Sacubitril and valsartan and Spironolactone and hydrochlorothiazide interaction

Sacubitril and valsartan and Spironolactone and hydrochlorothiazide: both prescribing labels describe an interaction that usually calls for monitoring, a dose change, or spacing the doses.

Moderate

Usually manageable with monitoring or a dose change. Tell your pharmacist you take both.

What the FDA labels say

From the Sacubitril and valsartan (ENTRESTO) label · effective 2026-07-06

Moderate

Patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), are at greater risk.

Warnings and precautionsby drug classView label on DailyMed
Moderate

If hypotension occurs, consider dose adjustment of diuretics, concomitant antihypertensive drugs, and treatment of other causes of hypotension (e.g., hypovolemia).

Warnings and precautionsby drug classView label on DailyMed
Moderate

Potassium-sparing diuretics: May lead to increased serum potassium.

Drug interactionsby drug classView label on DailyMed
Moderate

Potassium-Sparing Diuretics As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium [see Warnings and Precautions (5.5)] .

Drug interactionsby drug classView label on DailyMed
Moderate

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, concomitant use of NSAIDs, including COX-2 inhibitors, with ENTRESTO may result in worsening of renal function, including possible…

Drug interactionsby drug classView label on DailyMed

From the Spironolactone and hydrochlorothiazide label · effective 2026-02-10

Moderate

…spironolactone and hydrochlorothiazide tablets with the following drugs or potassium sources may lead to severe hyperkalemia: • other potassium-sparing diuretics • ACE inhibitors • angiotensin II receptor antagonists • aldosterone blockers • non-steroidal anti-inflammatory drugs (NSAIDs), e.g., indomethacin • heparin and low molecular weight heparin • other drugs…

Warningsby drug classView label on DailyMed
Moderate

Thiazides may add to or potentiate the action of other antihypertensive drugs.

Warningsby drug classView label on DailyMed
Moderate

Drug interactions ACE inhibitors, Angiotensin II receptor antagonists, aldosterone blockers, potassium supplements, heparin, low molecular weight heparin, and other drugs known to cause hyperkalemia: Concomitant administration may lead to severe hyperkalemia.

Drug interactionsby drug classView label on DailyMed

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

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.