PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Antidiuretic Hormones
    Vasopressin (ADH) and Analogs

    BOXED WARNING

    Children, cystic fibrosis, diarrhea, electrolyte imbalance, fever, hyponatremia, infection, vomiting

    Desmopressin is contraindicated in patients with hyponatremia and in patients with a history of hyponatremia. Desmopressin nasal spray and sublingual tablets for nocturia are contraindicated in patients with an increased risk of severe hyponatremia, such as patients with excessive fluid intake, and in patients with illnesses that can cause fluid or electrolyte imbalances, including gastroenteritis, salt-wasting nephropathies, systemic infection, known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and polydipsia. Before initiating or resuming therapy with desmopressin for nocturia, ensure serum sodium concentrations are normal. Measure serum sodium within 7 days and approximately 1 month after initiating therapy or increasing the dose, and periodically during treatment. Monitor serum sodium more frequently in patients 65 years and older and in patients at increased risk of hyponatremia. Females are more sensitive to the effects of desmopressin sublingual tablets for nocturia compared to men; the recommended dose for women is lower than for men because women had a higher risk of hyponatremia with the 55.3 mcg dose in clinical trials. If hyponatremia occurs, consider temporarily or permanently discontinuing desmopressin. Due to the reports of hyponatremia-related seizures in pediatric patients treated with other intranasal formulations of desmopressin, use of desmopressin nasal spray for nocturia is contraindicated in patients with primary nocturnal enuresis (PNE). When used for indications other than nocturia, use desmopressin cautiously in patients with conditions that are associated with fluid and electrolyte imbalance such as cystic fibrosis, heart failure, and renal disease. Patients receiving desmopressin who have a preexisting fluid and electrolyte imbalance or who have no need of the antidiuretic effects are at an increased risk of developing water intoxication and hyponatremia. Patients with any other condition that causes fluid and electrolyte imbalance (e.g., habitual polydipsia, psychogenic polydipsia) or being treated with hypertonic fluids or drugs that cause SIADH should also be treated with caution. Young children and the elderly are more prone to water intoxication and hyponatremia. Some experts recommend against the use of desmopressin in children younger than 2 years. Decrease fluid intake in an effort to lower the potential risk of developing water intoxication and hyponatremia with accompanying signs and symptoms (e.g., headache, nausea/vomiting, decreased serum sodium, and weight gain). Avoid excessive fluid intake. Caution patients who do not have need of antidiuretic hormone for its antidiuretic effect to ingest only enough fluid to satisfy thirst, in an effort to decrease the potential for water intoxication and hyponatremia. Patients being treated for primary nocturnal enuresis (PNE) and nocturia should not drink water at night, especially for the 1 hour before and 8 hours after tablet administration. Interrupt treatment for PNE with the tablets during acute illnesses (e.g., systemic infection, fever, recurrent vomiting, or diarrhea), during extremely hot weather, vigorous exercise, or other conditions associated with increased fluid intake. For all uses of desmopressin, give particular attention to an extreme decrease in plasma osmolality. This is a rare occurrence, but can lead to seizures, possible coma, and death. In patients with diabetes insipidus or polyuria and polydipsia associated with head injury or surgery, monitor urine volume and osmolality, and in some cases, plasma osmolality periodically during therapy. In patients treated for nocturnal enuresis, monitor serum electrolytes if therapy is continued beyond 7 days. Patients with polydipsia should not receive desmopressin for the treatment of bleeding abnormalities due to its antidiuretic effects.

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic structural analog of vasopressin (antidiuretic hormone or ADH); more potent and much longer acting than vasopressin; many dosage forms including oral, injectable, sublingual, and intranasal forms
    Used for the treatment of central diabetes insipidus, primary nocturnal enuresis (PNE), spontaneous bleeding or trauma-induced hemorrhage, bleeding prophylaxis (e.g., surgical bleeding), hemophilia A or mild to moderate von Willebrand's disease, and nocturia due to nocturnal polyuria in adults
    The intranasal formulation is no longer indicated to treat PNE secondary to reports of hyponatremic-related seizures sometimes resulting in death

    COMMON BRAND NAMES

    DDAVP, Minirin, Nocdurna, Noctiva, Stimate

    HOW SUPPLIED

    DDAVP Nasal Sol: 0.1mg, 1mL
    DDAVP/Desmopressin/Desmopressin Acetate Intravenous Inj Sol: 1ml, 4mcg
    DDAVP/Desmopressin/Desmopressin Acetate Oral Tab: 0.1mg, 0.2mg
    DDAVP/Desmopressin/Desmopressin Acetate Subcutaneous Inj Sol: 1ml, 4mcg
    DDAVP/Desmopressin/Desmopressin Acetate/Minirin/Noctiva/Stimate Nasal Spray Met: 0.1mg, 0.1mL, 0.75mcg, 1mL, 1.5mcg, 1.5mg
    Nocdurna Sublingual Tablet, SL: 27.7mcg, 55.3mcg

    DOSAGE & INDICATIONS

    For the management of patients with central diabetes insipidus (neurohypophyseal diabetes insipidus) including polydipsia and polyuria which occurs after head surgery or trauma.
    Oral dosage
    Adults

    Initially, 0.05 mg PO twice daily, then titrate to response. The usual dosage range is 0.1 mg to 1.2 mg PO per day, given in 2 to 3 divided doses. If patients are receiving intranasal therapy, begin oral therapy 12 hours after the last intranasal dose. During the initial titration period and continued therapy, observe and monitor closely. Adjust treatment according to the diurnal pattern of response. Response should be estimated by 2 parameters, adequate duration of sleep and adequate, not excessive, water turnover. In the elderly, careful fluid intake restrictions are required to prevent hyponatremia and water intoxication.

    Children and Adolescents 4 to 17 years

    Initially, 0.05 mg PO twice daily. Adjust doses based on patient's diurnal pattern of response. The usual dosage range is 0.1 mg to 1.2 mg PO per day, given in 2 to 3 divided doses. If patients are receiving intranasal therapy, begin oral therapy 12 hours after last intranasal dose. During initial titration and continued therapy, observe and monitor closely; adjust treatment to the diurnal pattern of response. Response should be estimated by 2 parameters, adequate duration of sleep and adequate, not excessive, water turnover. Careful fluid intake restrictions are required in pediatric patients to prevent hyponatremia and water intoxication.

    Children younger than 4 years

    Initially, 0.05 mg PO once daily. Individualize dosing to prevent an excessive decrease in plasma osmolality, which can lead to hyponatremia and possible seizures. During the initial titration period and continued therapy, observe and monitor closely; treatment should be adjusted according to the diurnal pattern of response. Response should be estimated by 2 parameters: adequate duration of sleep and adequate, not excessive, water turnover. Fluid intake restrictions in these patients are recommended.

    Intranasal dosage (DDAVP 0.01% nasal solution)
    Adults

    Initially, 10 mcg (0.1 mL) intranasally into 1 nostril, may increase to 40 mcg until the patient can sleep for an adequate period of time without incidence of polyuria. Maintenance dose range: 10 mcg/day to 40 mcg/day intranasally (0.1 mL/day to 0.4 mL/day) in 1 to 3 divided doses. If administered more than once a day, adjust for an adequate diurnal rhythm of urine output. If the patient was previously receiving desmopressin injection, administer 10 times the amount of desmopressin acetate, rounding down to the nearest 10 mcg. If the patient was previously receiving desmopressin tablets, dose titration is required because intranasal desmopressin is approximately 10 to 40 fold more potent than oral (tablet) desmopressin.[33605]

    Children and Adolescents 4 to 17 years

    Initially, 10 mcg (0.1 mL) intranasally into 1 nostril, may increase to 30 mcg until the patient can sleep for an adequate period of time without incidence of polyuria. Maintenance dose range: 10 mcg/day to 30 mcg/day intranasally (0.1 mL/day to 0.3 mL/day) in 1 to 2 divided doses. If 30 mcg is divided, typically 20 mcg is given in the morning, and 10 mcg is given at night. Adjust for an adequate diurnal rhythm of urine output. If the patient was previously receiving desmopressin injection, administer 10 times the amount of desmopressin acetate, rounding down to the nearest 10 mcg. If the patient was previously receiving desmopressin tablets, dose titration is required because intranasal desmopressin is approximately 10 to 40 fold more potent than oral (tablet) desmopressin.[33605]

    Intranasal dosage (DDAVP rhinal tube solution)
    Adults

    Initially, 10 mcg (0.1 mL) intranasally, given in 1 to 3 divided doses, then titrated to response. The recommended maintenance dose is 10 mcg/day to 40 mcg/day intranasally (0.1 mL/day to 0.4 mL/day) in 1 to 3 divided doses. Most adults require a maintenance dose of 20 mcg/day, administered as 10 mcg intranasally twice daily. Adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover. Fluid restrictions should be observed. In the elderly, careful dosage selection and monitoring of renal function are recommended.[61810]

    Adolescents 13 to 17 years

    Initially, 10 mcg (0.1 mL) intranasally, given in 1 to 3 divided doses, then titrated to response. The recommended maintenance dose is 10 mcg/day to 40 mcg/day intranasally (0.1 mL/day to 0.4 mL/day) in 1 to 3 divided doses. Most patients require a maintenance dose of 20 mcg/day, administered as 10 mcg intranasally twice daily. Adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover. Fluid restrictions should be observed. In the elderly, careful dosage selection and monitoring of renal function are recommended.[61810]

    Infants and Children 3 months to 12 years

    Initially, 5 mcg (0.05 mL) intranasally, given in 1 to 2 divided doses, then titrated to response. In infants, doses less than 5 mcg (0.05 mL) may be necessary. The recommended maintenance dose is 5 mcg/day to 30 mcg/day (0.05 mL/day to 0.3 mL/day) intranasally in single or divided doses. About 1/4 to 1/3 of patients can be controlled by a single daily dose. Fluid restrictions should be observed.[61810]

    Intravenous and Subcutaneous dosage
    Adults

    2 to 4 mcg IV or subcutaneously given in 2 divided doses daily. The morning and evening doses should be separately adjusted for an adequate diurnal rhythm of water turnover. Alternatively, if the patient was previously receiving intranasal therapy, the usual dose is one-tenth (1/10) of the intranasal maintenance dose. Careful fluid intake restrictions are required to prevent hyponatremia and water intoxication.[42295]

    Adolescents and Children 12 to 17 years

    2 to 4 mcg IV or subcutaneously given in 2 divided doses daily. The morning and evening doses should be separately adjusted for an adequate diurnal rhythm of water turnover. Alternatively, if the patient was previously receiving intranasal therapy, the usual dose is one-tenth (1/10) of the intranasal maintenance dose. Careful fluid intake restrictions are required to prevent hyponatremia and water intoxication.[42295]

    For the treatment of primary nocturnal enuresis.
    Oral dosage
    Adults

    Initially, 0.2 mg PO once daily at bedtime. Doses may be titrated up to 0.6 mg PO once daily at bedtime, depending on individual patient response. Fluid restriction should be observed, and fluid intake should be limited to a minimum from 1 hour before administration, until the next morning, or at least 8 hours after administration. Interrupt therapy for acute illness (e.g., systemic infection, fever, recurrent vomiting or diarrhea), extremely hot weather, vigorous exercise, or other conditions associated with increased water intake. Patients previously receiving intranasal treatment may begin oral therapy the night following (24 hours) the last intranasal dose.

    Children and Adolescents 6 years and older

    Initially, 0.2 mg PO once daily at bedtime. Doses may be titrated up to 0.6 mg PO once daily at bedtime, depending on individual patient response. Fluid restriction should be observed, and fluid intake should be limited to a minimum from 1 hour before administration, until the next morning, or at least 8 hours after administration. Interrupt therapy for acute illness (e.g., systemic infection, fever, recurrent vomiting or diarrhea), extremely hot weather, vigorous exercise, or other conditions associated with increased water intake. Treatment has been given safely to pediatric patients for up to 6 months. Patients previously receiving intranasal treatment may begin oral therapy the night following (24 hours) the last intranasal dose.

    Intranasal dosage (DDAVP 0.01% nasal solution or generic equivalents)†
    Adults

    As of 2007 in response to a FDA request for removal of the indication, the intranasal formulation is no longer indicated for the treatment of primary nocturnal enuresis secondary to post-marketing reports of hyponatremic-related seizures, which most often occurred in pediatric patients. Consider other treatment options for this condition. The previously recommended dose: 20 mcg (0.2 mL) intranasally of the 0.01% nasal solution at bedtime, with one-half of the dose administered into each nostril. If no response after 3 days, the dose was adjusted upward to 40 mcg/day (20 mcg per nostril) intranasally at bedtime. Typical maintenance dose was 10 to 40 mcg/day (0.1 to 0.4 mL/day). If patient responded to 20 mcg/day, the dose was adjusted downward to 10 mcg/day to see if response could be maintained. Fluid restriction was to be observed, with fluid intake was limited to a minimum from 1 hour before intranasal administration, until the next morning, or at least 8 hours after administration. Treatment longer than 4 to 8 weeks has not been studied. Patients receiving intranasal treatment could begin oral therapy the night following (24 hours) the last intranasal dose.

    Children and Adolescents 6 years and older

    As of 2007 the intranasal formulation is no longer FDA-approved for the treatment of primary nocturnal enuresis secondary to postmarketing reports of hyponatremia-related seizures, which most often occurred in children using the intranasal formulation. Consider other treatment options for this condition. The previously recommended dose: 20 mcg (0.2 mL) intranasally of the 0.01% nasal solution at bedtime, with one-half of the dose administered into each nostril. If no response after 3 days, the dose was adjusted upward to 40 mcg/day (20 mcg per nostril) intranasally at bedtime. Typical maintenance dose was 10 to 40 mcg/day (0.1 to 0.4 mL/day). If patient responded to 20 mcg/day, the dose was adjusted downward to 10 mcg/day to see if response could be maintained. Fluid restriction was to be observed, with fluid intake was limited to a minimum from 1 hour before intranasal administration, until the next morning, or at least 8 hours after administration. Patients receiving intranasal treatment could begin oral therapy the night following (24 hours) the last intranasal dose.

    For bleeding prophylaxis and prevention and control of surgical bleeding or spontaneous or traumatic hemorrhage in patients with hemophilia A or mild to moderate classic von Willebrand's disease (type 1) and factor VIII activity concentrations more than 5%.
    NOTE: Desmopressin has been designated an orphan drug by the FDA for mild hemophilia A and von Willebrand's disease.
    NOTE: Confirm responsiveness before using desmopressin for therapeutic interventions. A desmopressin response requires an increase of at least 2 times the baseline vWF activity and an increase of both von Willebrand factor (vWF) and factor VIII concentrations of more than 0.5 International Units/mL for at least 4 hours. If a desmopressin challenge is not practical, it can be presumed adult patients with type 1 von Willebrand's disease whose baseline vWF concentrations are 0.3 International Units/mL or more are desmopressin responsive. Obtain vWF concentrations after desmopressin administration to confirm response.
    Intranasal dosage (Stimate 1.5 mg/mL nasal spray)

    NOTE: Use parenteral desmopressin in patients for whom the intranasal route is compromised or inappropriate.

    Adults weighing 50 kg or more

    150 mcg into each nostril once for a total dose of 300 mcg. If used preoperatively, administer 2 hours before surgery. Determine need for repeat dosage based on laboratory response and patient's clinical condition. Most patients respond to 1 to 2 doses; administer a second dose 8 to 24 hours after the first dose if needed. To minimize risk of hyponatremia and seizures, administer no more than once every 24 hours or for more than 3 consecutive days. Tachyphylaxis may occur with repeated administration given more frequently than once every 48 hours.

    Adults weighing less than 50 kg

    150 mcg into 1 nostril once for a total dose of 150 mcg. If used preoperatively, administer 2 hours before surgery. Determine need for repeat dosage based on laboratory response and patient's clinical condition. Most patients respond to 1 to 2 doses; administer a second dose 8 to 24 hours after the first dose if needed. To minimize risk of hyponatremia and seizures, administer no more than once every 24 hours or for more than 3 consecutive days. Tachyphylaxis may occur with repeated administration given more frequently than once every 48 hours.

    Children and Adolescents weighing 50 kg or more

    150 mcg into each nostril once for a total dose of 300 mcg. If used preoperatively, administer 2 hours before surgery. Determine need for repeat dosage based on laboratory response and patient's clinical condition. Most patients respond to 1 to 2 doses; administer a second dose 8 to 24 hours after the first dose if needed. To minimize risk of hyponatremia and seizures, administer no more than once every 24 hours or for more than 3 consecutive days. Tachyphylaxis may occur with repeated administration given more frequently than once every 48 hours.

    Infants, Children, and Adolescents 11 months to 17 years weighing less than 50 kg

    150 mcg into 1 nostril once for a total dose of 150 mcg. If used preoperatively, administer 2 hours before surgery. Determine need for repeat dosage based on laboratory response and patient's clinical condition. Most patients respond to 1 to 2 doses; administer a second dose 8 to 24 hours after the first dose if needed. To minimize risk of hyponatremia and seizures, administer no more than once every 24 hours or for more than 3 consecutive days. Tachyphylaxis may occur with repeated administration given more frequently than once every 48 hours.

    Intravenous dosage
    Adults

    0.3 mcg/kg/dose (Max: 20 mcg/dose) IV once. If used preoperatively, administer 30 minutes before surgery. Determine need for repeat dosage based on laboratory response and patient's clinical condition. To minimize risk of hyponatremia and seizures, administer no more than once every 24 hours or for more than 3 consecutive days. Tachyphylaxis may occur with repeated administration given more frequently than once every 48 hours.

    Infants, Children, and Adolescents 3 months to 17 years

    0.3 mcg/kg/dose (Max: 20 mcg/dose) IV once. If used preoperatively, administer 30 minutes before surgery. Determine need for repeat dosage based on laboratory response and patient's clinical condition. To minimize risk of hyponatremia and seizures, administer no more than once every 24 hours or for more than 3 consecutive days. Tachyphylaxis may occur with repeated administration given more frequently than once every 48 hours.

    For the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void.
    Intranasal dosage (Noctiva nasal spray, solution)
    Adults 50 to 64 years

    PATIENTS NOT AT INCREASED RISK FOR HYPONATREMIA: 1 spray (1.66 mcg) in either the left or right nostril approximately 30 minutes before going to bed. THOSE AT INCREASED RISK FOR HYPONATREMIA: 1 spray (0.83 mcg) in either the left or right nostril approximately 30 minutes before going to bed. After at least 7 days of treatment, the dose may be increased to 1.66 mcg, if needed, provided the serum sodium is within the normal range during treatment with the 0.83 mcg dose. The 0.83 mcg dose did not meet all prespecified efficacy endpoints in clinical trials, but may have a lower risk of hyponatremia.

    Geriatric Adults

    The recommended starting dose is 1 spray (0.83 mcg) in either the left or right nostril approximately 30 minutes before going to bed. After at least 7 days of treatment, the dose may be increased to 1.66 mcg, if needed, provided the serum sodium is within the normal range during treatment with the 0.83 mcg dose. The 0.83 mcg dose did not meet all prespecified efficacy endpoints in clinical trials, but may have a lower risk of hyponatremia.

    Sublingual dosage (Nocdurna sublingual tablet)
    Adult Females

    27.7 mcg sublingually once daily, 1 hour before bedtime without water. Only start or resume therapy in patients with a normal serum sodium concentration. The recommended dose for women is lower than for men because women are more sensitive to the effects of desmopressin sublingual tablet and had a higher risk of hyponatremia with the 55.3 mcg dose in clinical trials.

    Adult Males

    55.3 mcg sublingually once daily, 1 hour before bedtime without water. Only start or resume therapy in patients with a normal serum sodium concentration.

    For the treatment of symptomatic hyponatremia† or hyponatremia overcorrection†.
    For the treatment of symptomatic hyponatremia†.
    Intravenous dosage
    Adults

    1 to 2 mcg IV every 6 to 8 hours in combination with hypertonic saline. Guidelines describe preemptive desmopressin administration to prevent sodium overcorrection.

    For the management of hyponatremia overcorrection in chronic hyponatremia†.
    Intravenous dosage
    Adults

    2 to 4 mcg IV every 8 hours.

    For the treatment of uremic bleeding†.
    Intravenous or Subcutaneous dosage
    Adults

    0.3 to 0.4 mcg/kg/dose IV or subcutaneously once. Repeat dosing is not recommended due to tachyphylaxis.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Dependent on route of administration and indication for therapy.

    Geriatric

    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.

    Infants

    3 months and older: Dependent on route of administration and indication for therapy.
    Less than 3 months: Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments are needed.

    Renal Impairment

    CrCl 50 mL/minute or more: No dosage adjustment is needed.
    CrCl less than 50 mL/minute OR eGFR less than 50 mL/minute/1.73 m2: Use is contraindicated. Single-dose administration has been used for uremic bleeding in patients with renal failure; however, repeat doses are not recommended.

    ADMINISTRATION

    Oral Administration

    Oral Tablets
    If converting from intranasal therapy, administer oral dose 12 hours after last intranasal dose.
    Patient response to each dose should be determined by adequate duration of sleep and adequate, not excessive, water turnover.
     
    Sublingual Tablets
    The patient should place the tablet under their tongue 1 hour before bedtime until it dissolves.
    Have the patient empty their bladder just before bedtime.
    Advise patients to limit the amount of water or liquids they drink from 1 hour before taking desmopressin sublingual tablet and until 8 hours after. They should also avoid drinks containing caffeine and alcohol before bedtime.

    Injectable Administration

    Desmopressin is administered intravenously or subcutaneously.
    Desmopressin (DDAVP) injection has an antidiuretic hormone activity of 16 International Units/mL; 1 mcg desmopressin is equivalent to 4 International Units antidiuretic hormone activity.
    If given preoperatively, desmopressin injection should be given 30 minutes before the scheduled procedure.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Direct intravenous injection
    No dilution necessary.
    Inject IV over 1 minute.
     
    Intermittent intravenous infusion
    For adults and children weighing greater than 10 kg, dilute dose in 50 mL of 0.9% Sodium Chloride for injection. For children weighing less than 10 kg, dilute dose in 10 mL 0.9% Sodium Chloride for injection.
    Infuse IV slowly over 15 to 30 minutes.
    Pulse and blood pressure should be monitored during infusion.

    Subcutaneous Administration

    Inject subcutaneously taking care not to inject intradermally.

    Inhalation Administration
    Intranasal Inhalation Administration

    Desmopressin nasal sprays may not be substituted for each other due to significant differences in concentration.
     
    DDAVP Nasal Spray
    DDAVP nasal spray delivers doses in 0.1 mL (10 mcg) increments. If doses other than these are required, the rhinal tube delivery system may be used.
    One spray (10 mcg) has an antidiuretic activity of about 40 International Units.
    The nasal spray must be primed prior to first use. To prime, press down 4 times. The pump will stay primed for up to 1 week. If the product has not been used for a period of 1 week, re-prime the pump by pressing once.
    Instruct patient on the proper technique for administering the nasal spray. Tilt bottle so that the tube inside the bottle draws from the deepest portion of the medication.
    To avoid the spread of infection, do not use the container for more than 1 person.
    For 5 mL bottles, discard after 50 sprays (doses), and for 2.5 mL bottles, discard after 25 sprays (doses) because the amount delivered thereafter per spray may be substantially less than the recommended dose. Do not transfer any remaining solution to another bottle.
     
    DDAVP Rhinal Tube
    DDAVP Rhinal tube is used to administer desmopressin doses less than 10 mcg (less than 0.1 mL).
    Break the seal on the bottle and remove cap. Twist off the seal from the dropper. Keep this seal as it is reversed to prevent leakage from the dropper.
    Squeeze the correct dose into this tube from the dropper bottle. Once the dose is in the tube, hold the tube with your fingers, about 3/4 inch from the end.
    Put the tube into a nostril, until your fingers touch the nostril. Put the other end of the tube into the patients mouth; the patient should hold their breath.
    Tilt the patient's head back and have them blow with a short strong puff through the tube. This places the solution in the nasal cavity and not down your throat.
    After use, reseal the dropper tip and close the bottle. Wash the rhinal tube in water and shake well, until no water is left in the tube.
    To avoid the spread of infection, do not use the container for more than 1 person.
    For 2.5 mL bottles, discard after 25 sprays (doses) because the amount delivered thereafter per spray may be substantially less than the recommended dose. Do not transfer any remaining solution to another bottle.
     
    Stimate Nasal Spray
    Stimate nasal spray delivers doses in 0.1 mL (150 mcg) increments. If doses other than these are required, parenteral desmopressin injection must be used.
    One spray (150 mcg) has an antidiuretic activity of about 600 International Units.
    The nasal spray must be primed prior to first use. To prime, press down 4 times. The pump will stay primed for up to 1 week. If the product has not been used for a period of 1 week, re-prime the pump by pressing once.
    Instruct patient on the proper technique for administering the nasal spray. Tilt bottle so that the tube inside the bottle draws from the deepest portion of the medication.
    If given preoperatively, intranasal desmopressin should be administered 2 hours before surgery.
    To avoid the spread of infection, do not use the container for more than 1 person.
    Discard spray pump after 25 sprays since the amount delivered thereafter per spray may be substantially less than the recommended dose. Do not transfer any remaining solution to another bottle.
     
    Noctiva Nasal Spray
    Noctiva nasal spray delivers either 0.83 mcg or 1.66 mcg of desmopressin acetate (equivalent to 0.75 mcg or 1.5 mcg of desmopressin) per spray (0.1 mL).
    Two sprays of the 0.83 mcg nasal spray are not interchangeable with 1 spray of the 1.66 mcg nasal spray; the 1.66 mcg/0.1 mL nasal spray should be prescribed for patients who are or will be taking the 1.66 mcg dose.
    Do NOT shake the bottle.
    Prime the nasal spray before using for the first time by pumping 5 actuations into the air away from the face. If the product has not been used for more than 3 days, re-prime by pumping 2 actuations into the air.
    Instruct the patient to blow their nose, tilt the head back slightly, and insert the nasal applicator into the left or right nostril, keeping the nasal applicator upright. The patient should close the open nostril with a finger from the empty hand and gently inhale while the nasal applicator is pumped 1 time. Avoid spraying in the eyes. Gently breathe in through the nose and out through the mouth several times.
    Wipe the nasal applicator using a clean tissue and replace the cap on the bottle.
    To avoid the spread of infection, do not use the container for more than 1 person.
    Do not co-administer with other intranasal products.
    Discard nasal spray 60 days after opening.

    STORAGE

    Generic:
    - Refrigerate (between 36 and 46 degrees F)
    DDAVP:
    - Store between 36 to 46 degrees F
    Minirin:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store upright
    Nocdurna:
    - Product should always be stored in the blister and only removed immediately before use
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in the original carton to protect from light
    Noctiva:
    - Product must be used within 60 days after removal from refrigeration to room temperature (77 degrees F)
    - Store in refrigerator (36 to 46 degrees F), excursions permitted between 32 to 59 degrees F
    - Store upright
    Stimate:
    - Store at room temperature (up to 77 degrees F)
    - Store upright

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Desmopressin should not be used in patients with known desmopressin hypersensitivity. Severe allergic reactions, including anaphylaxis, have been reported.

    Angina, cardiac disease, coronary artery disease, heart failure, hypertension, increased intracranial pressure, thromboembolic disease, urinary retention

    Desmopressin sublingual tablets for nocturia are contraindicated in patients with heart failure. Desmopressin nasal spray for nocturia is contraindicated in patients with congestive heart failure (New York Heart Association Class II to IV) and should be used with caution (e.g., monitoring of volume status) in patients with New York Heart Association Class I congestive heart failure. Both the nasal spray and sublingual tablets for nocturia are contraindicated in patients with uncontrolled hypertension and are not recommended in patients at risk for increased intracranial pressure or those with a history of urinary retention. The vasoactive effects (decrease in blood pressure with increase in heart rate) associated with the administration of desmopressin are minimal. Nonetheless, when used for indications other than nocturia, the drug should be used with caution in patients with cardiac disease, especially hypertension, heart failure, or coronary artery disease. Because of the risk of fluid overload and electrolyte abnormalities, patients with heart failure may also be at increased risk for low sodium concentrations. Additionally, patients with unstable angina or severe congestive heart failure should not receive desmopressin for bleeding abnormalities due to its antidiuretic effects. In addition, desmopressin should be used with caution in patients with a history of thromboembolic disease because the drug rarely can precipitate such events. In a review desmopressin given during cardiac, orthopedic, or other major surgery, no increase incidence of thrombosis was found.

    Renal disease, renal failure, renal impairment

    Desmopressin is contraindicated in patients with moderate to severe renal impairment (CrCl less than 50 mL/minute or eGFR below 50 mL/minute/1.73 m2) and renal failure. Because of the risk of fluid overload and electrolyte abnormalities, patients with renal disease may be at increased risk for low sodium concentrations and fluid and electrolyte imbalance. However, desmopressin is used off-label as a single injection for uremic bleeding in patients with renal failure. Repeat dosing is not recommended; therefore, the risk of toxicities associated with accumulation of desmopressin is expected to be low, especially with single-dose intermittent use and appropriate monitoring.

    Children, cystic fibrosis, diarrhea, electrolyte imbalance, fever, hyponatremia, infection, vomiting

    Desmopressin is contraindicated in patients with hyponatremia and in patients with a history of hyponatremia. Desmopressin nasal spray and sublingual tablets for nocturia are contraindicated in patients with an increased risk of severe hyponatremia, such as patients with excessive fluid intake, and in patients with illnesses that can cause fluid or electrolyte imbalances, including gastroenteritis, salt-wasting nephropathies, systemic infection, known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and polydipsia. Before initiating or resuming therapy with desmopressin for nocturia, ensure serum sodium concentrations are normal. Measure serum sodium within 7 days and approximately 1 month after initiating therapy or increasing the dose, and periodically during treatment. Monitor serum sodium more frequently in patients 65 years and older and in patients at increased risk of hyponatremia. Females are more sensitive to the effects of desmopressin sublingual tablets for nocturia compared to men; the recommended dose for women is lower than for men because women had a higher risk of hyponatremia with the 55.3 mcg dose in clinical trials. If hyponatremia occurs, consider temporarily or permanently discontinuing desmopressin. Due to the reports of hyponatremia-related seizures in pediatric patients treated with other intranasal formulations of desmopressin, use of desmopressin nasal spray for nocturia is contraindicated in patients with primary nocturnal enuresis (PNE). When used for indications other than nocturia, use desmopressin cautiously in patients with conditions that are associated with fluid and electrolyte imbalance such as cystic fibrosis, heart failure, and renal disease. Patients receiving desmopressin who have a preexisting fluid and electrolyte imbalance or who have no need of the antidiuretic effects are at an increased risk of developing water intoxication and hyponatremia. Patients with any other condition that causes fluid and electrolyte imbalance (e.g., habitual polydipsia, psychogenic polydipsia) or being treated with hypertonic fluids or drugs that cause SIADH should also be treated with caution. Young children and the elderly are more prone to water intoxication and hyponatremia. Some experts recommend against the use of desmopressin in children younger than 2 years. Decrease fluid intake in an effort to lower the potential risk of developing water intoxication and hyponatremia with accompanying signs and symptoms (e.g., headache, nausea/vomiting, decreased serum sodium, and weight gain). Avoid excessive fluid intake. Caution patients who do not have need of antidiuretic hormone for its antidiuretic effect to ingest only enough fluid to satisfy thirst, in an effort to decrease the potential for water intoxication and hyponatremia. Patients being treated for primary nocturnal enuresis (PNE) and nocturia should not drink water at night, especially for the 1 hour before and 8 hours after tablet administration. Interrupt treatment for PNE with the tablets during acute illnesses (e.g., systemic infection, fever, recurrent vomiting, or diarrhea), during extremely hot weather, vigorous exercise, or other conditions associated with increased fluid intake. For all uses of desmopressin, give particular attention to an extreme decrease in plasma osmolality. This is a rare occurrence, but can lead to seizures, possible coma, and death. In patients with diabetes insipidus or polyuria and polydipsia associated with head injury or surgery, monitor urine volume and osmolality, and in some cases, plasma osmolality periodically during therapy. In patients treated for nocturnal enuresis, monitor serum electrolytes if therapy is continued beyond 7 days. Patients with polydipsia should not receive desmopressin for the treatment of bleeding abnormalities due to its antidiuretic effects.

    Surgery, von Willebrand's disease

    Desmopressin is not effective in patients with type 3 von Willebrand's disease (vWD) and can cause increased platelet binding with subsequent thrombocytopenia in patients with type 2B vWD. Many patients with type 2 vWD do not respond to desmopressin and require alternate treatment; however, a desmopressin trial can help confirm diagnosis and may be useful in some instances of mild bleeding in patients with type 2 vWD. Confirm responsiveness before using desmopressin for therapeutic interventions. Patients with vWD type 1 and von Willebrand factor (vWF) concentrations less than 0.3 International Units/mL or factor VIII activity equal to or less than 5% of normal may not respond to desmopressin. Desmopressin is not indicated for patients with severe classic vWD (type 1), for the treatment of hemophilia B, or in patients with factor VIII antibodies. In certain clinical situations, it may be justified to try desmopressin in patients with factor VIII concentrations of 2% to 5%; however, carefully monitor these patients. Patients with vWD subtype 1C, which is characterized by a shorted vWF half-life, may require alternative management in the setting of surgery. Do not use desmopressin as sole therapy in patients with vWD undergoing major surgery.

    Nasal surgery, nasal trauma

    Administration of intranasal desmopressin may be compromised by nasal mucosa changes (e.g., nasal trauma, nasal surgery, nasal blockage, nasal mucosal atrophy, congestion, or severe atrophic rhinitis), cranial surgery, and nasal packing. Chronic desmopressin administration may result in changes to nasal mucosa (scarring and edema), which may cause erratic and unreliable absorption. Intravenous desmopressin should be considered when indicated. Although the manufacturer states that nasal congestion does not affect the absorption of intranasal desmopressin, some clinicians recommend a higher dose. In patients receiving desmopressin nasal spray for nocturia, discontinue treatment in patients with concurrent nasal conditions that may increase systemic absorption of desmopressin (e.g., atrophy of nasal mucosa, and acute or chronic rhinitis), because the increased absorption may increase the risk of hyponatremia. Desmopressin nasal spray can be resumed when these conditions resolve.

    Geriatric

    In general, most reported clinical experience with desmopressin has not identified efficacy response differences between geriatric and younger patients. Geriatric patients 65 years of age and older treated with desmopressin for nocturia had a higher incidence of hyponatremia compared to patients less than 65 years old; therefore, monitor serum sodium more frequently in these patients. The risk of toxic reactions (including water intoxication and low sodium concentrations) appears to be greater in the geriatric patient and other patients with impaired renal function. In general, dose selection for the geriatric patient should be cautious, usually starting at the low end of the dosing range. Baseline renal function should be assessed. Desmopressin is contraindicated in patients with moderate to severe renal impairment (e.g., CrCl less than 50 mL/minute or eGFR less than 50 mL/minute/1.73 m2). Monitor renal function and clinical status closely during use. According to the Beers Criteria, desmopressin is considered a potentially inappropriate medication (PIM) in geriatric adults and avoidance is recommended for treating nocturia or nocturnal polyuria because there is a high risk of hyponatremia and safer alternatives are available.

    Preeclampsia, pregnancy

    There are no adequate studies of the effects of desmopressin on the human fetus, but animal reproduction studies have shown no adverse fetal effects. The use of desmopressin for nocturia is not recommended in pregnant women; nocturia is usually related to normal, physiologic changes during pregnancy that do not require treatment with desmopressin. Although data regarding the use of desmopressin in the management of diabetes insipidus during pregnancy include a few reports of congenital anomalies and low birth weight infants, no causal connection between these events and desmopressin acetate has been established. In a 15-year study of desmopressin acetate in pregnant women with diabetes insipidus, the rate of birth defects was no greater than that in the general population; however, the statistical power of this study is low. As opposed to preparations containing natural hormones, desmopressin acetate in antidiuretic doses has no uterotonic action. In addition, a systematic review of 30 studies (216 pregnancies total) of desmopressin for the treatment and prophylaxis of bleeding disorders in pregnancy concluded that in selected cases desmopressin is effective in reducing bleeding complications associated with pregnancy and childbirth with a good safety record; more research is needed since these were small studies. In patients with von Willebrand's disease, avoid desmopressin trials for therapeutic efficacy during pregnancy. Avoid desmopressin use in patients with preeclampsia. Use desmopressin with caution in the peripartum and immediate postpartum period, with careful attention to fluid management to avoid hyponatremia. Weigh the possible therapeutic advantages against the possible risks in each case.

    Breast-feeding

    Caution should be exercised when desmopressin is administered to a woman who is breast-feeding. Desmopressin is present in small amounts in human milk and is poorly absorbed by an infant. There is no information on the effects of desmopressin on the breast-fed infant or on milk production. In a single study of postpartum women receiving a single dose of intranasal desmopressin, a marked change in plasma concentration of desmopressin was seen; however, little, if any, change in assayable desmopressin was found in breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / 0-1.0
    anaphylactic shock / Rapid / 0-1.0
    seizures / Delayed / Incidence not known
    water intoxication / Delayed / Incidence not known
    coma / Early / Incidence not known
    thrombosis / Delayed / Incidence not known
    thromboembolism / Delayed / Incidence not known
    stroke / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known

    Moderate

    hyponatremia / Delayed / 0.9-12.0
    hypertension / Early / 1.7-2.6
    photophobia / Early / 0-2.0
    conjunctivitis / Delayed / 0-2.0
    confusion / Early / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    infertility / Delayed / Incidence not known
    balanitis / Delayed / Incidence not known
    tolerance / Delayed / Incidence not known

    Mild

    xerostomia / Early / 0-14.0
    rhinitis / Early / 3.0-8.0
    headache / Early / 2.0-5.0
    pharyngitis / Delayed / 2.3-3.8
    dizziness / Early / 0-3.0
    epistaxis / Delayed / 2.0-3.0
    nasal congestion / Early / 1.4-2.9
    sneezing / Early / 2.3-2.6
    back pain / Delayed / 1.1-2.3
    chills / Rapid / 0-2.0
    asthenia / Delayed / 0-2.0
    rhinalgia / Early / 2.0-2.0
    ocular pruritus / Rapid / 0-2.0
    lacrimation / Early / 0-2.0
    diarrhea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    dyspepsia / Early / Incidence not known
    nausea / Early / Incidence not known
    lethargy / Early / Incidence not known
    flushing / Rapid / Incidence not known
    cough / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    oligospermia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (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 phenylephrine only with careful patient monitoring.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (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 phenylephrine only with careful patient monitoring.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Acetaminophen; Dextromethorphan; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Acetaminophen; Guaifenesin; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Amlodipine; Celecoxib: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Articaine; Epinephrine: (Minor) The antidiuretic response to desmopressin may be reduced in patients receiving high doses of epinephrine concomitantly. Caution should be used when coadministering these agents.
    Azelastine; Fluticasone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Beclomethasone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Betamethasone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Brompheniramine; Carbetapentane; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Brompheniramine; Dextromethorphan; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Brompheniramine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Budesonide: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Budesonide; Formoterol: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Budesonide; Glycopyrrolate; Formoterol: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Bumetanide: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with loop diuretics because of the risk of severe hyponatremia.
    Bupivacaine; Epinephrine: (Minor) The antidiuretic response to desmopressin may be reduced in patients receiving high doses of epinephrine concomitantly. Caution should be used when coadministering these agents.
    Bupivacaine; Meloxicam: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Carbamazepine: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including carbamazepine. The administration of carbamazepine prior to administration of desmopressin may act to reduce the duration of action of desmopressin. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Carbetapentane; Diphenhydramine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Carbetapentane; Guaifenesin; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Carbetapentane; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Carbetapentane; Phenylephrine; Pyrilamine: (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 phenylephrine only with careful patient monitoring.
    Carbinoxamine; Hydrocodone; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Carbinoxamine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Celecoxib: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Celecoxib; Tramadol: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Chlophedianol; Guaifenesin; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Chlorpheniramine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Chlorpromazine: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including chlorpromazine. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
    Chlorpropamide: (Moderate) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with SIADH including chlorpropamide. Use this combination with caution, and monitor patients for signs and symptoms of hyponatremia. Although rare, chlorpropamide has caused a reaction identical to symptom of inappropriate antidiuretic hormone (SIADH).
    Ciclesonide: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Cisplatin: (Moderate) Frequently monitor serum sodium levels if concurrent use of desmopressin and cisplatin is necessary. Cisplatin can cause hyponatremia, which may increase the risk of water intoxication in patients receiving treatment with desmopressin.
    Codeine; Phenylephrine; Promethazine: (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 phenylephrine only with careful patient monitoring.
    Corticosteroids: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Cortisone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Deflazacort: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Demeclocycline: (Major) The antidiuretic response to desmopressin or vasopressin (ADH) may be reduced in patients concomitantly receiving demeclocycline. Caution should be used when coadministering these agents.
    Dexamethasone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Dextromethorphan; Guaifenesin; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Diclofenac: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Diclofenac; Misoprostol: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Diflunisal: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Diphenhydramine; Hydrocodone; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Diphenhydramine; Ibuprofen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Diphenhydramine; Naproxen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Diphenhydramine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Dopamine: (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 dopamine only with careful patient monitoring.
    Epinephrine: (Minor) The antidiuretic response to desmopressin may be reduced in patients receiving high doses of epinephrine concomitantly. Caution should be used when coadministering these agents.
    Ethacrynic Acid: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with loop diuretics because of the risk of severe hyponatremia.
    Ethanol: (Minor) Acute alcohol intoxication causes diuresis presumably resulting from inhibition of vasopressin release from the posterior pituitary gland. Based on this response, the antidiuretic response to desmopressin may be reduced in patients receiving ethanol concomitantly. Caution should be used when coadministering these agents. (Minor) Acute ethanol intoxication causes diuresis presumably resulting from inhibition of vasopressin release from the posterior pituitary gland. Based on this response, the antidiuretic response to desmopressin may be reduced in patients receiving ethanol concomitantly. Caution should be used when coadministering these agents.
    Etodolac: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Famotidine; Ibuprofen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Fenoprofen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Fludrocortisone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Flunisolide: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Flurbiprofen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Fluticasone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Fluticasone; Salmeterol: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Fluticasone; Umeclidinium; Vilanterol: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Fluticasone; Vilanterol: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Formoterol; Mometasone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Furosemide: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with loop diuretics because of the risk of severe hyponatremia.
    Guaifenesin; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Heparin: (Minor) Desmopressin has been shown to have an additive effect on the anticoagulant activity of heparin. Caution should be used when coadministering these agents.
    Hydrocodone; Ibuprofen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Hydrocodone; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Hydrocortisone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Ibuprofen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Ibuprofen; Oxycodone: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Ibuprofen; Pseudoephedrine: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Indomethacin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Ketoprofen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Ketorolac: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Lamotrigine: (Major) Caution is recommended if a drug that may increase the risk of water intoxication with hyponatremia, such as lamotrigine, is administered with desmopressin acetate. Two children with diabetes insipidus had decreasing desmopressin requirements with lamotrigine initiation.
    Lansoprazole; Naproxen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Lidocaine; Epinephrine: (Minor) The antidiuretic response to desmopressin may be reduced in patients receiving high doses of epinephrine concomitantly. Caution should be used when coadministering these agents.
    Lithium: (Moderate) The antidiuretic response to desmopressin may be reduced in patients receiving lithium concomitantly. Caution should be used when coadministering these agents.
    Loop diuretics: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with loop diuretics because of the risk of severe hyponatremia.
    Meclofenamate Sodium: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Mefenamic Acid: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Meloxicam: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Methylprednisolone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Mometasone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Monoamine oxidase inhibitors: (Moderate) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia and SIADH including monoamine oxidase inhibitors (MAOIs). Use combination with caution and monitor patients for signs and symptoms of hyponatremia, which may include seizures.
    Nabumetone: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Naproxen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Naproxen; Esomeprazole: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Naproxen; Pseudoephedrine: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Nonsteroidal antiinflammatory drugs: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Opiate Agonists: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including opiate agonists. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
    Oxaprozin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Oxybutynin: (Major) Hyponatremia-induced convulsions have been rarely reported when oxybutynin and desmopressin are used concomitantly. Use these drugs together with caution, and monitor patients for signs and symptoms of hyponatremia.
    Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Piroxicam: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Prednisolone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Prednisone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Prilocaine; Epinephrine: (Minor) The antidiuretic response to desmopressin may be reduced in patients receiving high doses of epinephrine concomitantly. Caution should be used when coadministering these agents.
    Promethazine; Phenylephrine: (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 phenylephrine only with careful patient monitoring.
    Rofecoxib: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Selective serotonin reuptake inhibitors: (Minor) Additive hyponatremic effects may be seen in patients treated with desmopressin 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.
    Sulindac: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Sumatriptan; Naproxen: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Tolmetin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Tolvaptan: (Major) Coadministration of tolvaptan and desmopressin (DDAVP) is not recommended. Tolvaptan is a V2 receptor antagonist and may interfere with the V2 agonist activity of DDAVP. In a male subject with mild Von Willebrand (vW) disease, intravenous infusion of DDAVP 2 hours after administration of oral tolvaptan did not produce the expected increases in vW Factor Antigen or Factor VIII activity.
    Torsemide: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with loop diuretics because of the risk of severe hyponatremia.
    Triamcinolone: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Tricyclic antidepressants: (Moderate) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with SIADH including tricyclic antidepressants. Hyponatremia-induced convulsions have been rarely reported when imipramine and desmopressin are used concomitantly. Use these drugs together with caution, and monitor patients for signs and symptoms of hyponatremia.
    Urea: (Minor) The manufacturer notes that the antidiuretic effect of desmopressin can be enhanced by the concomitant administration of urea. Dosage adjustments of desmopressin may be necessary to maintain proper sodium and water balance.
    Valdecoxib: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia
    Vasopressin, ADH: (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.
    Vincristine Liposomal: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with SIADH including vincristine. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
    Vincristine: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with SIADH including vincristine. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate studies of the effects of desmopressin on the human fetus, but animal reproduction studies have shown no adverse fetal effects. The use of desmopressin for nocturia is not recommended in pregnant women; nocturia is usually related to normal, physiologic changes during pregnancy that do not require treatment with desmopressin. Although data regarding the use of desmopressin in the management of diabetes insipidus during pregnancy include a few reports of congenital anomalies and low birth weight infants, no causal connection between these events and desmopressin acetate has been established. In a 15-year study of desmopressin acetate in pregnant women with diabetes insipidus, the rate of birth defects was no greater than that in the general population; however, the statistical power of this study is low. As opposed to preparations containing natural hormones, desmopressin acetate in antidiuretic doses has no uterotonic action. In addition, a systematic review of 30 studies (216 pregnancies total) of desmopressin for the treatment and prophylaxis of bleeding disorders in pregnancy concluded that in selected cases desmopressin is effective in reducing bleeding complications associated with pregnancy and childbirth with a good safety record; more research is needed since these were small studies. In patients with von Willebrand's disease, avoid desmopressin trials for therapeutic efficacy during pregnancy. Avoid desmopressin use in patients with preeclampsia. Use desmopressin with caution in the peripartum and immediate postpartum period, with careful attention to fluid management to avoid hyponatremia. Weigh the possible therapeutic advantages against the possible risks in each case.

    MECHANISM OF ACTION

    Desmopressin acts similarly to native vasopressin. Also known as antidiuretic hormone (ADH), vasopressin is secreted by the hypothalamus in response to hyperosmolarity, volume depletion, stress (emotional or physiological), certain drugs, and painful stimuli. Vasopressin also causes constriction of vascular smooth muscle and contraction of smooth muscle in the GI tract and uterus. Response to vasopressin is mediated through two receptors: the V1 receptor, which mediates smooth muscle contraction in the peripheral vasculature, and the V2 receptor, which regulates water resorption in the collecting ducts. Desmopressin is a strong V2 agonist and has no effect on V1 receptors. Desmopressin has slight structural variations that reduce its affinity for V1 receptors and lessen its vasopressin activity and contractile action on visceral smooth muscle. In contrast to vasopressin, desmopressin does not induce the release of adrenocorticotropic hormone or increase plasma cortisol concentrations. When administered to patients with central diabetes insipidus, desmopressin exerts antidiuretic effects similar to those of vasopressin; a reduction in urine output with an accompanying increase in urine osmolality and a decrease in clinical symptoms of urinary frequency and nocturia are noted following desmopressin treatment. Serum concentrations of potassium, sodium, and creatinine do not change following the administration of desmopressin, and urinary excretion of potassium and sodium also remains the same.
     
    Desmopressin increases plasma factor VIII (FVIII) and von Willebrand factor (vWF) to a greater extent than equivalent weights of vasopressin. The hemostatic effects of desmopressin are mediated through V2 receptor agonist activity, as patients with nephrogenic diabetes insipidus, who lack this receptor, do not have a hemostatic response to desmopressin. It is postulated that desmopressin-induced increases in FVIII and vWF are mediated through low-affinity, extrarenal V2 receptors. Proposed sites of these receptors include endothelial cells, megakaryocytes, blood monocytes, and mast cells. The resultant increases in FVIII and vWF are similar to those seen with replacement therapy using blood products. Increased FVIII and vWF levels are thought to be due to their release from endogenous reservoirs and not increased synthesis since the response is so rapid. Desmopressin has also been used in congenital or acquired bleeding disorders, including drug-induced platelet dysfunction (e.g., aspirin, dextran, ticlopidine, and heparin). The presence of platelet-vWF and normally functioning platelet glycoprotein (GP) IIb/IIIa seem to be essential for desmopressin's effect on platelets. Desmopressin may promote an increased exposure of platelet vWF to GPIIb/IIIa on the platelet surface upon activation of the platelet. Levels of FVIII are also increased, which increases hemostasis by accelerating fibrin formation. Plasminogen activator activity increases after intravenous desmopressin, but clinically significant fibrinolysis has not been detected in patients treated with desmopressin.

    PHARMACOKINETICS

    Desmopressin is administered orally, intranasally, or parenterally (intravenous or subcutaneously). The distribution of the drug is unknown, and it is not clear whether desmopressin crosses the placenta. Desmopressin is found in breast milk, but not in significant amounts. It is not known if the drug is metabolized; however, in contrast to vasopressin, desmopressin does not appear to be degraded by the peptidase enzymes responsible for metabolizing endogenous vasopressin during the last trimester of pregnancy. Desmopressin is primarily excreted in the urine, with a significant portion excreted as unchanged drug (65% after oral and 92% after intranasal administration). Following an intranasal dose of 1.66 mcg of desmopressin for nocturia, the median apparent terminal half-life was 2.8 hours; the half-life range in patients with an eGFR above 50 mL/minute/1.73 m2 was 1.4 to 3.8 hours.

    Oral Route

    Following oral administration, the bioavailability of desmopressin is about 5% and 0.16% compared to intranasal and intravenous administration, respectively. The time to reach maximum plasma desmopressin levels is 0.9 hours. Following oral administration, the onset of antidiuretic effect occurs around 1 hour and reaches a maximum at 4 to 7 hours. Oral doses of 0.2 and 0.4 mg produce similar responses on urine volume and urine osmolality as 0.01 mg and 0.02 mg intranasal doses. However, individualized dosing is recommended due to high inter-patient variability in response. Following oral administration, the half-life of desmopressin is about 1.5 to 2.5 hours and is independent of dosage.

    Intravenous Route

    Maximal dose-response increase in Factor VIII activity occurs at 0.3 to 0.4 mcg/kg desmopressin. This increase is dose-dependent, with an IV dosage of 0.4 mcg/kg producing a 300% to 400% maximum increase in Factor VIII activity. There is no increase in activity with doses greater than 0.4 mcg/kg, despite increases in desmopressin concentrations. This is probably due to saturation of receptor sites. Increased Factor VIII activity is noted 30 minutes after IV administration, with peak activity occurring in 90 minutes to 2 hours. The initial and terminal half-lives for desmopressin are 7.8 and 75.5 minutes, respectively, resulting in a prompt onset of action with a long duration of action. Other evaluations have indicated that the terminal half-life for desmopressin is approximately 3 hours.

    Other Route(s)

    Intranasal Route
    Approximately 3% to 4% of an intranasally administered dose is absorbed across the nasal mucosa. Intranasal desmopressin has an antidiuretic effect of about one-tenth that of an equivalent dose administered by injection. Peak plasma concentrations are noted within 40 to 45 minutes of a dose. Antidiuretic effects usually occur within 15 to 60 minutes, with peak effects evident 1 to 5 hours after nasal administration. The antidiuretic effects of the drug last for about 5 to 21 hours, followed by an abrupt cessation of activity that occurs over a 60- to 90-minute period. Increased Factor VIII activity is noted 30 minutes after intranasal administration, with peak activity occurring in 90 minutes to 2 hours. Intranasal desmopressin 300 mcg results in maximal Factor VIII and von Willebrand Factor activity levels 150% to 250% of normal. After a 300 mcg intranasal dose of desmopressin levels of Factor VIII and vWF remain greater than 30 units/dL for 8 hours. The initial and terminal half-lives for desmopressin are 7.8 and 75.5 minutes, respectively, resulting in a prompt onset of action with a long duration of action. Following administration of intranasal desmopressin for nocturia, the median time to peak plasma concentrations (Tmax) was 0.25 hour for the 0.83 mcg dose and 0.75 hour for the 1.66 mcg dose. The mean (+/- S.D.) peak plasma concentration (Cmax) was 4 (+/- 3.85) pg/mL for the 0.83 mcg dose and 9.11 (+/- 6.90) pg/mL for the 1.66 mcg dose. The plasma concentrations generally declined below 2 pg/mL (lower limit of quantitation) 4 to 6 hours post-dose.