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 medicines both cause your body to keep potassium instead of flushing it out. Taking them together can lead to a dangerous increase in blood potassium levels.
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
- Aliskiren major
- Lisinopril minor
- Losartan minor
- Hydrochlorothiazide minor
- Spironolactone minor
Frequently Asked Questions
What SPL severity band is on file for Eplerenone + Hydrochlorothiazide/Lisinopril?
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 12 (also Lisinopril, Losartan, Hydrochlorothiazide, Spironolactone).
What mechanism field is on file for Eplerenone and Hydrochlorothiazide/Lisinopril?
These medicines both cause your body to keep potassium instead of flushing it out. Taking them together can lead to a dangerous increase in blood potassium levels.
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 Diuretic / ACE Inhibitor Combination).
Eplerenone has 5 major-labeled pairs vs Hydrochlorothiazide's 1. 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
1 major · 0 moderate · 12 minor · 13 total
- Other minor peers for Hydrochlorothiazide
- Lisinopril
- Losartan
- Hydrochlorothiazide
- Spironolactone
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.