Desmopressin (DDAVP): Clinical Applications and Mechanism of Action
Desmopressin (DDAVP) is a synthetic analog of vasopressin primarily used for central diabetes insipidus, nocturnal enuresis, mild hemophilia A, and von Willebrand disease type I, with mechanism of action involving increased water reabsorption in kidneys and elevation of factor VIII and von Willebrand factor levels. 1
Mechanism of Action
Desmopressin works through two primary mechanisms:
Antidiuretic effects: Stimulates vasopressin-2 (V2) receptors in the kidneys, increasing water reabsorption, reducing urine production, increasing urine osmolality, and decreasing plasma osmolality 1
Hemostatic effects: Increases plasma levels of factor VIII activity and von Willebrand factor in patients with hemophilia and von Willebrand's disease Type I 1
Key pharmacological properties:
- Terminal half-life: 2.8 hours in patients with normal renal function 1
- Not metabolized by human CYP450 system 1
- 52% excreted unchanged in urine within 24 hours after IV administration 1
Clinical Indications
1. Central Diabetes Insipidus
- Replacement therapy for antidiuretic hormone deficiency 1
- Oral dosage: 0.2-0.4 mg daily (tablets) or 120-240 mcg (oral melt formulation) 2
2. Nocturnal Enuresis
- Recommended for children with monosymptomatic enuresis, particularly those with nocturnal polyuria 2
- Oral melt dose: 120-240 mcg at bedtime, 30-60 minutes before sleep 2
3. Bleeding Disorders
- Indicated for mild type I von Willebrand disease and mild hemophilia A with factor VIII levels at least 5% of normal 3
- Increases factor VIII levels 300-400% from baseline after infusion of 0.4 mcg/kg 1
- Effect begins within 30 minutes, peaks at 90 minutes to 2 hours 1
- Duration of hemostatic effect: 8-12 hours (based on factor VIII half-life) 1
4. Platelet Dysfunction
- May be used in patients with inherited or acquired platelet dysfunction 3
- Used for patients taking aspirin or clopidogrel with bleeding or requiring surgery 2
Administration Routes and Dosing
- Intravenous: 0.3-0.4 mcg/kg infused over 30 minutes 2
- Subcutaneous: Similar dosing to IV route
- Intranasal: Available as 0.01% solution (10 mcg per spray) 4
- Oral: Available as tablets (0.2-0.4 mg) or oral melt formulation (120-240 mcg) 2
Monitoring and Precautions
Important Monitoring Parameters
- Serum sodium levels should be monitored within 1 week and approximately 1 month after starting therapy, then periodically 2
- More frequent monitoring in patients ≥65 years and those at increased risk of hyponatremia 2
Key Precautions
- Fluid restriction: Limit evening fluid intake to 200 ml (6 ounces) or less with no drinking until morning to minimize hyponatremia risk 2
- Renal impairment: Contraindicated in moderate to severe renal impairment (creatinine clearance <50 mL/min) 1
- Elderly patients: Require careful fluid intake restrictions to prevent hyponatremia 1
- Intercurrent illness: Consider temporarily suspending desmopressin to prevent water intoxication 2
Limitations in Clinical Use
- Not effective for all bleeding disorders: Not indicated for patients with factor VIII levels ≤5% or for patients with factor VIII antibodies 2
- Limited efficacy with newer antiplatelet agents: Ineffective in correcting platelet dysfunction induced by ticagrelor 3
- Cardiac surgery: Meta-analyses indicate no benefit for prophylactic use in cardiac surgery without platelet hemostatic defects 3
Adverse Effects
- Systemic vasodilator effects: Arterial hypotension, reactive tachycardia, facial flushing 3
- Fluid-related complications: Oliguria, hypervolemia, hyponatremia 3
- Rare thromboembolic events have been reported 3
- Overdosage signs: Headaches, abdominal cramps, nausea, confusion, drowsiness, urination problems, and rapid weight gain due to fluid retention 1
Desmopressin represents an important non-transfusional hemostatic agent for specific bleeding disorders, while also serving as the cornerstone therapy for central diabetes insipidus and nocturnal enuresis when properly administered with appropriate monitoring.