Cifenline Succinate- Antiarrhythmic agent- Investigational drug
Drug Name:Cifenline Succinate- Antiarrhythmic agent- Investigational drug
List Of Brands:
Indication Type Description:
Drug Interaction
Adverse Reaction
Pharmacology/ Pharmacokinetics
Drug Interaction:
Artial flutter
Ventricular Arrhythmias
Summary-
Cifenline is a unique antiarrhythmic agent which may offer similar efficacy with a more
favourable side effect profile than currently available Class IA agents. The long half-life
which permits twice daily dosing may also be considered an advantage.
Cifenline will be co-marketed as Cipralan by Roche and Glaxo. The NDA has been pending
since December 1985. The official generic name was recently changed from cibenzoline to
cifenline
Adverse Reaction:
Side Effects-
Cifenline appears to be well tolerated , especially when compared to other Class IA
antiarrhythmics .
Gastrointestinal intolerance is the most common reason cited for discontinuation of therapy
due to side effects. Other adverse reported include- lightheadeness, dizziness, nervousness, tremulousness, blurred vision and dry mouth.
Worsening of preexisting left ventricular dysfunction has occurred. The drug should be used
with caution in patients with CHF , especially if baseline ejection fraction is less than 30%.
The proarrhythmic effect that may occur (as with all antiarrhythmic agents ) has occured in 10% to 15% of patients receiving cifenline.
No serious hematologic or laboratory abnormalities have been reported
Pharmacology/ Pharmacokinetics:
Pharmacology-
Cifeniline succinate (formerly cibenzoline) is a new antiarrhythmic agent. It is an imidazole
derivative , structurally unrelated to any other currently available antiarrhythmic.
Cifenlines primary electrophysiologic effects are similar to those produced by quinidine
(eg. duraquin, Quinidex). The drug acts predominently on the fast sodium current reducing
the rate of rise of phase 0 of the action potential and prolonging the effective refractory
period. These effects are characterstic of class IA- (Vaughn-Williams classification)
agents such as quinidine, procainamide (eg.Pronestyl, Procan-SR) and disopyramide
(eg. Norpace)
The drug has also been shown to increase the action potential duration, a property of
Class III agents, and may produce blockade of the slow inward calcium channel similar to
Class IV agents. The contribution of these secondary effects to the drugs clinical usefulness has not been clearly delineated
The drug produces a plasma concentration-dependent prolongation of QRS duration.
The prolongation of PR interval and the rate -correlated QT interval have not been
consistently observed, but these effects are compatible with the drugs known
electrophysiologic effects and may be seen at higher doses or in patients with
underlying conduction disburances
Pharmacokinetics-
Cifenline is well absorbed after oral administration. Absolute bioavailability is approximately
85%, with peak concentrations occuring approximately 1.5 hrs after administration.
Coadministration with food slightly decreases the rate, but not the extent of absorption.
Approximately, 55% of the drug is bound to plasma proteins, primarily albumin.
Following multiple doses, the elimination half-life of the drug is approximately 12 hours
(range 8 to 12 hours). As much as 60% of the dose excreted unchanged in the urine, and
total body clearance correlates with creatinine clearance.
Therefore, in patients with chronic renal failure, dosage should be reduced. Older
patients also clear the drug more slowly, probably as a result of age-related reductions
in renal functions.
The plasma concentrations of the unchanged drug are apparently responsible for its
antiarrhythmic effect. Studies have shown that the antiarrhythmic response following
twice-daily administration of cifenline is equivalent to a 4 times a day regimen.
Clinical studies-
Cifeniline is efective in suppressing a variety of ventricular arrhythmias, including
complex PVCs and non-sustained ventricular tachycardia. In these appications,
the drug has produced response rares similar to or higher than those for quinidine,
procainamide, fisopyramide and tocainde (Tonocard)
Data with patients with sustained ventricular tachycardia resistent to conventional
therapy is limited, however, response rates of 25% have occurred. Long term follow-up
studies ( 12 to 24 months) have reported sustained therapeutic efficacy in 36% to 86%
of initial responders
