Flecainide acetate dose-concentration relationship in cardiac arrhythmias: influence of heart failure and amiodarone.
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 less than 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 less than 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 less than 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 flecainide-amiodarone interaction seems time dependent.
Leclercq
J F
JF
Department of Cardiology, Lariboisière Hospital, Paris, France.
Denjoy
I
I
Mentré
F
F
Coumel
P
P
D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000378:metabolism; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005424:Flecainide / Q000097:blood* / Q000627:therapeutic use; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
D005424:Flecainide; D000638:Amiodarone