Eplerenone and Lisinopril and hydrochlorothiazide interaction

Eplerenone and Lisinopril 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

ACE Inhibitors and Angiotensin II Receptor Antagonists The risk of hyperkalemia increases when eplerenone is used in combination with an ACE inhibitor and/or an ARB.

Drug interactionsby 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 Lisinopril and hydrochlorothiazide (Zestoretic) label · effective 2025-03-31

Moderate

Hypotension and Related Effects: Excessive hypotension was rarely seen in uncomplicated hypertensive patients but is a possible consequence of lisinopril use in salt/volume-depleted persons such as those treated vigorously with diuretics or patients on dialysis (see PRECAUTIONS, Drug Interactions and ADVERSE REACTIONS ).

Warningsby drug classView label on DailyMed
Moderate

Such patients should be followed closely for the first two weeks of treatment and whenever the dose of lisinopril and/or diuretic is increased.

Warningsby drug classView label on DailyMed
Moderate

Drug Interactions Lisinopril Hypotension - Patients on Diuretic Therapy: Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with lisinopril.

Drug interactionsby drug classView label on DailyMed
Moderate

If it is necessary to continue the diuretic, initiate therapy with lisinopril at a dose of 5 mg daily, and provide close medical supervision after the initial dose for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS , and DOSAGE AND ADMINISTRATION ).

Drug interactionsby drug classView label on DailyMed
Moderate

When a diuretic is added to the therapy of a patient receiving lisinopril, an additional antihypertensive effect is usually observed (see DOSAGE AND ADMINISTRATION ).

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.