What is the recommended dosage and administration of Desmopressin for various medical conditions?

Desmopressin Dosing and Administration

Desmopressin dosing varies significantly by indication: for hemostatic purposes use 0.3-0.4 μg/kg IV, for nocturnal enuresis use oral tablets 0.2-0.4 mg or oral melt 120-240 μg, and for central diabetes insipidus use intranasal 0.1-0.4 mL daily or oral melt 120-240 μg with individualized titration based on urine output and sleep duration. 1, 2, 3

Hemostatic Indications (Bleeding/Platelet Dysfunction)

Dosing for Antiplatelet Reversal and Bleeding Disorders

• Standard hemostatic dose: 0.3 μg/kg (or 0.4 μg/kg) diluted in 50 mL saline infused over 30 minutes 1, 4
• For patients on antiplatelet agents requiring neurosurgical intervention: desmopressin 0.4 μg/kg IV × 1 dose 4
• This 15-fold higher dose compared to antidiuretic use is well-tolerated for hemostatic purposes 5
• Consider platelet function testing (PFA-100 or whole blood multiple electrode aggregometer) to identify patients who would benefit from therapy 1

Special Bleeding Scenarios

• Desmopressin can be considered in special cases of coagulopathy or thrombopathy when managing bleeding from direct thrombin inhibitors or factor Xa inhibitors 4
• Not recommended for routine use in bleeding trauma patients, but may be considered in refractory microvascular bleeding if patient has been treated with platelet-inhibiting drugs 1
• Useful for nosebleeds in patients taking platelet-inhibiting drugs or with von Willebrand disease 6

Nocturnal Enuresis

Oral Formulations (Preferred)

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 6, 4

• Oral tablets: 0.2-0.4 mg taken at least 1 hour before sleep 1, 6
• Oral melt tablets: 120-240 μg taken 30-60 minutes before bedtime 1, 6
• Dose is not influenced by body weight or age 1
• Physicians may start with the higher dose and taper down, or use the opposite strategy 1

Treatment Strategy

• Anticholinergics are only indicated when standard treatment (alarm therapy) has failed, and often combination treatment with desmopressin at standard dose is needed 4
• Approximately 40% of therapy-resistant children respond to anticholinergics combined with desmopressin 4
• Anti-enuretic effect should appear within maximum of 2 months, sometimes much earlier 4

Central Diabetes Insipidus

Intranasal Administration

The usual adult dosage range is 0.1-0.4 mL daily (10-40 mcg), either as single dose or divided into 2-3 doses, with most adults requiring 0.2 mL daily in two divided doses 3, 5

• For children aged 3 months to 12 years: 0.05-0.3 mL daily, either as single dose or divided into two doses 3
• About 1/4 to 1/3 of patients can be controlled by single daily dose 3
• The nasal spray pump delivers only 0.1 mL (10 mcg) increments; if other doses required, use rhinal tube delivery system 3
• Discard nasal spray after 50 sprays as amount delivered thereafter may be substantially less than 10 mcg 3

Oral Melt Formulation

• Oral melt tablets: 120-240 μg per dose 2
• Dose should be adjusted based on adequate duration of sleep and adequate but not excessive water turnover 2
• Morning and evening doses should be separately adjusted to establish adequate diurnal rhythm of water turnover 2, 3

Parenteral Administration

• Subcutaneous or intravenous: 2-4 μg for antidiuretic effect 5, 7
• Dose-response relationship demonstrated between 0.5-4 μg subcutaneously 8
• Generally 1-2 μg injected subcutaneously is effective 8

Monitoring and Titration

• Response should be estimated by two parameters: adequate duration of sleep and adequate (not excessive) water turnover 3, 2
• Urine volume should be monitored intermittently 2
• Laboratory tests include urine volume and osmolality; in some cases plasma osmolality measurements may be required 3

Critical Safety Precautions (All Indications)

Fluid Restriction (Essential)

Fluid restriction is absolutely essential to prevent water intoxication and hyponatremia 1, 2, 6

• Evening fluid intake should be limited to 200 mL (6 ounces) or less, with no drinking until morning 1, 2, 6, 3
• Fluid intake should be adjusted downward based on discussion with physician 3
• This is particularly critical in pediatric and geriatric patients 3

Contraindications and High-Risk Populations

• Polydipsia is an absolute contraindication to desmopressin treatment 1, 6
• Use in infants and children requires careful fluid intake restriction to prevent hyponatremia and water intoxication 3
• Dose should start at 0.05 mL or less in very young children, with attention to danger of extreme decrease in plasma osmolality with resulting convulsions 3
• Contraindicated in patients with moderate to severe renal impairment (creatinine clearance <50 mL/min) 3

Drug Interactions

• Concomitant administration of drugs that increase risk of water intoxication with hyponatremia (tricyclic antidepressants, SSRIs, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine, carbamazepine) should be performed with caution 3
• Use of large doses with other pressor agents should only be done with careful patient monitoring 3

Monitoring and Follow-up

• Regular short drug holidays are important when using desmopressin daily to assess whether medication is still needed 1, 6
• There are reports of occasional change in response with time (usually >6 months), with some patients showing decreased responsiveness or shortened duration of effect 3
• In pediatric studies, 40% of patients on nasal desmopressin experienced hypo/hypernatremia compared to 18.1% on oral formulation 9

Geriatric Considerations

• Elderly patients are more likely to have decreased renal function; care should be taken in dose selection, usually starting at low end of dosing range 3
• May be useful to monitor renal function in elderly patients 3
• Careful fluid intake restriction required to prevent hyponatremia and water intoxication 3