Desmopressin Acetate

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containing 0.1 mg/mL) initially received approval by FDA for treatment of primary nocturnal enuresis, this approval was withdrawn in 2007 because of the risk of serious hyponatremia that may result in seizures and death, particularly in children.^{101 115 117} (See Water Intoxication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.)

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 postoperatively^{100 108 111 113 114 116} 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 postoperatively^a 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 (Cl_cr <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 disease^{101 102 111 112 114 116 117 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}