Desmopressin can cause hyponatremia. Severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death. Desmopressin is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids. Ensure serum sodium concentrations are normal before starting or resuming desmopressin. Measure serum sodium within 7 days and ~1 month after initiating therapy or increasing the dose and periodically during treatment. More frequently monitor serum sodium in patients ≥65 years of age and in patients at increased risk of hyponatremia. If hyponatremia occurs, desmopressin may need to be temporarily or permanently discontinued.
Note: Dosing presented is in mcg, mg, and mL (dependent upon product formulation); use extra precaution to verify product formulation and dosing units. Intranasal dosage forms have unique concentrations and indications for use and should not be used interchangeably; use in pediatric patients is contraindicated for some products (eg, Noctiva); consult product labeling.
Diabetes insipidus: Note: Fluid restriction should be observed in these patients; younger patients are more susceptible to plasma osmolality shifts and possible hyponatremia. Dosing should be individualized to response.
Oral: Children ≥4 years and Adolescents: Initial: 0.05 mg twice daily; titrate to desired response; optimal daily dose range: 0.1 to 0.8 mg/day in 2 to 3 divided doses; reported daily dose range: 0.1 to 1.2 mg/day
Intranasal:
DDAVP nasal spray (10 mcg/spray): Note: The nasal spray pump can only deliver fixed doses in 10 mcg (0.1 mL) increments; if doses other than this are needed, the rhinal tube delivery system is preferred.
Children ≥4 years and Adolescents: Initial: 10 mcg once daily into 1 nostril, may titrate dose up to 30 mcg/day in 1 to 2 divided doses; if administered twice daily, adjust morning and evening doses separately to provide for an adequate diurnal rhythm of urine output.
Rhinal tube (100 mcg/mL nasal solution):
Infants ≥3 months and Children: Initial: 5 mcg/day in 1 to 2 divided doses; usual range: 5 to 30 mcg/day in 1 to 2 divided doses; if administered twice daily, adjust morning and evening doses separately to provide for an adequate diurnal rhythm of urine output.
Adolescents: Usual range: 5 to 40 mcg/day in 1 to 3 divided doses; usual adult dose is 20 mcg/day in 2 divided doses; adjust morning and evening doses separately to provide for an adequate diurnal rhythm of urine output.
Parenteral:
Infants and Children <12 years: IV, SubQ: No definitive dosing available. Adult dosing should not be used in this age group; adverse events such as hyponatremia-induced seizures may occur. Dose should be reduced. Some have suggested an initial dosage range of 0.1 to 1 mcg/day in 1 or 2 divided doses (Cheetham 2002). Initiate at low dose and increase as necessary. Closely monitor serum sodium levels and urine output; fluid restriction is recommended.
Children ≥12 years and Adolescents: IV, SubQ: 2 to 4 mcg/day in 2 divided doses or one-tenth (1/10) of the maintenance intranasal dose; adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover
Sublingual: Canadian labeling: DDAVP Melt [Canadian product]: Children and Adolescents: Sublingual: Initial: 60 mcg 3 times daily; total daily dose should be increased or decreased as needed to obtain adequate antidiuresis. Usual maintenance dose: 120 to 720 mcg in divided doses 2 to 3 times daily; divide daily doses so that the evening dose is 2 times higher than the morning or afternoon dose to ensure adequate antidiuresis during the night; fluid restriction should be observed.
Hemophilia A and von Willebrand disease (type 1; mild to moderate): Note: Adverse events such as hyponatremia-induced seizures have been reported especially in young children with IV use (Das 2005; Molnár 2005; Smith 1989; Thumfart 2005; Weinstein 1989). Fluid restriction and careful monitoring of serum sodium levels and urine output are necessary.
IV: Infants ≥3 months, Children, and Adolescents: 0.3 mcg/kg; if used preoperatively administer 30 minutes before procedure; may repeat dose if needed
Intranasal: High concentration spray 1.5 mg/mL: Infants ≥11 months, Children, and Adolescents:
<50 kg: 150 mcg (1 spray)
≥50 kg: 300 mcg (1 spray in each nostril)
Repeat use is determined by the patient's clinical condition and laboratory work; if using preoperatively, administer 2 hours before surgery
Subcutaneous: Canadian labeling: Octostim [Canadian product]: Infants ≥3 months, Children, and Adolescents: SubQ: 0.3 mcg/kg; if used preoperatively administer 30 minutes before procedure
Nocturnal enuresis: Note: Intranasal formulations are not recommended for nocturnal enuresis treatment.
Oral:
Children ≥6 years and Adolescents: Initial: 0.2 mg once before bedtime; titrate as needed to a maximum of 0.6 mg/day; fluid intake should be limited to a minimum from 1 hour before desmopressin administration until the next morning, or at least 8 hours after administration
Canadian labeling: Children ≥5 years and Adolescents: Initial: 0.2 mg once before bedtime; may titrate by 0.2 mg/day every 3 days as needed to a maximum dose of 0.6 mg/day; fluid intake should be limited to a minimum from 1 hour before desmopressin administration until the next morning, or at least 8 hours after administration. Treatment period is up to 3 months and then reassess with 1 week off treatment; if additional therapy is necessary, resume at same dosage prior to discontinuation.
Sublingual: Canadian labeling: DDAVP Melt [Canadian product]: Children ≥5 years and Adolescents: Sublingual: Initial: 120 mcg administered 1 hour before bedtime; may titrate by 120 mcg/day every 3 days as necessary to a maximum dose of 360 mcg/day to achieve desired response. Treatment period is up to 3 months and then reassess with 1 week off treatment; if additional therapy is necessary, resume at same dosage prior to discontinuation.
CrCl ≥50 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
CrCl <50 mL/minute: Use is contraindicated according to the manufacturer (except 1.5 mg/mL nasal spray); however, has been used in acute and chronic renal failure adult patients experiencing uremic bleeding or for prevention of surgical bleeding (Mannucci 1983; Watson 1984a).
There are no dosage adjustments provided in manufacturer's labeling.
(For additional information see "Desmopressin: Drug information")
Note : Noctiva intranasal spray has been discontinued in the US for more than 1 year.
Deceased organ donor management (hormonal replacement therapy) (off-label use): Note: Use if diabetes insipidus with hypernatremia is present without associated hypotension or in combination with vasopressin in hemodynamically unstable patients with severe hypernatremia. Use as part of combination hormone therapy (SCCM/ACCP/AOPO [Kotloff 2015]).
IV: Initial: 1 to 4 mcg once; titrate dose based on urine osmolality, urine output, and serum sodium, if needed. Usual maintenance dose: 1 to 2 mcg every 6 hours (SCCM/ACCP/AOPO [Kotloff 2015]).
Diabetes insipidus, central: Note: To avoid hyponatremia, use the minimum effective dose to control polyuria. In patients undergoing transsphenoidal surgery, diabetes insipidus may spontaneously resolve or revert to syndrome of inappropriate antidiuretic hormone secretion/hyponatremia (ES [Fleseriu 2016]; Prete 2017).
IV, SUBQ (4 mcg/mL solution for injection):
Initial:
Treatment-naive individuals: 0.25 to 1 mcg every 12 to 24 hours (Bichet 2021; Snyder 2020).
Individuals converting from intranasal desmopressin: Administer one-tenth of the maintenance intranasal dose at the regular intervals.
Dosage adjustment: Adjust dose, if needed, to maintain urine volume and serum sodium within normal limits; may increase to 2 mcg IV if no response to the 1 mcg dose (Bichet 2021; Snyder 2020).
Intranasal (100 mcg/mL nasal solution [nasal spray or rhinal tube]): Note: Avoid intranasal administration within the first day after transsphenoidal surgery due to variable absorption (Snyder 2020).
Initial: 5 to 10 mcg once daily at bedtime; adjust bedtime dosage in 5 mcg increments, if needed, to control nocturia. Assess need for daytime dose based on subsequent daytime polyuria. Usual maintenance dose: 5 to 20 mcg once or twice daily; suggested maximum dose: 40 mcg/day (Bichet 2021). Note: The nasal spray pump can only deliver doses of 10 mcg or multiples of 10 mcg; if doses other than this are needed, the rhinal tube delivery system is preferred.
Conversion from injection to intranasal: Administer 10 times the amount of desmopressin acetate, rounded down to the nearest 10 mcg.
Conversion from oral to intranasal: Individual dose titration is required (intranasal desmopressin is ~10- to 40-fold more potent than oral desmopressin).
Oral: Initial: 0.05 to 0.2 mg once daily at bedtime; adjust bedtime dosage in 0.05 mg increments, if needed, to control nocturia. Assess need for daytime dose based on subsequent daytime polyuria. Usual maintenance dose: 0.1 to 0.8 mg/day in 2 to 3 equally divided doses; suggested maximum dose: 1.2 mg/day (Bichet 2021; manufacturer’s labeling).
Sublingual (DDAVP Melt [Canadian product]): Initial: 60 mcg 3 times daily; total daily dose should be increased or decreased as needed to obtain adequate antidiuresis. Usual maintenance dose: 120 to 720 mcg/day in 2 to 3 equally divided doses.
Duration of therapy: Continue therapy for as long as symptoms persist; consider weekly therapy withdrawal to determine ongoing need for therapy and discontinue if polyuria does not recur (Bichet 2021; ES [Fleseriu 2016]).
Hemophilia A, mild:
Note: May be used short-term for minor bleeding or before minor invasive procedures in patients who have previously demonstrated an adequate response to a therapeutic trial. Desmopressin is not effective in patients with hemophilia B (Hoots 2021; WFH [Srivastava 2020]).
IV, SUBQ (off label): 0.3 mcg/kg once (maximum recommended dose: 20 to 30 mcg). If used for prevention of surgical bleeding, administer 30 to 60 minutes before procedure (Hoots 2021; WFH [Srivastava 2020]).
Intranasal: Note: If used for prevention of surgical bleeding, administer 2 hours before procedure.
Using high-concentration spray (1.5 mg/mL):
Patient weight <50 kg: 150 mcg (1 spray) in a single nostril.
Patient weight ≥50 kg: 150 mcg (1 spray) in each nostril (total dose: 300 mcg).
Repeat doses: For treatment of minor bleeding, dose may be repeated after 8 to 12 hours and once daily thereafter, if needed, based on clinical condition and von Willebrand factor and factor VIII activity levels; duration of use is generally limited to 3 days due to tachyphylaxis. In patients who are hospitalized or who receive repeat doses, restrict free water intake and monitor for hyponatremia (Hoots 2021; WFH [Srivastava 2020]).
Intracranial hemorrhage associated with antiplatelet agents (off-label use):
Note: For use in combination with other first-line therapies (eg, platelet transfusion) (NCS/SCCM [Frontera 2016]).
IV: 0.4 mcg/kg once over 30 minutes (maximum suggested dose: 40 mcg [not well established]) (Feldman 2019; Kapapa 2014; Naidech 2014; NCS/SCCM [Frontera 2016]).
Nocturia, refractory:
Note: For use in patients with symptoms refractory to nonpharmacologic and other first-line therapy options. Monitor closely for hyponatremia (eg, within 3 to 7 days after dosage change or change in clinical status); discontinue treatment if serum sodium is <135 mEq/L (Johnson 2021).
Sublingual (Nocdurna): Note: Dosage expressed as desmopressin acetate; desmopressin acetate 27.7 mcg is equivalent to desmopressin (base) 25 mcg.
Females: 27.7 mcg once daily 1 hour before bedtime.
Males: 55.3 mcg once daily 1 hour before bedtime.
Oral (off label): Initial: 0.05 to 0.1 mg once daily at bedtime; doses >0.1 mg/day are unlikely to provide additional benefit and may increase risk of hyponatremia (Ebell 2014).
Intranasal (Noctiva):
No risk for hyponatremia: 1.66 mcg in either nostril ~30 minutes before bedtime. Note: Two 0.83 mcg sprays are not equivalent to one 1.66 mcg spray.
Possible risk for hyponatremia or ≥65 years of age: Initial: 0.83 mcg in either nostril ~30 minutes before bedtime. After ≥7 days, may increase to 1.66 mcg, if needed, provided serum sodium is within the normal range. Note: The 0.83 mcg dose may be associated with a lower risk of hyponatremia; however, this dose did not meet all prespecified efficacy end points in clinical trials (manufacturer’s labeling).
Prevention of overly rapid sodium correction in patients with chronic severe hyponatremia (adjunct to hypertonic saline infusion) (off-label use):
Note: Hyponatremia is listed as a contraindication for use of desmopressin in some instances. Use only in consultation with clinicians experienced in the management of hyponatremia. For use only as adjunctive therapy to hypertonic saline in patients with severe hyponatremia (<120 mEq/L) due to rapidly reversible causes (eg, hypovolemia) who are likely to develop water diuresis during the course of therapy, or in those who are at high risk of osmotic demyelination syndrome (eg, severe liver disease, malnutrition, concurrent hypokalemia, chronic excess alcohol intake) (Sterns 2021; Verbalis 2013).
IV, SUBQ: 1 to 2 mcg every 6 to 8 hours; titrate to response; maximum reported dose: 4 mcg every 6 to 8 hours (Sood 2013; Sterns 2021). Restrict free water intake during treatment (Sterns 2021).
Duration of therapy: Continue therapy for 24 to 48 hours or until serum sodium increases to ≥125 mEq/L; goal of therapy is to correct serum sodium by ≤8 mEq/L in any 24-hour period (Sterns 202; Verbalis 2013).
Uremic bleeding (off-label use):
Note: For SUBQ dosing, may either use the 4 mcg/mL formulation (administered as separate smaller injections due to volume) or, if available, the high-concentration injectable formulation (Octostim [Canadian product], 15 mcg/mL) should be used (Usach 2019; Octostim Canadian product monograph).
IV (preferred), SUBQ: 0.3 to 0.4 mcg/kg once at the onset of bleeding (usual dosage range: 20 to 30 mcg; doses >40 mcg have not been described in the literature for bleeding indications) (Hong 1996; Kapapa 2014; Köhler 1989; Mannucci 1983; Watson 1984a). For prevention of surgical bleeding, administer dose 30 to 60 minutes before procedure (Berns 2020).
Repeat doses: If bleeding continues or at the time of bleeding recurrence, may administer a second dose; additional doses may be ineffective due to tachyphylaxis (Berns 2020).
von Willebrand disease, mild to moderate:
Note: May be used short-term for minor bleeding or before minor invasive procedures in patients with type 1 von Willebrand disease (VWD) (labeled use) or type 2 VWD (off-label use) who have previously demonstrated an adequate response to a therapeutic trial; in patients with type 2B VWD, only consider if prolonged thrombocytopenia does not occur during therapeutic trial. Desmopressin is not effective in patients with type 3 VWD (Rick 2021).
IV, SUBQ (off label): 0.3 mcg/kg once (maximum recommended dose: 20 to 30 mcg). If used for prevention of surgical bleeding, administer 30 to 60 minutes before procedure (Rick 2021; DDAVP injection Canadian product monograph; US manufacturer’s labeling).
Intranasal: Note: If used for prevention of surgical bleeding, administer 2 hours before procedure.
Using high-concentration spray (1.5 mg/mL):
Patient weight <50 kg: 150 mcg (1 spray) in a single nostril.
Patient weight ≥50 kg: 150 mcg (1 spray) in each nostril (total dose: 300 mcg).
Repeat doses: For treatment of minor bleeding, dose may be repeated after 8 to 12 hours and once daily thereafter, if needed, based on the patient's clinical condition and von Willebrand factor and factor VIII activity levels; duration of use is generally limited to 3 to 5 days due to tachyphylaxis. In patients who are hospitalized or who receive repeat doses, restrict free water intake and monitor for hyponatremia (Rick 2021).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
IV, intranasal, SUBQ, sublingual, oral:
Altered kidney function:
CrCl ≥50 mL/minute: No dosage adjustment necessary (manufacturer’s labeling; expert opinion).
CrCl <50 mL/minute: Use is contraindicated according to some manufacturers' labeling due to prolonged half-life and predisposition to developing hyponatremia in patients with kidney impairment. However, no dosage adjustment is necessary for bleeding-related indications if limited to short-term use. In patients with central diabetes insipidus, no empiric dosage adjustment is necessary; lower doses may be required, use with caution (Sica 2006; expert opinion).
Hemodialysis, intermittent (thrice weekly): Dose as for CrCl <50 mL/minute. The risk of developing hyponatremia from desmopressin in intermittent hemodialysis patients is minimal (Sica 2006; Ulusoy 2004; expert opinion).
Peritoneal dialysis: Dose as for CrCl <50 mL/minute. The risk of developing hyponatremia from desmopressin in peritoneal dialysis patients is minimal (expert opinion).
CRRT/PIRRT: Dose as for CrCl <50 mL/minute (expert opinion).
There are no dosage adjustments provided in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Emulsion, Nasal, as acetate:
Noctiva: 0.83 mcg/0.1 mL (3.8 g [DSC]); 1.66 mcg/0.1 mL (3.8 g [DSC])
Solution, Injection, as acetate:
DDAVP: 4 mcg/mL (10 mL) [contains chlorobutanol (chlorobutol)]
DDAVP Pf: 4 mcg/mL (1 mL)
Generic: 4 mcg/mL (1 mL, 10 mL)
Solution, Injection, as acetate [preservative free]:
Generic: 4 mcg/mL (1 mL)
Solution, Nasal, as acetate:
DDAVP: 0.01% (5 mL [DSC]) [contains benzalkonium chloride]
DDAVP Rhinal Tube: 0.01% (2.5 mL [DSC]) [contains chlorobutanol (chlorobutol)]
Stimate: 1.5 mg/mL (2.5 mL) [contains benzalkonium chloride]
Generic: 0.01% (5 mL)
Tablet, Oral, as acetate:
DDAVP: 0.1 mg
DDAVP: 0.2 mg [scored]
Generic: 0.1 mg, 0.2 mg
Tablet Sublingual, Sublingual:
Nocdurna: 27.7 mcg, 55.3 mcg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Octostim: 15 mcg/mL (1 mL)
Solution, Injection, as acetate:
Bipazen: 4 mcg/mL (1 mL)
DDAVP: 4 mcg/mL (1 mL)
Solution, Nasal, as acetate:
DDAVP: 0.01% ([DSC]) [contains benzalkonium chloride]
DDAVP Rhinyle: 0.01% ([DSC]) [contains chlorobutanol (chlorobutol)]
Octostim: 1.5 mg/mL ([DSC]) [contains chlorobutanol hemihydrate]
Generic: 0.01% (2.5 mL, 5 mL)
Tablet, Oral, as acetate:
DDAVP: 0.1 mg, 0.2 mg
Generic: 0.1 mg, 0.2 mg
Tablet Disintegrating, Sublingual:
DDAVP Melt: 60 mcg, 120 mcg, 240 mcg
Nocdurna: 50 mcg [DSC]
Tablet Disintegrating, Sublingual, as acetate:
Nocdurna: 25 mcg [DSC]
DDAVP and Minirin 5 mL bottles contain 50 sprays.
Stimate 2.5 mL bottles contain 25 sprays.
Noctiva intranasal spray has been discontinued in the US for more than 1 year.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Nocdurna sublingual tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022517s000lbl.pdf#page=14
Intranasal: Ensure that nasal passages are intact, clean, and free of obstruction prior to administration.
DDAVP (100 mcg/mL): Nasal pump spray: Delivers 0.1 mL (10 mcg); for doses <10 mcg or for other doses which are not multiples, use rhinal tube. DDAVP nasal spray delivers fifty 10 mcg doses in the 5 mL bottle. For 10 mcg dose, administer in one nostril. Any solution remaining after 50 doses should be discarded. Pump must be primed prior to first use by pressing down on pump 4 times; if pump not used for ≥1 week, re-prime by pressing down on pump once.
DDAVP Rhinal tube (100 mcg/mL): Insert top of dropper into tube (arrow marked end) in downward position. Squeeze dropper until solution reaches desired calibration mark. Disconnect dropper. Grasp the tube 3/4-inch from the end and insert tube into nostril until the fingertips reach the nostril. Place opposite end of tube into the mouth (holding breath). Tilt head back and blow with a strong, short puff into the nostril (for very young patients, an adult should blow solution into the child's nose). Reseal dropper after use.
Stimate (1.5 mg/mL): Nasal pump spray: Delivers 0.1 mL (150 mcg); for doses <150 mcg, injection is recommended. Stimate nasal spray delivers twenty-five 150 mcg doses. For 150 mcg dose, administer in one nostril. Any solution remaining after 25 doses should be discarded. Pump must be primed prior to first use or if not used for ≥1 week.
Oral: Tablets: May administer with or without food. In adults, food may reduce/delay absorption although does not affect antidiuretic activity (Rittig 1998).
Diabetes insipidus: Fluid restriction should be observed.
Primary nocturnal enuresis: Fluid intake should be limited to a minimum of 1 hour prior to dose and until at least 8 hours after administration.
Sublingual: Primary nocturnal enuresis (DDAVP Melt [Canadian product]): Tablet should be kept under the tongue until completely dissolved. Fluid restriction should be observed. Fluid intake should be limited to a minimum of 1 hour prior to dose and until at least 8 hours after administration.
Parenteral:
Central diabetes insipidus: IV push or SubQ: Administer as direct injection; dilution is not required.
Hemophilia A and von Willebrand disease (type 1): IV infusion: Infuse over 15 to 30 minutes.
IV push:
Central diabetes insipidus, deceased organ donor management (off-label use), and prevention of overly rapid sodium correction in patients with chronic severe hyponatremia (off-label use): Administer as direct injection; dilution is not required (Benck 2011; DDAVP Injection Canadian product monograph; US manufacturer’s labeling).
IV infusion:
Hemophilia A, von Willebrand disease, and uremic bleeding (off-label use in United States): Infuse over 15 to 30 minutes. If used preoperatively, administer 30 to 60 minutes prior to procedure (Berns 2020; Hoots 2020b; Mannucci 1983; Rick 2020; US manufacturer’s labeling).
Intranasal: Ensure that nasal passages are intact, clean, and free of obstruction prior to administration.
DDAVP: Nasal pump spray: Delivers 0.1 mL (10 mcg); for doses <10 mcg or for other doses which are not multiples, use rhinal tube. DDAVP Nasal spray delivers fifty 10 mcg doses. For 10 mcg dose, administer in one nostril. Any solution remaining after 50 doses should be discarded. Pump must be primed prior to first use by pressing down on pump 4 times; if pump not used for ≥1 week, re-prime by pressing down on pump once.
DDAVP Rhinal tube: Insert top of dropper into tube (arrow marked end) in downward position. Squeeze dropper until solution reaches desired calibration mark. Disconnect dropper. Grasp the tube 3/4 inch from the end and insert tube into nostril until the fingertips reach the nostril. Place opposite end of tube into the mouth (holding breath). Tilt head back and blow with a strong, short puff into the nostril. Reseal dropper after use.
Noctiva: Do not shake. Prime before using for the first time by pumping 5 actuations into the air away from the face. Re-prime by pumping 2 actuations into the air if the product has not been used for more than 3 days. Note: 2 sprays of 0.83 mcg/0.1 mL are not interchangeable with 1 spray of 1.66 mcg/0.1 mL; do not administer 2 sprays of the 0.83 mcg/0.1 mL product.
Stimate: Press pump down 4 times to prime prior to initial use. Once ready, tilt pump, place nozzle tip in nostril, then spray. If pump has not been used for one week it must be primed again by pressing down once or until a fine mist is present. Discard after 25 sprays (excluding priming sprays). Note: A test dose to measure response is recommended prior to initiating therapy.
Oral: Tablets: May administer with or without food. Food may reduce/delay absorption although does not affect antidiuretic activity (Rittig 1998).
Diabetes insipidus: Fluid restriction should be observed.
Primary nocturnal enuresis: Fluid intake should be limited a minimum of 1 hour prior to dose until at least 8 hours after administration.
Sublingual:
Nocturia (Nocdurna, DDAVP Melt [Canadian product]): Tablet should be kept under the tongue until completely dissolved without water. Administer 1 hour prior to bedtime. Fluid intake should be limited a minimum of 1 hour prior to dose until at least 8 hours after administration.
SUBQ:
Central diabetes insipidus and prevention of overly rapid sodium correction in patients with chronic severe hyponatremia (off-label use): Administer as direct injection; dilution is not required (Sood 2013; DDAVP Injection Canadian product monograph; US manufacturer’s labeling).
Uremic bleeding (off-label use in United States): If administered SUBQ, the high-concentration injectable formulation (Octostim [Canadian product], 15 mcg/mL) should be used; if using the 4 mcg/mL formulation, must administer as separate smaller injections (eg, ≤1.5 to 3 mL per injection) due to total dose volume (Usach 2019). Administer as direct injection; dilution is not required (Octostim Canadian product monograph).
DDAVP:
Nasal spray: Store at 20°C to 25°C (68°F to 77°F). Keep nasal spray in upright position.
Rhinal Tube solution: Store at 2°C to 8°C (36°F to 46°F). May store at 20°C to 25°C (68°F to 77°F) for up to 3 weeks.
Solution for injection: Store at 2°C to 8°C (36°F to 46°F).
Tablet: Store at 20°C to 25°C (68°F to 77°F). Avoid excessive heat. Protect from light.
DDAVP Melt [Canadian product]: Store at 15°C to 25°C (59°F to 77°F) in original container. Protect from moisture.
Nocdurna: Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture and light.
Noctiva: Store at 2°C to 8°C (36°F to 46°F); excursions permitted between 0°C and 15°C (32°F and 59°F). Keep nasal spray in upright position. After opening, store at 20°C to 25°C (68°F to 77°F). Discard 60 days after opening.
Octostim [Canadian product]: Solution for injection: Store at 2°C to 8°C (36°F to 46°F). Do not freeze. Following dilution in NS may store at room temperature for up to 24 hours.
Stimate nasal spray: Store at room temperature not to exceed 25°C (77°F). Discard 6 months after opening bottle. Store bottle in upright position.
Oral: Tablets: Treatment of diabetes insipidus (FDA approved in ages ≥4 years and adults); primary nocturnal enuresis (FDA approved in ages ≥6 years)
Injection: Treatment of diabetes insipidus (FDA approved in ages ≥12 years and adults); control of bleeding in hemophilia A (with factor VIII levels >5%) and mild to moderate type I von Willebrand disease (FDA approved in ages ≥3 months and adults)
Intranasal:
Nasal spray:
DDAVP: Treatment of diabetes insipidus (FDA approved in ages ≥4 years and adults)
Noctiva: Treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void (FDA approved in ages ≥50 years)
Stimate: Control of bleeding in hemophilia A (with factor VIII levels >5%) and mild to moderate type I von Willebrand disease (FDA approved in ages ≥11 months and adults)
Rhinal tube: Treatment of diabetes insipidus (FDA approved in ages ≥3 months and adults)
Desmopressin may be confused with vasopressin
Beers Criteria: Desmopressin is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older for the treatment of nocturia or nocturnal polyuria due to its high risk of causing hyponatremia; safer alternatives exist (Beers Criteria [AGS 2019]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Hyponatremia (<1%; intranasal: 2% to 12%; sublingual: 3% to 4%)
Gastrointestinal: Xerostomia (sublingual: ≤14%)
1% to 10%:
Cardiovascular: Hypertension (intranasal: 2% to 3%)
Central nervous system: Headache (2% to 5%), dizziness (intranasal, sublingual: 2% to 3%), chills (intranasal: 2%), nostril pain (intranasal: 2%)
Gastrointestinal: Abdominal pain (intranasal: 2%), gastrointestinal disease (intranasal: 2%), nausea (intranasal: 2%)
Neuromuscular & skeletal: Asthenia (intranasal: 2%), back pain (intranasal: 1% to 2%)
Ophthalmic: Abnormal lacrimation (intranasal: 2%), conjunctivitis (intranasal: 2%), ocular edema (intranasal: 2%)
Respiratory: Rhinitis (intranasal: 3% to 8%), nasal discomfort (intranasal: 6%), nasopharyngitis (intranasal: 4%), nasal congestion (intranasal: ≤3%), epistaxis (intranasal: 2% to 3%), sneezing (intranasal: 2% to 3%), bronchitis (intranasal: 2%)
Frequency not defined:
Cardiovascular: Altered blood pressure, chest pain (intranasal), edema, facial flushing, flushing (intranasal), palpitations (intranasal), tachycardia (intranasal)
Central nervous system: Abnormality in thinking, agitation (intranasal), drowsiness (intranasal), insomnia (intranasal), localized warm feeling (intranasal), pain (intranasal)
Endocrine & metabolic: Weight gain
Gastrointestinal: Abdominal cramps, diarrhea, dyspepsia (intranasal), sore throat (intranasal), vomiting (intranasal)
Genitourinary: Balanitis (intranasal), vulvar pain
Hepatic: Increased serum aspartate aminotransferase (oral; transient)
Local: Burning sensation at injection site, erythema at injection site, swelling at injection site
Ophthalmic: Eye pruritus (intranasal), photophobia (intranasal)
Respiratory: Cough (intranasal), upper respiratory tract infection
<1%, postmarketing, and/or case reports: Anaphylaxis, atrial fibrillation, dysuria, serum hyposmolality, severe hypersensitivity, water intoxication
Known hypersensitivity to desmopressin or any component of the formulations; hyponatremia or a history of hyponatremia
Additional product specific contraindications:
DDAVP (injection, intranasal, oral): Moderate to severe renal impairment (CrCl <50 mL/minute)
Nocdurna, Noctiva: Renal impairment (eGFR <50 mL/minute/1.73 m2); polydipsia; primary nocturnal enuresis; concomitant use with loop diuretics or glucocorticoids (inhaled or systemic); syndrome of inappropriate antidiuretic hormone (SIADH) secretion (known or suspected); illnesses that may cause fluid or electrolyte imbalance (eg, gastroenteritis, salt-wasting nephropathies, systemic infection); heart failure (Noctiva labeling specifies NYHA Class II to IV); uncontrolled hypertension
Stimate: There are no contraindications listed in the Stimate prescribing information.
Canadian labeling: Additional contraindications (not in US labeling): Note: May not be applicable to all available dosage forms; refer to manufacturer labeling for further detail. Type 2B or platelet-type (pseudo) von Willebrand disease; habitual or psychogenic polydipsia, cardiac insufficiency or other conditions requiring diuretic therapy; nephrosis or any other condition associated with impaired water excretion, severe hepatic dysfunction; primary nocturnal enuresis; sodium losing conditions; SIADH secretion; lactose intolerance
Concerns related to adverse effects:
• Allergic reactions: Severe allergic reactions have been reported with desmopressin; anaphylactic reactions have only occurred rarely with IV and intranasal administration.
• Fluid retention: May cause fluid retention, which can worsen underlying conditions susceptible to volume status. Use with caution in patients with heart failure; some products are specifically contraindicated in heart failure or uncontrolled hypertension. Some products are not recommended in patients at risk for increased intracranial pressure or those with a history of urinary retention.
• Hyponatremia: [US Boxed Warning]: Nocdurna, Noctiva: Desmopressin can cause hyponatremia. Severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death. Desmopressin is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids. Ensure serum sodium concentrations are normal before starting or resuming desmopressin. Measure serum sodium within 7 days and ~1 month after initiating therapy or increasing the dose and periodically during treatment. More frequently monitor serum sodium in patients ≥65 years of age and in patients at increased risk of hyponatremia. If hyponatremia occurs, desmopressin may need to be temporarily or permanently discontinued. Desmopressin use may rarely lead to hyponatremia with associated signs and symptoms (eg, confusion, decreased consciousness, depressed reflexes, disorientation, fatigue, hallucinations, headache, irritability, lethargy, loss of appetite, muscle weakness/spasms/cramps, nausea/vomiting, restlessness, weight gain) and extreme decreases in plasma osmolality, resulting in seizures, coma, respiratory arrest, and death. Other risk factors for hyponatremia with desmopressin use include cystic fibrosis, renal impairment, heart failure, young age, advanced age, inappropriate high fluid intake, a higher than recommended dose, and concomitant use of medications known to either increase thirst or cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction during use is recommended. Fluid intake in the evening and nighttime hours should be moderated to decrease the risk of hyponatremia. Monitor for signs/symptoms of hyponatremia; more frequent monitoring is recommended for patients on concomitant medications that increase the risk of hyponatremia (eg, TCAs, SSRIs, NSAIDs, chlorpromazine, carbamazepine, thiazide diuretics).
• Hypotension: Severe hypotension may occur with rapid IV infusions.
• Thrombotic events: Acute cerebrovascular thrombosis and acute myocardial infarction have occurred (rare) with desmopressin injection; use with caution in patients predisposed to thrombus formation.
Disease-related concerns:
• Cardiovascular disease: Injection and high-dose intranasal (used in hemophilia A and von Willebrand disease [VWD]) desmopressin may cause a slight increase or transient decrease in blood pressure, and a compensatory increase in heart rate. Use with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease.
• Polydipsia (habitual or psychogenic): Use with caution in patients with habitual or psychogenic polydipsia. Patients consuming excessive amounts of water are at greater risk of hyponatremia. Products used for the treatment of nocturia are specifically contraindicated in patients with polydipsia.
• Primary nocturnal enuresis: When using desmopressin for primary nocturnal enuresis, treatment should be interrupted if the patient experiences an acute illness (eg, fever, recurrent vomiting or diarrhea), vigorous exercise, or any condition associated with an increase in water consumption to prevent hyponatremia. Products used for the treatment of nocturia are specifically contraindicated in patients with primary nocturnal enuresis.
• Type 2B von Willebrand disease: The manufacturer’s labeling states that patients with type 2B VWD requiring hemostasis should not be treated with desmopressin since use may result in platelet aggregation, thrombocytopenia, and possibly thrombosis. However, desmopressin may be considered in patients with type 2B VWD if prolonged significant thrombocytopenia does not occur during a therapeutic trial (NHLBI 2007; Rick 2020).
Special populations:
• Elderly: Fluid intake should be adjusted downward in the elderly to decrease the possibility of water intoxication and hyponatremia.
• Pediatric: Fluid intake should be adjusted downward in very young patients to decrease the possibility of water intoxication and hyponatremia.
Dosage form specific issues:
• Intranasal: Consider alternative route of administration if changes in the nasal mucosa (scarring, edema) occur leading to unreliable absorption. Some patients may demonstrate a change in response after long-term therapy (>6 months) characterized as decreased response or a shorter duration of response. Discontinue in patients with concurrent nasal conditions that may increase systemic absorption of desmopressin (eg, acute or chronic rhinitis, severe atrophic rhinitis, nasal blockage, nasal mucosal atrophy, recent nasal surgery); may resume desmopressin when conditions resolve.
• Tablet: Consider alternative route of administration (IV or intranasal) with inadequate therapeutic response at maximum recommended oral doses.
The FDA has reviewed 61 postmarketing cases of hyponatremia-related seizures associated with the use of desmopressin acetate. Intranasal desmopressin was used in the majority of cases. Many of the patients were children being treated for primary nocturnal enuresis (PNE). An association with at least one concomitant drug or disease that also may cause hyponatremia and/or seizures was noted. As a result, intranasal desmopressin is no longer indicated for the treatment of PNE.
None known.
ChlorproMAZINE: May enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hyponatremic effect of Desmopressin. Risk X: Avoid combination
Corticosteroids (Systemic): May enhance the hyponatremic effect of Desmopressin. Risk X: Avoid combination
Demeclocycline: May diminish the therapeutic effect of Desmopressin. Risk C: Monitor therapy
Hyponatremia-Associated Agents: May enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Lithium: May diminish the therapeutic effect of Desmopressin. Desmopressin may increase the serum concentration of Lithium. Risk C: Monitor therapy
Loop Diuretics: Desmopressin may enhance the hyponatremic effect of Loop Diuretics. Risk X: Avoid combination
Loperamide-Loperamide Oxide: May increase the serum concentration of Desmopressin. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Opioid Agonists: May enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Tolvaptan: May diminish the therapeutic effect of Desmopressin. Risk X: Avoid combination
Tricyclic Antidepressants: May enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
In vitro studies demonstrate poor placental transfer of desmopressin.
Pregnant carriers of hemophilia A and those with von Willebrand disease may have an increased bleeding risk following invasive procedures, spontaneous miscarriage, termination of pregnancy, and delivery; close surveillance is recommended. Factor VIII concentrations may increase in pregnant patients; changes in von Willebrand factor (VWF) levels may vary during pregnancy depending on type. Patients should be monitored at the first antenatal visit, once or twice during the third trimester, prior to surgical or invasive procedures, and at delivery. Desmopressin may be used to increase factor VIII and VWF if concentrations are <50 units/dL and any of the following occur: need for invasive procedures (including delivery), spontaneous miscarriage, insertion and removal of epidural catheters, or active bleeding. Use should be limited to those patients who had a known response to desmopressin prior to pregnancy. Use with caution during labor and delivery. Due to the antidiuretic properties of desmopressin, restrict fluids and avoid use in patients with pre-eclampsia and eclampsia when used antenatally. BP should also be monitored (RCOG [Pavord 2017]; WFH [Srivastava 2020]).
Pregnant patients previously treated with desmopressin for diabetes insipidus should continue treatment, adjusting doses if needed (ES [Fleseriu 2016]). Desmopressin is also the treatment of choice for gestational diabetes insipidus; close monitoring is recommended (Aleksandrov 2010; Ananthakrishnan 2020).
Desmopressin is not recommended for nocturia caused by normal physiologic changes that occur during pregnancy
For all uses, fluid intake, urine volume, and signs and symptoms of hyponatremia should be closely monitored especially in high risk patient subgroups (eg, young children, elderly, patients with heart failure).
Diabetes insipidus: Urine specific gravity, plasma and urine osmolality, serum electrolytes
Nocturnal enuresis: Serum electrolytes if used for >7 days
Hemophilia A: Factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII antigen levels, aPTT
von Willebrand disease: Factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII von Willebrand antigen levels, bleeding time
Synthetic analogue of the antidiuretic hormone arginine vasopressin. In a dose dependent manner, desmopressin increases cyclic adenosine monophosphate (cAMP) in renal tubular cells which increases water permeability resulting in decreased urine volume and increased urine osmolality; increases plasma levels of von Willebrand factor, factor VIII, and t-PA contributing to a shortened activated partial thromboplastin time (aPTT) and bleeding time.
Onset of action:
Intranasal: Antidiuretic: 15 to 30 minutes; Increased factor VIII and von Willebrand factor (vWF) activity (dose related): 30 minutes
Peak effect: Antidiuretic: 1 hour; Increased factor VIII and vWF activity: 1.5 hours; Nocturia: 0.25 to 0.75 hour
IV infusion: Increased factor VIII and vWF activity: 30 minutes (dose related)
Peak effect: 1.5 to 2 hours
Oral tablet: Antidiuretic: ~1 hour
Peak effect: 4 to 7 hours
Sublingual: Antidiuretic: ~30 minutes
Duration: Intranasal, Injection, Oral tablet, Sublingual: ~6 to 14 hours
Absorption: Sublingual: Rapid
Bioavailability: Intranasal: ~3.5%; Oral tablet: 5% compared to intranasal, 0.16% compared to IV; Sublingual: 0.25%
Half-life elimination: 2 to 4 hours; Severe renal impairment: ~9 hours
Excretion: Urine (primarily)
Renal function impairment: AUC and T1/2 are ~3- to 4-fold higher in patients with eGFR <50 mL/minute/1.73 m2.
1 mcg of desmopressin acetate injection is approximately equal to 4 units of antidiuretic activity; desmopressin acetate injection has an antidiuretic effect about ten times that of an equivalent dose administered intranasally
Solution (DDAVP Injection)
4 mcg/mL (per mL): $98.58
Solution (DDAVP Pf Injection)
4 mcg/mL (per mL): $97.37
Solution (Desmopressin Ace Spray Refrig Nasal)
0.01% (per mL): $49.25
Solution (Desmopressin Acetate Injection)
4 mcg/mL (per mL): $23.16 - $71.42
Solution (Desmopressin Acetate PF Injection)
4 mcg/mL (per mL): $38.10 - $70.55
Solution (Desmopressin Acetate Spray Nasal)
0.01% (per mL): $47.28 - $49.25
Solution (Stimate Nasal)
1.5 mg/mL (per mL): $351.36
Sublingual (Nocdurna Sublingual)
27.7 mcg (per each): $19.86
55.3 mcg (per each): $19.86
Tablets (DDAVP Oral)
0.1 mg (per each): $9.35
0.2 mg (per each): $13.47
Tablets (Desmopressin Acetate Oral)
0.1 mg (per each): $3.02 - $7.36
0.2 mg (per each): $4.35 - $10.60
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