Flecainide acetate dose-concentration relationship in cardiac arrhythmias: Influence of heart failure and amiodarone

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Abstract
The trough concentration-dose (C/D) ratio of flecainide was prospectively studied in 78 patients with various cardiac arrhythmias. After the removal of two outlier values, no influence of body weight on C/D ratio was evidenced. Coadministration of amiodarone, and, moreover, the presence of heart failure increase the C/D ratio, from 2.01±0.78 to 2.55±0.37 and 2.9±1.19 ng/ml/mg, respectively (p<0.001 by two-factor analysis of variance). The presence of both heart failure and amiodarone therapy increases the C/D ratio to 3.88±1.07 ng/ml/mg. A single loading oral dose (30 mg/kg) of amiodarone increased C/D measured at the sixth hour in nine patients from 2.27±0.50 to 2.57±0.73 ng/ml/mg (p<0.05). The trough C/D ratio increased more during chronic treatment from 2.03±0.86 to 2.92±1.32 ng/ml/mg (p<0.05). Thus, a dosage reduction of flecainide (of 50% in some cases) is mandatory, in case of heart failure or the combination with amiodarone therapy, to obtain a plasma level of the drug that is similar to those observed in patients with a normal heart and without amiodarone therapy. The flecainideamiodarone interaction seems time dependent.