Digoxin and Spironolactone and hydrochlorothiazide interaction
Digoxin and Spironolactone 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 Spironolactone and hydrochlorothiazide label · effective 2026-02-10
Thiazide-induced electrolyte disturbances, i.e. hypokalemia, hypomagnesemia, increase the risk of digoxin toxicity, which may lead to fatal arrhythmic events (see Precautions ).
Digoxin: Spironolactone has been shown to increase the half-life of digoxin.
Monitor serum digoxin levels and adjust dose accordingly.
This may result in increased serum digoxin levels and subsequent digitalis toxicity.
From the Digoxin label · effective 2025-04-10
…Conivaptan 33% 43% Diltiazem 20% NA Indomethacin 40% NA Mirabegron 29% 27% Nefazodone 27% 15% Nifedipine 45% NA Propantheline 24% 24% Quinine NA 33% Rabeprazole 29% 19% Saquinavir 27% 49% Spironolactone 25% NA Telmisartan 20 to 49% NA Ticagrelor 31% 28% Tolvaptan 30% 20% Trimethoprim 22 to 28% NA Digoxin Concentrations Increased, but Magnitude is Unclear Alprazolam,…
Serum potassium levels should be carefully monitored when digoxin is given to patients at high risk of hypokalemia ( e.g. , those receiving diuretics, corticosteroids, or other drugs that commonly lead to potassium loss; those with gastrointestinal losses through diarrhea, vomiting, or nasogastric suction; or those with potassium-losing endocrinopathies or nephropathies).
In some assays, spironolactone, canrenone and potassium canrenoate may be falsely detected as digoxin, at levels up to 0.5 ng/mL.
Spironolactone and DLIS are much more extensively protein-bound than digoxin.
As a result, assays of free digoxin levels in protein-free ultrafiltrate (which tend to be about 25% less than total levels, consistent with the usual extent of protein binding) are less affected by spironolactone or DLIS.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
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.