Desmopressin Acetate

Pronunciation
( 1-Deamino-8-D-Arginine Vasopressins )

Pronunciation: DES-moe-PRES-in AS-e-tate
Class: Posterior pituitary hormone

Trade Names

DDAVP
- Tablets 0.1 mg
- Tablets 0.2 mg
- Injection 4 mcg/mL

DDAVP Rhinal Tube
- Nasal solution 0.1 mg (0.1 mg/mL equals arginine vasopressin 400 units)

Stimate
- Nasal spray 1.5 mg/mL

Apo-Desmopressin (Canada)
DDAVP Rhinyle Nasal Solution (Canada)
Minirin (Canada)
Novo-Desmopressin (Canada)
Octostim (Canada)

Pharmacology

Has antidiuretic effect that decreases urinary volume and increases urine osmolality.

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Pharmacokinetics

Absorption

Oral

T max is 0.9 h.

Stimate nasal spray

T max is 1.5 h.

Elimination

Oral

Half-life is 1.5 to 2.5 h.

IV and DDAVP nasal solution

Half-life is 7.8 and 75.5 min for the fast and slow phases, respectively.

Stimate nasal spray

Half-life is 3.3 to 3.5 h.

Onset

Approximately 1 h (oral), within 30 min to increase factor VIII (IV and intranasal).

Peak

4 to 7 h (oral), 1.5 to 2 h to increase factor VIII (IV and intranasal).

Duration

8 to 12 h (oral).

Indications and Usage

Injection, tablets, DDAVP nasal solution

Antidiuretic replacement therapy in the management of central diabetes insipidus; management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region.

Injection, Stimate nasal spray

Maintenance of hemostasis in patients with hemophilia A or mild to moderate von Willebrand disease (type I) with factor VIII coagulant activity more than 5%.

Tablets

Control of primary nocturnal enuresis.

Unlabeled Uses

Treatment of chronic autonomic failure.

Contraindications

Moderate to severe renal function impairment (CrCl below 50 mL/min); hyponatremia or a history of hyponatremia; hypersensitivity to any component of the product.

Dosage and Administration

Central Diabetes Insipidus
Adults and Children 4 yr of age and older

PO Start with 0.05 mg 2 times daily and adjust for an adequate diurnal rhythm of water turnover. Increase or decrease the dose in the range of 0.1 to 1.2 mg divided into 2 or 3 daily doses as needed to obtain adequate antidiuresis.

Adults and Children 12 yr of age and older

IV / Subcutaneous Adult range is 2 mcg (0.5 mL) to 4 mcg (1 mL) daily, usually in 2 divided doses.

Adults and Children 12 yr of age and older

DDAVP nasal solution 0.1 to 0.4 mL daily, either as a single dose or divided into 2 or 3 doses.

Children 3 months to 12 yr of age

DDAVP nasal solution 0.05 to 0.3 mL daily, either as a single dose or divided into 2 doses.

Hemophilia A, Type I von Willebrand Disease
Adults and Children 3 mo of age and older

IV Administer 0.3 mcg/kg diluted in sterile physiologic saline infused slowly over 15 to 30 min. In patients weighing more than 10 kg, use 50 mL diluent; in children weighing up to 10 kg, use 10 mL.

Adults and Children 11 mo of age and older

Stimate nasal spray Administer by nasal insufflation, 1 spray per nostril, to provide a total dose of 300 mcg. In patients weighing less than 50 kg, 150 mcg administered as a single spray provided the expected effect on factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and skin bleeding time.

Primary Nocturnal Diuresis
Adults and Children 6 yr of age and older

PO Start with 0.2 mg at bedtime. The dose may be titrated up to 0.6 mg to achieve the desired response. Fluid restriction should be observed and fluid intake should be limited to a minimum from 1 h before desmopressin administration until the next morning or at least 8 h after administration.

General Advice

  • For intranasal administration, ensure that nasal passages are intact, clean, and free of obstruction before administration of drug. Calibrated plastic tube is provided in nasal tube delivery system. Draw solution up into this tube and insert into nostril. Place opposite end of tube in mouth and blow into tube to deliver medication.
  • Cranial surgery, changes in nasal mucosa, and nasal packing can compromise Stimate nasal spray delivery. In this situation, parenteral therapy should be considered.
  • If used preoperatively, administer injection 30 min prior to procedure; administer intranasally 2 h before.
  • The nasal spray pump only delivers doses of 10 mcg ( DDAVP ) or 150 mcg ( Stimate ). If doses other than these are required, consider injection.
  • The Stimate pump must be primed prior to the first use. To prime pump, press down 4 times. Discard the bottle after 25 doses because the amount delivered thereafter per spray may be substantially less than 150 mcg.
  • The tablet dosage must be determined for each individual patient and adjusted according to the diurnal pattern of response (ie, adequate duration of sleep and adequate, but not excessive, water turnover).
  • Children receiving tablet therapy require careful fluid intake restriction to prevent possible hyponatremia and water intoxication.
  • Treatment for primary nocturnal enuresis should be interrupted during acute intercurrent illness characterized by fluid and/or electrolyte imbalance (eg, systemic infection, fever, diarrhea, or vomiting) or under conditions of extremely hot weather, vigorous exercise, or other conditions associated with increased water intake.
  • When desmopressin injection is administered to patients who do not need antidiuretic hormone for its antidiuretic effects, in particular pediatric and elderly patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia.
  • For patients controlled on DDAVP nasal solution who must be switched to the injectable form, the comparable antidiuretic dose of the injection is about one-tenth the intranasal dose.
  • DDAVP nasal solution should only be used when administration of the oral form is not feasible.

Storage/Stability

Refrigerate nasal solution (36° to 46°F). Nasal solution will maintain stability for up to 3 wk when stored at room temperature. Store Stimate nasal spray at room temperature, below 77°F. Refrigerate injectable solution (36° to 46°F). Store oral tablets at 68° to 77°F. Avoid exposure to excessive heat or light.

Drug Interactions

Drugs that may increase the risk of water intoxication with hyponatremia (eg, carbamazepine, chlorpromazine, lamotrigine, NSAIDs, opiate analgesics, SSRIs)

Use with caution because of increased risk of water intoxication with hyponatremia.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Blood pressure changes causing slight elevation or transient falls and a compensatory increase in heart rate (injection); facial flushing (injection, intranasal); palpitations, tachycardia ( Stimate ); thrombotic events including acute cerebrovascular thrombosis and acute MI (injection) (postmarketing).

CNS

Headache (5%); dizziness (3%); asthenia (2%); abnormal thinking (injection, intranasal, oral); agitation, insomnia, somnolence ( Stimate ).

EENT

Rhinitis (8%); epistaxis (3%); conjunctivitis, eye edema, lacrimation disorder, nostril pain (2%); nasal congestion, nosebleed, rhinitis, sore throat (intranasal); itchy or light-sensitive eyes ( Stimate ).

GI

Abdominal pain, GI disorder, nausea (2%); diarrhea; mild abdominal cramps (injection, intranasal); dyspepsia, vomiting ( Stimate ).

Genitourinary

Vulval pain (injection); balanitis ( Stimate ).

Hypersensitivity

Severe allergic reactions including anaphylaxis (injection).

Lab Tests

Transient increases in AST (oral).

Local

Burning pain, local erythema, swelling (injection).

Metabolic-Nutritional

Hyponatremia, water intoxication, weight gain due to edema.

Respiratory

Cough, upper respiratory tract infections (intranasal).

Miscellaneous

Chills (2%); chest pain, edema, pain, warm feeling ( Stimate ).

Precautions

Monitor

Monitor BP and pulse during infusion. Monitor I&O closely and accurately when drug is administered to very young and elderly patients. Monitor patient at regular intervals during the course of tablet therapy to ensure adequate antidiuretic response. Laboratory tests for monitoring patients with central diabetes insipidus or postsurgical or head trauma-related polyuria and polydipsia include urine volume and osmolarity. Perform laboratory tests assessing factor VIII coagulant activity before giving desmopressin for hemostasis. If factor VIII coagulant activity is less than 5% of normal, do not rely on desmopressin.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Use in infants and children requires careful fluid intake restriction to prevent possible hyponatremia and water intoxication.

Central diabetes insipidus

The desmopressin tablets have been used safely in children 4 yr of age and older. In younger children, the dose must be individually adjusted in order to prevent an excessive decrease in plasma osmolality, leading to hyponatremia and possible convulsions. Safety and efficacy not established for desmopressin injection in patients younger than 12 yr of age.

DDAVP nasal solution

Dosing recommendations are available for children 3 mo of age and older.

Primary nocturnal enuresis

The tablets have been used safely in children 6 yr of age and older.

Hemophilia A or von Willebrand disease

Desmopressin 4 mcg/mL injection should not be used in infants younger than 3 mo of age. Safety and efficacy not established for use of Stimate nasal spray in children younger than 11 mo of age.

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Hypersensitivity

Rare, severe allergic reactions have been reported; anaphylaxis has been reported with IV and intranasal, but not oral, administration.

Special Risk Patients

Use with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water; use with caution in patients with conditions associated with fluid and electrolyte imbalance (eg, cystic fibrosis, heart failure, renal disorder) because these patients are prone to hyponatremia. Because rare thrombotic events have been reported, use with caution in patients predisposed to thrombus formation. Use with caution in patients with coronary artery insufficiency and/or hypertensive CV disease.

Coagulation

Check coagulation status prior to treating patients with hemophilia A and type I von Willebrand disease. Coagulation testing may include factor VIII coagulant activity, factor VIII antigen, ristocetin cofactor, activated PTT, and skin bleeding time.

Decrease in plasma osmolality

An extreme decrease in plasma osmolality occurs rarely and may result in seizures and coma.

Elevated blood pressure

Parenteral and high-dose intranasal administration may cause slight elevation of BP, which reverses with dose reduction

Fluid restriction

Since water intoxication and/or hyponatremia may occur, fluid restriction is recommended. In children and elderly patients, in particular, adjust fluid intake downward to decrease the potential for water intoxication and hyponatremia.

Nasal mucosa

Changes in the nasal mucosa such as scarring, edema, or other disease may cause erratic, unreliable absorption; in which case, discontinue the intranasal route until the problem resolves and consider the injection.

Overdosage

Symptoms

Confusion, drowsiness, headache, problems with passing urine, rapid weight gain due to fluid retention.

Patient Information

  • Instruct patient on proper intranasal administration techniques and have patient or family demonstrate ability to perform.
  • Remind patient receiving drug intranasally to frequently inspect nasal passages.
  • Explain that it is important to reduce fluid intake when therapy is initiated to decrease chance of water intoxication.
  • Instruct patient to report the following symptoms to health care provider: headache, shortness of breath, heartburn, nausea, abdominal cramps, vulvar pain.
  • Inform patients that DDAVP nasal spray accurately delivers 50 doses. Discard any solution remaining after the 50 doses because the amount delivered thereafter may be substantially less than prescribed.

Copyright © 2009 Wolters Kluwer Health.

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