Spironolactone and Lithium Carbonate: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Spironolactone
Lithium Carbonate
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased lithium exposure and increased risk of lithium toxicity (weakness, tremor, excessive thirst, confusion)
Interaction Deep Dive
Do not coadminister lithium with diuretics, such as spironolactone9. Concomitant use of lithium with spironolactone may increase lithium exposure and lead to lithium toxicity 9101. When concurrent use is required, initiate lithium at lower doses or reduce current doses, monitor lithium exposure frequently, and observe for signs of lithium toxicity 1.
Why it happens (mechanism)
Reduced renal lithium clearance
Literature reports
4 reports — tap to read
a) A 24% reduction in lithium clearance in 22 patients on long-term therapy with bendroflumethiazide and hydroflumethiazide has been demonstrated. Bendroflumethiazide may impair renal elimination of lithium, and should be used with caution in patients receiving lithium 4.
b) The effects of concomitant administration of lithium with either furosemide or hydroCHLOROthiazide has been studied in six health volunteers. The subjects received lithium 300 mg three times daily for nine days, furosemide 40 mg daily plus lithium for 14 days, lithium alone for seven days, and lithium plus hydroCHLOROthiazide 50 mg daily for 14 days. Serum lithium was measured intermittently throughout the 44-day study. Of the six subjects, one withdrew after developing adverse effects during the lithium-only portion of the study. During coadministration of lithium with hydroCHLOROthiazide, serum lithium levels rose significantly compared to the lithium-only phase and the lithium plus furosemide phase. The authors suggested that patients given thiazide diuretics may need a downward adjustment of their lithium dosage to maintain acceptable serum lithium levels 2.
c) A case report exists describing a 60-year old woman who developed lithium toxicity after the addition of a thiazide diuretic to control hypertension. The patient had taken lithium 600 mg twice daily and maintained serum lithium levels of 0.8 to 1.2 mEq/L. Two weeks after hydroCHLOROthiazide 50 mg daily was added to the patient's regimen, the patient developed insomnia, confusion, tremor, muscle fasciculations, dysarthria, and ataxia. The patient's serum lithium level was measured at 3.9 mEq/L. After hemodialysis, the patient's lithium level was 1.4 mEq/L but mental status continued to deteriorate. The patient's condition gradually improved over the next five days with osmotic diuresis and supportive treatment 3.
d) Renal clearance of lithium is reduced by spironolactone and other diuretics 11 potentially resulting in elevated serum levels of lithium and lithium toxicity 1 due to reabsorption of sodium and lithium ions at the proximal renal tubule 56. Cotherapy is useful in cases of lithium polyuria 7 or lithium-induced nephrogenic diabetes insipidus 8.
Common questions
Can I take Spironolactone and Lithium Carbonate together?
Increased lithium exposure and increased risk of lithium toxicity (weakness, tremor, excessive thirst, confusion) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Spironolactone and Lithium Carbonate interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Spironolactone or Lithium Carbonate need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (11)
- Product Information: LITHOBID(R) oral extended release tablets, lithium carbonate oral extended release tablets. ANI Pharmaceuticals, Inc. (per FDA), Baudette, MN, 2016. DailyMed
- Jefferson JW & Kalin NH: Serum lithium levels and long-term diuretic use. JAMA 1979; 241:1134-1136. DOI
- Nurnberger JI Jr: Diuretic-induced lithium toxicity presenting as mania. J Nerv Ment Dis 1985; 173:316-318. PubMed
- Petersen V, Hvidt S, Thomsen K, et al: Effect of prolonged thiazide treatment on renal lithium clearance. Br Med J 1974; 3:143-145. PubMed
- Singer I & Rotenberg P: Mechanisms of lithium action. N Engl J Med 1973; 289:254. DOI
- Davis JM & Fann WE: Lithium. Ann Rev Pharmacol 1971; 11:285.
- MacNeil S, Hanson-Nortey E, Paschalis C, et al: Diuretics during lithium therapy (letter). Lancet 1975; 1:1295-1296. DOI
- Himmelhoch JM, Forrest J, Neil JF, et al: Thiazide-lithium synergy in refractory mood swings. Am J Psychiatry 1977; 134:149-152. PubMed
- Product Information: Aldactazide® oral tablets, spironolactone hydrochlorothiazide oral tablets. Pfizer Labs (per FDA), New York, NY, 2025.
- Product Information: ALDACTONE® oral tablets, spironolactone oral tablets. Pfizer Labs (per FDA), New York, New York, 2025. DailyMed
- Product Information: CAROSPIR(R) oral suspension, spironolactone oral suspension. CMP Pharma, Inc (per manufacturer), Farmville, NC, 2017. DailyMed
Keep reading about Spironolactone
Keep reading about Lithium Carbonate
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