Hydrochlorothiazide and Spironolactone interaction

Hydrochlorothiazide and Spironolactone: 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 Hydrochlorothiazide (INZIRQO) label · effective 2025-12-16

Moderate

NSAID: May lead to increased risk of renal impairment and loss of diuretic and antihypertensive effect (7.1).

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Moderate

Potential for Other Drugs to Affect INZIRQO Non-Steroidal Anti-Inflammatory Agents: Administration of a nonsteroidal anti-inflammatory agent, including a selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics.

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Minor

Diuretics can cause hypovolemia which may precipitate acute kidney injury.

Warnings and precautionsby drug classView label on DailyMed
Minor

Systemic Lupus Erythematosus Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Warnings and precautionsby drug classView label on DailyMed
Minor

Therefore, when INZIRQO and nonsteroidal anti-inflammatory agents are used concomitantly, check to determine if the desired effect of the diuretic is obtained.

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From the Spironolactone label · effective 2026-08-26

Moderate

NSAIDs: May reduce the diuretic, natriuretic and antihypertensive effect of spironolactone oral suspension ( 7.3 )

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Moderate

…drugs that can increase potassium include: ACE inhibitors angiotensin receptor blockers aldosterone blockers non-steroidal anti-inflammatory drugs (NSAIDs) heparin and low molecular weight heparin trimethoprim 7.2 Lithium Like other diuretics, spironolactone oral suspension reduces the renal clearance of lithium, thus increasing the risk of lithium toxicity.

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Moderate

Nonsteroidal Anti-inflammatory Drugs (NSAIDs) In some patients, the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing, and thiazide diuretics.

Drug interactionsby drug classView label on DailyMed
Moderate

Therefore, when spironolactone oral suspension and NSAIDs are used concomitantly, monitor closely to determine if the desired effect of the diuretic is obtained [see Clinical Pharmacology ( 12.3 )] .

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.

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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.