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PubMed2001

Normalization of ventricular repolarization with flecainide in long QT syndrome patients with SCN5A:DeltaKPQ mutation.

BACKGROUND: The Long QT Syndrome (LQTS) is a genetic channelopathy with life-threatening implications. The LQT3 form of this disease is caused by mutations of the SCN5A sodium-channel gene. A specific mutation, SCN5A:DeltaKPQ, is associated with repetitive reopenings of the sodium channel and prolonged inward current. This dominant inward current is manifest on the electrocardiogram as QT prolongation. Flecainide is a potent blocker of the open sodium channel. METHODS AND RESULTS: The effect of flecainide on the duration of the QT-interval and the T-wave morphology was systematically evaluated in five male patients age 2-64 years having the SCN5A:DeltaKPQ mutation. After baseline electrocardiograms were obtained, low-dose oral flecainide was administered for 48 hours. Serial electrocardiograms and blood flecainide levels were obtained during flecainide therapy. The QTc interval decreased on average by 104 ms, from a baseline value of 565 +/- 60 ms to 461 +/- 23 ms (P < 0.04) at a mean flecainide level of 0.28 +/- 0.08 mg/L, with shortening of the QTonset interval (P < 0.003) and normalization of T-wave morphology. The effects of flecainide were compared with oral mexiletine in two patients, with flecainide showing greater QTc shortening and more complete normalization of repolarization. No adverse side effects or proarrhythmia were observed with flecainide in this study. CONCLUSION: Low-dose, oral flecainide consistently shortened the QTc interval and normalized the repolarization T-wave pattern in five LQT3 patients with SCN5A:DeltaKPQ mutation. This preliminary study indicates that low-dose flecainide is a promising therapeutic agent for LQTS patients with the SCN5A:DeltaKPQ sodium channel mutation.

Administration, Oral↗
PubMed1997

Beta-adrenergic augmentation of flecainide-induced conduction slowing in canine Purkinje fibers.

BACKGROUND: This study was undertaken to test the hypothesis that beta-adrenergic stimulation in the setting of membrane depolarization will potentiate flecainide-induced conduction slowing. METHODS AND RESULTS: To elucidate the potential mechanism for the flecainide proarrhythmia observed in CAST, the voltage dependence of beta-adrenergic modulation of impulse propagation in eight flecainide-superfused canine Purkinje fibers was examined with a dual-microelectrode technique. At physiological membrane potentials (Vm) ([K+]o=5.4 micromol), 1 micromol flecainide decreased Vmax from 698+/-55 to 610+/-72 V/s (P=.003) and squared conduction velocity (theta2) from 2.11+/-1.1 to 1.72+/-0.9 (m/s)2 (P=.001). With K+ depolarization to Vm=-70 mV, flecainide further reduced Vmax from 306+/-101 to 245+/-65 V/s and theta2 from 1.12+/-0.4 to 0.99+/-0.6 (m/s)2, producing a 2.0-mV hyperpolarizing shift of apparent Na+ channel availability curves derived from theta2. The addition of 1 micromol isoproterenol to flecainide-superfused fibers at physiological Vm increased theta2 by 8% to 1.84+/-0.6 (m/s)2 (P<.01) without altering Vmax. At -70 mV, the addition of isoproterenol magnified the flecainide-induced reduction of Vmax an additional 24% to 185+/-52 V/s (P<.01) and theta2 by 17% to 0.82+/-0.5 (m/s)2 (P=.04), producing an additional 1.8-mV (P=.002) and 1.9-mV (P=.002) hyperpolarizing shift in the apparent Na+ channel inactivation curves generated from Vmax and theta2, respectively. At physiological Vm, the action potential duration (APD95) was reduced from 307+/-35 to 269+/-27 ms (P<.001) by flecainide and subsequently to 217+/-4 ms (P<.001) with isoproterenol addition. With 12 mmol/L K+, APD95 decreased from 198+/-23 to 182+/-17 ms (P=.005) with flecainide and to 164+/-10 ms (P=.004) with isoproterenol. CONCLUSIONS: At depolarized Vm, isoproterenol amplified the flecainide-induced reduction of Vmax and theta2, suggesting a further adrenergic-mediated reduction of Na+ current. Consequently, the synergy between catecholamines and flecainide at depolarized Vm and the shortened APD95 could facilitate arrhythmogenesis in the presence of underlying ischemia.

Action Potentials↗
PubMed2005

Assessment of serum flecainide trough levels in patients with tachyarrhythmia.

The reported therapeutic range for trough flecainide concentration is 200-1000 ng mL(-1). Severe adverse events, such as ventricular arrhythmias, have occurred occasionally in patients whose serum flecainide exceeded 1000 ng mL(-1). However, the lower limit remains controversial. We have evaluated blood flecainide concentrations in patients with tachyarrhythmia who received the drug to control palpitation. We measured the flecainide trough levels and incidence and frequency of palpitation of 44 outpatients receiving oral flecainide (150-300 mg daily). Mean serum flecainide trough concentrations differed significantly between patients with (n = 14) and without (n = 30) palpitation (259.5 +/- 85.2 vs 462.2 +/- 197.7 ng mL(-1), P < 0.01). The frequency of palpitation decreased as the serum flecainide concentration increased. The incidence of palpitation was 65% at serum flecainide concentrations < 300 ng mL(-1) and 11% at > or = 300 ng mL(-1). QRS values were increased significantly in patients with serum flecainide < 300 ng mL(-1) compared with > or = 300 ng mL(-1) (0.110 +/- 0.016 s vs 0.093 +/- 0.019 s, P < 0.05). We concluded that to control paroxysm in patients receiving flecainide for tachyarrhythmia serum flecainide concentrations should be maintained at > or = 300 ng mL(-1).

Anti-Arrhythmia Agents↗
PubMed1995

Voltage dependent inhibition of ATP sensitive potassium channels by flecainide in guinea pig ventricular cells.

OBJECTIVE: The aim was to examine the effects of flecainide, a class Ic antiarrhythmic drug, on the ATP sensitive potassium channel (KATP channel) current in guinea pig ventricular cells, using the inside-out patch clamp technique. METHODS: KATP channel activities were recorded from inside-out membrane patches with 140 mM KCl solution bathing both the external and internal surfaces of the membrane (20-22 degrees C). Flecainide was added to the intracellular medium (ATP-free, pH = 7.3). RESULTS: Flecainide (1-300 microM) inhibited the outward KATP channel current evoked at the holding potential of +40 mV, in a concentration dependent manner. The flecainide concentration for half maximum inhibition of the channel activity (IC50) and Hill coefficient of the flecainide inhibition were estimated to be 17.3 microM and 1.1, respectively. However, flecainide did not affect the inwardly directed KATP channel current measured at the potential of -40 mV. When the inhibitory effects of flecainide on the outward current were examined under conditions in which pH was decreased from 7.3 (control) to 6.8, the IC50 and Hill coefficient became 27.3 microM and 1.2, respectively. Furthermore, in the presence of 0.1 mM ADP on the cytosolic side of the membrane (pH = 7.3), flecainide blocked the outward currents with the IC50 of 47.0 microM and a Hill coefficient of 0.9. After 1 min exposure of the cytoplasmic side of the membrane to trypsin (1 mg.ml-1), glibenclamide (2 microM) did not inhibit the KATP channel currents, while flecainide (30 microM) reversibly inhibited this trypsin enhanced KATP channel activity. CONCLUSIONS: Flecainide at relatively high concentrations blocks the cardiac KATP channels only when the currents are directed outward, and in a concentration dependent manner. The potency of flecainide in blocking KATP channels decreased under conditions of increased H+ or ADP concentrations on the cytosolic side of the membrane, as may occur in myocardial ischaemia or hypoxia.

Adenosine Diphosphate↗
PubMed1988

Clinical and electrophysiologic effects of flecainide in patients with refractory ventricular tachycardia.

The electrophysiologic effects and antiarrhythmic efficacy of flecainide were evaluated by electrophysiologic study (EPS) in 20 patients with ventricular tachycardia (VT) refractory to an average 2.9 drugs. In 19 patients EPSs were performed with patients not receiving antiarrhythmic medications and receiving oral flecainide therapy at steady state (mean dose, 235 +/- 67 mg/day). Flecainide significantly increased the QRS complex duration (27%, P less than .001), PR interval (17%, P less than .001), and right ventricular effective refractory periods 8.5% and 21.1% (P less than .01) for the first and second extrastimuli, respectively. During baseline EPS, 17 patients were induced into VT and two were noninducible. Flecainide prevented EPS-induced VT in five patients and the induced VT became slow and hemodynamically stable in three. Two patients who failed flecainide monotherapy were induced into slow hemodynamically stable VT with flecainide in combination with amiodarone. The two noninducible patients, during baseline EPS, had suppression of spontaneous VT with flecainide. Overall, 13 of 20 patients received flecainide either alone or in combination with amiodarone for chronic therapy. Side effects encountered during the study consisted of blurred vision, dizziness, weakness, lethargy, nausea, worsened heart failure and bradyarrhythmias. After a mean 9-month follow-up (3 to 16 months) nine patients remain on flecainide therapy. There were three recurrences of slow, hemodynamically stable VT and no episodes of sudden death. Low-dose flecainide, either alone or in combination with other agents, is effective therapy for certain patients with refractory VT but heart failure remains a significant concern in patients with depressed left ventricular function.

Aged↗
PubMed1986

Treatment of paroxysmal reentrant supraventricular tachycardia with flecainide acetate.

The electrophysiologic effects and therapeutic efficacy of intravenous and oral flecainide were studied in 15 patients with spontaneous and inducible sustained paroxysmal supraventricular tachycardia (SVT). Twelve patients had atrioventricular (AV) reentrance using an accessory pathway for retrograde conduction and 3 had AV nodal reentrance. Fourteen patients received intravenous flecainide (2 mg/kg body weight over 15 minutes) during an initial electrophysiologic study. Nine patients were restudied during oral flecainide administration (200 to 400 mg/day). After intravenous or oral flecainide therapy, reentrant SVT was noninducible in 6 patients with AV reentrance and in the 3 with AV nodal reentrance. In these 9 patients, intravenous flecainide prevented induction of reentrant SVT by depressing conduction over the retrograde limb of the reentry circuits. In the 6 patients with inducible sustained AV reentrant SVT before and after flecainide therapy, the cycle length of tachycardia increased significantly, mainly as the result of an increase in ventriculoatrial conduction time. There was concordance between the intravenous and the oral effects of flecainide on the mechanism of the SVT. Twelve patients continued oral flecainide treatment for a mean of 16 months (range 5 to 28). Tachycardia recurred in 3 of 4 patients whose arrhythmia remained inducible after flecainide therapy and in 1 of 8 patients whose SVT was suppressed. It is concluded that flecainide is an effective and convenient antiarrhythmic agent to treat patients who have AV nodal or AV reentrant SVT.

Administration, Oral↗
PubMed1989

Reversal of electrophysiologic effects of flecainide on the accessory pathway by isoproterenol in the Wolff-Parkinson-White syndrome.

To determine the reversibility of the effects of flecainide on accessory pathways, electrophysiologic studies were performed in the drug-free control state, after flecainide loading and with isoproterenol infusion during flecainide treatment in 12 patients with symptomatic preexcitation syndrome. After the baseline drug-free evaluation, oral flecainide was given in dosages of 50 to 200 mg twice daily (mean daily dose 282 +/- 75) for at least 4 days before the repeat electrophysiologic study. Isoproterenol infusion was given in dosages of 1 to 4 micrograms/min to increase the heart rate at rest by 50%. Anterograde block in the accessory pathway was observed in 3 patients with flecainide therapy, whereas in the other patients the anterograde refractory period increased from 243 +/- 20 to 315 +/- 23 ms (p less than 0.05). The shortest preexcited RR interval during atrial fibrillation lengthened from 234 +/- 27 ms before flecainide to 313 +/- 38 ms (p less than 0.05). Retrograde block occurred in 2 patients after flecainide, whereas the retrograde refractory period of the accessory pathway increased from 247 +/- 26 to 337 +/- 45 ms in the other patients. Orthodromic atrioventricular reciprocating tachycardia, inducible in 10 patients before therapy, became noninducible in 3 patients. Its rate was significantly slowed in the other 7 patients (from 346 +/- 50 to 471 +/- 81 ms). In 2 patients the tachycardia was nonsustained during flecainide treatment. Atrial fibrillation, inducible in all patients at baseline, was rendered nonsustained and more difficult to induce in 7 patients with flecainide. When isoproterenol was infused during flecainide treatment, complete anterograde (3 patients) or retrograde block (2 patients) persisted in the accessory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1996

Efficacy and safety of long-term oral flecainide acetate in patients with responsive supraventricular tachycardia.

In 102 patients with inducible supraventricular tachycardia (SVT), 56 women and 46 men aged 20-86 (mean, 52) years, underwent electrophysiologic study. SVTs observed at electrophysiologic study were atrial flutter or atrial fibrillation (32%), the "slow-fast" form of atrioventricular (AV) nodal reentrant tachycardia (45%), orthodromic AV reentrant tachycardia (25%), and atrial tachycardia (9%). More than 1 SVT occurred in some patients. Spontaneous symptomatic SVT frequency prior to oral flecainide varied from 3/day to 1/3 months (mean, 3/month). At electrophysiologic study and during SVT, intravenous flecainide, 2 mg/kg body weight, was given at an infusion rate of 10 mg/min up to a maximum dose of 150 mg. Patients were commenced on oral flecainide if SVT termination occurred during intravenous flecainide administration and if reinitiation was not possible after the total dose of flecainide had been given. In patients with AV nodal reentrant tachycardia and AV reentrant tachycardia further criteria for commencing oral flecainide were SVT termination by ventricular-atrial conduction block and persistent ventricular-atrial block after intravenous flecainide administration. Initial oral flecainide dosage was determined by assessing ability to reinitiate SVT after 50 mg, 100 mg, and the total dose of intravenous flecainide had been given. Eighty-nine patients (87%) remained free of symptomatic SVT over a mean follow-up period of 3.9 years (range, 3 months to 6.5 years). Two thirds were still taking the original dosage of flecainide and the rest were SVT-free on a higher dosage. Oral dosages ranged from 50 to 300 mg/day (median dosage, 100 mg twice daily) Nine patients experienced minor side effects, including, lethargy, dizziness, headache, and blurred vision. There were no deaths and no reports of major proarrhythmic events or other major adverse effects.

Administration, Oral↗
PubMed1989

The pharmacodynamic and pharmacokinetic interaction between single doses of flecainide acetate and verapamil: effects on cardiac function and drug clearance.

Flecainide and verapamil are antiarrhythmic agents that may be used in combination. We have examined their pharmacodynamic interaction by M-mode echocardiography and electrocardiography in eight normal male volunteers (24 +/- 1.8 years of age). Flecainide decreased the left ventricular ejection fraction (LVEF) (-4.4 +/- 1.2%, p less than 0.008), but verapamil did not. Neither drug affected cardiac output or vascular resistance. Both drugs increased the PR interval (12 +/- 4 msec, p less than 0.01 for flecainide; 12 +/- 5, p less than 0.04 for verapamil). Flecainide, but not verapamil, increased the QTc interval (23 +/- 8 msec, p less than 0.02). Both drugs also increased the systolic time interval ratio (PEPc/LVETc) (0.074 +/- 0.012, p less than 0.0004 for flecainide; 0.029 +/- 0.008, p less than 0.007 for verapamil). The combination of flecainide and verapamil had additive effects on myocardial contractility and on atrioventricular conduction. Verapamil slightly decreased the plasma clearance of flecainide (7.78 +/- 0.60 ml/kg/min for flecainide alone, 7.34 +/- 0.48 ml/kg/min for flecainide and verapamil together, p less than 0.05). On the other hand, flecainide had no effect on the plasma clearance of verapamil, which suggests that there was little interaction between the two drugs on their pharmacokinetic parameters.

Administration, Oral↗
PubMed1994

Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone.

We studied the influence of cytochrome P450 2D6 (CYP2D6) on the steady-state disposition kinetics and the electrocardiographic effects of flecainide at two doses and during combination with amiodarone. Seven extensive and five poor metabolizers of dextromethorphan were studied during a three-period crossover study. All subjects received 50 mg flecainide every 12 hours, alone or together with 200 mg amiodarone every 12 hours, and 100 mg flecainide every 12 hours for 5 days. Mean steady-state plasma concentration of flecainide and QRS change from predrug value did not differ significantly among extensive and poor metabolizer subjects during each study period. Except for a shortened elimination half-life and nonlinear kinetics in extensive metabolizer subjects, phenotype had no significant influence on flecainide pharmacokinetics. Combination with amiodarone resulted in an increase in mean flecainide plasma concentration and effect in subjects with both phenotypes. Our findings indicate that CYP2D6 phenotype predicts flecainide nonlinear kinetics and flecainide half-life but has no influence on electrocardiographic effects during repeated administration of flecainide or on the extent of the amiodarone-flecainide interaction.

Administration, Oral↗
PubMed2005

Pilot study: Noninvasive monitoring of oral flecainide's effects on atrial electrophysiology during persistent human atrial fibrillation using the surface electrocardiogram.

BACKGROUND: The relation between flecainide's plasma level and its influence on human atrial electrophysiology during acute and maintenance therapy of atrial fibrillation (AF) is unknown. Therefore, this study determined flecainide plasma levels and atrial fibrillatory rate obtained from the surface ECG during initiation and early maintenance of oral flecainide in patients with persistent lone AF and assessed their relationship. METHODS AND RESULTS: In 10 patients (5 males, mean age 63 +/- 14 years, left atrial diameter 46 +/- 3 mm) with persistent lone AF, flecainide was administered as a single oral bolus (day 1) followed by 200-400 mg/day (days 2-5). The initial 300 mg flecainide bolus resulted in therapeutic plasma levels in all patients (range 288-629 ng/ml) with no side effects. Flecainide plasma levels increased on day 3 and remained stable thereafter. Day 5 plasma levels were lower (508 +/- 135 vs 974 +/- 276 ng/ml, P = 0.009) in patients with daily mean flecainide doses of 200 mg compared to patients with higher maintenance doses. Fibrillatory rate obtained from the surface electrocardiogram measuring 378 +/- 17 fpm at baseline was reduced to 270 +/- 18 fpm (P < 0.001) after the flecainide bolus but remained stable thereafter. Fibrillatory rate reduction was independent of flecainide plasma levels or clinical variables. CONCLUSION: A 300 mg oral flecainide bolus is associated with electrophysiologic effects that are not increased during early maintenance therapy in persistent human lone AF. In contrast to drug plasma levels, serial analysis of fibrillatory rate allows monitoring of individual drug effects on atrial electrophysiology.

Aged↗
PubMed1993

Flecainide-induced arrhythmia in canine ventricular epicardium. Phase 2 reentry?

BACKGROUND: We recently reported that sodium channel block can produce opposite effects on action potential duration (APD) and refractoriness in epicardial versus endocardial tissues of the canine ventricle. In addition, strong sodium channel current inhibition was found to cause loss of the action potential dome in epicardium but not endocardium, thus inducing a marked dispersion of repolarization and refractoriness between epicardium and endocardium as well as among neighboring epicardial sites. The marked heterogeneity that evolves under these conditions provides a substrate for the development of arrhythmias. Flecainide was found to induce extrasystolic activity more readily than other sodium blockers. The present study contrasts the electrophysiological actions of flecainide in canine ventricular epicardium and endocardium and examines the characteristics of flecainide-induced arrhythmias in epicardial sheets of canine ventricle. METHODS AND RESULTS: Standard microelectrode techniques were used. Flecainide (10-20 microM) produced either prolongation or marked abbreviation of APD in epicardium but only minor changes in the APD of endocardium. Marked abbreviation of APD in epicardium was due to loss of the action potential dome (plateau phase). Arrhythmias displaying characteristics of reentry could be readily induced in flecainide-treated preparations either by increasing the stimulation rate or by introduction of extrastimuli. Flecainide-induced slowing of conduction, more accentuated at the faster stimulation rates, appeared to act synergistically with the drug-induced dispersion of repolarization to generate reentry in these relatively small sheets of epicardium. 4-Aminopyridine, a transient outward current (Ito) blocker, reversed the flecainide-induced marked abbreviation of APD in epicardium and abolished reentrant activity in all cases. Flecainide failed to induce reentry in preparations pretreated with 4-aminopyridine. CONCLUSIONS: Our data suggest that the presence of a prominent Ito in epicardium contributes the development of marked electrical heterogeneity in the ventricle after exposure to flecainide. Flecainide-induced dispersion of repolarization, especially when accompanied by prominent conduction delays, results in extrasystolic activity via a mechanism that we have termed "phase 2 reentry." Our results also suggest a role for Ito blockers in the treatment of reentrant arrhythmias.

4-Aminopyridine↗
PubMed1992

Mechanism of flecainide's antiarrhythmic action in experimental atrial fibrillation.

Class Ic antiarrhythmic drugs are effective in the treatment of atrial fibrillation, but their mechanism of action is unknown. In previous work, we have found that flecainide causes tachycardia-dependent increases in atrial action potential duration (APD) and effective refractory period (ERP) by reducing APD accommodation to heart rate. The present study was designed to evaluate the efficacy and mechanisms of action of flecainide in an experimental model of sustained atrial fibrillation (AF). AF was produced by a brief burst of atrial pacing in the presence of vagal stimulation and persisted spontaneously until vagal stimulation was stopped. The actions of flecainide at two dose levels were compared with those of isotonic glucose placebo in each dog, with a randomized order of blinded drug administration. Flecainide terminated AF in all 16 dogs, while glucose was effective in none (p less than 0.0001). Flecainide increased atrial ERP and reduced conduction velocity in a tachycardia-dependent manner. Doses of flecainide that converted AF resulted in larger changes in ERP than in conduction velocity, increasing the minimum path-length capable of supporting reentry (wavelength). In addition, flecainide reduced regional heterogeneity in ERP and wavelength, an action opposite that of vagal stimulation. Atrial epicardial mapping with a 112-electrode atrial array was used to study the mechanism of flecainide action on AF. Under control conditions, multiple small zones of reentry coexisted. Flecainide progressively increased the size of reentry circuits, decreased their number, and slowed the frequency of atrial activation until the arrhythmia finally terminated; all changes were compatible with an increase in wavelength. We conclude that flecainide terminates atrial fibrillation in this experimental model by causing tachycardia-dependent increases in atrial ERP, which increase the wavelength at the rapid rates characteristic of AF to the point that the arrhythmia can no longer sustain itself.

Action Potentials↗
PubMed2006

[Flecainide controlled-release for prevention of atrial fibrillation relapse].

UNLABELLED: Flecainide acetate instant release (LI) has been prescribed for years in the prevention of atrial fibrillation (AF) relapse after sinus rate conversion. A new controlled-release (LP) formulation of flecainide was recently introduced. The objectives of this observational study were to evaluate the benefit/risk ratio of LI or LP flecainide treatment for prevention of AF relapse. METHODS: EPIFLEC study was an open, prospective, observational study conducted by 151 cardiologists who had prescribed either flecainide LI (group 1) to 838 patients or flecainide LP (group 2) to 214 patients or flecainide LI before LP (group 3) to 242 patients. In these patients, AF was either paroxystic (35%) or persistant (65%). Concomitant pathologies were observed in 80% of these patients (mean age 68 years) with a high incidence (50%) of hypertension. The mean duration of treatment was 6.9 +/- 6.7 months in group 1 (LI), 6.2 +/- 3.1 months in group 2 (LP) and 12.7 +/- 5.4 months in group 3 (LI-LP). RESULTS: mean daily dosages of flecainide were similar among the 3 groups. Antithrombotic drugs were prescribed in 74% (group 1) to 83% (group 2) of the patients and another antiarrhythmic drug was associated to flecainide among 12 to 21% of the patients. AF relapse was observed in 171 patients in group 1 (LI), 38 patients in group 2 (LP) and 39 patients in group 3 (LI-LP). The incidence of AF relapse was compared in groups 1 and 2 at 10 months of follow-up and AF relapse probability was not significantly different between flecainide LI and LP :26 +/- 2% and 23 +/- 4% respectively (OR = 0.99, CI 95%:0.69-1.4; p = 0.96). A multivariate analysis showed that previous multiples episodes of AF, electrical shock rate conversion and history of flutter and hypertension were independent predictors of AF relapse. Among 11 deaths observed during follow-up, only 2 were cardiovascular. The most frequent non lethal cardiovascular adverse events were arrhythmias or cardiac conduction disorders and were limited to less than 5% of the patients. Only 5 supraventricular transient pro arrhythmias episodes were recorded. CONCLUSION: this pharmaco-epidemiological study in private practice confirms that flecainide is able to prevent AF relapse in 75% of patients at 10 months and that the tolerance of the treatment is acceptable in these patients.

Aged↗
PubMedDate not supplied

Dose-dependent tissue uptake of flecainide during chronic administration in rabbits.

This study was designed to examine the metabolism of flecainide after repeated administration to rabbits. New Zealand White rabbits were administered either 7.5 mg/kg body weight (dose I) or 20 mg/kg body weight (dose II) flecainide twice daily intraperitoneally for 12-14 days. Serum, heart, liver, lung, kidney, muscle, fat, and brain were collected upon death. Flecainide concentrations in serum and tissues were determined by a liquid chromatographic procedure standardized in our laboratory. Serum and tissue flecainide concentrations showed a significant, dose-dependent increase after chronic administration. Flecainide accumulated in lung, liver, kidney, and heart, its concentration decreasing in that order. Tissue to serum flecainide ratios also followed a similar pattern. Cornea and urine contained flecainide metabolites which were not characterized. Only traces of flecainide were detected in brain and fat tissues. Substantial tissue uptake of flecainide should be considered in long term flecainide therapy.

Animals↗
PubMed1987

[Inhibition of flecainide resorption by activated charcoal].

The effect of orally administered activated charcoal on plasma concentrations of flecainide were studied in eight volunteers (24-38 years of age). A single dose of 200 mg flecainide were given at 3 days: control (day 1); simultaneous application of flecainide and 30 g charcoal (day 2); application of 30 g charcoal 90 min after flecainide (day 3). Plasma concentrations were determined by HPLC after 2, 4 and 6 h. Absorption of flecainide was almost completely prevented, when flecainide and charcoal was ingested immediately. When charcoal was taken 90 min after flecainide, the following flecainide plasma levels were found: after 2 h 231 +/- 62 ng/ml (266 +/- 30 ng/ml control; n.s.), after 4 h 199 +/- 49 ng/ml (232 +/- 27 ng/ml control; P less than 0.05) and after 6 h 155 +/- 42 ng/ml (231 +/- 51 ng/ml control; P less than 0.01). Charcoal seems to be effective in prevention of the absorption of flecainide. A drug interaction may occur if charcoal is given therapeutically, for example in hypercholesterolaemia. Charcoal may be indicated as an additional treatment of flecainide intoxication.

Administration, Oral↗
PubMed1995

Flecainide and amiodarone: combined therapy for refractory tachyarrhythmias in infancy.

OBJECTIVES: This study assessed the safety and efficacy of combined flecainide and amiodarone therapy in controlling refractory tachyarrhythmias in infants. BACKGROUND: Single-drug as well as standard combination medical therapy for tachyarrhythmias in infants sometimes fails. In those cases, one may consider interventional therapy. However, this option may carry a high risk of morbidity and mortality in infants. The natural history of tachyarrhythmias in infants often favors eventual resolution and reinforces the importance of selecting an effective medical regimen. METHODS: We performed a retrospective analysis of nine infants (median age 2 months) who received combined flecainide and amiodarone therapy for attempted control of refractory tachyarrhythmias. Trough serum drug levels of flecainide were monitored, and 24-h ambulatory electrocardiographic monitoring was used to determine efficacy of therapy. RESULTS: Single-drug treatment with flecainide or amiodarone failed in all of the infants studied. An average of four drugs failed (range one to six) before administration of combined flecainide and amiodarone therapy. During combined therapy, the flecainide dose was 70 to 110 mg/m2 per day, and that for amiodarone was 7.5 to 13.5 mg/kg per day for a mean (+/- SD) of 9 +/- 2 days to load and 5 to 12 mg/kg per day as maintenance. Successful control of tachyarrhythmias was demonstrated in seven (78%) of nine infants (95% confidence interval 46% to 99%) (three of three with congenital junctional ectopic tachycardia, three of three with supraventricular tachycardia and one of three with ventricular tachycardia). During combined therapy, flecainide trough levels ranged from 350 to 731 ng/ml. Corrected QT intervals varied from 0.440 to 0.488 ms. No proarrhythmia occurred. None of the infants required a pacemaker, and all had normal left ventricular dimensions and fractional shortening by echocardiography. Eight of nine infants had a structurally normal heart. One infant had surgical correction of an atrioventricular septal defect. CONCLUSIONS: Combination therapy with flecainide and amiodarone appears to be safe and effective in controlling refractory tachyarrhythmias in infants. The combination of flecainide and amiodarone may obviate the need for early interventional therapy or may allow delay until the child is older.

Amiodarone↗
PubMed2005

Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome.

OBJECTIVES: The purpose of this study was to compare the effect of intravenous flecainide and ajmaline with respect to their ability to induce or accentuate the typical ECG pattern of Brugada syndrome. BACKGROUND: Brugada syndrome is associated with a high incidence of sudden cardiac death. The typical ECG pattern of ST-segment elevation in the right precordial leads often is concealed, but it can be unmasked with sodium channel blockers such as flecainide and ajmaline. Little is known about the relative effectiveness of these provocative agents in unmasking Brugada syndrome. METHODS: Intravenous pharmacologic challenge with flecainide and ajmaline was performed. Whole-cell patch clamp techniques were used to assess the relative potency of ajmaline and flecainide to inhibit the transient outward current (I(to)). RESULTS: A coved-type ST-segment elevation in the right precordial leads was induced or enhanced in 22 of 22 patients following ajmaline administration. Among the 22 patients, only 15 patients showed positive response to flecainide, resulting in a positive concordance of 68%. Both drugs produced equivalent changes in QRS and PQ intervals, suggesting similar effects on sodium channel current. Whole-cell patch clamp experiments revealed a reduction of the total charge provided by I(to) with an IC(50) of 216 and 15.2 microM for ajmaline and flecainide, respectively. CONCLUSIONS: Our data demonstrate disparate response of Brugada patients to flecainide and ajmaline, with a failure of flecainide in 7 of 22 cases (32%). Greater inhibition of I(to) by flecainide may render it less effective. These observations have important implication for identification of patients at risk for sudden death.

Ajmaline↗