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Desmopressin Acetate

Pronunciation

Class: Pituitary
ATC Class: H01BA02
VA Class: HS702
CAS Number: 62357-86-2
Brands: DDAVP, Minirin, Stimate

Introduction

Synthetic polypeptide analog of arginine vasopressin (antidiuretic hormone [ADH]);101 102 111 112 114 116 117 a reduces urinary output and plasma osmolality and increases urine osmolality, as well as dose-dependent increases in plasma factor VIII (antihemophilic factor), plasminogen activator, and, to a lesser degree, factor VIII-related antigen and ristocetin cofactor activities.101 102 112 114 117 a

Uses for Desmopressin Acetate

Diabetes Insipidus

Intranasally, orally, or parenterally for prevention or control of polydipsia, polyuria, and dehydration in diabetes insipidus caused by a deficiency of endogenous posterior pituitary ADH (neurohypophyseal diabetes insipidus).101 102 111 112 116 117 a

Intranasal desmopressin considered drug of choice for chronic treatment of mild to severe neurohypophyseal diabetes insipidus, because of relatively long duration of action and relative lack of adverse effects.a

Polyuria and Polydipsia

Intranasally, orally, or parenterally for management of temporary polyuria and polydipsia associated with trauma or surgery in the pituitary region.101 102 111 112 116 117 a

Not effective in controlling polyuria caused by renal disease, nephrogenic diabetes insipidus, hypokalemia or hypercalcemia; variable efficacy in controlling polyuria secondary to administration of lithium.101 102 111 112 116 117 a

Primary Nocturnal Enuresis

Orally for management of primary nocturnal enuresis.103 105 106 107 112

Used alone or as an adjunct to behavioral therapy and/or other nondrug measures; may be effective in some cases refractory to standard therapies (e.g., imipramine, enuresis alarms).105 107 112

Although some desmopressin intranasal preparations (i.e., solutions containing 0.1 mg/mL) initially received approval by FDA for treatment of primary nocturnal enuresis, this approval was withdrawn in 2007 because of the risk of serious hyponatremia that may result in seizures and death, particularly in children.101 115 117 (See Water Intoxication under Cautions.)

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Treatment usually not indicated until a child reaches 6 years of age; condition will spontaneously remit in 15% of patients every year thereafter.103 104 105 106

Rule out other possible etiologies (e.g., neurologic and/or spinal abnormalities, diabetes insipidus or diabetes mellitus, chronic renal failure, bacteriuria [especially in girls]) before initiation of drug therapy.104 106

Hemophilia A

Generally indicated in patients with hemophilia A with factor VIII coagulant activity >5%;100 111 114 designated an orphan drug by FDA for this use.a

Intranasally or parenterally for management of spontaneous or trauma-induced bleeding episodes (e.g., hemarthrosis, intramuscular hematoma, mucosal bleeding) in patients with mild hemophilia A.100 108 111 114

Intranasally or parenterally for maintenance of hemostasis during surgical procedures and postoperatively100 108 111 113 114 116 when administered 30 minutes prior to scheduled procedure.116

Not indicated for patients with hemophilia A with factor VIII coagulant activity ≤5%,100 111 114 a 116 hemophilia B,a or patients with factor VIII antibodies.a Use may be justified in patients with factor VIII coagulant activity between 2–5% in certain clinical situations; carefully monitor patient if drug is used in this situation.a 111 116

Not effective in patients with severe hemophilia A.a

von Willebrand Disease

Generally indicated in patients with mild to moderate classic von Willebrand disease (type 1) with factor VIII coagulant activity >5%;111 114 116 designated an orphan drug by FDA for this use.a

Intranasally or parenterally for management of spontaneous or trauma-induced bleeding episodes (e.g., hemarthrosis, intramuscular hematoma, mucosal bleeding) in patients with mild to moderate type 1 von Willebrand disease.100 108 109 110 111 114 116

Parenterally for maintenance of hemostasis during surgical procedures and postoperativelya when administered 30 minutes prior to scheduled procedure in patients with mild to moderate type 1 von Willebrand disease.111 116

Drug of choice for management of mild to moderate type 1 von Willebrand disease,108 109 110 especially in patients with plasma factor VIII activity >5%.100 111 114 116

Patients with severe homozygous von Willebrand disease with factor VIII coagulant activity and factor VIII/von Willebrand antigen concentrations <1% least likely to respond; variable response in other patients depending on type of molecular defect associated with disease.111 116 a

Not indicated for patients with severe type 1 von Willebrand disease or when there is evidence of an abnormal molecular form of factor VIII antigen.111 114 116 a

May be effective for management of bleeding in some, but not all, patients with type 2A, 2M, or 2N von Willebrand disease.108 109 110 118 119 120

Usually not used in patients with type 2B von Willebrand disease because of an increased risk of thromboembolic events and transient thrombocytopenia;100 110 111 114 118 119 120 although, has been effectively used in some patients with type 2B von Willebrand disease.110 119

Not effective for management of bleeding in patients with type 3 von Willebrand disease.110 118 119 120

Uremia

Has been used IV to increase factor VIII activity and reduce bleeding time in uremic patients with prolonged bleeding times and hemorrhagic tendencies.a Reduced bleeding time and normal hemostasis observed in some additional uremic patients who received IV drug before surgery or renal biopsy.a

Diagnostic Uses

Has been used intranasally in adults and children to evaluate ability of kidneys to concentrate urine.a

Sickle Cell Anemia

Has been used intranasally in a small number of patients with sickle cell anemia to induce hyponatremia resulting in decreased mean corpuscular hemoglobin concentrations and degree of sickling for the prevention and treatment of sickle cell crisis, but safety and efficacy not established.a

Desmopressin Acetate Dosage and Administration

Administration

Administer intranasally, orally, or by sub-Q injection, direct IV injection, or slow IV infusion.100 101 102 111 112 114 116 117

Repeated administration every 12–24 hours may result in a gradual diminution of the increase in plasma factor VIII activity observed with a single dose; initial response reproducible when a period of 2–3 days or 1–6 weeks elapses between IV or intranasal administration, respectively.111 114 116 117 a

Intranasal Administration

Use intranasal preparations in children under adult supervision in order to monitor dose and fluid intake.101 115 117

Nasal solutions containing 0.1 mg of drug per mL used for treatment of diabetes insipidus;101 102 117 nasal solution containing 1.5 mg of drug per mL used for treatment of hemophilia A or von Willebrand disease.114

Administer nasal solutions containing 0.1 or 1.5 mg of drug per mL using the spray pump supplied by manufacturers;101 114 alternatively, nasal solutions containing 0.1 mg/mL may be administered using a calibrated nasal tube supplied by manufacturers.101 102 117

Intranasal spray pump provided by manufacturers delivers 0.1 mL of solution per actuation.101 114 When administering nasal solution containing 0.1 mg/mL using the spray pump, each 0.1-mL spray delivers a dose of 10 mcg; administer the solution using a nasal tube if a dose other than a multiple of 10 mcg is required (e.g., in pediatric patients).101

Nasal tube has 4 graduation markings that measure 0.05, 0.1, 0.15, or 0.2 mL and may be used to administer 5, 10, 15, or 20 mcg, respectively.102 117

When administering nasal solution containing 1.5 mg/mL using the spray pump, each 0.1-mL spray delivers a dose of 150 mcg; use parenteral therapy if a dose other than a multiple of 150 mcg is required.114

Administer a test dose of the nasal solution containing 1.5 mg/mL prior to initial use to establish appropriate patient response in coagulation profile.

Administer nasal solution intranasally according to the manufacturer’s instructions to ensure that drug is deposited high in nasal cavity and does not pass down the throat.a

Generally not administered intranasally when changes in nasal mucosa (e.g., scarring, edema) may cause erratic, unreliable absorption of drug;101 102 114 117 a do not use or discontinue drug until nasal problems resolve.101 102 114 117 Consider using desmopressin injection.101 102 114 117

Do not administer intranasally when nasal congestion and blockage, nasal discharge, atrophy of nasal mucosa, or severe atrophic rhinitis is present;101 102 111 114 116 117 however, patients with nasal congestion and blockage have often responded well to intranasal therapy.101 102 117

Intranasal therapy may be inappropriate when patient has impaired consciousness.101 102 111 114 116 117

Alternative route of administration may be needed when nasal packing is present or during recovery from surgery in patients who have undergone cranial surgical procedures (e.g., transsphenoidal hypophysectomy).101 102 116 117 111

IV Administration

For solution and drug compatibility information, see Stability: Compatibility.

Monitor BP and pulse during infusion.a

Dilution

Hemophilia A or von Willebrand disease, IV infusion: Dilute the appropriate dose in 10 or 50 mL of 0.9% sodium chloride injection for administration in children weighing ≤10 kg or in adults and children weighing >10 kg, respectively.a

Rate of Administration

Hemophilia A or von Willebrand disease, IV infusion: Slowly infuse IV over 15–30 minutes.111 116 a

Dosage

Available as desmopressin acetate; dosage expressed in terms of salt.102 111 114 116 117

Diabetes Insipidus or Polyuria and Polydipsia: Adjust dosage according individual requirements (e.g., diurnal pattern of response).101 102 111 112 116 117 a Estimate response by both adequate duration of sleep and adequate, not excessive, water turnover.101 102 111 112 116 117 a Adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover.101 102 111 112 116 117 a

Primary Nocturnal Enuresis: Adjust dosage according individual requirements and response.112

Hemophilia A or von Willebrand Disease: Determine need for additional doses of drug or use of blood products for hemostasis based on clinical response (determined by laboratory tests) and condition of patient.111 114 116 a Consider tendency toward tachyphylaxis (decreasing responsiveness) to drug when doses are repeated more frequently than every 48 hours.111 114 116 a

von Willebrand Disease: Recommended (by National Hemophilia Foundation’s Medical and Scientific Advisory Council [MASAC]) that drug be administered no more frequently than once every 24 hours and used for no more than 3 consecutive days, unless such therapy is recommended by a clinician with expertise in treatment of the disease.109

Pediatric Patients

Diabetes Insipidus
Neurohypophyseal
Intranasal

Children 3 months to 12 years of age: Initially, ≤5 mcg (0.05 mL of a solution containing 0.1 mg/ml).101 102 117 a

Usual dosage range: 5–30 mcg (0.05–0.3 mL of a solution containing 0.1 mg/mL) daily given intranasally in a single evening dose or in 2 divided doses.101 102 117 a

Use lowest effective dosage; about 25–33% of children and adults controlled with a single daily dose.101 102 117 a

Restrict fluid intake.101 117

Oral

Children ≥4 years of age: Initially, 0.05 mg twice daily; adjust subsequent dosage according to response.112

0.1–0.8 mg daily given in divided doses is optimal dosage range for most patients.112

Increase or decrease total daily dosage in the range of 0.1–1.2 mg divided into 2 or 3 daily doses as needed to obtain adequate antidiuresis.112

Initiate oral therapy 12 hours after the last intranasal dose in patients who previously received intranasal therapy.112

Restrict fluid intake.112

IV

Children ≥12 years of age: Usually, 2–4 mcg daily by direct IV injection given in 2 divided doses.111 116 a

Generally, administer one-tenth of the maintenance intranasal dosage parenterally in patients being switched from intranasal to direct IV injection therapy.111 116 a

Use lowest effective dosage.a During long-term use, patients rarely may develop tolerance to drug and require cautious increase in dosage to achieve an adequate therapeutic response.a

Restrict fluid intake.116

Sub-Q

Children ≥12 years of age: Usually, 2–4 mcg daily by sub-Q injection given in 2 divided doses.111 116 a

Generally, administer one-tenth of the maintenance intranasal dosage parenterally in patients being switched from intranasal to sub-Q injection therapy.111 116 a

Use lowest effective dosage.a During long-term use, patients rarely may develop tolerance to drug and require cautious increase in dosage to achieve an adequate therapeutic response.a

Restrict fluid intake.116

Primary Nocturnal Enuresis
Oral

Children ≥6 years of age: Initially, 0.2 mg at bedtime; dose may be adjusted up to 0.6 mg to achieve desired response.112 In children being switched from intranasal to oral therapy, initiate oral therapy the night following (24 hours after) the last intranasal dose.112 Duration of therapy not established in pediatric patients responding to therapy; some experts have suggested it is reasonable to continue therapy for 3–6 months, and after 3–6 months, therapy can be withdrawn and the patient reevaluated.121 122 123 124

Restrict fluid intake for a minimum of 1 hour before drug administration and continue fluid restriction until next morning or at least 8 hours after drug administration.112 115 Some experts recommend that not more than 240 mL of fluid be consumed by children on any night when drug is used.121

Interrupt drug therapy during episodes of fluid and/or electrolyte imbalance (e.g., systemic infections, fever, recurrent vomiting or diarrhea) and under conditions associated with increased water intake (e.g., extremely hot weather, vigorous exercise).112 115

Hemophilia A
Intranasal

Children 11 months to 12 years of age: Usually, 300 mcg (0.1 mL or 1 spray from the spray pump into each nostril of a solution containing 1.5 mg/mL).114 Dosage of 150 mcg (0.1 mL or 1 spray from the spray pump into a single nostril of a solution containing 1.5 mg/mL) may be sufficient in patients who weigh <50 kg.114 Administer 2 hours prior to surgery if using preoperatively.114

IV

Children ≥3 months of age: Usually, 0.3 mcg/kg by slow IV infusion; administer 30 minutes prior to scheduled procedure if using preoperatively.111 116 a

Restrict fluid intake.116

von Willebrand Disease
Type 1
Intranasal

Children 11 months to 12 years of age: Usually, 300 mcg (0.1 mL or 1 spray from the spray pump into each nostril of a solution containing 1.5 mg/mL).114 Dosage of 150 mcg (0.1 mL or 1 spray from the spray pump into a single nostril of a solution containing 1.5 mg/mL) may be sufficient in patients who weigh <50 kg.114 Administer 2 hours prior to surgery if using preoperatively.114

IV

Children ≥3 months of age: Usually, 0.3 mcg/kg by slow IV infusion; administer 30 minutes prior to scheduled procedure if using preoperatively.111 116 a

Restrict fluid intake.116

Diagnostic Uses
Testing for Renal Urine Concentrating Capacity
Intranasal

10 mcg (0.1 mL of a solution containing 0.1 mg of drug per mL) has been administered intranasally in nonfasting infants 1–12 weeks of age.a 17

20 mcg (0.2 mL of a solution containing 0.1 mg of drug per mL) has been administered intranasally in nonfasting children 2–15 years of age.a 17

Urine sample was collected in 1–5 hours and specific gravity of urine was determined.a An average individual usually concentrates urine to a specific gravity of ≥1.020 under test conditions.a

Adults

Diabetes Insipidus
Neurohypophyseal
Intranasal

10–40 mcg (0.1–0.4 mL or 1–4 sprays from the spray pump of a solution containing 0.1 mg/mL) given intranasally in 1–3 divided doses daily.101 102 117 a

Alternatively, 5–40 mcg (0.05–0.4 mL of a solution containing 0.1 mg/mL) has been recommended.a

Most adults require 20 mcg daily administered in 2 divided doses in the morning and the evening.101 102 117 a

Use lowest effective dosage; about 25–33% of adults and children controlled with a single daily dose.102 117 a

Restrict fluid intake.101 117

Oral

Initially, 0.05 mg twice daily; adjust subsequent dosage according to response.112

0.1–0.8 mg daily given in divided doses is optimal dosage range for most patients.112

Increase or decrease total daily dosage in the range of 0.1–1.2 mg divided into 2 or 3 daily doses as needed to obtain adequate antidiuresis.112

Initiate oral therapy 12 hours after the last intranasal dose in patients who previously received intranasal therapy.112

Restrict fluid intake.112

IV

Usually, 2–4 mcg daily by IV injection given in 2 divided doses.111 116 a

Generally, administer one-tenth of the maintenance intranasal dosage parenterally in patients being switched from intranasal to direct IV injection therapy.111 116 a

Use lowest effective dosage.a During long-term use, patients rarely may develop tolerance to drug and require cautious increase in dosage to achieve an adequate therapeutic response.a

Restrict fluid intake.116

Sub-Q

Usually, 2–4 mcg daily by sub-Q injection given in 2 divided doses.111 116 a

Generally, administer one-tenth of the maintenance intranasal dosage parenterally in patients being switched from intranasal to sub-Q injection therapy.111 116 a

Use lowest effective dosage.a During long-term use, patients rarely may develop tolerance to drug and require cautious increase in dosage to achieve an adequate therapeutic response.a

Restrict fluid intake.116

Primary Nocturnal Enuresis
Oral

Initially, 0.2 mg at bedtime; dose may be adjusted up to 0.6 mg to achieve desired response.112 Initiate oral therapy the night following (24 hours after) the last intranasal dose in patients previously on intranasal therapy.112

Restrict fluid intake for a minimum of 1 hour before drug administration and continue fluid restriction until next morning or at least 8 hours after drug administration.112 115

Interrupt drug therapy during episodes of fluid and/or electrolyte imbalance (e.g., systemic infections, fever, recurrent vomiting or diarrhea) and under conditions associated with increased water intake (e.g., extremely hot weather, vigorous exercise).112 115

Hemophilia A
Intranasal

Usually, 300 mcg (0.1 mL or 1 spray from the spray pump into each nostril of a solution containing 1.5 mg/mL).114 Dosage of 150 mcg (0.1 mL or 1 spray from the spray pump into a single nostril of a solution containing 1.5 mg/mL) may be sufficient in patients who weigh <50 kg.114 Administer 2 hours prior to surgery if using preoperatively.114

IV

Usually, 0.3 mcg/kg by slow IV infusion; administer 30 minutes prior to scheduled procedure if using preoperatively.111 116 a

Restrict fluid intake.116

von Willebrand Disease
Type 1
Intranasal

Usually, 300 mcg (0.1 mL or 1 spray from the spray pump into each nostril of a solution containing 1.5 mg/mL).114 Dosage of 150 mcg (0.1 mL or 1 spray from the spray pump into a single nostril of a solution containing 1.5 mg/mL) may be sufficient in patients who weigh <50 kg.114 Administer 2 hours prior to surgery if using preoperatively.114

IV

Usually, 0.3 mcg/kg by slow IV infusion; administer 30 minutes prior to scheduled procedure if using preoperatively.111 116 a

Restrict fluid intake.116

Diagnostic Uses
Testing for Renal Urine Concentrating Capacity
Intranasal

10–40 mcg (0.1–0.4 mL of a solution containing 0.1 mg of drug per mL) has been administered intranasally to fasting or nonfasting adults.a 12 22 23

Urine sample was collected in 1–5 hours and specific gravity of urine was determined.a Average individual usually concentrates urine to a specific gravity of ≥1.020 under test conditions.a

Special Populations

Geriatric Patients

Select dosage with caution, usually initiating therapy at the low end of the dosing range because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.101 112 116 117 (See Geriatric Use under Cautions.)

Cautions for Desmopressin Acetate

Contraindications

  • Known hypersensitivity to desmopressin acetate or any ingredient in the formulation.101 102 111 112 114 116 117 a

  • Moderate to severe renal impairment (Clcr <50 mL/minute).101 112 116 117

  • Hyponatremia or a history of hyponatremia.101 112 115 116 117

Warnings/Precautions

Warnings

Water Intoxication

In late 2007, FDA reported results of a review of 61 postmarketing cases of hyponatremic-related seizures associated with use of desmopressin.115 In 55 cases, sodium concentrations ranged from 104–130 mEq/L during the seizure event.115 Two of these 55 cases were fatal; both patients experienced hyponatremia and seizures.115 However, direct contribution of drug to fatalities not clear.115 Intranasal formulations were used in 36 cases; 25 of these cases involved pediatric patients (i.e., patients <17 years of age).115 Most commonly reported indication for use in the 25 pediatric patients was nocturnal enuresis.115 In 39 of the 61 cases, patients received at least one concomitant drug or disease that also may be associated with hyponatremia and/or seizures.115 As a result, use of intranasal preparations for treatment of primary nocturnal enuresis no longer is approved by FDA; other approved indications for individual intranasal preparations were not changed.115

Reserve intranasal preparations for situations in which oral therapy is not feasible.101 117

Use with caution in patients at risk for water intoxication with hyponatremia.115

Hyponatremia reported very rarely during international postmarketing surveillance.101 112 115 116 117 Desmopressin is a potent antidiuretic and use may result in water intoxication and/or hyponatremia; hyponatremia may be fatal unless properly diagnosed and treated.101 112 116 117 Fluid restriction recommended; careful medical supervision required.101 112 115 116 117

Carefully adjust fluid intake downwards, particularly in pediatric and geriatric patients, to reduce the risk of potential water intoxication and hyponatremia.101 112 116 117 Observe all patients for signs and symptoms associated with hyponatremia (i.e., headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, appetite loss, irritability, muscle weakness, spasms or cramps, abnormal mental status [e.g., hallucinations, decreased consciousness, confusion]); severe symptoms may include seizure, coma, and/or respiratory arrest.101 112 115 116 117 Consider the possibility of a rare occurrence of a substantial decrease in plasma osmolality that may result in seizures, which may lead to coma.101 102 111 112 114 116 117

Use with caution in patients with habitual or psychogenic polydipsia and in patients who are receiving certain drugs (e.g., tricyclic antidepressants, SSRIs) as these patients may be more likely to drink excessive amounts of water resulting in an increased risk for hyponatremia.101 112 115 116 117 (See Specific Drugs under Interactions.)

Type 2B von Willebrand Disease

Do not use in patients with type 2B or platelet-type (pseudo) von Willebrand disease because of the risk of platelet aggregation and thrombocytopenia.111 114 116 a (See von Willebrand Disease under Uses.)

Sensitivity Reactions

Hypersensitivity Reactions

Severe allergic reactions reported rarely.101 102 111 112 114 116 117 Anaphylaxis reported rarely with IV and intranasal administration, including isolated cases of fatal anaphylaxis with IV administration.101 102 111 112 114 116 117

Not known whether antibodies to drug are produced after repeated administration.111 114 116

General Precautions

Cardiovascular Effects

Changes in BP resulting in either a slight increase in BP, which may respond to dosage reduction, or a transient decrease in BP and a compensatory increase in heart rate reported infrequently.101 102 111 112 114 116 117 a

Thrombotic events (e.g., thrombosis, acute cerebrovascular thrombosis, acute MI) reported rarely in patients predisposed to thrombus formation; causal relationship to drug not determined.111 114 116 a

Use with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease101 102 111 112 114 116 117 a or in patients predisposed to thrombus formation.111 114 116 a

Diseases Associated with Fluid and Electrolyte Imbalances

Use with caution in patients with conditions associated with fluid and electrolyte imbalances (e.g., cystic fibrosis, heart failure, renal disorders); these patients are prone to hyponatremia.101 102 111 112 114 116 117 (See Water Intoxication under Cautions.)

Patient Monitoring

Diabetes Insipidus or Polyuria and Polydipsia Associated with Head Trauma or Surgery: Monitor urine volume and osmolality, and in some cases, plasma osmolality.101 102 111 112 116 117 a

Primary Nocturnal Enuresis: Monitor serum electrolytes at least once if therapy is continued for >7 days.101 102 117 a

Hemophilia A: Monitor factor VIII and factor VIII/ristocetin cofactor (von Willebrand factor) activities, factor VIII antigen concentrations, and aPTT.111 114 116 a Determine factor VIII coagulant activity prior to initiating therapy for hemostasis; do not rely upon drug if factor VIII coagulant activity is <5% of normal.111 114 116 a

von Willebrand Disease: Monitor factor VIII and factor VIII/ristocetin cofactor activities and factor VIII/von Willebrand factor antigen concentrations to ensure an adequate response is being achieved; determination of skin bleeding time also may be useful.111 114 116 a

Specific Populations

Pregnancy

Category B.101 102 111 112 114 116 117

Lactation

Not known whether drug is distributed into milk; use with caution.101 102 111 112 114 116 117 a

Pediatric Use

Carefully restrict fluid intake in pediatric patients to prevent possible hyponatremia and water intoxication.101 102 111 112 114 116 117 a (See Water Intoxication under Cautions.)

Intranasal therapy has no effect on growth hormone, prolactin, or LH concentrations in children.a

Diabetes Insipidus:Desmopressin tablets have been used safely for up to 44 months in pediatric patients ≥4 years of age with diabetes insipidus.112 In younger pediatric patients, adjust dosage according to individual need to prevent excessive decrease in plasma osmolality resulting in hyponatremia and possible seizures.112

Safety and efficacy of desmopressin injection not established in pediatric patients <12 years of age with diabetes insipidus.111 116 a

Carefully adjust dosage of oral therapy or nasal solution (containing 0.1 mg of drug per mL) according to individual needs and tolerance in pediatric patients with diabetes insipidus, with particular attention to the risk of an extreme decrease in plasma osmolality and resulting hyponatremia or seizures in young children.101 102 112 117 a

Occasional change in response to nasal solution containing 0.1 mg of drug per mL in pediatric patients with diabetes insipidus reported (e.g., decreased responsiveness, shortened duration of effect), usually after periods >6 months.102 117 a No evidence that change in responsiveness results from development of binding antibodies; may result from local inactivation of peptide.102 117 a

Intranasal drug preferred to vasopressin injection and oral antidiuretic agents (e.g., chlorpropamide) because of frequency of adverse effects of these agents in pediatric patients with diabetes insipidus.a

Nocturnal Enuresis: Desmopressin tablets have been used safely for <6 months in pediatric patients ≥6 years of age with primary nocturnal enuresis.112

Interrupt therapy during acute intercurrent illness characterized by fluid and/or electrolyte imbalance (e.g., systemic infections, fever, recurrent vomiting or diarrhea) and under conditions associated with increased water intake (e.g., extremely hot weather, vigorous exercise).112 115

Hemophilia or von Willebrand Disease: Do not use the nasal solution containing 1.5 mg of drug per mL for the treatment of hemophilia A or von Willebrand disease in pediatric patients <11 months of age; safety and efficacy established in pediatric patients 11 months to 12 years of age.114

Do not use desmopressin injection for the management of hemophilia A or von Willebrand disease in pediatric patients <3 months of age.111 116 a

Geriatric Use

Carefully restrict fluid intake in geriatric patients to prevent possible hyponatremia and water intoxication.101 112 114 116 117 (See Water Intoxication under Cautions.) Hyponatremia and fluid overload reported during postmarketing surveillance.114

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.101 112 114 116 117 Other reported clinical experience has not identified differences in response between geriatric patients and younger adults.101 112 116 117

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.101 112 116 117 (See Geriatric Patients under Dosage and Administration.)

Substantially eliminated by kidneys; risk of toxic reactions may be greater in patients with impaired renal function.101 112 116 117 Monitor renal function and adjust dosage accordingly since geriatric patients are more likely to have decreased renal function.101 112 116 117

Renal Impairment

Contraindicated in patients with moderate to severe renal impairment (Clcr <50 mL/minute).101 112 116 117

Common Adverse Effects

With intranasal therapy, adverse effects may include transient headache,101 102 112 114 117 a nausea,101 102 112 114 117 a nasal congestion,101 102 114 117 a rhinitis,101 102 114 117 a flushing (e.g., facial),101 102 112 114 117 a mild abdominal cramps or pain,101 102 112 114 117 a epistaxis,101 102 114 117 a sore throat,101 102 114 117 a cough,101 102 114 117 a upper respiratory infection,101 102 114 117 a dizziness,101 102 114 117 a conjunctivitis,101 102 117 a ocular edema,101 102 117 a lacrimation disorder,101 102 117 a itchy or light-sensitive eyes,114 asthenia,101 102 117 a chills,101 102 114 117 a warm feeling,114 nostril pain,101 102 117 a vomiting,114 a GI disorder,101 102 117 a somnolence,114 a insomnia,114 a pain,114 a chest pain,114 a palpitations,114 a tachycardia,114 a dyspepsia,114 edema,114 agitation,114 a balanitis,114 a vulval pain,114 a increased BP,101 102 117 a hyponatremia,a severe allergic reactions (including anaphylaxis),101 102 117 convulsion,a coma.a

With oral therapy, adverse effects may include increased AST,112 headache,112 abnormal thinking,112 diarrhea,112 edema-weight gain.112

With parenteral therapy, adverse effects may include transient headache,111 112 116 a nausea,112 114 116 a mild abdominal cramps,112 114 116 a vulval pain,114 116 a injection site reactions (local erythema, swelling, burning or severe pain),114 116 facial flushing,112 114 116 a BP changes (increased BP; decreased BP with compensatory increased heart rate),116 a tachycardia,a hyponatremia,116 a excessive water retention,a water intoxication,114 116 a severe allergic reactions (including anaphylaxis),116 a thrombotic events (acute cerebrovascular thrombosis, acute MI).114 116 a

Interactions for Desmopressin Acetate

Drugs that Increase the Risk of Water Intoxication with Hyponatremia

Use with caution in patients receiving concomitant therapy with drugs that may increase the risk of water intoxication with hyponatremia.101 112 115 116 117 (See Water Intoxication under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Alcohol

Possible decreased antidiuretic response to desmopressina

Use with cautiona

Aminocaproic acid

Concomitant therapy has been used without adverse effects111 114 116

Antidepressants, tricyclics (e.g., imipramine)

Hyponatremic seizures reported rarely in patients receiving desmopressin and imipramine during postmarketing surveillance101 112 116 117

Possible increased risk of water intoxication with hyponatremia.101 112 115 116 117

Use with caution101 112 115 116 117

Carbamazepine

Prior administration of carbamazepine decreased duration of action of desmopressina

Possible increased risk of water intoxication with hyponatremia.101 112 115 116 117

Use with caution101 112 116 117

Chlorpromazine

Possible increased risk of water intoxication with hyponatremia.101 112 115 116 117

Use with caution101 112 116 117

Chlorpropamide

Possible potentiation of antidiuretic responsea

Clofibrate

Potentiation and prolongation of antidiuretic effect of desmopressina

Demeclocycline

Possible decreased antidiuretic response to desmopressina

Use with cautiona

Epinephrine

Large doses of epinephrine may decrease the antidiuretic response to desmopressina

Use with cautiona

Fludrocortisone

Possible potentiation of antidiuretic responsea

Heparin

Possible decreased antidiuretic response to desmopressina

Use with cautiona

Lamotrigine

Possible increased risk of water intoxication with hyponatremia.101 112 115 116 117

Use with caution101 112 116 117

Lithium

Possible decreased antidiuretic response to desmopressina

Use with cautiona

NSAIAs

Possible increased risk of water intoxication with hyponatremia.101 112 115 116 117

Use with caution101 112 116 117

Opiates

Possible increased risk of water intoxication with hyponatremia.101 112 115 116 117

Use with caution101 112 116 117

Oxybutynin

Hyponatremic seizures reported rarely in patients receiving desmopressin and oxybutynin during postmarketing surveillance101 112 116 117

SSRIs

Possible increased risk of water intoxication with hyponatremia.101 112 115 116 117

Use with caution101 112 115 116 117

Urea

Possible potentiation of antidiuretic responsea

Vasopressor agents

Carefully monitor patient if desmopressin doses as large as 0.3 mcg/kg are used with other vasopressor agents101 102 111 112 114 116 117

Desmopressin Acetate Pharmacokinetics

Absorption

Bioavailability

About 10–20% of a dose is absorbed through nasal mucosa following intranasal administration.a

Minimally absorbed from GI tract following oral administration; bioavailability is about 5% compared with intranasal administration and about 0.16% compared with IV administration of the drug.112

Peak plasma concentrations attained by 0.9 or 1.5 hours following oral or intranasal administration, respectively.112

Bioavailability of a nasal solution (containing 1.5 mg of drug per mL) is about 3.3–4.1%; peak plasma concentrations attained 40–45 minutes after a dose.114

Exact fraction of drug absorbed following sub-Q injection not quantitatively determined; bioavailability determined qualitatively using urine output data.111 116

Onset

Antidiuretic effects occur within 15–60 minutes or at 60 minutes and peak in 1–5 or 4–7 hours following intranasal or oral administration, respectively.a 112

Increased plasma concentrations of factor VIII and von Willebrand factor evident within 30 minutes and peak at about 1.5 hours following intranasal administration of 150–450 mcg of drug (1–3 sprays of a solution containing 1.5 mg of drug per mL).114

Increased plasma factor VIII activity occurs within 15–30 minutes and peaks between 1.5–2 hours following IV infusion.111 116 a

Duration

Varies among patients with a specific dose.a

Antidiuretic effects persist 5–21 hours and abruptly end over a period of 60–90 minutes following intranasal administration.a

Special Populations

Nasal congestion reportedly does not interfere with efficacy of intranasal drug, however, increased dosage may be required.a

Percentage increase of factor VIII concentrations in patients with mild hemophilia A and von Willebrand disease not substantially different from healthy individuals.111 114 116

Distribution

Extent

Not known whether distributed into human milk 101 102 111 112 114 116 117 or crosses placenta.a

Elimination

Metabolism

Metabolic fate not known.a

Does not appear to be degraded by aminopeptidases or other peptidases that cleave oxytocin and endogenous vasopressin in the plasma during late pregnancy.a

Elimination Route

Excreted principally in urine.101 112 116 117

Half-life

3.3–3.5 hours following intranasal administration of 150–450 mcg of drug (1–3 sprays of a solution containing 1.5 mg of drug per mL).114

1.5–2.5 hours (on average and independent of dosage) following oral administration.112

Biphasic; mean initial and terminal plasma half-life of 7.8 and 75.5 minutes (range: 0.4–4 hours), respectively, following IV or intranasal (solution containing 0.1 mg of drug per mL) administration.101 102 111 116 117 a

Special Populations

Renal clearance of drug decreases with decreasing renal function.101 112 116 117 125 Terminal half-lives of desmopressin averaged 3.7, 4.8, 7.2, or 10 hours following administration of a single IV dose of 2 mcg of drug in individuals with normal renal function (average ClCr of 103 mL/minute), mild renal impairment (average ClCr of 72 mL/minute), moderate renal impairment (average ClCr of 37 mL/minute), or severe renal impairment (average ClCr of 16 mL/minute; not on dialysis), respectively.125 (See Contraindications under Cautions.)

Stability

Storage

Intranasal

Solution

Commercially available nasal solutions preserved with benzalkonium chloride: Controlled room temperature (20–25°C, not to exceed 25°C);101 114 store container in upright position.101

Commercially available nasal solutions preserved with chlorobutanol: 2–8°C; stable for 3 weeks at controlled room temperature (20–25°C).102 117

Commercially available nasal solutions containing 1.5 mg of drug per mL: Discard 6 months after opening.114

Oral

Tablets

20–25°C; avoid exposure to excessive heat or light.112

Parenteral

Injection

2–8°C;100 111 avoid freezing.111 116 a

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

Sodium chloride 0.9%111 116 a

Actions

  • Synthetic analog of arginine vasopressin (antidiuretic hormone [ADH]); vasopressin maintains serum osmolality within a normal range by increasing reabsorption of water by the collecting ducts in the kidneys resulting in increased urine osmolality and decreased urinary flow rate.101 102 111 112 114 116 117 a

  • Desmopressin has same effects on water reabsorption as does vasopressin in patients with neurohypophyseal diabetes insipidus.a

  • Elicits a greater antidiuretic response, on a weight basis, than does arginine vasopressin.a

  • Therapeutic doses do not directly affect urinary sodium or potassium excretion, or serum sodium, potassium, or creatinine concentrations.a

  • Antidiuretic potency of IV administration is about 10 times that following intranasal administration.101 102 111 116 117 a

  • Dose-dependent increases in plasma factor VIII (antihemophilic factor), plasminogen activator, and, to a lesser degree, factor VIII-related antigen and ristocetin cofactor activities.a

  • Rapidly increases plasminogen activator activity following IV administration; however, clinically important fibrinolysis not reported to date.111 114 116 a

  • Elicits a greater increase in plasma factor VIII activity, on a weight basis, than does arginine vasopressin in patients with hemophilia or type I von Willebrand disease.111 114 116 a

  • Reduced smooth muscle contracting and vasopressor properties compared with vasopressin and lypressin (no longer commercially available in the US);101 102 111 112 114 116 117 a mean arterial pressure may increase as much as 15 mm Hg with intranasal doses of ≥40 mcg.a

  • Usual intranasal doses do not cause skin pallor or severe smooth muscle or abdominal cramps, unlike vasopressin and lypressin.a

  • Not reported to stimulate uterine contractions.a

  • Does not stimulate adrenocorticotropic hormone release or increase plasma cortisol concentrations, unlike vasopressin.a

Advice to Patients

  • Importance of discussing with patient and/or guardian the risk of potential water intoxication and/or hyponatremia, fluid restriction (particularly in pediatric and geriatric patients), and monitoring of fluid intake (particularly during acute intercurrent illness [e.g., systemic infections, fever, recurrent vomiting or diarrhea] and under conditions associated with increased water intake [e.g., extremely hot weather, vigorous exercise]).101 112 115 116 117 Importance of promptly informing clinicians if the patient’s fluid intake changes or if symptoms of hyponatremia (e.g., nausea, vomiting, fatigue, muscle cramps or weakness) occur.115

  • Importance of instructing patients on proper use of nasal tube or spray pump in order to obtain optimum results.a Importance of informing patients to consult patient instructions on nasal spray provided by the manufacturer before use.101 114 Importance of administering intranasal preparations in children under adult supervision in order to monitor dose and fluid intake.101 115 117

  • Importance of informing patients that a bottle of nasal solution containing 0.1 mg of drug per mL accurately delivers 50 doses of 10 mcg of drug per dose.101 Discard any solution remaining after 50 doses, since the amount delivered thereafter may be substantially <10 mcg of drug.101 Do not attempt to transfer any remaining solution to another bottle.101

  • Importance of informing patients that a bottle of nasal solution containing 1.5 mg of drug per mL accurately delivers 25 doses of 150 mcg of drug per dose.114 Discard any solution remaining after 25 doses, since the amount delivered thereafter may be substantially <150 mcg of drug.114 Do not attempt to transfer any remaining solution to another bottle.114

  • Importance of patients receiving nasal solution containing 1.5 mg of drug per mL to inform clinicians if bleeding is not controlled.114

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., tricyclic antidepressants, SSRIs, chlorpromazine, opiates, NSAIAs, lamotrigine, carbamazepine), as well as any concomitant illnesses (e.g., hyponatremia, habitual or psychogenic polydipsia, cystic fibrosis, heart failure, renal disorders).101 102 111 112 114 116 117

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.101 102 111 112 114 116 117

  • Importance of informing patients of other important precautionary information.101 102 111 112 114 116 117 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Desmopressin Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Nasal

Solution*

0.1 mg/mL*

DDAVP Nasal Spray (with benzalkonium chloride; with spray pump)

Sanofi-Aventis

DDAVP Rhinal Tube (with chlorobutanol; with 2 calibrated nasal tubes; refrigerate)

Sanofi-Aventis

Desmopressin Acetate Nasal Spray (with chlorobutanol)

Apotex, Bausch & Lomb

Desmopressin Acetate Rhinal Tube (with chlorobutanol; with 2 calibrated nasal tubes; refrigerate)

Ferring

Minirin (with chlorobutanol)

Apotex, Ferring

1.5 mg/mL

Stimate Nasal Spray (with benzalkonium chloride; with spray pump)

CSL Behring

Oral

Tablets

0.1 mg*

DDAVP (with povidone)

Sanofi-Aventis

Desmopressin Acetate Tablets

Apotex, Barr, Teva

0.2 mg*

DDAVP (with povidone)

Sanofi-Aventis

Desmopressin Acetate Tablets

Apotex, Barr, Teva

Parenteral

Injection

4 mcg/mL*

DDAVP (with chlorobutanol)

Sanofi-Aventis

Desmopressin Acetate Injection (with chlorobutanol)

Ferring, Hospira, Teva

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

DDAVP 0.01% Solution (SANOFI-AVENTIS U.S.): 5/$267.98 or 15/$786.01

DDAVP 0.1MG Tablets (SANOFI-AVENTIS U.S.): 30/$151.73 or 90/$408.28

DDAVP 0.2MG Tablets (SANOFI-AVENTIS U.S.): 30/$203.39 or 90/$584.78

DDAVP Rhinal Tube 0.01% Solution (SANOFI-AVENTIS U.S.): 3/$154.52 or 8/$459.81

Desmopressin Ace Rhinal Tube 0.01% Solution (FERRING): 3/$86.36 or 8/$230.98

Desmopressin Ace Spray Refrig 0.01% Solution (BAUSCH &amp; LOMB): 5/$209.99 or 15/$625.97

Desmopressin Acetate 0.1MG Tablets (TEVA PHARMACEUTICALS USA): 30/$86.99 or 90/$231.96

Desmopressin Acetate 0.2MG Tablets (TEVA PHARMACEUTICALS USA): 90/$339.97 or 180/$655.97

Stimate 1.5MG/ML Solution (CSL BEHRING): 3/$649.01 or 5/$1,292.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

12. Scheitza E, Birr E, Heidland A. Response to vasopressin analogues in diabetes insipidus. N Engl J Med. 1976; 295:393. [PubMed 778620]

17. Aronson AS, Svenningsen NW. DDAVP test for estimation of renal concentrating capacity in infants and children. Arch Dis Child. 1974; 49:654-9. [PubMed 4425527]

22. Monson JP, Richards P. Desmopressin urine concentration test. Br Med J. 1978; 1:24. [PubMed 563756]

23. Delin K, Aurell M, Ewald J. Urinary concentration test with desmopressin. Br Med J. 1978; 1:757-8. [PubMed 630334]

100. Rhone-Poulenc Rorer. DDAVP (desmopressin acetate) injection 4 mcg/mL prescribing information (dated 1997 Sep) and DDAVP (desmopressin acetate) injection 15 mcg/mL prescribing information (dated 1997 Nov). In: Physician’s desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2582-4.

101. Sanofi-Aventis. DDAVP (desmopressin acetate) nasal spray prescribing information. Bridgewater, NJ; 2007 Jul.

102. Ferring Pharmaceuticals. Desmopressin acetate rhinal tube prescribing information. Tarrytown, NY; 1998 Aug.

103. Anon. Desmopressin for nocturnal enuresis. Med Lett Drugs Ther. 1990; 32:38-9. [PubMed 2182991]

104. Voiding dysfunction: nocturnal enuresis. In: Lehrman RE, Vaughn VC III, eds. Nelson textbook of pediatrics. 12th ed. Philadelphia: WB Saunders Company; 1983:1160-1.

105. Klauber GT. Clinical efficacy and safety of desmopressin in the treatment of nocturnal enuresis. J Pediatr. 1989; 114(Suppl 4, Part 2):719-22. [IDIS 253281] [PubMed 2647954]

106. Rushton HG. Nocturnal enuresis: epidemiology, evaluation, and currently available treatment options. J Pediatr. 1989; 114(Suppl 4, Part 2):691-6. [IDIS 253279] [PubMed 2647951]

107. Miller K, Goldberg S, Atkin B. Nocturnal enuresis: experience with long-term use of intranasally administered desmopressin. J Pediatr. 1989; 114(Suppl 4, Part 2):723-6. [IDIS 253282] [PubMed 2926586]

108. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations concerning the treatment of hemophilia and other bleeding disorders (revised October 2006). MASAC Recommendation #177. From National Hemophilia Foundation website.

109. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations regarding the treatment of von Willebrand disease (October 2006). MASAC recommendation #173. From National Hemophilia Foundation website.

110. Phillips MD, Santhouse A. von Willebrand disease: recent advances in pathophysiology and treatment. Am J Med Sci. 1998; 316:77-86. [IDIS 412301] [PubMed 9704661]

111. Ferring Pharmaceuticals. Desmopressin acetate injection 4 mcg/mL prescribing information. Tarrytown, NY; 1998 Aug.

112. Sanofi-Aventis. DDAVP (desmopressin acetate) tablets prescribing information. Bridgewater, NJ; 2007 Jul.

113. Rose EH, Aledort LM. Nasal spray desmopressin (DDAVP) for mild hemophilia A and von Willebrand disease. Ann Intern Med. 1991; 114:463-8.

114. CSL Behring. Stimate (desmopressin acetate) nasal spray 1.5 mg/mL prescribing information. King of Prussia, PA; 2007 Jul.

115. Food and Drug Administration (FDA). FDA alert for healthcare professionals on desmopressin acetate (marketed as DDAVP Nasal Spray, DDAVP Rhinal Tube, DDAVP, DDVP, Minirin, and Stimate Nasal Spray). From FDA website. Accessed 2007 Dec 4.

116. Sanofi-Aventis. DDAVP (desmopressin acetate) injection 4 mcg/mL prescribing information. Bridgewater, NJ; 2007 Jul.

117. Sanofi-Aventis. DDAVP (desmopressin acetate) rhinal tube prescribing information. Bridgewater, NJ; 2007 Jul.

118. Franchini M. The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol. 2007; 82:731-5. [PubMed 17492648]

119. Shord SS, Lindley CM. Coagulation products and their uses. Am J Health Syst Pharm. 2000; 57:1403-17; quiz 1418-20. [PubMed 10938981]

120. Mannucci PM. Treatment of von Willebrand’s Disease. N Engl J Med. 2004; 351:683-94. [PubMed 15306670]

121. Glazener CMA, Evans JHC. Desmopressin for nocturnal enuresis in children. Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No.:CD002112. DOI: 10.1002/14651858.CD002112.

122. Fritz G, Rockney R, and the Work Group on Quality Issues and the American Academy of Child and Adolescent Psychiatry. AACP official action: practice parameter for the assessment and treatment of children and adolescents with enuresis. J Am Acad Child Adloesc Psychiatry. 2004; 43:1540-50.

123. Voiding dysfunction: nocturnal enuresis. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson textbook of pediatrics. 17th ed. Philadelphia: WB Saunders Company; 2004:1809.

124. Thiedke CC. Nocturnal enuresis. Am Fam Physician. 2003; 67:1499-1506. [PubMed 12722850]

125. Agersø H, Seiding Larsen L, Riis A et al. Pharmacokinetics and renal excretion of desmopressin after intravenous administration to healthy subjects and renally impaired patients. Br J Clin Pharmacol. 2004; 58:352-8.

a. AHFS Drug Information 2007. McEvoy GK, ed. Desmopressin Acetate. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 3219-22.

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