Trimethoprim and Spironolactone Interaction
Drug interaction information between Trimethoprim and Spironolactone.
Trimethoprim and Spironolactone have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Trimethoprim 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 of these medications can cause your body to hold onto potassium. Taking them together increases the risk of having too much potassium in your blood.
FDA Label Information
Examples of drugs that can increase potassium include: ACE inhibitors angiotensin receptor blockers non-steroidal anti-inflammatory drugs (NSAIDs) heparin and low molecular weight heparin trimethoprim 7.2 Lithium Like other diuretics, spironolactone reduces the renal clearance of lithium, thus increasing the risk of lithium toxicity.
Trimethoprim Also Interacts With
- Theophylline major
- Prenatal Multivitamin moderate
- Spironolactone (Acne) moderate
- Metformin minor
- Glipizide minor
Spironolactone Also Interacts With
- Lithium moderate
- Heparin moderate
- Amlodipine/Benazepril moderate
- Benazepril moderate
- Lovastatin moderate
Frequently Asked Questions
What SPL severity band is on file for Trimethoprim + Spironolactone?
Compiled FDA labeling labels this pair moderate. 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 Trimethoprim's 22. In the moderate band specifically: Trimethoprim has 3 (also Prenatal Multivitamin, Spironolactone); Spironolactone has 9 (also Lithium, Heparin, Amlodipine/Benazepril, Benazepril).
What mechanism field is on file for Trimethoprim and Spironolactone?
Both of these medications can cause your body to hold onto potassium. Taking them together increases the risk of having too much potassium in your blood.
Trimethoprim carries more major-labeled pairs than Spironolactone
SPL source-record counts only. This page's band is moderate · classes on file: Trimethoprim (Dihydrofolate Reductase Inhibitor); Spironolactone (Potassium-Sparing Diuretic / Aldosterone Antagonist).
Trimethoprim has 1 major-labeled pair vs Spironolactone's 0. This page itself is in the moderate band, not the major band.
1 major · 3 moderate · 18 minor · 22 total
- Other moderate peers for Trimethoprim
- Prenatal Multivitamin
- Spironolactone
0 major · 9 moderate · 14 minor · 23 total
- Other moderate peers for Spironolactone
- Lithium
- Heparin
- Amlodipine/Benazepril
- Benazepril
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.