Metolazone and Sacubitril and valsartan interaction

Metolazone and Sacubitril and valsartan: 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 Metolazone label · effective 2026-01-15

Major

Other Antihypertensive Drugs When metolazone tablets, USP, are used with other antihypertensive drugs, particular care must be taken to avoid excessive reduction of blood pressure, especially during initial therapy.

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Moderate

Dosage adjustments of other antihypertensives may be necessary.

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Minor

Other Antihypertensives When metolazone tablets, USP, are used with other antihypertensive drugs, care must be taken, especially during initial therapy.

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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.

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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)] .

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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…

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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.