From the Guidelines
Spironolactone is not commonly associated with hyponatremia, as this condition is more commonly linked to loop diuretics, especially in patients who excrete approximately 80 mmol of sodium in their urine per day 1.
Key Points
- Hyponatremia is more common with loop diuretics, especially in patients with high sodium excretion 1.
- Spironolactone is an aldosterone antagonist that can cause hyperkalemia, especially if concomitant impaired renal perfusion occurs 1.
- The usual diuretic regimen for patients with cirrhosis and ascites consists of single morning doses of oral spironolactone and furosemide, beginning with 100 mg of the former and 40 mg of the latter 1.
- Spironolactone is recommended as the initial treatment for ascites in cirrhosis, with furosemide added if there is a suboptimal response 1.
- Diuretic doses should be increased simultaneously every 3 to 5 days, maintaining the 100 mg:40 mg ratio, if weight loss and natriuresis are inadequate 1.
- Monitoring for diuretic adverse events, including electrolyte imbalance, is crucial, and diuretics should be temporarily discontinued if necessary 1.
- The mechanism of action of anti-mineralocorticoids, such as spironolactone, explains their slow effect, and the dosage should not be increased earlier than 72 h 1.
From the FDA Drug Label
In addition to causing hyperkalemia, spironolactone can cause hyponatremia, hypomagnesemia, hypocalcemia, hypochloremic alkalosis, and hyperglycemia. Metabolism: Hyperkalemia, electrolyte disturbances [see Warnings and Precautions ( 5.1,5. 3)] , hyponatremia, hypovolemia. Rarely, instances of hyponatremia, hyperkalemia, or hepatic coma may occur in patients with severe liver disease, but these are unlikely due to acute overdosage.
Spironolactone is associated with hyponatremia. Key points:
- The drug label directly states that spironolactone can cause hyponatremia 2, 2, and 2.
- Hyponatremia is listed as a potential electrolyte and metabolic abnormality caused by spironolactone.
- Monitoring of serum electrolytes is recommended to detect hyponatremia and other electrolyte disturbances.
From the Research
Association between Spironolactone and Hyponatremia
- The use of spironolactone has been associated with an increased risk of hyponatremia in several studies 3, 4, 5.
- A study published in 2020 found that patients receiving spironolactone were more likely to be hyponatremic, particularly at higher doses 3.
- Another study published in 2021 found that the use of spironolactone was associated with an increased risk of hospitalization due to hyponatremia, with an adjusted odds ratio of 1.96 (1.78-2.18) 4.
- A retrospective study published in 2023 found that spironolactone use was associated with an increased risk of severe hyponatremia, with an odds ratio of 2.3 (p=0.05) 5.
Clinical Characteristics and Outcomes
- Hyponatremia is a common electrolyte disturbance that can be associated with significant morbidity and mortality 5.
- The clinical characteristics and outcomes of patients presenting with hyponatremia can vary, with older patients and those using certain medications such as proton pump inhibitors and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers being at increased risk of severe hyponatremia 5.
- The use of spironolactone has been identified as a potential risk factor for hyponatremia in several studies, highlighting the need for careful monitoring and management of patients receiving this medication 3, 4, 5.
Mechanisms and Pathophysiology
- The exact mechanisms by which spironolactone contributes to hyponatremia are not fully understood, but may involve changes in renal function and electrolyte balance 3.
- Spironolactone is a potassium-sparing diuretic that can increase the risk of hyperkalemia, but may also contribute to hyponatremia through other mechanisms 6.
- Further research is needed to fully understand the relationship between spironolactone and hyponatremia, and to identify strategies for preventing and managing this condition in patients receiving this medication.