Clinical Repercussions of Analytical Interferences Due to Aldosterone Antagonists in Digoxin Immunoassays: An Assessment

Abstract

Analytical interferences in digoxin immunoassays constitute a well-known problem, with repercussions for therapeutic drug monitoring. Clinically effective doses of spironolactone and potassium canrenoate cross-react in several digoxin immunoassays, producing falsely elevated or lowered concentrations. This study evaluates the interferences caused by these drugs in the microparticle enzyme immunoassay (MEIA III) in comparison with another 3 immunoassays used for digoxin therapeutic drug monitoring: MEIA II, fluorescence polarization immunoassay, and enzyme multiplied immunoassay. The potential clinical implications of assay discrepancies in patient care are also assessed. To evaluate assay performance, in vitro specimens and real patient samples were measured using the 4 assays. Five serum pools were spiked with digoxin to achieve concentrations of 1 and 2.25 ng/mL digoxin and measured with the immunoassays before and after supplementation. Real samples from patients receiving digoxin (n = 39), digoxin and spironolactone (n = 35), or digoxin and potassium canrenoate (n = 4) were also quantified. The influence of ultrafiltration was evaluated in 3 pools from 29 additional patients. The implications of assay discrepancies for dose recommendations were also evaluated. In general, the results obtained for the in vitro and in vivo approaches coincided, confirming statistically significant differences in the assays regardless of the type of sample. MEIA III showed positive interference against the well-known negative interference attributed to MEIA II. According to Bland-Altman analysis, it is not possible to assume the interchangeability of the immunoassays evaluated. Thus, individual patients must be monitored with the same technique even in the absence of potential interferences. Discordant digoxin dose recommendations were estimated in 31% of patients not treated with interfering drugs and in 43% of cotreated patients. From a clinical perspective, analytical interferences in digoxin immunoassays are a real and frequent problem, which seems even more important in view of the lower therapeutic range now recommended.

Clinical Consequences of a Miscalibrated Digoxin Immunoassay

“…[3][4][5][6][7] This can lead to inappropriate digoxin dosing, which can potentially lead to serious problems for patients' health. [3][4][5][6][7] This can lead to inappropriate digoxin dosing, which can potentially lead to serious problems for patients' health.…”

“…[4][5][6][7] However, a New Zealand study has shown that clinicians were more inclined to dose patients based on their clinical situation when serum digoxin concentrations were low, whereas high digoxin concentrations were deemed to represent toxicity regardless of the patient's clinical impression. [4][5][6][7] However, a New Zealand study has shown that clinicians were more inclined to dose patients based on their clinical situation when serum digoxin concentrations were low, whereas high digoxin concentrations were deemed to represent toxicity regardless of the patient's clinical impression.…”