Flecainide
New England Journal of MedicinePublished 3 July 1986
Dan M. Roden, Raymond L. Woosley
Citations169
SJR quartileQ1
SJR score19.08
SNIP13.47
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Abstract
FLECAINIDE acetate (Tambocor, Riker Laboratories) has recently become available in this country for the management of ventricular arrhythmias. The synthesis of flecainide in 1972 was the culmination of a systematic search for fluorinated local anesthetic analogues of procainamide (Fig. 1).1 Early screening experiments showed that this structure, N-(2-Piperidylmethyl)-2,5-bis(2,2,2-trifluoroethoxy) benzamide, was active in a variety of animal models of arrhythmia.2 Clinical testing of the agent began in 1975. Only oral flecainide is currently available, although an intravenous form is under investigation.Flecainide is the first of a number of agents with similar electrophysiologic properties to be approved in the United . . .
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
The American Journal of CardiologyFlecainide: Its proarrhythmic effect and expected changes on the surface electrocardiogram
278 Citations1984Joel Morganroth, Leonard N. Horowitz
Proarrhythmic effects appear to be more common in patients with left ventricular dysfunction and life-threatening ventricular arrhythmias, and depression of atrioventricular conduction produced by flecainide is similar to that seen with other class IC agents.
Cardiovascular ResearchKinetics of onset of rate-dependent effects of Class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification
277 Citations1983Terence J. Campbell
Using the parameters of speed of onset of rate-dependent depression of Vmax and APD it was possible to subdivide the nine Class I anti-arrhythmic drugs into three distinct subclasses.
New England Journal of MedicineOral Flecainide Acetate for the Treatment of Ventricular Arrhythmias
222 Citations1981Jeffrey L. Anderson, James R. Stewart +7 more
Fleckcainide appears to be a highly effective and well-tolerated antiarrhythmic agent with favorable pharmacokinetics.
The American Journal of CardiologyMetabolism of flecainide
197 Citations1984Gordon J. Conard, Robert E. Ober
Overall, the plasma pharmacokinetics of flecainide appear to be reasonably linear (not dose- or concentration-dependent) and should be reduced in patients with more severe renal disease and in some CHF patients.
The American Journal of CardiologySuppression of resistant ventricular arrhythmias by twice daily dosing with flecainide
149 Citations1981Henry J. Duff, Dan M. Roden +7 more
Fleckcainide acetate was highly effective in suppressing ventricular arrhythmias when administered twice daily and was associated with progressive prolongation of the ventricular ectopic coupling interval before suppression of vent cardiac ectopic beats.
CirculationFlecainide versus quinidine for treatment of chronic ventricular arrhythmias. A multicenter clinical trial.
144 Citations1983Joel Morganroth, Loannis Panidis +189 more
CirculationSuppression of ventricular ectopic depolarizations by flecainide acetate, a new antiarrhythmic agent.
134 Citations1982Morrison Hodges, J. Mark Haugland +5 more
Flecainide acetate was given orally to 11 hospitalized patients with chronic high-frequency ventricular ectopic depolarizations to indicate that flecainides is a very effective antiarrhythmic agent that merits further clinical investigation.
Journal of the American College of CardiologyEffects of flecainide on the electrophysiologic properties of isolated canine and rabbit myocardial fibers
97 Citations1985Nobuo Ikeda, Bramah N. Singh +2 more
The data indicate that the overall electrophysiologic effects of flecainide in isolated cardiac muscle are complex with a major depressant action on Vmax that may account for its dominant antiarrhythmic effects.
Clinical Pharmacology & TherapeuticsAntiarrhythmic effects of flecainide
89 Citations1980Pitambar Somani
A new class I antiarrhythmic, flecainide, was investigated in 10 patients to assess short‐term efficacy and safety and did not induce significant changes in P‐R, QRS, or Q‐T intervals.
The American Journal of CardiologyEffects of flecainide on ventricular function: Clinical and experimental correlations
86 Citations1984Martin A. Josephson, Nobuo Ikeda +1 more
In patients undergoing coronary angiography for ischemic heart disease and given 1 and 2 mg/kg of flecainide acetate i.v., there was no change in heart rate or mean arterial pressure, and both doses produced comparable hemodynamic effects irrespective of the level of the left ventricular ejection fraction.
The American Journal of CardiologyCardiac electrophysiologic effects of flecainide acetate for paroxysmal reentrant junctional tachycardias
82 Citations1983Kevin J. Hellestrand, Anthony W. Nathan +3 more
Flecainide acetate is an effective agent for the acute termination of both orthodromic AV and intra-AV nodal reentrant tachycardias and appears to be mediated through a predominant effect on either accessory AV pathway or retrograde fast A-H pathway refractoriness.
Journal of the American College of CardiologyElectrophysiologic and antiarrhythmic effects of oral flecainide in patients with inducible ventricular tachycardia
78 Citations1983Jeffrey L. Anderson, Joan R. Lutz +1 more
Oral flecainide is an important antiarrhythmic agent for the management of inducible ventricular tachyarrhythmias and favorable responses to programmed stimulation are frequent and generally predict outpatient safety and efficacy.
The American Journal of CardiologyElectrophysiologic effects of flecainide acetate on sinus node function, anomalous atrioventricular connections, and pacemaker thresholds
73 Citations1984Kevin J. Hellestrand, Anthony W. Nathan +2 more
The acute electrophysiologic effects of i.v. flecainide acetate (2 mg/kg body weight) were assessed in 71 patients undergoing electrophYSiologic study and significantly prolonged accessory AV pathway anterograde and retrograde refractoriness.
American Heart JournalClinical electrophysiologic study of antiarrhythmic properties of flecainide: Acute intraventricular delayed conduction and prolonged repolarization in regular paced and premature beats using intracardiac monophasic action potentials with programmed stimulation
72 Citations1981S. Bertil Olsson, Nils Edvardsson
Fcainide acetate is one of the few antiarrhythmic drugs that substantially delay myocardial repolarization in tissue preparations and induced significant prolongations of monophasic action potentials from the right ventricle during induction of ventricular ectopic beats.
The American Journal of CardiologyElectrophysiologic effects of flecainide acetate in patients with sinus nodal dysfunction
65 Citations1982Harald Vik‐Mo, Ole‐Jørgen Ohm +1 more
It is concluded that flecainide acetate prolongs atrial and ventricular conduction and refractoriness, and thus appears to be a potent antiarrhythmic agent, however, the sinus nodal function is depressed, and therefore caution is advised in the use of flecains nodal dysfunction in patients with sinus nodsal dysfunction.
Journal of the American College of CardiologyFlecainide and amiodarone interaction
61 Citations1986Patrick J. Shea, Roop Lal +3 more
The mean dose of flecainide required to maintain similar plasma levels of the drug was one-third lower during combined treatment than during therapy with flec Cainide alone, which must be accounted for when amiodarone and flecainside are used concomitantly.
The American Journal of CardiologyHemodynamic effects of a new antiarrhythmic agent, flecainide (R-818), in coronary heart disease
60 Citations1983Victor Legrand, Michel Vandormael +2 more
The American Journal of CardiologyInteraction of flecainide with digoxin and propranolol
60 Citations1984G. P. Lewis, Jordan L. Holtzman
Both drugs caused a decrease in blood pressure, with the systolic pressure affected more than the diastolic; the effects of propranolol and flecainide were additive.
The American Journal of CardiologyA double-blind, crossover comparison of flecainide acetate and disopyramide phosphate in the treatment of ventricular premature complexes
60 Citations1984John Kjekshus, Jørn Batmen +2 more
Fleckcainide may be a well-tolerated and valuable alternative to currently available antiarrhythmic agents and show any significant effect on blood pressure or heart rate.
Drug Metabolism and DispositionBiotransformation and elimination of 14C-flecainide acetate in humans.
56 Citations1984Roy L. McQuinn, G. Quarfoth +6 more
The metabolism of 14C-flecainide acetate, a new antiarrhythmic, was investigated in four healthy human subjects, after a single, 200-mg oral dose and the cumulative recovery of radioactivity ranged from 81 to 90% in urine and from 4 to 6% in feces; thus, flecainid does not appear to undergo extensive biliary excretion, unless reabsorption occurs after biliary elimination.
The American Journal of CardiologyFlecainide: Electrophysiologic and antiarrhythmic properties in refractory ventricular tachycardia
50 Citations1985Edward V. Platia, N.A. Mark Estes +5 more
Although flecainide suppresses complex ventricular arrhythmias on Holter recordings, it rarely alters the response to programmed stimulation, and caution is recommended in its use for recurrent sustained VT or VF and in the interpretation of electrophysiologic studies until the predictive value of programmed stimulation with flecainside therapy is established.
American Heart JournalHemodynamic effects of intravenous flecainide relative to the level of ventricular function in patients with coronary artery disease
48 Citations1985Martin A. Josephson, Sanjiv Kaul +3 more
Flecainide exerts a moderate but significant negative inotropic effect which may be clinically significant in patients with severely compromised ventricular function and were associated with borderline and variable increases in pulmonary and systemic vascular resistances.
British Journal of Clinical PharmacologyThe haemodynamic effect of intravenous flecainide acetate in patients with coronary artery disease.
42 Citations1983PW Serruys, G. Vanhaleweyk +4 more
It is demonstrated that flecainide has a negative inotropic effect, not only under resting conditions, but also less apparently during pacing-induced tachycardia and may result in a reduction of cardiac performance.
The American Journal of CardiologyClinical and electrophysiologic assessment of oral flecainide acetate for recurrent ventricular tachycardia: Evidence for exacerbation of electrical instability
41 Citations1983William J. Oetgen, Paul A. Tibbits +2 more
S sustained oral flecainide administration may precipitate serious electrical instability in susceptible patients, and ventricular stimulation studies and other clinical variables may be useful in selecting patients with recurrent VT who may benefit or may be endangered by oral fleCainide therapy.
The American Journal of CardiologyAntiarrhythmic and electrophysiologic actions of flecainide in animal models
41 Citations1984Donald C. Kvam, Elden H. Banitt +1 more
It is indicated that flecainide acetate has potent antiarrhythmic activity, and is active against both ventricular and supraventricular arrhythmias from a number of causes.
The American Journal of CardiologyFlecainide dose-response relations in stable ventricular arrhythmias
31 Citations1984Raymond L. Woosley, Lyle A. Siddoway +2 more
Flecainide acetate is an effective antiarrhythmic with a narrow range of effective dosages with no evidence of chronic toxicity in patients with stable, high-frequency ventricular arrhythmias.
British Journal of Clinical PharmacologyThe influence of urinary pH on flecainide excretion and its serum pharmacokinetics.
30 Citations1984KA Muhiddin, A. E. Johnston +1 more
The effect of urinary pH on flecainide excretion has been evaluated in six healthy subjects after a single oral dose of 300 mg flecainside administered as the acetate salt and under alkaline conditions, tmax (time to reach peak concentration) was reduced and elimination half-life, AUC(0-32) and AUC (0-infinity) were increased.
The American Journal of CardiologyDiscovery and development of flecainide
30 Citations1984John M. Hudak, Elden H. Banitt +1 more
The flecainide discovery and development process started in 1966 with the broad goal of investigating the effects of fluorine substitution in potential drug molecules and evolved slowly, with a change in focus from local anesthetic programs to the antiarrhythmic project.
Annals of Internal MedicineComparison of Flecainide with Quinidine for Suppression of Chronic Stable Ventricular Ectopic Depolarizations
25 Citations1983David M. Salerno, Morrison Hodges +2 more
In a randomized placebo-controlled double-blind trial, flecainide was compared to quinidine for treatment of ventricular ectopic depolarizations in 19 patients and produced 100% suppressed of nonsustained ventricular tachycardia and 99.5% suppression of paired ventricular depolarization.
The American Journal of CardiologyElectrophysiologic effects of flecainide acetate and its major metabolites in the canine heart
25 Citations1985Janel Guehler, Charles C. Gornick +5 more
The maximal electrophysiologic effects of flecainide and S-24623 were approximately equivalent, but the metabolite was about one-half as potent on a milligram-permilligram basis, and lacked marked effects on infranodal (HV interval) conduction.
Clinical Pharmacology & TherapeuticsSuppression of complex ventricular arrhythmias by oral flecainide
24 Citations1982Dumar Durán, Edward V. Platia +3 more
Oral flecainide slowed heart rate by 10% and prolonged PR, QRS, and QTC intervals by 31%, 47% and 6%.
The American Journal of CardiologyFlecainide: Long-term treatment using a reduced dosing schedule
24 Citations1985David Flowers, Deborah O'Gallagher +3 more
In the patients protected by flecainide, the effective refractory periods increased by a 17 +/- 2% and 21 +/- 3%, in contrast to only a 7 +/- 3% and 6 +/- 4% increase in the nonprotected group, despite a higher mean dose.
The Journal of Clinical PharmacologyThe Effect of Flecainide Acetate, a New Antiarrhythmic, on Plasma Digoxin Levels
22 Citations1986Charles E. Weeks, Gordon J. Conard +5 more
On an average for each subject, predose and six‐hour postdose digoxin levels increased by 24 ± 35% and 13 ± 19%, respectively, during coadministration, which were not clinically significant.
Clinical Pharmacology & TherapeuticsEffect of flecainide on cardiac output
21 Citations1985Khulood A. Muhiddin, Paul Turner +1 more
The effect of intravenous flecainide (2 mg/kg) on cardiac output was evaluated by a dye dilution method in six healthy nonsmokers and alertness was reduced 60 minutes after fle cainide, but there was no increase in dryness of the mouth.
CHEST JournalSinusoidal Ventricular Tachycardia Associated with Flecainide Acetate
19 Citations1984T. Duncan Sellers, John Dimarco
The authors' experience suggests that the early reports of successful suppression of ventricular premature beats in stable patients may not be directly applicable to sicker patients with recurrent sustained ventricular arrhythmias, and in these patients, life-threatening arrh rhythmias may appear as the first manifestation of drug toxicity.
Journal of the American College of CardiologyImproved method for evaluating ventriculoatrial conduction before implantation of atrial-sensing dual chamber pacemakers
9 Citations1985Charles R. Webb, Scott R. Spielman +3 more
The ventricular extrastimulus technique during AV sequential pacing reveals substantially longer VA intervals than does ventricular pacing and explains why pacemaker-mediated tachycardia might occur when pacemaker atrial refractory periods are designed or programmed according to VA intervals measured only during ventricular paced.