Spironolactone and Lithium Interaction
Drug interaction information between Spironolactone and Lithium.
Spironolactone and Lithium have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Spironolactone and Lithium. 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
Spironolactone makes it harder for the kidneys to remove lithium from the body. This can cause lithium to build up to dangerous levels.
FDA Label Information
Lithium: Increased risk of lithium toxicity ( 7.2 ). 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. Monitor lithium levels periodically when spironolactone is co-administered [see Clinical Pharmacology (12.3) ] .
Spironolactone Also Interacts With
- Trimethoprim moderate
- Heparin moderate
- Amlodipine/Benazepril moderate
- Benazepril moderate
- Lovastatin moderate
Lithium Also Interacts With
- Amlodipine/Benazepril major
- Risperidone major
- Amiloride moderate
- Amiodarone moderate
- Amlodipine/Valsartan moderate
Frequently Asked Questions
What SPL severity band is on file for Spironolactone + Lithium?
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?
Lithium has 90 labeled pairs on file vs Spironolactone's 23. In the moderate band specifically: Spironolactone has 9 (also Trimethoprim, Heparin, Amlodipine/Benazepril, Benazepril); Lithium has 23 (also Amiloride, Amiodarone, Amlodipine/Valsartan, Azilsartan).
What mechanism field is on file for Spironolactone and Lithium?
Spironolactone makes it harder for the kidneys to remove lithium from the body. This can cause lithium to build up to dangerous levels.
Lithium carries more major-labeled pairs than Spironolactone
SPL source-record counts only. This page's band is moderate · classes on file: Spironolactone (Potassium-Sparing Diuretic / Aldosterone Antagonist); Lithium (Mood Stabilizer).
Lithium has 2 major-labeled pairs vs Spironolactone's 0. This page itself is in the moderate band, not the major band.
0 major · 9 moderate · 14 minor · 23 total
- Other moderate peers for Spironolactone
- Trimethoprim
- Heparin
- Amlodipine/Benazepril
- Benazepril
2 major · 23 moderate · 65 minor · 90 total
- Other moderate peers for Lithium
- Amiloride
- Amiodarone
- Amlodipine/Valsartan
- Azilsartan
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.