desmopressin acetate (1-deamino-8-D-arginine vasopressin)
DDAVP, Stimate

Available forms
Available by prescription only
Injection: 4 mcg/ml in 1-ml single-dose ampules and 10-ml multidose vials
Nasal solution: 0.1 mg/ml, 1.5 mg/ml
Tablets: 0.1 mg, 0.2 mg

Indications and dosages
 Central cranial diabetes insipidus, temporary polyuria, polydipsia related to pituitary trauma. Adults: 0.1 to 0.4 ml (10 to 40 mcg) intranasally in one to three divided doses daily. Adjust morning and evening doses separately for adequate diurnal rhythm of water turnover. Use the lowest effective dosage. Or, 0.05 mg P.O. b.i.d. initially. Adjust individual dosage in increments of 0.1 mg to 1.2 mg daily, divided into two or three doses. Optimal dosage range is 0.1 to 0.8 mg daily in divided doses. Or, give 0.5 ml (2 mcg) to 1 ml (4 mcg) I.V. or S.C. daily, usually in two divided doses.
Children ages 3 months to 12 years: 0.05 to 0.3 ml (5 to 30 mcg) intranasally daily in one or two doses.
 Hemophilia A, von Willebrand’s disease. Adults and children who weigh more than 10 kg: 0.3 mcg/kg diluted in 50 ml normal saline solution and infused I.V. slowly over 15 to 30 minutes. If child weighs 10 kg or less, dilute in 10 ml. May repeat dosage, if needed, as indicated by laboratory response and patient’s condition. Or, one spray per nostril to give 300 mcg total dose.
 Primary nocturnal enuresis. Children age 6 and older: 20 mcg (two to four metered sprays), intranasally h.s. Dosage adjusted according to response. Maximum recommended dose is 40 mcg daily.

Pharmacodynamics
Antidiuretic action: Drug is used to control or prevent signs and complications of neurogenic diabetes insipidus. The site of action is primarily at the renal tubular level. Desmopressin increases water permeability at the renal tubule and collecting duct, resulting in increased urine osmolality and decreased urinary flow rate.
Hemostatic action: Desmopressin increases factor VIII activity by releasing endogenous factor VIII from plasma storage sites.

Pharmacokinetics
Absorption: Destroyed in the GI tract. After intranasal administration, 10% to 20% of dose is absorbed through nasal mucosa.
Distribution: Not fully understood.
Metabolism: Unknown.
Excretion: Plasma levels decline in two phases: Half-life of fast phase is about 8 minutes; slow phase, 75 minutes. Duration of action after intranasal administration is 8 to 20 hours; after I.V. administration, 12 to 24 hours for mild hemophilia and about 3 hours for von Willebrand’s disease.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in patients with type IIB von Willebrand’s disease. Use cautiously in patients with coronary artery insufficiency or hypertensive CV disease and in those with conditions related to fluid and electrolyte imbalances, such as cystic fibrosis, because these patients are susceptible to hyponatremia.

Interactions
Drug-drug. Carbamazepine, chlorpropamide, clofibrate: May potentiate antidiuretic action of desmopressin. Avoid use together.
Demeclocycline, epinephrine, heparin, lithium, norepinephrine: May decrease antidiuretic effect. Use together cautiously.
Drug-lifestyle. Alcohol use: May increase risk of adverse effects. Discourage alcohol use.

Adverse reactions
CNS: headache.
CV: flushing, slight rise in blood pressure at high dosage.
EENT: rhinitis, epistaxis, nasal congestion, sore throat, cough.
GI: nausea, abdominal cramps.
GU: vulvar pain.
Skin: local erythema, swelling, burning (after injection).

Effects on lab test results
None reported.

Overdose and treatment
Signs and symptoms of overdose include drowsiness, listlessness, headache, confusion, anuria, weight gain (water intoxication), abdominal pain, dyspnea, and fluid retention.
 There is no antidote for desmopressin. Treatment requires water restriction and temporary withdrawal of desmopressin until polyuria occurs. Severe water intoxication may require osmotic diuresis with mannitol, hypertonic dextrose, or urea-alone or with furosemide.

Special considerations
• Desmopressin may be administered intranasally through a flexible catheter called a rhinyle. A measured quantity is drawn up into the catheter, one end is inserted into patient’s nose, and patient blows on the other end to deposit drug into nasal cavity. Drug is also available in nasal spray, which may be easier for some patients.
• Desmopressin isn’t indicated for patients with hemophilia B, patients with hemophilia A who have factor VIII levels up to 5%, patients with factor VIII antibodies, or patients with severe von Willebrand’s disease.
• Drug therapy may enable some patients to avoid the hazards of contaminated blood products.
• If using preoperatively, administer 30 minutes before procedure.
• Monitor patient for early signs of water intoxication-drowsiness, listlessness, headache, confusion, anuria, and weight gain-to prevent seizures, coma, and death.
• Adjust fluid intake, especially in young or elderly patients, to reduce risk of water intoxication and sodium depletion.
• Weigh patient daily and observe for edema.
• Monitor urine volume and osmolarity of urine and plasma in patients with diabetes insipidus.
• Monitor factor VIII coagulant and factor VIII antigen, ristocetin cofactor, and aPTT in patients with hemophilia A.
• Monitor factor VIII coagulant and factor VIII antigen, ristocetin cofactor in patients with von Willebrand’s disease.
Pediatric patients
• Drug isn’t recommended for infants younger than age 3 months because of their increased tendency to develop fluid imbalance.
• Use cautiously in infants because of risk of hyponatremia and water intoxication.
• Safety and efficacy of parenteral desmopressin haven’t been established for management of diabetes insipidus in children younger than age 12.
Geriatric patients
• These patients have an increased risk of hyponatremia and water intoxication; therefore, restriction of their fluid intake is recommended.
• Because elderly patients are more sensitive to effects of drug, they may need a lower dosage.

Patient education
• Teach patient correct administration technique. Evaluate patient’s proficiency at drug administration and accurate measurement on return visits; some patients have trouble measuring drug and inhaling it into nostrils.
• Emphasize that patient shouldn’t increase or decrease dosage unless prescribed.
• Assist patient in planning a schedule for fluid intake if oral fluids must be reduced to decrease the possibility of water intoxication and hyponatremia. A diuretic may be administered if excessive fluid retention occurs.
• Tell patient to store drug away from heat and direct light, not in bathroom, where heat and moisture can cause drug to deteriorate.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use