Eplerenone and Hydrochlorothiazide interaction

Eplerenone and Hydrochlorothiazide: 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 Hydrochlorothiazide (INZIRQO) label · effective 2025-12-16

Moderate

NSAID: May lead to increased risk of renal impairment and loss of diuretic and antihypertensive effect (7.1).

Drug interactionsby drug classView label on DailyMed
Moderate

Potential for Other Drugs to Affect INZIRQO Non-Steroidal Anti-Inflammatory Agents: Administration of a nonsteroidal anti-inflammatory agent, including a selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics.

Drug interactionsby drug classView label on DailyMed
Minor

Diuretics can cause hypovolemia which may precipitate acute kidney injury.

Warnings and precautionsby drug classView label on DailyMed
Minor

Systemic Lupus Erythematosus Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Warnings and precautionsby drug classView label on DailyMed
Minor

Therefore, when INZIRQO and nonsteroidal anti-inflammatory agents are used concomitantly, check to determine if the desired effect of the diuretic is obtained.

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.