Can spironolactone and triamterene/hydrochlorothiazide (HCTZ) be taken together?

From the Guidelines

Taking spironolactone and triamterene/HCTZ together is not recommended due to the increased risk of hyperkalemia, as both medications are potassium-sparing diuretics that can cause potassium levels to rise too high, potentially leading to serious heart rhythm problems or cardiac arrest. According to the most recent and highest quality study, 1, mineralocorticoid receptor antagonists, such as spironolactone, should be avoided in patients with serum creatinine >2.5 mg/dL or serum K+ >5.0 mmol/L. Additionally, the study warns that the combination of potassium-sparing diuretics, such as triamterene, with other medications that increase potassium levels, can lead to hyperkalemia.

The use of potassium-sparing diuretics, such as triamterene and spironolactone, should be monitored by repeated measurements of serum creatinine and potassium, as recommended by 1. The study also suggests that oral potassium supplements are less effective in maintaining body potassium stores during diuretic treatment.

In terms of alternative treatment options, 1 recommends that diuretics, such as loop diuretics or thiazides, can be used as first-line therapy for hypertension, and that potassium-sparing diuretics, such as amiloride or triamterene, can be considered in patients with hypokalemia on thiazide monotherapy. However, the study warns that the combination of potassium-sparing diuretics with other medications that increase potassium levels should be avoided in patients with significant chronic kidney disease (CKD).

Key points to consider:

• The combination of spironolactone and triamterene/HCTZ can increase the risk of hyperkalemia
• Regular blood tests to monitor potassium levels are essential if this combination is used
• Alternative treatment options, such as loop diuretics or thiazides, can be considered
• The use of potassium-sparing diuretics should be monitored by repeated measurements of serum creatinine and potassium.

From the FDA Drug Label

Triamterene should not be given to patients receiving other potassium-sparing agents, such as spironolactone, amiloride hydrochloride, or other formulations containing triamterene. Two deaths have been reported in patients receiving concomitant spironolactone and triamterene or Dyazide® Although dosage recommendations were exceeded in one case and in the other serum electrolytes were not properly monitored, these two drugs should not be given concomitantly.

• Concomitant use is not recommended: The use of spironolactone and triamterene/hctz together is contraindicated due to the risk of hyperkalemia and potentially fatal outcomes, as reported in two cases 2.
• Risk of hyperkalemia: The combination of these two potassium-sparing agents can lead to elevated serum potassium levels, which can be life-threatening.
• Alternative treatments should be considered: Patients should not be given triamterene if they are already taking spironolactone, and vice versa.

From the Research

Potential Interactions between Spironolactone and Triamterene/HCTZ

• The use of spironolactone with triamterene/HCTZ may increase the risk of hyperkalemia, as both medications can affect potassium levels in the body 3, 4.
• A study comparing the relative potency of spironolactone, triamterene, and potassium chloride in thiazide-induced hypokalemia found that spironolactone and triamterene had significant and parallel dose-response curves for plasma potassium, with a relative potency for triamterene:spironolactone of 0.25:1 5.
• The combination of spironolactone with other medications that may cause hyperkalemia, such as ACE inhibitors or ARBs, should be used with caution and monitored closely, especially in patients with renal insufficiency, diabetes, or older age 3, 6, 4.
• The risk of hyperkalemia-associated hospitalization was higher in patients with chronic kidney disease who used spironolactone, highlighting the need for strategic treatments to prevent hyperkalemia 7.

Key Considerations

• Patients taking spironolactone and triamterene/HCTZ should be monitored closely for signs of hyperkalemia, such as elevated serum potassium levels, and for any changes in renal function 3, 6, 4, 7.
• The dose of spironolactone should not exceed 25 mg daily, especially in patients with renal insufficiency or those taking other medications that may cause hyperkalemia 3.
• The use of spironolactone with triamterene/HCTZ may require regular monitoring of serum potassium levels and renal function to minimize the risk of hyperkalemia and other adverse effects 3, 6, 4, 7.