Download Desmopressin (68:28)

Desmopressin (Systemic)
AHFS Class: Pituitary (68:28)
VA Class: HS702
ATC Class: H01BA02
AHFS Class: 20:28.16
Brands: DDAVP® , Minirin® , Stimate® ; also available generically
Introduction
Synthetic polypeptide analog of arginine vasopressin (antidiuretic hormone [ADH]); 101 102 111 112 114 116 117
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
a
Uses
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approval by FDA for treatment of primary nocturnal enuresis, this approval was withdrawn in 2007 because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
designated an orphan drug by FDA for this use. a
111 114
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
patients with plasma factor VIII activity >5%.100 111 114 116
109 110
especially in
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
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
116
Restrict fluid intake.
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 agerelated decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. 101
112 116 117 (See Geriatric Use under Cautions.)
Cautions
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
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
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 (Cl cr
<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
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
Use with cautiona
a
response to desmopressin
Aminocaproic
Concomitant therapy has been used
acid
without adverse effects111 114 116
Antidepressants, Hyponatremic seizures reported rarely Use with caution101 112 115 116 117
tricyclics (e.g., in patients receiving desmopressin
imipramine)
and imipramine during postmarketing
surveillance 101 112 116 117
Possible increased risk of water
intoxication with hyponatremia.101
112 115 116 117
Carbamazepine Prior administration of carbamazepine Use with caution101 112 116 117
decreased duration of action of
desmopressina
Possible increased risk of water
intoxication with hyponatremia.101
112 115 116 117
Chlorpromazine Possible increased risk of water
intoxication with hyponatremia.101
Use with caution101 112 116 117
112 115 116 117
Chlorpropamide Possible potentiation of antidiuretic
response a
Clofibrate
Potentiation and prolongation of
antidiuretic effect of desmopressina
Demeclocycline Possible decreased antidiuretic
response to desmopressina
Epinephrine
Large doses of epinephrine may
decrease the antidiuretic response to
desmopressina
Fludrocortisone Possible potentiation of antidiuretic
response a
Heparin
Possible decreased antidiuretic
response to desmopressina
Lamotrigine
Possible increased risk of water
intoxication with hyponatremia.101
Use with cautiona
Use with cautiona
Use with cautiona
Use with caution101 112 116 117
112 115 116 117
Lithium
NSAIAs
Possible decreased antidiuretic
response to desmopressina
Possible increased risk of water
intoxication with hyponatremia.101
112 115 116 117
Use with cautiona
Use with caution101 112 116 117
Opiates
Possible increased risk of water
intoxication with hyponatremia.101
Use with caution101 112 116 117
112 115 116 117
Oxybutynin
SSRIs
Hyponatremic seizures reported rarely
in patients receiving desmopressin
and oxybutynin during postmarketing
surveillance 101 112 116 117
Possible increased risk of water
Use with caution101 112 115 116 117
intoxication with hyponatremia.101
112 115 116 117
Urea
Vasopressor
agents
Possible potentiation of antidiuretic
response a
Carefully monitor patient if
desmopressin doses as large as 0.3
mcg/kg are used with other
vasopressor agents 101 102 111 112
114 116 117
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
116 117 a
Special Populations
102 111
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 Cl Cr of 103 mL/minute), mild renal impairment
(average Cl Cr of 72 mL/minute), moderate renal impairment (average Cl Cr of 37 mL/minute), or severe
renal impairment (average Cl Cr 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
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.
Routes
Nasal
Desmopressin Acetate
Forms Strengths Brand Names
Solution* 0.1
DDAVP® Nasal Spray (with
mg/mL*
benzalkonium chloride; with spray
Manufacturer
Sanofi-Aventis
pump)
DDAVP® Rhinal Tube (with
Sanofi-Aventis
Desmopressin Acetate Nasal Spray
Desmopressin Acetate Rhinal Tube
Apotex,
Bausch &
Lomb
Ferring
Minirin® (with chlorobutanol)
Apotex, Ferring
chlorobutanol; with 2 calibrated nasal
tubes; refrigerate)
(with chlorobutanol)
(with chlorobutanol; with 2 calibrated
nasal tubes; refrigerate)
1.5 mg/mL Stimate® Nasal Spray (with
CSL Behring
0.1 mg*
Sanofi-Aventis
benzalkonium chloride; with spray
pump)
Oral
Tablets
0.2 mg*
Parenteral Injection 4
mcg/mL*
DDAVP® (with povidone)
Desmopressin Acetate Tablets
DDAVP® (with povidone)
Desmopressin Acetate Tablets
DDAVP® (with chlorobutanol)
Apotex, Barr,
Teva
Sanofi-Aventis
Apotex, Barr,
Teva
Sanofi-Aventis
Desmopressin Acetate Injection (with Ferring,
chlorobutanol)
Hospira, Teva
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information
was updated 05/2010. For the most current and up-to-date pricing information, please visit
www.drugstore.com. 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/$227.2 or 15/$672.8
DDAVP 0.1MG Tablets (SANOFI-AVENTIS U.S.): 30/$130.09 or 90/$350.04
DDAVP 0.2MG Tablets (SANOFI-AVENTIS U.S.): 30/$174.38 or 90/$501.35
DDAVP Rhinal Tube 0.01% Solution (SANOFI-AVENTIS U.S.): 2/$132.48 or 7/$394.22
Desmopressin Ace Rhinal Tube 0.01% Solution (FERRING): 2/$86.36 or 7/$230.98
Desmopressin Ace Spray Refrig 0.01% Solution (BAUSCH & LOMB): 5/$107.99 or 15/$309.96
Desmopressin Acetate 0.1MG Tablets (BARR LABS): 30/$86.99 or 90/$231.96
Desmopressin Acetate 0.2MG Tablets (TEVA PHARMACEUTICALS USA): 90/$325.99 or 180/$639.99
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
AHFS Drug Information. © Copyright, 1959-2010, Selected Revisions February 2008. American
Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
Only references cited for selected revisions after 1984 are available electronically.
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[Web]
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[PubMed]
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Rhinal Tube, DDAVP, DDVP, Minirin, and Stimate Nasal Spray). From FDA website. Accessed 2007 Dec 4. [Web]
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3219-22.
American Society of Health-System Pharmacists, Inc. © 2010. All rights reserved. Any duplication in any form must be authorized by ASHP.