What are the indications, dosages, and precautions for using desmopressin (DDAVP)?

Desmopressin (DDAVP): Indications, Dosing, and Critical Safety Precautions

Primary Indications

Desmopressin is indicated for central diabetes insipidus, hemophilia A, von Willebrand disease (Type I), nocturnal enuresis, and as an adjunct for bleeding in patients with platelet dysfunction from antiplatelet drugs or uremia. 1

Hemostatic Uses

• For bleeding disorders or platelet-inhibiting drug effects, administer 0.3 μg/kg diluted in 50 mL saline infused over 30 minutes intravenously. 2, 3
• The hemostatic effect begins within 1 hour and lasts 6-8 hours through increased factor VIII and von Willebrand factor levels, promoting platelet adhesion. 2, 3
• Desmopressin does NOT effectively reverse ticagrelor or prasugrel effects and should not be used for this purpose. 2
• For uremic bleeding specifically, the same dose (0.3 μg/kg IV) can be given via intravenous, subcutaneous, or intranasal routes, though IV/subcutaneous are preferred for acute bleeding. 3
• Platelet function testing (PFA-100 or whole blood multiple electrode aggregometer) may identify patients most likely to benefit from therapy. 2

Central Diabetes Insipidus

• Intranasal dosing: 10-40 μg per dose 4
• Parenteral dosing: 2-4 μg intravenously or subcutaneously 4
• Desmopressin is the drug of choice for central diabetes insipidus due to its selective antidiuretic activity without adverse vasopressor effects. 4

Nocturnal Enuresis

• Oral tablets: 0.2-0.4 mg taken at least 1 hour before sleep 2, 5
• Oral melt tablets: 120-240 μg taken 30-60 minutes before bedtime 2, 5
• Dosing is not influenced by body weight or age; physicians may start with higher doses and taper down or use the opposite strategy. 2
• Oral formulations are strongly preferred over nasal spray due to higher risk of water intoxication, hyponatremia, and convulsions with nasal spray, leading to removal of the enuresis indication for nasal spray in many countries. 5

Critical Safety Precautions

Hyponatremia Risk (Most Important Adverse Effect)

Fluid restriction is absolutely essential to prevent water intoxication and hyponatremia, which can be fatal. 2, 5, 1

• Evening fluid intake must be limited to 200 mL (6 ounces) or less, with no drinking until morning. 2, 5
• Polydipsia is an absolute contraindication to desmopressin treatment. 2, 5
• Elderly patients are at particularly high risk for severe hyponatremia, with documented fatalities in this population. 3, 6
• Monitor serum sodium levels, especially when initiating therapy or using with other medications affecting water balance. 3, 7

Cardiovascular Considerations

• Desmopressin can cause thromboembolic events; use with extreme caution in at-risk patients. 2
• Systemic vasodilator effects may cause arterial hypotension, reactive tachycardia, and facial flushing. 2
• In patients with von Willebrand disease Type IIB, desmopressin increases thrombosis risk and should be avoided. 1

Monitoring and Drug Holidays

• Regular short drug holidays are essential when using desmopressin daily to reassess whether medication is still needed. 2, 5
• Close monitoring of renal function is required, as desmopressin clearance is affected by kidney function. 8

Special Populations and Contraindications

• Not recommended for isolated liver disease unless concomitant end-stage renal disease is present 3
• Avoid in dialysis patients and those with severe renal impairment (CrCl <30 mL/min) for routine use 8
• Hypersensitivity reactions can occur and represent a contraindication to further use 1

Formulation Considerations

• When switching between desmopressin formulations, doses are NOT bioequivalent and require careful adjustment. 1
• Injectable and oral formulations have different pharmacokinetics and cannot be directly substituted. 1
• The hemostatic dose (0.3 μg/kg) is approximately 15-fold higher than antidiuretic doses but remains well-tolerated. 4, 9

Common Pitfalls to Avoid

• Do not use desmopressin for routine bleeding in trauma patients; reserve for refractory microvascular bleeding in patients on platelet-inhibiting drugs. 2
• Do not assume efficacy against all antiplatelet agents—it does not reverse P2Y12 inhibitors like ticagrelor or prasugrel. 2
• Do not neglect fluid restriction counseling, as this is the primary preventable cause of serious adverse events. 2, 5, 7
• Do not use nasal spray formulation for enuresis given the superior safety profile of oral formulations. 5