Risks Associated with Desmopressin (DDAVP)
The most significant risk of desmopressin (DDAVP) is water intoxication leading to hyponatremia and potentially seizures, which can occur if fluid intake is not appropriately restricted during treatment. 1, 2
Major Adverse Effects
Hyponatremia and Water Intoxication
- Desmopressin increases water reabsorption in the kidneys, which can lead to decreased serum sodium concentration 3
- Risk of water intoxication with hyponatremia and seizures is the most serious concern, particularly when combined with excessive fluid intake 2, 1
- Hyponatremia can develop rapidly and may be severe (Na < 115 mEq/L) even with minimal symptoms 4
- Risk is higher when using the nasal spray formulation compared to oral formulations 2
Cardiovascular Effects
- Can cause fluid retention, which may worsen underlying conditions susceptible to volume status 1
- Patients with heart failure or uncontrolled hypertension are at increased risk 1
- May cause hypertension, hypotension, or tachycardia 1
- Thrombotic events have been reported in post-marketing surveillance 1
Other Adverse Effects
- Hypersensitivity reactions may occur during administration 1
- Gastrointestinal effects including nausea and abdominal cramps 1
- Headache is commonly reported 1
- Facial flushing, erythema, and burning pain may occur 1
High-Risk Populations
Elderly Patients
- More susceptible to adverse effects due to decreased renal function 1
- Require careful dose selection, typically starting at the lower end of dosing range 1
- Need more stringent fluid intake restrictions to prevent hyponatremia 1
Patients with Renal Impairment
- Desmopressin is substantially excreted by the kidney 1
- Contraindicated in patients with moderate to severe renal impairment (creatinine clearance below 50 mL/min) 1
- Higher risk of adverse reactions in these patients 1
Children
- Require careful fluid intake restriction to prevent hyponatremia 1
- Fluid restriction should be discussed with the patient and/or guardian 1
Drug Interactions
- Increased risk of hyponatremia when used with:
- Tricyclic antidepressants
- Selective serotonin re-uptake inhibitors
- Chlorpromazine
- Opiate analgesics
- Thiazide diuretics
- NSAIDs
- Lamotrigine
- Sulfonylureas (particularly chlorpropamide)
- Oxybutynin
- Carbamazepine 1
- Use with other vasoconstrictors may require dose reduction of desmopressin 1
Risk Mitigation Strategies
Fluid Restriction
- Evening fluid intake should be limited to 200 ml (6 ounces) or less with no drinking until morning 2
- Polydipsia (excessive drinking) is a contraindication to desmopressin treatment 3
- Fluid restriction should be discussed with all patients prior to initiating therapy 1
Monitoring
- More frequent serum sodium monitoring is required when desmopressin is used with medications that increase hyponatremia risk 1
- Monitoring is especially important during intercurrent illnesses that might affect hydration status 3
- Particular caution is needed in patients with a history of seizures, cystic fibrosis, or renal impairment 5
Special Considerations in Hyponatremia Management
- If hyponatremia with neurologic symptoms occurs, desmopressin should not be abruptly discontinued as this could lead to rapid changes in serum sodium levels 6
- In cases of symptomatic hyponatremia, continuing desmopressin while administering hypertonic saline may be necessary to prevent overly rapid correction 6, 7
Specific Clinical Contexts
Acquired Hemophilia A
- Desmopressin should be reserved for minor bleeding episodes and very low titer inhibitors 2
- Water retention with consecutive hyponatremia and convulsions may occur following repeated injections 2
- Particularly concerning in elderly patients who commonly have this condition 2