Hydrochlorothiazide/Lisinopril and Spironolactone Interaction
Drug interaction information between Hydrochlorothiazide/Lisinopril and Spironolactone.
Hydrochlorothiazide/Lisinopril and Spironolactone have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Hydrochlorothiazide/Lisinopril and Spironolactone. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Both of these medicines can cause your body to keep too much potassium, which can lead to dangerously high levels in your blood.
What To Do
Your doctor will need to perform regular blood tests to check your potassium levels while you take these drugs.
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/Lisinopril Also Interacts With
- Aliskiren major
- Lisinopril minor
- Losartan minor
- Hydrochlorothiazide minor
- Propranolol minor
Spironolactone Also Interacts With
- Lithium moderate
- Trimethoprim moderate
- Heparin moderate
- Amlodipine/Benazepril moderate
- Benazepril moderate
Frequently Asked Questions
Can I take Hydrochlorothiazide/Lisinopril and Spironolactone together?
This is a minor interaction. Your doctor will need to perform regular blood tests to check your potassium levels while you take these drugs.
How serious is the interaction between Hydrochlorothiazide/Lisinopril and Spironolactone?
This interaction is classified as "minor" severity by the FDA. Minor interactions are unlikely to cause significant problems but should still be mentioned to your healthcare provider.
Why do Hydrochlorothiazide/Lisinopril and Spironolactone interact?
Both of these medicines can cause your body to keep too much potassium, which can lead to dangerously high levels in your blood.
Understanding the Hydrochlorothiazide/Lisinopril and Spironolactone Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Hydrochlorothiazide/Lisinopril belongs to the Thiazide Diuretic / ACE Inhibitor Combination class and Spironolactone belongs to the Potassium-Sparing Diuretic / Aldosterone Antagonist class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Both of these medicines can cause your body to keep too much potassium, which can lead to dangerously high levels in your blood. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Hydrochlorothiazide/Lisinopril has 13 total documented interactions on file in this dataset, and Spironolactone has 23. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Your doctor will need to perform regular blood tests to check your potassium levels while you take these drugs. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Hydrochlorothiazide/Lisinopril or Spironolactone based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.