Can spironolactone cause hyponatremia?

Can Spironolactone Cause Hyponatremia?

Yes, spironolactone can cause hyponatremia, as explicitly stated in its FDA drug label under adverse effects and warnings. 1

Mechanism and Risk

Spironolactone is a potassium-sparing diuretic that works as a mineralocorticoid receptor antagonist, primarily blocking the effects of aldosterone. While it is commonly known for causing hyperkalemia, it can also lead to hyponatremia through several mechanisms:

• Direct effect: The FDA drug label clearly lists hyponatremia as one of the electrolyte disturbances that can occur with spironolactone use 1
• Increased risk with higher doses: Higher doses of spironolactone (50-100 mg) are significantly associated with hyponatremia compared to lower doses (25 mg) 2
• Timing of effect: The risk of hyponatremia is most prominent early in treatment with spironolactone, with newly initiated therapy showing higher odds ratios for hospitalization due to hyponatremia (aOR 3.55) compared to ongoing use (aOR 1.75) 3

Clinical Evidence

Recent research provides strong evidence for this association:

• A 2021 population-based case-control study found that spironolactone use was associated with an adjusted odds ratio of 1.96 for hospitalization due to hyponatremia 3
• A 2020 study of heart failure patients found that spironolactone doses of 50-100 mg were independently associated with hyponatremia (p=0.0003) 2
• In clinical practice, approximately 6% of heart failure patients treated with spironolactone developed dehydration/hyponatremia requiring drug withdrawal 4

Risk Factors for Spironolactone-Induced Hyponatremia

Certain patient factors increase the risk of developing hyponatremia with spironolactone:

• Advanced age 2
• Diabetes mellitus 2
• Alcohol consumption 2
• Concomitant use with other diuretics, particularly loop diuretics at high doses 2
• Heart failure, especially advanced heart failure 4

Monitoring Recommendations

Guidelines recommend the following monitoring approach:

• Check serum electrolytes (including sodium) within 1 week of initiation or titration of spironolactone 1
• Continue regular monitoring thereafter, with more frequent monitoring in high-risk patients 1
• For patients with heart failure, check electrolytes at 1,2,3, and 6 months after achieving maintenance dose, and 6-monthly thereafter 5

Management of Hyponatremia

If hyponatremia develops:

• Consider dose reduction or discontinuation of spironolactone 1
• Evaluate for other contributing factors (other medications, fluid status)
• Fluid restriction may be warranted if serum sodium falls below 120-125 mmol/L 5
• Avoid rapid correction of hyponatremia as this can lead to more complications than the hyponatremia itself 5

Clinical Pearls and Pitfalls

• Pitfall: Focusing only on hyperkalemia risk while overlooking hyponatremia risk when prescribing spironolactone
• Pitfall: Failing to recognize that combination therapy with loop diuretics and spironolactone significantly increases hyponatremia risk 2
• Pearl: Patients with cirrhosis and ascites are particularly susceptible to hyponatremia with diuretic therapy, including spironolactone 5
• Pearl: Symptoms of hyponatremia in cirrhotic patients typically don't appear until sodium levels fall below 110 mmol/L or if the decline is very rapid 5

In conclusion, while spironolactone is a valuable medication for various conditions including heart failure, cirrhosis with ascites, and resistant hypertension, clinicians should be vigilant about monitoring for hyponatremia, particularly when initiating therapy, using higher doses, or in patients with additional risk factors.