Evaluation of Dosing Interval and Optimum Dose of Cibenzoline

Abstract

Fifteen patients with ventricular premature complexes (VPCs) were included in this open study designed to assess the relative efficacy of bid (two times daily) and tid (three times daily) dosing regimens for cibenzoline as compared with qid (four times daily) administration. Patients started therapy with qid administration; this was followed in sequence by tid and bid administration at the maximum effective total daily dose determined during the qid administration. Of the nine patients evaluated for efficacy for suppression of VPCs, eight demonstrated a 75% or greater suppression of VPCs with cibenzoline administered qid (total daily dose of 130–325 mg). This effectiveness was maintained in four patients with a bid regimen and in three with a tid regimen. All four patients who had ventricular tachycardia (VT) had a decrease in the number of VT episodes while receiving cibenzoline (only one of these patients had satisfactory supression of VPCs at the same dosage regimen). Twelve patients continued to receive extended therapy with cibenzoline for up to two years, as this was considered to be the optimum antiarrhythmic treatment for these patients. Two patients had to be removed from the study and two had the dosage lowered because of adverse reactions (dry mouth, blurred vision, dizziness, congestive heart failure) although in one instance, the congestive heart failure was subsequently considered to be unrelated to cibenzoline. One patient was able to complete the short‐term phase of the trial, but was not given extended treatment because of persistent dry mouth. Two patients had treatment discontinued during the extended therapy phase because of adverse reactions (fever, nausea, vomiting, asthenia). This pilot study gives pharmacodynamic support to the pharmacokinetic findings of the long half‐life of cibenzoline, enabling a bid dosing regimen to be used in patients and permitting better patient compliance.