Spironolactone as a Source of Interference in Commercial Digoxin Immunoassays

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Abstract
Eight commercial digoxin immunoassay methods were tested in 17 subjects taking spironolactone (but not digoxin) to evaluate cross-reactivity from parent drug and/or metabolites. Four of these methods showed significant (up to 1.9 nmol/L) and variable "apparent digoxin" concentrations, despite the absence of digoxin in the drug regimen. The results suggest that clinical laboratories (a) require a knowledge of their method with respect to spironolactone-related cross-reactivity and (b) should exercise caution when interpreting digoxin results where spironolactone is coadministered. Further, the presence of concurrent renal and/or hepatic impairment could delay clearance of spironolactone metabolites (as well as digoxin metabolites and endogenous substances) and further distort a genuine digoxin result.

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