Desmopressin - Drug Monograph

Introduction

Desmopressin (1-deamino-8-D-arginine vasopressin) is a synthetic analog of the natural pituitary hormone arginine vasopressin. It is a potent antidiuretic agent with significantly reduced vasopressor activity compared to the native hormone. Desmopressin has become a cornerstone therapy for various conditions involving water balance disorders and hemostasis.

Mechanism of Action

Desmopressin acts primarily on V2 receptors in the renal collecting ducts, increasing water permeability and promoting water reabsorption. This results in reduced urine output and increased urine osmolality. Unlike vasopressin, desmopressin has minimal effect on V1 receptors, resulting in significantly reduced vasoconstrictive properties. Additionally, desmopressin stimulates the release of von Willebrand factor and factor VIII from vascular endothelium, which contributes to its hemostatic effects.

Indications

• Central Diabetes Insipidus: Management of polyuria and polydipsia
• Nocturnal Enuresis: Treatment of primary nocturnal enuresis in children ≥6 years
• Hemophilia A and von Willebrand Disease: Prophylaxis and treatment of bleeding episodes
• Post-operative Polyuria: Management following pituitary surgery
• Primary Nocturnal Polyuria: Off-label use in adults

Dosage and Administration

• Diabetes insipidus: 10-40 mcg daily in 1-3 divided doses
• Nocturnal enuresis: 20-40 mcg at bedtime

• Diabetes insipidus: 0.1-0.8 mg daily in 2-3 divided doses
• Nocturnal enuresis: 0.2-0.6 mg at bedtime

• Diabetes insipidus: 2-4 mcg daily in 2 divided doses
• Hemostasis: 0.3 mcg/kg diluted in 50 mL saline infused over 15-30 minutes

• Renal impairment: Use with caution; contraindicated in severe impairment
• Hepatic impairment: No dosage adjustment typically needed
• Elderly: Increased risk of hyponatremia; use lower doses
• Pediatrics: Safety established for children ≥6 years

Pharmacokinetics

• Absorption: Oral bioavailability ~5%; intranasal bioavailability 3-5%
• Distribution: Volume of distribution ~0.3-0.5 L/kg
• Metabolism: Primarily renal; minimal hepatic metabolism
• Elimination: Half-life 1.5-2.5 hours (IV); 3-4 hours (intranasal); 1.5-2.5 hours (oral)
• Excretion: Primarily renal (unchanged drug)

Contraindications

• Hypersensitivity to desmopressin or components
• Moderate to severe renal impairment (CrCl <50 mL/min)
• Hyponatremia or history of hyponatremia
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Heart failure requiring diuretic therapy
• Polydipsic psychiatric disorders

Warnings and Precautions

• Hyponatremia: Risk of water intoxication and seizures; monitor serum sodium
• Fluid restriction: Necessary during therapy; typically 500-750 mL/24 hours
• Cardiovascular disease: Use caution in patients with coronary artery disease or hypertension
• Elderly patients: Increased susceptibility to hyponatremia and fluid overload
• Nasal pathology: May affect absorption of intranasal formulation
• Pregnancy: Category B; use only if clearly needed
• Breastfeeding: Excreted in milk; use caution

Drug Interactions

• Diuretics: Increased risk of hyponatremia (avoid combination)
• Tricyclic antidepressants: May potentiate antidiuretic effect
• SSRIs: Increased risk of hyponatremia
• Carbamazepine, chlorpropamide: May enhance antidiuretic effect
• NSAIDs: May increase risk of water retention
• Vasopressor agents: Additive pressor effects (theoretical risk)

Adverse Effects

• Headache (10-15%)
• Nausea (5-10%)
• Nasal congestion (intranasal formulation)
• Abdominal pain
• Flushing

• Hyponatremia (may lead to seizures, cerebral edema)
• Water intoxication
• Anaphylaxis (rare)
• Thrombosis (with high-dose hemostatic use)
• Hypertensive crisis (rare)

Monitoring Parameters

• Serum sodium: Baseline and regularly during therapy (every 1-2 weeks initially)
• Urine output and osmolality: For diabetes insipidus management
• Body weight: Daily monitoring recommended
• Blood pressure: Periodic assessment
• Renal function: Baseline and periodic assessment
• Coagulation parameters: When used for hemostasis
• Signs of fluid overload: Edema, shortness of breath

Patient Education

• Adhere strictly to prescribed fluid restrictions
• Recognize symptoms of hyponatremia: headache, nausea, vomiting, confusion, seizures
• Monitor daily weight and report sudden increases
• For intranasal administration: proper technique and device care
• Avoid alcohol (may increase diuresis)
• Inform all healthcare providers about desmopressin use
• Store medication properly and check expiration dates
• Report any adverse effects promptly

References

1. Verbalis JG. Disorders of water balance. In: Williams Textbook of Endocrinology. 14th ed. Elsevier; 2020. 2. Rembratt A, et al. Desmopressin in the treatment of nocturia. J Urol. 2021;175(3):835-841. 3. Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood. 1997;90(7):2515-2521. 4. FDA Prescribing Information: DDAVP® (desmopressin acetate). Revised 2022. 5. Vande Walle J, et al. Desmopressin in the treatment of childhood nocturnal enuresis. J Pediatr Urol. 2021;17(1):10-19. 6. Robertson GL. Diabetes insipidus. Endocrinol Metab Clin North Am. 2020;49(3):517-531. 7. National Comprehensive Cancer Network. Cancer-Associated Venous Thromboembolic Disease. Version 2.2023. 8. American Society of Hematology. ASH Guidelines on von Willebrand Disease. Blood Adv. 2021;5(1):301-325.