COMBINATION THERAPY OF CIBENZOLINE WITH DIGOXIN - EFFECTS ON DIGOXIN PLASMA-LEVELS AND SAFETY IN PATIENTS WITH SUPRAVENTRICULAR ARRHYTHMIAS

Chronic co-administration of digoxin and several antiarrhythmic drugs increases digoxin plasma levels. To determine the effects of the administration of oral cibenzoline on digoxin plasma levels and its effects on clinical and electrocardiographic parameters, we conducted a prospective multicenter study in 22 cardiac patients with a mean age of 66 +/- 12 years (39-85), who where on long term digoxin therapy (0.25 mg once daily for at least 2 weeks) and who required oral cibenzoline therapy in the prevention of recurrence of symptomatic atrial tachyarrhythmias. Cibenzoline was given for 4 weeks at a dose of 130 mg twice daily in patients aged less than 70 years (groupe I, n = 15) and this dosage was reduced by half in patients over 70 years of age (groupe II, n = 7). Evaluation of the effects of this combination on clinical and electrocardiographic tolerability as well as the drawing of blood samples for assay of cibenzoline and digoxin took place before and after 4 weeks treatment with cibenzoline. The digoxin plasma levels were (mean +/- sem) 0.96 +/- 0.1 ng.ml-1 before cibenzoline administration and remained unchanged after 4 weeks of combination therapy (1.0 +/- 0.1 ng.ml-1), p > 0.05. Digoxin plasma levels in group I varied from respectively 0.8 +/- 0.1 ng.ml-1 (0.5-1.7) to 0.8 +/- 0.1 ng.ml-1 (0.4-1.5) and in group II from 1.2 +/- 0.2 ng.ml-1 (0.6-2) to 1.4 +/- 0.3 ng.ml-1(0.7-2.5). This therapy was well tolerated in 16 patients out of 21 evaluable patients (76 %) and there was no significant change in vital signs during the study. Two pts discontinued the study for intolerance (nausea and dizziness); cibenzoline daily dose was reduced in 2 pts for transient epigastric pain (1 pt) and dizziness (1 pt). One pt complained of mild pruritus which did not require any change in treatment. There was a small but not significant increase in mean PR duration (+ 4 %) and in mean QRS duration (+ 8 %), p > 0.05. A marked (> 25 %) increase of PR and QRS duration was seen in 1 pt and 3 pts respectively. No proarrhythmic effect was seen. Disappearance of symptoms present during the month prior to inclusion was noted in 18 of the 19 patients (96 %) with an initially symptomatic arrhythmia. In conclusion, the combination of cibenzoline and digoxin did not cause a rise in mean plasma digoxin levels. The good tolerability and efficacy of this combination in patients aged under 70 makes it particularly useful in the preventive treatment of certain rhythm disorders.