Eplerenone and Hydrochlorothiazide Interaction
Drug interaction information between Eplerenone and Hydrochlorothiazide.
Eplerenone and Hydrochlorothiazide have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Eplerenone and Hydrochlorothiazide. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
How They Interact
These drugs work in a similar way to keep potassium in the body instead of letting it leave through urine. This can cause potassium levels to rise too high, which can affect your heart rhythm.
FDA Label Information
Use of lisinopril with potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium.
Eplerenone Also Interacts With
- Fluconazole major
- Verapamil major
- Erythromycin major
- Itraconazole major
- Nirmatrelvir/Ritonavir major
Hydrochlorothiazide Also Interacts With
- Hydrochlorothiazide major
- Aliskiren major
- Lisinopril minor
- Losartan minor
- Spironolactone minor
Frequently Asked Questions
What SPL severity band is on file for Eplerenone + Hydrochlorothiazide/Triamterene?
Compiled FDA labeling labels this pair minor. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Hydrochlorothiazide has 13 labeled pairs on file vs Eplerenone's 12. In the minor band specifically: Eplerenone has 7 (also Lithium, Hydrochlorothiazide, Hydrochlorothiazide, Lisinopril); Hydrochlorothiazide has 11 (also Lisinopril, Losartan, Spironolactone, Propranolol).
What mechanism field is on file for Eplerenone and Hydrochlorothiazide/Triamterene?
These drugs work in a similar way to keep potassium in the body instead of letting it leave through urine. This can cause potassium levels to rise too high, which can affect your heart rhythm.
Eplerenone carries more major-labeled pairs than Hydrochlorothiazide
SPL source-record counts only. This page's band is minor · classes on file: Eplerenone (Aldosterone Antagonist); Hydrochlorothiazide (Thiazide / Potassium-Sparing Diuretic Combination).
Eplerenone has 5 major-labeled pairs vs Hydrochlorothiazide's 2. This page itself is in the minor band, not the major band.
5 major · 0 moderate · 7 minor · 12 total
- Other minor peers for Eplerenone
- Lithium
- Hydrochlorothiazide
- Hydrochlorothiazide
- Lisinopril
2 major · 0 moderate · 11 minor · 13 total
- Other minor peers for Hydrochlorothiazide
- Lisinopril
- Losartan
- Spironolactone
- Propranolol
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.
Read our methodology - how this data is sourced, computed, and verified.