units/kg/dose IV (Max: 20 units) followed by 0.002 to 0.005 units/kg/minute continuous IV infusion. May increase up to 0.01 units/kg/minute.

    For the treatment of variceal bleeding† in adults.
    Intravenous dosage
    Adults

    0.2 to 0.4 units/minute continuous IV infusion for 24 hours. May increase up to 0.8 units/minute. Always use in combination with IV nitroglycerin.

    For the treatment of cardiac arrest† including ventricular asystole† and pulseless electrical activity† (PEA) during cardiopulmonary resuscitation† (CPR).
    Intravenous
    Adults

    20 units IV per CPR cycle (Max: 100 units) plus epinephrine IV for up to 5 CPR cycles and methylprednisolone IV once intra-arrest followed by stress-dose hydrocortisone IV beginning 4 hours after resuscitation for in-hospital cardiac arrest (IHCA) requiring vasopressors. Combined vasopressin, epinephrine, and methylprednisolone during CPR and stress-dose hydrocortisone postresuscitation improved survival to hospital discharge with favorable neurological status vs. epinephrine and placebo. Clinical practice guidelines no longer recommend vasopressin as the sole vasoactive drug during CPR as vasopressin offers no advantage as a substitute for epinephrine. The combination of intra-arrest vasopressin, epinephrine, and methylprednisolone and post-arrest hydrocortisone may be considered in IHCA; however, further studies are needed before suggesting routine use.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Dependent on route of administration and indication for therapy.

    Elderly

    Dependent on route of administration and indication for therapy.

    Adolescents

    Dependent on route of administration and indication for therapy.

    Children

    Dependent on route of administration and indication for therapy.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Continuous IV infusion:
    Dilute to a concentration of 0.1 or 1 unit/mL in 0.9% Sodium Chloride Injection or 5% Dextrose Injection. A concentration of 1 unit/mL is suggested for patients with fluid restrictions.
    Storage: Discard unused solution after 18 hours at room temperature or 24 hours under refrigeration.

    Intramuscular Administration

    Inject vasopressin deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.
    When used for gastrointestinal radiography, consider administering an enema before the first dose of vasopressin.

    Subcutaneous Administration

    Inject vasopressin subcutaneously taking care not to inject intradermally.
    When used for gastrointestinal radiography, consider administering an enema before the first dose of vasopressin.

    Other Injectable Administration

    Continuous intra-arterial infusion†:
    NOTE: Intra-arterial administration requires specialized techniques. Only clinicians familiar with this method of administration and with management of potential complications should administer vasopressin intra-arterially.
    Dilute to a concentration of 0.1 or 1 unit/mL in 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
    Infuse into the superior mesenteric artery using a controlled infusion device.

    STORAGE

    Generic:
    - Store at room temperature (between 59 to 86 degrees F)
    Pitressin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Vasostrict:
    - Discard penetrated multi-dose vial after 30 days
    - Do not expose product to temperatures above 77 degrees F
    - Do not freeze
    - May be stored at room temperature (68 to 77 degrees F) for up to 12 months after removal from refrigeration
    - Refrigerate (between 36 and 46 degrees F)
    - Refrigerate after opening
    - See package insert for detailed storage information

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Vasopressin is contraindicated in patients with a known hypersensitivity to 8-L-arginine vasopressin. The 10 mL multiple dose vasopressin vial contains chlorobutanol and is therefore contraindicated in patients with a known hypersensitivity to chlorobutanol.

    Coronary artery disease, heart failure

    Vasopressin should be administered with caution to patients with impaired cardiac response, like heart failure, as use in these patients may worsen cardiac output. Similarly, vasopressin should be used with caution or avoided, if possible, in patients with vascular disease, including coronary artery disease, as even small doses may precipitate anginal pain; with larger doses, the possibility of myocardial infarction should be considered.

    Renal disease

    Vasopressin is contraindicated for use in patients with chronic nephritis accompanied by nitrogen retention. The hormone should not be administered to patients with this renal disease until acceptable nitrogen concentrations are attained.

    Water intoxication

    Patients receiving vasopressin should be monitored for signs of water intoxication which include listlessness, drowsiness, confusion, and headache. Vasopressin-induced water intoxication can lead to seizures, coma, and death.

    Migraine, seizure disorder

    Use vasopressin with caution in patients with seizure disorder or migraine. A rapid addition to extracellular water may exacerbate these conditions.

    Asthma

    Use vasopressin with caution in patients with asthma. A rapid addition to extracellular water may exacerbate this condition.

    Geriatric

    Clinical studies involving vasopressin did not contain sufficient numbers of patients older than 65 years to determine if they respond differently than younger patients. Reported clinical experiences with vasopressin have not identified differences in response between geriatric and younger patients. In general, initiate dose at the low end of the dosing range, taking into account the greater frequency of decreased hepatic, renal, and cardiac function, and of concomitant disease or drug use.

    Pregnancy

    Vasopressin is classified as FDA pregnancy category C. No adequate studies have been conducted in pregnant women. It is not known if vasopressin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Due to increased drug clearance in the second and third trimesters, the dose of vasopressin may need to be increased to doses exceeding 0.1 units/minute in post-cardiotomy shock and 0.07 units/minute in septic shock. While the antidiuretic doses of vasopressin are not likely to produce tonic uterine contractions, doses for shock may do so and could threaten the pregnancy. Use vasopressin during pregnancy only if clearly needed.

    Breast-feeding

    It is not known if vasopressin is present in human milk; however, oral absorption by a nursing infant is unlikely because vasopressin is rapidly degraded in the gastrointestinal tract. Use vasopressin with caution in a breast-feeding woman. Consider advising a breast-feeding woman to pump and discard breast milk for 1.5 hours after receiving vasopressin. Women treated with vasopressin for diabetes insipidus have been reported to breast-feed without negative effects in the infant.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    coma / Early / Incidence not known
    anuria / Delayed / Incidence not known
    water intoxication / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    cardiac arrest / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    AV block / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    thrombosis / Delayed / Incidence not known

    Moderate

    hyponatremia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    wheezing / Rapid / Incidence not known
    angina / Early / Incidence not known
    peripheral vasoconstriction / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    bleeding / Early / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known

    Mild

    tremor / Early / Incidence not known
    vertigo / Early / Incidence not known
    drowsiness / Early / Incidence not known
    weight gain / Delayed / Incidence not known
    headache / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    pallor / Early / Incidence not known
    premature atrial contractions (PACs) / Early / Incidence not known
    eructation / Early / Incidence not known
    nausea / Early / Incidence not known
    flatulence / Early / Incidence not known
    diarrhea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    vomiting / Early / Incidence not known
    hyperhidrosis / Delayed / Incidence not known

    DRUG INTERACTIONS

    Amitriptyline: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Amitriptyline; Chlordiazepoxide: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Articaine; Epinephrine: (Minor) Use of vasopressin with catecholamines, such as epinephrine, is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters.
    Carbamazepine: (Minor) Carbamazepine may cause additive hyponatremia or antidiuretic effects when combined with vasopressin, ADH.
    Chlorpropamide: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as chlorpropamide, may increase the pressor and antidiuretic effects of vasopressin.
    Citalopram: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Clomipramine: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Clozapine: (Minor) Use of vasopressin with drugs suspected of causing diabetes insipidus, such as clozapine, may decrease the pressor and antidiuretic effects of vasopressin.
    Corticorelin, Ovine: (Major) The coadministration of corticorelin, ovine and vasopressin, ADH has resulted in a synergistic effect on the secretion of corticotropin, with a less marked synergistic response on cortisol secretion. The concomitant use of corticorelin and vasopressin should be avoided.
    Cyclophosphamide: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as cyclophosphamide, may increase the pressor and antidiuretic effects of vasopressin.
    Demeclocycline: (Minor) Use of vasopressin with drugs suspected of causing diabetes insipidus, such as demeclocycline, may decrease the pressor and antidiuretic effects of vasopressin.
    Desipramine: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Desmopressin: (Moderate) Although the pressor activity of desmopressin is very low compared to its antidiuretic activity, large doses of desmopressin should be used with other pressor agents like vasopressin, ADH only with careful patient monitoring.
    Dopamine: (Minor) Use of vasopressin with catecholamines, such as dopamine, is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters.
    Doxepin: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Enalapril, Enalaprilat: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as enalapril, may increase the pressor and antidiuretic effects of vasopressin.
    Enalapril; Felodipine: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as enalapril, may increase the pressor and antidiuretic effects of vasopressin.
    Enalapril; Hydrochlorothiazide, HCTZ: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as enalapril, may increase the pressor and antidiuretic effects of vasopressin.
    Epinephrine: (Minor) Use of vasopressin with catecholamines, such as epinephrine, is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters.
    Escitalopram: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Felbamate: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as felbamate, may increase the pressor and antidiuretic effects of vasopressin.
    Fludrocortisone: (Minor) Fludrocortisone can enhance the antidiuretic effect of vasopressin.
    Fluoxetine: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Fluoxetine; Olanzapine: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Fluvoxamine: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Foscarnet: (Minor) Use of vasopressin with drugs suspected of causing diabetes insipidus, such as foscarnet, may decrease the pressor and antidiuretic effects of vasopressin.
    Furosemide: (Minor) Use of furosemide with vasopressin increases the effect of vasopressin on osmolar clearance and urine flow. Furosemide increases osmolar clearance 4-fold and urine flow 9-fold when coadministered with exogenous vasopressin in healthy subjects.
    Haloperidol: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as haloperidol, may increase the pressor and antidiuretic effects of vasopressin.
    Heparin: (Minor) Heparin can decrease the antidiuretic response to vasopressin.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as methyldopa, may increase the pressor and antidiuretic effects of vasopressin.
    Ifosfamide: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as ifosfamide, may increase the pressor and antidiuretic effects of vasopressin.
    Imipramine: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Indomethacin: (Minor) Use of indomethacin with vasopressin may prolong the effect of vasopressin on cardiac index and systemic vascular resistance. Indomethacin more than doubles the time to offset for vasopressin's effect on peripheral vascular resistance and cardiac output in healthy subjects.
    Lithium: (Minor) Use of vasopressin with drugs suspected of causing diabetes insipidus, such as lithium, may decrease the pressor and antidiuretic effects of vasopressin.
    Methyldopa: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as methyldopa, may increase the pressor and antidiuretic effects of vasopressin.
    Norepinephrine: (Minor) Use of vasopressin with catecholamines, such as norepinephrine, is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters.
    Nortriptyline: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Paroxetine: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Pentamidine: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as pentamidine, may increase the pressor and antidiuretic effects of vasopressin.
    Perphenazine; Amitriptyline: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Prilocaine; Epinephrine: (Minor) Use of vasopressin with catecholamines, such as epinephrine, is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters.
    Protriptyline: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Selective serotonin reuptake inhibitors: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Sertraline: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Tricyclic antidepressants: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Trimipramine: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as tricyclic antidepressants, may increase the pressor and antidiuretic effects of vasopressin.
    Urea: (Minor) Systemic urea can potentiate the antidiuretic effect of vasopressin, ADH when both drugs are used concurrently. Dosage adjustments may be required.
    Vincristine Liposomal: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as vincristine, may increase the pressor and antidiuretic effects of vasopressin.
    Vincristine: (Minor) Use of vasopressin with drugs suspected of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as vincristine, may increase the pressor and antidiuretic effects of vasopressin.

    PREGNANCY AND LACTATION

    Pregnancy

    Vasopressin is classified as FDA pregnancy category C. No adequate studies have been conducted in pregnant women. It is not known if vasopressin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Due to increased drug clearance in the second and third trimesters, the dose of vasopressin may need to be increased to doses exceeding 0.1 units/minute in post-cardiotomy shock and 0.07 units/minute in septic shock. While the antidiuretic doses of vasopressin are not likely to produce tonic uterine contractions, doses for shock may do so and could threaten the pregnancy. Use vasopressin during pregnancy only if clearly needed.

    It is not known if vasopressin is present in human milk; however, oral absorption by a nursing infant is unlikely because vasopressin is rapidly degraded in the gastrointestinal tract. Use vasopressin with caution in a breast-feeding woman. Consider advising a breast-feeding woman to pump and discard breast milk for 1.5 hours after receiving vasopressin. Women treated with vasopressin for diabetes insipidus have been reported to breast-feed without negative effects in the infant.

    MECHANISM OF ACTION

    Vasopressin exerts its antidiuretic effects by increasing the resorption of water at the renal collecting ducts. Subsequently, urinary flow is reduced and urine osmolality is increased, thereby maintaining serum osmolality within an acceptable physiological range. At the cellular level, vasopressin stimulates adenylate cyclase activity. Increased adenylate cyclase activity increases the levels of cyclic adenosine monophosphate (cAMP) in the distal convoluted tubule and the collecting duct, thereby enhancing the permeability of the membrane to free water. Physiologic doses of vasopressin are administered to patients with neurohypophyseal diabetes insipidus to conserve the large amounts of water that are normally lost in the urine. In contrast to desmopressin, vasopressin induces the release of adrenocorticotropic hormone, increases plasma cortisol concentrations, and exhibits vasopressive and contractile action on visceral smooth muscle.
     
    Vasopressin stimulates the contraction of vascular smooth muscle in coronary, splanchnic, GI, pancreatic, skin, and muscular vascular beds. This effect is most prominent in the capillaries, small arterioles, and venules with less effect on the smooth musculature of large veins. Neither adrenergic agents nor vascular denervation prevents the direct effect of vasopressin on smooth muscle contractile elements. This vasoconstrictive property has been used in managing massive GI hemorrhage; however, vasopressin is no longer indicated for this purpose.

    PHARMACOKINETICS

    Vasopressin must be administered parenterally because it is degraded by trypsin in the gastrointestinal tract. The hormone distributes throughout the extracellular fluid but does not bind to plasma proteins. Vasopressin is degraded primarily in the liver and kidneys and has a plasma half-life of 10 to 20 minutes. Vasopressin is predominantly metabolized and only about 6% of the dose is excreted unchanged in the urine.
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Intravenous Route

    Onset of the pressor effect of vasopressin is rapid, peaking within 15 minutes. After infusion discontinuation, pressor effect fades within 20 minutes. At infusion rates used in vasodilatory shock, vasopressin clearance is 9 to 25 mL/kg/minute. Apparent half-life at this concentration is 10 minutes or less.

    Intramuscular Route

    The duration of antidiuretic effect after IM administration of vasopressin is variable, but effects are usually maintained for 2 to 8 hours.

    Subcutaneous Route

    The duration of antidiuretic effect after subcutaneous administration of vasopressin is variable, but effects are usually maintained for 2 to 8 hours.