From the Guidelines
Furosemide and spironolactone have opposing effects on potassium levels, with furosemide causing potassium loss and spironolactone causing potassium retention, and their combined use requires careful monitoring of serum potassium levels to prevent hyperkalemia or hypokalemia, as recommended by the most recent guidelines 1.
Mechanism of Action
- Furosemide, a loop diuretic, inhibits sodium and chloride reabsorption in the ascending loop of Henle, increasing sodium delivery to the distal tubule and promoting potassium excretion, leading to hypokalemia.
- Spironolactone, a potassium-sparing diuretic, blocks aldosterone receptors in the distal tubule, reducing sodium reabsorption and potassium excretion, thereby causing potassium retention.
Clinical Use
- The usual diuretic regimen consists of single morning doses of oral spironolactone and furosemide, beginning with 100 mg of the former and 40 mg of the latter, with doses adjusted every 3 to 5 days to maintain normokalemia 1.
- Furosemide can be temporarily withheld in patients presenting with hypokalemia, and spironolactone can be reduced or stopped in case of hyperkalemia 1.
- Regular electrolyte monitoring is recommended, especially when initiating therapy or changing doses, to prevent complications such as hyperkalemia or hypokalemia 1.
Monitoring and Adjustments
- Serum potassium levels should be monitored regularly, especially in patients with renal impairment or those taking other potassium-retaining medications or supplements.
- The doses of both oral diuretics can be increased simultaneously every 3 to 5 days, maintaining the 100 mg:40 mg ratio, to achieve adequate diuresis while maintaining potassium balance 1.
- In cases of severe hyponatremia, acute kidney injury, or overt hepatic encephalopathy, diuretics should be reduced or stopped, and the patient's status should be reevaluated 1.
From the FDA Drug Label
Information for Patients Patients receiving furosemide should be advised that they may experience symptoms from excessive fluid and/or electrolyte losses. The postural hypotension that sometimes occurs can usually be managed by getting up slowly. Potassium supplements and/or dietary measures may be needed to control or avoid hypokalemia
Laboratory Tests Serum electrolytes (particularly potassium), CO2, creatinine and BUN should be determined frequently during the first few months of furosemide therapy and periodically thereafter.
7.1 Drugs and Supplements Increasing Serum Potassium Concomitant administration of spironolactone with potassium supplementation or drugs that can increase potassium may lead to severe hyperkalemia.
The effect of furosemide on potassium levels is a potential decrease, which may lead to hypokalemia. On the other hand, spironolactone can increase potassium levels, potentially leading to hyperkalemia, especially when combined with other drugs that increase potassium. Therefore, when used together, furosemide and spironolactone may have opposing effects on potassium levels, with furosemide potentially decreasing potassium and spironolactone increasing it. Monitoring of serum potassium levels is necessary when these drugs are used concomitantly 2, 2, 3.
From the Research
Effect of Furosemide and Spironolactone on Potassium Levels
- Furosemide is known to decrease potassium levels, as it is a loop diuretic that increases urine production, leading to a loss of potassium ions 4.
- Spironolactone, on the other hand, is a potassium-sparing diuretic that can increase potassium levels by blocking the effects of aldosterone, a hormone that promotes potassium excretion 5.
- In a study of hypertensive African patients, the combination of frusemide (furosemide) and spironolactone resulted in a rise in mean plasma-potassium levels, whereas frusemide alone led to a decrease in potassium levels 4.
- Another study found that high-dose spironolactone had no significant effect on serum potassium concentration in critically ill patients receiving a furosemide infusion 6.
- The use of spironolactone can increase serum potassium values and occasionally result in clinically relevant hyperkalemia, particularly due to its long half-life and active metabolites 5.
- In a case study, a patient with chronic hyperkalemic acidosis presented with severe hypokalemic alkalosis, and spironolactone was used cautiously during the hypokalemic phase to help replenish potassium levels 7.
- A retrospective study of pediatric cardiac intensive care patients found that spironolactone supplementation did not reduce the need for potassium supplementation, and potassium laboratory values did not differ significantly between patients who received spironolactone and those who did not 8.