Eplerenone and Metolazone interaction

Eplerenone and Metolazone: 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 Metolazone label · effective 2026-01-15

Major

Other Antihypertensive Drugs When metolazone tablets, USP, are used with other antihypertensive drugs, particular care must be taken to avoid excessive reduction of blood pressure, especially during initial therapy.

Warningsby drug classView label on DailyMed
Moderate

WARNINGS Rapid Onset Hyponatremia And/Or Hypokalemia Rarely, the rapid onset of severe hyponatremia and/or hypokalemia has been reported following initial doses of thiazide and non-thiazide diuretics.

Warningsby drug classView label on DailyMed
Moderate

Serum potassium should be determined at regular and appropriate intervals, and dose reduction, potassium supplementation or addition of a potassium-sparing diuretic instituted whenever indicated.

Warningsby drug classView label on DailyMed
Moderate

Concomitant Therapy Lithium In general, diuretics should not be given concomitantly with lithium because they reduce its renal clearance and add a high risk of lithium toxicity.

Warningsby drug classView label on DailyMed
Moderate

Drug Interactions Diuretics Furosemide and probably other loop diuretics given concomitantly with metolazone can cause unusually large or prolonged losses of fluid and electrolytes (see WARNINGS ).

Drug interactionsby 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.