Eplerenone and Olmesartan and hydrochlorothiazide interaction

Eplerenone and Olmesartan 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

• Hyperkalemia: Patients with decreased renal function, diabetes, proteinuria or patients who are taking ACEs and ARBs, NSAIDs or moderate CYP3A inhibitors are at increased risk.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Hyperkalemia The risk of hyperkalemia is higher in patients with impaired renal function, proteinuria, diabetes and those concomitantly treated with ACEs, ARBs, NSAIDs and moderate CYP3A inhibitors.

Warnings and precautionsby 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

From the Olmesartan and hydrochlorothiazide (OLMESARTAN MEDOXOMIL and HYDROCHLOROTHIAZIDE) label · effective 2026-04-10

Moderate

Hypotension in Volume or Salt-Depleted Patients In patients with an activated renin-angiotensin system, such as volume-or salt-depleted patients ( e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with olmesartan medoxomil and hydrochlorothiazide tablets.

Warnings and precautionsby drug classView label on DailyMed
Moderate

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Reduced diuretic, natriuretic and antihypertensive effects; increased risk of renal toxicity ( 7.3 )

Drug interactionsby drug classView label on DailyMed
Moderate

Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) Olmesartan medoxomil In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including olmesartan…

Drug interactionsby drug classView label on DailyMed
Moderate

Hydrochlorothiazide In some patients the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics.

Drug interactionsby drug classView label on DailyMed
Moderate

Use of Hydrochlorothiazide with Other Drugs When administered concurrently the following drugs may interact with thiazide diuretics: Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.

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.