Eplerenone and Irbesartan and hydrochlorothiazide interaction
Eplerenone and Irbesartan 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.
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
…• 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)…
• Concomitant use of potassium supplements or potassium-sparing diuretics ( 4 )
• 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.
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.
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.
From the Irbesartan and hydrochlorothiazide (Avalide) label · effective 2025-10-07
Initiation of antihypertensive therapy may cause symptomatic hypotension in patients with intravascular volume or sodium depletion, e.g., in patients treated vigorously with diuretics or in patients on dialysis.
Coadministration of AVALIDE with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes or other drugs that raise serum potassium levels may result in hyperkalemia, sometimes severe.
NSAIDs and selective COX-2 inhibitors: Can reduce diuretic, natriuretic of diuretic, may lead to increased risk of renal impairment and reduced antihypertensive effect.
Nonsteroidal Anti-inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) Irbesartan In patients who are elderly, volume depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including irbesartan,…
Hydrochlorothiazide Administration of a nonsteroidal anti-inflammatory agent, including a selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics.
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Open in the checkerNot 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.