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|Desmopressin Acetate

Desmopressin Acetate

Trade Names:
DDAVP
- Tablets 0.1 mg
- Tablets 0.2 mg
- Nasal Solution 0.1 mg (0.1 mg/mL equals 400 IU arginine vasopressin)
- Injection 4 mcg/mL
- Injection 15 mcg/mL

Trade Names:
Stimate
- Nasal Solution 1.5 mg/mL
- Injection 4 mcg/mL

Mechanism of Action

Pharmacology

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

Pharmacokinetics

Absorption

T _max is 0.9 hr.

T _max is 1.5 hr.

Elimination

t _½ is 1.5 to 2.5 hr (oral), 7.8 and 75.5 min for the fast and slow phases, respectively (IV and intranasal).

Onset

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

Peak

4 to 7 hr (oral), 1.5 to 2 hr to increase Factor VIII (IV and intranasal).

Duration

8 to 12 hr (oral).

Indications and Usage

Control of primary nocturnal enuresis; control of central cranial diabetes insipidus; maintenance of hemostasis in patients with hemophilia A and type I von Willebrand disease during surgery and postoperatively.

Unlabeled Uses

Treatment of chronic autonomic failure.

Contraindications

Standard considerations.

Dosage and Administration

Intranasal 0.1 to 0.4 qd. IV/SC 0.5 to 1 mL qd in 2 divided doses. PO 0.05 mg bid adjusted for adequate diurnal rhythm (range 0.1 to 1.2 mg/day divided).

Intranasal 0.05 to 0.3 mL qd, either as a single dose or 2 divided doses. PO Begin dosing with 0.05 mg. Careful fluid intake restrictions in children is required to prevent hyponatremia and water intoxification.

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. Intranasal 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.

Intranasal 20 mcg (0.2 mL) at bedtime.

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 intranasal delivery. In this situation, parenteral therapy should be considered.
• If used preoperatively, administer injection 30 min prior to procedure; administer intranasally 2 hr before.
• The nasal spray pump only delivers doses of 10 mcg ( DDAVP ) or 150 mcg ( Stimate ). If doses other than these are required, consider nasal tube delivery or 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.

Storage/Stability

Refrigerate nasal solution. Nasal solution will maintain stability for up to 3 wk when stored at room temperature. Refrigerate injectable solution at 2° to 8°C (36° to 46°F).

Drug Interactions

May potentiate antidiuretic effects of desmopressin.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Slight elevation in BP, facial flushing (intranasal); chest pain, palpitations, tachycardia, edema ( Stimate ).

CNS

Headache (intranasal); somnolence, dizziness, insomnia, agitation ( Stimate ).

Dermatologic

Local erythema, swelling, pain (injection).

EENT

Rhinitis, nosebleed, sore throat (intranasal); itchy or light-sensitive eyes ( Stimate ).

GI

Nausea, mild abdominal cramps (intranasal); dyspepsia, vomiting ( Stimate ).

Genitourinary

Vulval pain (intranasal); balanitis ( Stimate ).

Hepatic

Elevated LFT (injection).

Respiratory

Cough, upper respiratory infection (intranasal).

Miscellaneous

Chills, warm feeling, pain ( Stimate ).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Infants and children require careful fluid intake restriction to prevent possible hyponatremia and water intoxication. Safety and efficacy of intranasal form have not been established in children younger than 11 mo. Safety and efficacy of parenteral form for control of diabetes insipidus have not been established for children younger than 12 yr.

Elderly

Elderly patients should ingest only enough fluid to satisfy thirst; water intoxication and hyponatremia are possible.

Hypersensitivity

Rare severe allergic reactions have been reported. Anaphylaxis has occurred with IV administration.

Special Risk Patients

Use drug with caution in patients with coronary artery insufficiency or hypertensive cardiovascular disease. Use with caution in patients with conditions associated with fluid and electrolyte imbalance (eg, cystic fibrosis). These patients are prone to hyponatremia. Use with caution in patients predisposed to thrombus formation. Rare thrombotic events have occurred in these patients.

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.

Overdosage

Symptoms

Headache, abdominal cramps, nausea, facial flushing.

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 25 or 50 doses. Discard any solution remaining after the 25 or 50 doses because the amount delivered thereafter may be substantially less than prescribed.