Chlorthalidone and Eplerenone interaction

Chlorthalidone and Eplerenone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Eplerenone label · effective 2025-06-23

Major

…• serum creatinine > 2.0 mg/dL in males or >1.8 mg/dL in females, • creatinine clearance < 50 mL/min, or • concomitant administration of potassium supplements or potassium-sparing diuretics (e.g., amiloride, spironolactone, or triamterene) [see Warnings and Precautions (5.1) , Adverse Reactions (6.2) , Drug Interactions (7) , and Clinical Pharmacology (12.3)…

Contraindicationsby drug classView label on DailyMed
Major

• Concomitant use of potassium supplements or potassium-sparing diuretics ( 4 )

Contraindicationsby drug classView label on DailyMed
Moderate

Lithium toxicity has been reported in patients receiving lithium concomitantly with diuretics and ACE inhibitors.

Drug interactionsby drug classView label on DailyMed
Moderate

The administration of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive effect in some patients and result in severe hyperkalemia in patients with impaired renal function.

Drug interactionsby drug classView label on DailyMed

From the Chlorthalidone (Thalitone) label · effective 2026-06-25

Moderate

Effect of chlorthalidone on other drugs Chlorthalidone may add to or potentiate the action of other antihypertensive drugs.

Drug interactionsby drug classView label on DailyMed
Minor

Impaired Renal Function Changes in renal function including acute renal failure can be caused by diuretics.

Warnings and precautionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.