Digoxin therapeutic drug monitoring: age influence and adverse events

Abstract

Introduction: Digoxin is a cardiac glycoside, used to control rapid ventricular rates in atrial fibrillation and to reduce the hospitalizations due to heart failure. Digoxin has a narrow therapeutic range. So, in the treatment of older patients (≥ 65 years), it is important to set the optimal dose of digoxin to prevent toxicity and therapeutic drug monitoring of digoxin trough plasmatic concentration (C0) may be useful.

Aim: To assess measured C0, to evaluate age influence on digoxin pharmacokinetic parameters and to report adverse events in patients administered digoxin.

Methods: It consisted in a retrospective study. We included all the patients addressed to the department of clinical pharmacology for digoxin C0 measurement by an automated fluorescence polarization immunoassay. Therapeutic ranges of digoxin C0 were: 1 to 2.5 ng.mL-1 in children, 0.8 to 2 ng.mL-1 in adults and 0.5 to 0.9 ng.mL-1 in older adults (≥ 65 years) in atrial fibrillation and heart failure.

Results: We collected 183 samples from 132 patients. Sex ratio M/W was 0.47. Mean age was 60 years and 57% of patients were older adults. Mean dose of digoxin was 0.3 mg.day-1. In older adults, 45% were administered daily doses over 0.125 mg.day-1. Mean digoxin C0 was 1.6 ng.mL-1. There was more supra-therapeutic C0 in older adults than younger ones (p<0.0001).There was no correlation between C0 and daily dose of digoxin. Adverse events, mainly cardiac and digestive, were reported in 47 patients (36%), among this population 47% were older adults.

Conclusion: TDM is useful to prevent toxicity, mainly in older adults where diagnosis may be difficult to establish.