What are the potential side effects of desmopressin (DDAVP) in older adults with nocturnal enuresis (nocturnal urination) and underlying medical conditions, such as impaired renal function or heart failure?

Side Effects of Desmopressin for Nocturnal Urination

Desmopressin carries a significant risk of hyponatremia in older adults, occurring in 15% as borderline (130-135 mmol/L) and 5% as severe hyponatremia, making it particularly dangerous in elderly patients with nocturia who have underlying cardiac, renal, or other medical conditions. 1

Critical Safety Concerns in Older Adults

Hyponatremia: The Primary Risk

• Hyponatremia is the most serious adverse effect, presenting with headache, nausea, vomiting, dizziness, and potentially progressing to somnolence, loss of consciousness, seizures, and death 2, 1
• The FDA mandates that serum sodium must be normal before starting desmopressin, with monitoring within 1 week, at 1 month, and periodically thereafter—with more frequent monitoring required in patients ≥65 years 2
• If hyponatremia develops, desmopressin must be interrupted or permanently discontinued depending on severity and duration 2

High-Risk Patient Populations

Desmopressin is absolutely contraindicated in patients with: 2

• Moderate to severe renal impairment (creatinine clearance <50 mL/min)
• Current hyponatremia or history of hyponatremia
• Heart failure or uncontrolled hypertension
• Polydipsia (excessive fluid intake)
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Concurrent use of loop diuretics or systemic/inhaled glucocorticoids
• Active illnesses causing fluid or electrolyte imbalance

Additional Risk Factors for Hyponatremia

Patients at increased risk include those: 2, 1

• Age >65 years
• Taking medications that increase hyponatremia risk: thiazide diuretics, tricyclic antidepressants, SSRIs, NSAIDs, chlorpromazine, carbamazepine, lamotrigine, opiates, oxybutynin, or sulfonylureas (especially chlorpropamide)
• With low-normal baseline serum sodium
• With high 24-hour urine volume
• With conditions affecting fluid/electrolyte balance (cystic fibrosis, renal disorders)

Cardiovascular Side Effects

• Fluid retention is a common adverse effect that can worsen underlying cardiac conditions 2, 3
• Hypertension may occur, requiring blood pressure monitoring during treatment, especially in patients with coronary artery disease or hypertensive cardiovascular disease 2
• Hypotension with compensatory tachycardia can also develop 2
• Three of four patients experiencing side effects in one study had fluid retention, emphasizing this risk in elderly men 3

Metabolic and Electrolyte Disturbances

• Increased urinary calcium excretion occurs with desmopressin, with nocturnal calcium excretion rising from 0.137 to 0.169 mg/kg/hour and whole-day excretion increasing from 165.9 to 200.0 mg/day 4
• Decreased urinary potassium excretion was observed, with nocturnal potassium dropping from 0.030 to 0.025 mEq/kg/hour 4
• These electrolyte changes deserve particular attention with long-term use 4

Other Adverse Reactions

Common side effects include: 2

• Abdominal cramps
• Nausea
• Headache
• Facial flushing
• Erythema and swelling at injection sites
• Burning pain

Thrombotic Risk

• In patients with von Willebrand's disease Type IIB, desmopressin can cause platelet aggregation, thrombocytopenia, and thrombosis 2
• General thrombotic events have been reported in post-marketing surveillance 2

Hypersensitivity Reactions

• Severe hypersensitivity reactions including fatal anaphylaxis have been reported with intravenous desmopressin 2
• Patients must be monitored during administration, with immediate discontinuation if reactions occur 2

Essential Safety Measures

Mandatory Fluid Restriction

• Patients must limit fluid intake to 200 mL (6 ounces) or less in the evening with no drinking until morning to prevent water intoxication 5, 6
• Fluid should be restricted from 1 hour before until 8 hours after desmopressin administration 2
• Failure to restrict fluids can lead to water intoxication with hyponatremia and seizures 5, 6

Monitoring Requirements

• Baseline serum sodium must be normal before initiating treatment 2, 7
• Monitor serum sodium within 1 week, at 1 month, and periodically during treatment 2, 7
• Elderly patients and those with risk factors require more frequent monitoring 2, 1, 7
• Patients should be educated about hyponatremia symptoms before starting treatment 7

Clinical Context: Older Adults vs. Children

• The safety profile differs significantly between populations—desmopressin is considered "overall safe with few side effects" in children with enuresis 5
• However, in elderly adults with nocturia, the high risk of hyponatremia (15-20% combined incidence) makes alternative treatments preferable as first-line therapy 1
• Two case reports documented hospitalization due to desmopressin-induced hyponatremia in older adults, highlighting real-world dangers 1

Common Pitfalls to Avoid

• Prescribing desmopressin without checking baseline serum sodium and renal function is a critical error 2, 7
• Inadequate patient education about fluid restriction leads to water intoxication 5, 6, 2
• Failing to identify contraindications, particularly heart failure, renal impairment, or concurrent high-risk medications 2, 1
• Insufficient monitoring of serum sodium in elderly patients during treatment 2, 1, 7
• Not recognizing that cardiac patients should not receive desmopressin due to fluid retention risk 3