Hydrochlorothiazide and Spironolactone Interaction
Drug interaction information between Hydrochlorothiazide and Spironolactone.
Hydrochlorothiazide and Spironolactone have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Hydrochlorothiazide and Spironolactone. 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
Both drugs stop the kidneys from getting rid of potassium. This can cause potassium to build up to unsafe levels in your blood.
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.
Hydrochlorothiazide Also Interacts With
- Hydrochlorothiazide major
- Aliskiren major
- Lisinopril minor
- Losartan minor
- Propranolol minor
Spironolactone Also Interacts With
- Lithium moderate
- Trimethoprim moderate
- Heparin moderate
- Amlodipine/Benazepril moderate
- Benazepril moderate
Frequently Asked Questions
What SPL severity band is on file for Hydrochlorothiazide/Triamterene + Spironolactone?
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?
Spironolactone has 23 labeled pairs on file vs Hydrochlorothiazide's 13. In the minor band specifically: Hydrochlorothiazide has 11 (also Lisinopril, Losartan, Propranolol, Lithium); Spironolactone has 14 (also Digoxin, Cholestyramine, Amlodipine/Valsartan, Enalapril).
What mechanism field is on file for Hydrochlorothiazide/Triamterene and Spironolactone?
Both drugs stop the kidneys from getting rid of potassium. This can cause potassium to build up to unsafe levels in your blood.
Hydrochlorothiazide carries more major-labeled pairs than Spironolactone
SPL source-record counts only. This page's band is minor · classes on file: Hydrochlorothiazide (Thiazide / Potassium-Sparing Diuretic Combination); Spironolactone (Potassium-Sparing Diuretic / Aldosterone Antagonist).
Hydrochlorothiazide has 2 major-labeled pairs vs Spironolactone's 0. This page itself is in the minor band, not the major band.
2 major · 0 moderate · 11 minor · 13 total
- Other minor peers for Hydrochlorothiazide
- Lisinopril
- Losartan
- Propranolol
- Lithium
0 major · 9 moderate · 14 minor · 23 total
- Other minor peers for Spironolactone
- Digoxin
- Cholestyramine
- Amlodipine/Valsartan
- Enalapril
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.