How to use desmopressin (vasopressin analog) in patients with impaired renal function?

From the Guidelines

Desmopressin should be used with caution in patients with impaired renal function, with careful monitoring of serum sodium levels and fluid intake required to minimize the risk of hyponatremia. When using desmopressin in patients with renal insufficiency, it is crucial to consider the potential for increased risk of hyponatremia due to the drug's antidiuretic effects.

• The dose of desmopressin may need to be adjusted based on the severity of renal impairment, with reduced dosing recommended for patients with mild to moderate renal impairment (GFR 30-60 mL/min) and careful consideration for those with severe renal impairment (GFR <30 mL/min) 1.
• Monitoring of serum sodium levels is essential before initiation, within 24 hours after the first dose, and regularly thereafter to promptly identify any signs of hyponatremia.
• Restricting fluid intake to 1-1.5 L/day during treatment can help reduce the risk of hyponatremia.
• Discontinuation of desmopressin is necessary if serum sodium falls below 130 mmol/L or if symptoms of hyponatremia develop, such as headache, nausea, or confusion.
• The prescribing physician may choose to start with a higher dose and taper down in cases of good effect or use the opposite strategy, but this should be done with caution in patients with renal impairment 1.
• Regular short drug holidays can help assess whether medication is still needed, but this should be balanced with the need for careful monitoring in patients with renal insufficiency.

From the FDA Drug Label

Desmopressin acetate is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with renal impairment than patients with normal renal function. Desmopressin acetate is contraindicated in patients with estimated CLcr by Cockcroft-Gault equation less than 50 mL/min [see Contraindications (4), Clinical Pharmacology (12. 3)].

In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Key Points:

• Desmopressin acetate is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min).
• Dose selection should be cautious in patients with impaired renal function, starting at the low end of the dosing range.
• Monitoring of renal function may be useful in patients with decreased renal function.

2

From the Research

Desmopressin Use in Renal Insufficiency

• Desmopressin is a synthetic vasopressin receptor agonist used to treat various conditions, including diabetes insipidus and nocturia 3, 4.
• In patients with impaired renal function, the use of desmopressin requires careful consideration due to the risk of hyponatremia 5.
• A study on patients with chronic renal failure found that high-dose desmopressin increased urine osmolality and decreased haematocrit without causing fluid overload or changes in serum electrolytes 6.

Pharmacokinetics and Antidiuretic Effect

• The pharmacokinetics of desmopressin in patients with renal insufficiency show a decreased total clearance and prolonged terminal half-life compared to healthy adults 6.
• The antidiuretic effect of desmopressin in patients with renal insufficiency is significant, with an increase in urine osmolality lasting for 48 hours 6.

Management of Central Diabetes Insipidus

• The treatment of central diabetes insipidus involves the use of desmopressin (dDAVP) and replacement of free water deficit 7.
• Oral dDAVP is preferred over nasal dDAVP for chronic central diabetes insipidus, and regular breaks from dDAVP are necessary to avoid hyponatremia 7.
• Management of adipsic DI requires initial inpatient assessment to establish the dose of dDAVP, daily fluid prescription, and eunatraemic weight, which can guide day-to-day fluid targets in the long-term 7.

Considerations for Patients with Renal Insufficiency

• Patients with renal insufficiency require close monitoring when using desmopressin due to the risk of hyponatremia and fluid overload 3, 5.
• The use of desmopressin in patients with renal insufficiency should be individualized, taking into account the patient's underlying condition, renal function, and other medications 6, 7.