Spironolactone Can Cause Hyponatremia
Yes, spironolactone can cause hyponatremia, particularly at higher doses or when used in combination with other diuretics. According to the FDA drug label, hyponatremia is a recognized adverse effect of spironolactone listed under electrolyte and metabolic abnormalities 1.
Mechanism and Risk Factors
- Spironolactone is an aldosterone antagonist that acts primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted tubule 2
- Hyponatremia occurs in 8-30% of patients treated with diuretics and is related to impaired ability of the kidneys to excrete free water 2
- Risk factors that increase the likelihood of spironolactone-induced hyponatremia include:
Evidence from Clinical Guidelines
- In patients with cirrhosis and ascites, hyponatremia is a common complication of diuretic therapy, with serum sodium <130 mmol/L occurring in 21.6% of patients 2
- Hyponatremia has been associated with higher prevalence of refractory ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, and increased mortality 2
- Recent guidelines define hyponatremia as serum sodium <135 mmol/L, with 130-135 mmol/L, 125-129 mmol/L, and <125 mmol/L constituting mild, moderate, and severe hyponatremia, respectively 2
Clinical Management
- Monitor serum electrolytes periodically during spironolactone therapy 1
- For patients with moderate hyponatremia (serum sodium 121-125 mmol/L), consider stopping diuretics and observing the patient 2
- All experts recommend stopping diuretics if serum sodium is ≤120 mmol/L 2
- If there is significant increase in serum creatinine or if creatinine is >150 μmol/L, volume expansion may be necessary 2
- Fluid restriction is generally not necessary in treating most patients with cirrhosis and ascites, as chronic hyponatremia in this setting is seldom morbid 2
- However, severe hyponatremia (serum sodium <120-125 mmol/L) may warrant fluid restriction 2
Comparison with Other Diuretics
- A population-based case-control study found that spironolactone was associated with an increased risk of hospitalization due to hyponatremia (adjusted OR 1.96) 4
- The risk was highest with newly initiated therapy (adjusted OR 3.55) 4
- In contrast, furosemide showed an inverse correlation with hospitalization due to hyponatremia during ongoing use (adjusted OR 0.52), suggesting a potential protective effect 4
- Hydrochlorothiazide can cause rapid development of hyponatremia when added to the combination of spironolactone and furosemide 2
Special Considerations
- In heart failure patients, the risk of hyponatremia with spironolactone may be lower when used as part of optimal therapy with close monitoring by a dedicated heart failure team 5
- The response to spironolactone varies significantly between patients, with up to sevenfold variation in potassium response, suggesting individualized dosing and monitoring is necessary 6
- In critically ill patients receiving furosemide infusions, high-dose spironolactone (100 mg three times daily) did not significantly affect serum sodium levels compared to placebo in a small pilot study 7
Common Pitfalls and Caveats
- Fixed-dose thiazide-spironolactone combination tablets may not reliably prevent hypokalemia due to variability in response between patients 6
- Patients with cirrhosis and chronic hyponatremia are often asymptomatic and seldom need treatment 2
- Attempts to rapidly correct hyponatremia in cirrhotic patients with hypertonic saline can lead to more complications than the hyponatremia itself 2
- When hyponatremia develops in a patient on long-term furosemide therapy, causes other than the diuretic should be sought 4