Metolazone and Spironolactone interaction
Metolazone and Spironolactone: 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 Metolazone label · effective 2026-01-15
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.
WARNINGS Rapid Onset Hyponatremia And/Or Hypokalemia Rarely, the rapid onset of severe hyponatremia and/or hypokalemia has been reported following initial doses of thiazide and non-thiazide diuretics.
Serum potassium should be determined at regular and appropriate intervals, and dose reduction, potassium supplementation or addition of a potassium-sparing diuretic instituted whenever indicated.
Concomitant Therapy Lithium In general, diuretics should not be given concomitantly with lithium because they reduce its renal clearance and add a high risk of lithium toxicity.
Drug Interactions Diuretics Furosemide and probably other loop diuretics given concomitantly with metolazone can cause unusually large or prolonged losses of fluid and electrolytes (see WARNINGS ).
From the Spironolactone label · effective 2026-08-26
NSAIDs: May reduce the diuretic, natriuretic and antihypertensive effect of spironolactone oral suspension ( 7.3 )
…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.
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.
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 )] .
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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.