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At least 19 recordsLinked to original sources

PubMed1991

Flecainide acetate prevents recurrence of symptomatic paroxysmal supraventricular tachycardia. The Flecainide Supraventricular Tachycardia Study Group.

Oral flecainide acetate was administered to 34 patients with documented symptomatic paroxysmal supraventricular tachycardia (PSVT) with a double-blind, placebo-controlled, 8-week crossover trial design. PSVT was defined as a regular tachycardia of at least 120 beats/min without evidence of atrioventricular dissociation. The study required considerable patient cooperation. Patients first entered a 4-week qualifying phase followed by a 3-week, open label, flecainide dose-ranging phase. They were then randomized in a blind fashion to receive either placebo or tolerated flecainide dose for an 8-week treatment period and then crossed over after four symptomatic documented episodes of PSVT or at the end of the treatment period. By all efficacy parameters analyzed, flecainide was superior to placebo. Flecainide was associated with an actuarial 79% freedom from symptomatic PSVT events compared with only 15% on placebo at 60 days (p less than 0.001). Of the 34 patients, 29 had recurrence of symptomatic PSVT at least once during the placebo phase; only eight patients had a recurrence during the flecainide phase (p less than 0.001). The median time to the first symptomatic PSVT event was 11 days in the placebo group and greater than 55 days in the flecainide group (p less than 0.001). Likewise, the interval between attacks was a median of 12 days on placebo compared with more than 55 days on flecainide (p less than 0.001). Finally, the flecainide slowed symptomatic PSVT heart rates to 143 +/- 12 beats/min from 178 +/- 12 on placebo (p less than 0.02) in the seven patients who had events in the placebo and flecainide treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1987

Chronic flecainide therapy selected by electrophysiology testing of intravenous flecainide.

The utility of flecainide acetate was evaluated in 93 patients by means of electrophysiologic studies before and after intravenous flecainide administration to determine long-term efficacy. Twenty patients had a prior history of at least one cardiac arrest and 73 patients had sustained ventricular tachycardia (VT). The mean radionuclear ejection fraction was 32 +/- 5%. Flecainide was evaluated in 93 patients, with 44 patients no longer having VT following flecainide (47% efficacy). Procainamide was evaluated in 69 patients; 24 patients had an adverse reaction to reaction to procainamide and 28 of the 69 patients were protected on procainamide (40% efficacy). The mean serum concentration of flecainide achieved in the protected group was 298 +/- 36 ng/ml and 4.3 micrograms/ml for procainamide. Both flecainide and procainamide significantly prolonged refractoriness, lengthened QRS duration, while only procainamide increased the QT interval. All 93 patients were discharged on antiarrhythmic therapy, 42 on flecainide, 27 on other antiarrhythmic therapy guided by electrophysiologic testing, and 24 on amiodarone (when all other agents failed). Six of the 42 patients on flecainide complained of adverse side effects, but none were severe enough to warrant stopping therapy. Of the 42 patients on flecainide, four (9%) died suddenly over 18 +/- 4 months. Twenty-seven patients were on other therapy; eight of these have died, three suddenly (11%), four with myocardial infarctions, and one due to congestive heart failure. Twenty-four patients started amiodarone; 11 have died, five (21%) suddenly, four of congestive heart failure, one of pulmonary fibrosis, and one with myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1988

[Concentrations of amiodarone and flecainide in plasma and saliva--indications for the active transport of flecainide].

UNLABELLED: Only the free protein-unbound drug concentration in plasma is pharmacologically active. The concentration of some drugs in saliva is equal to the free drug level. We compared concentrations (in plasma before, 30 and 60 min after the morning dose, in saliva before, 30, 60, 90 and 120 min after the morning dose) of amiodarone (n = 8, 2 x 200 mg orally per day) and flecainide (n = 16, 2 x 100 mg) administered as chronic antiarrhythmic treatment. Drug levels were measured by "high performance liquid chromatography". RESULTS: Just prior to the first morning dose, amiodarone concentrations in plasma were 1.0-2.9 (2.0 +/- 0.6) micrograms/ml, in saliva 0.02-0.25 micrograms/ml; flecainide in plasma 80-560 (316 +/- 163) ng/ml, in saliva 630-3700 (1749 +/- 963) ng/ml. After the morning dose we found maximal flecainide plasma levels of 462 +/- 203 and saliva levels of 3218 +/- 2857 ng/ml. The highest flecainide concentrations in the saliva (13,400 and 11,300 ng/ml) were found in two patients 30 and 60 min after the morning dose. Flecainide, but not amiodarone, is excreted actively in the saliva, probably indicating an enteroenteric circulation. This should be considered to reduce life-threatening flecainide intoxications by gastric and intestinal lavage and suction. The concentration of flecainide in the saliva does not represent the non-protein-bound free drug level in the plasma.

Adult↗

PubMed1991

Usefulness of flecainide for prevention of paroxysmal atrial fibrillation and flutter. Danish-Norwegian Flecainide Multicenter Study Group.

To evaluate the efficacy of flecainide acetate in the prevention of paroxysmal atrial fibrillation and flutter, 43 patients (23 men) (mean age 53 years) were randomized blindly to receive either placebo or 150 mg of flecainide twice per day for consecutive periods of 3 months. Attacks were verified by a minielectrocardiogram event recorder. If intolerable symptoms developed, the protocol allowed patients to cross over between treatments before the end of the first 3-month period. Four patients crossed over prematurely, between 1 week and 1 month, and 15 between 1 month and 3 months. The remaining 24 patients completed both 3-month periods. In all 3 treatment intervals, there was a significant reduction in the number of attacks during flecainide treatment (p less than 0.002). Complete suppression was seen in 15 of 43 patients (35%) treated with flecainide for 1 week, in 18 of 39 (46%) treated for 1 month and in 12 of 24 (50%) completing all 3 months in each period. Adverse effects were reported in 32 of the 43 patients (74%) treated with flecainide, but only 2 were withdrawals. One patient died suddenly. In comparison, 3 of 43 patients (7%) reported adverse effects in the placebo group. In conclusion, flecainide significantly suppressed the number of attacks of paroxysmal atrial fibrillation and flutter. Adverse effects were frequent but were mostly tolerable.

Adult↗

PubMed1987

[Treatment of recurrent supraventricular tachyarrhythmias with flecainide or a flecainide and amiodarone combination].

The acute electrophysiologic effects and therapeutic efficacy of intravenous and oral flecainide were assessed in 18 patients with recurrent supraventricular tachyarrhythmias, resistant to conventional antiarrhythmic agents. They were 22 to 76 years old (mean 50). Twelve patients underwent electrophysiologic study for the investigation of tachyarrhythmias. Of the whole four patients had functional longitudinal AH dissociation (dual AV pathways). These patients had provocable intra-AV nodal reentrant tachycardia (Group I). Six patients had a direct accessory AV pathway, that showed bidirectional conduction in 5 and retrograde conduction alone in 1 (Group II). These patients had provocable atrioventricular reentrant tachycardia using the accessory pathway as the retrograde limb of the tachycardia circuit. Two patients suffered from automatic supraventricular tachycardia (Group III). Group IV included patients with paroxysmal atrial flutter or fibrillation. The patients of this group did not discontinue chronic treatment with amiodarone. After baseline electrophysiologic evaluation, intravenous flecainide (2 mg/Kg body weight over 5 minutes) was given to patients of I and II group during induced reentrant tachycardia. Flecainide was administered to other patients during spontaneous episodes of tachyarrhythmias. Flecainide resulted in tachycardia termination in all patients of group I and in 4 patients of group II (66%). Tachycardia termination was due to block in the retrograde limb of the circuit. Before termination tachycardia cycle length increased significantly, mainly as the result of an increase in ventriculo-atrial conduction time. After intravenous flecainide therapy, reentrant SVT was non inducible in the patients of group I and in 4 patients of group II. Flecainide was successful in the acute termination of 100% of automatic supraventricular tachycardia and 75% of fibrillation. The patients with atrial flutter developed a faster ventricular rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1991

Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group.

The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2).

Adult↗

PubMed1989

Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group.

Paroxysmal atrial fibrillation (PAF) is a problematic clinical arrhythmia that is usually symptomatic. Unfortunately, few adequate trials and trial methods are available for assessment of the value of therapy, and traditional treatment has often been ineffective or associated with unacceptable side effects. Transtelephonic monitoring is a new method that allows evaluation of paroxysmal arrhythmias and arrhythmia-related symptoms in outpatients. We used a patient-initiated transtelephonic monitor system to evaluate the potential of flecainide, a class 1C antiarrhythmic, in prevention of symptomatic recurrences of PAF. Sixty-four patients qualified for the study (two or more PAF attacks documented within a 4-week baseline period) and entered a dose-finding phase to determine drug tolerance. Dose was incremented at weekly intervals from 200-300 and finally to 400 mg/day. The largest dose that was well tolerated was selected for the 4-month, double-blind, randomized, crossover comparison with placebo. Fifty-five patients entered and 53 received both treatments in the double-blind phase; 48 of these patients without protocol violations were evaluable for efficacy comparisons. Evaluable patients had undergone an average of 3.8 previous drug trials (range, 1-8); 30 were men, 18 had hypertension, and 14 had ischemic heart disease. The study demonstrated a highly significant correlation (p less than 0.0001) between perceived symptoms and documented PAF by transtelephonic monitoring. The rate of symptoms and PAF attacks was also significantly reduced by therapy (median dose, 300 mg/day). The first PAF attack occurred after a median of 3 days on placebo versus 14.5 days on flecainide (p less than 0.001) therapy. Similarly, the time interval between attacks was lengthened, from a median of 6.2 days on placebo to 27.0 days on flecainide (p less than 0.001) therapy. PAF was prevented in 15 patients (31%) during flecainide and four (9%) during placebo therapy (p = 0.013). However, during the study, 13 patients dropped out, seven because of adverse effects (five cardiac), five for other reasons, and one because of cardiac arrest/death. Adverse cardiac events occurred in a total of seven patients (11%) during flecainide therapy. Thus, transtelephonic monitoring is a useful method for documentation of the occurrence of paroxysmal arrhythmias such as PAF and its related symptoms during daily living and for assessment of new therapies in an outpatient setting.

Atrial Fibrillation↗

PubMed1992

Long-term safety and efficacy of flecainide in the treatment of supraventricular tachyarrhythmias: the United States experience. The Flecainide Supraventricular Tachyarrhythmia Investigators.

Information about long-term safety and effectiveness is important for appropriate use of antiarrhythmic drug therapy. We report the results of an open-label, long-term (mean, 15 months) therapy extension for 66 patients with paroxysmal supraventricular tachycardia (PSVT) or atrial fibrillation (PAF) in whom short-term therapy in 2 controlled studies was deemed beneficial by both patient and investigator. Follow-up was accomplished by clinic visits and telephone calls. Results indicated excellent ongoing tolerance and safety. Only 3 (5%) of 66 patients discontinued therapy due to possible noncardiac adverse effects. Only 5 (7.6%) discontinued therapy due to inadequate clinical response. Only 1 discontinuation was ascribed to a worsening arrhythmia (increased frequency of sustained PAF). In PSVT patients, 75% of months were arrhythmia free; in PAF patients, 64% of months were attack free. No clinically significant laboratory, electrocardiographic, or physical abnormalities were ascribed to flecainide. Thus, the long-term safety and efficacy profile of the drug for treatment of PSVT and PAF is encouraging. This promising clinical experience is relatively small and so should be reinforced by larger patient trials in the future.

Atrial Fibrillation↗

PubMed1990

Electrophysiologic effects of isoproterenol in patients with atrioventricular reentrant tachycardia treated with flecainide.

UNLABELLED: The electrophysiologic effects of isoproterenol in patients treated with flecainide for atrioventricular (AV) reentrant tachycardia were studied to evaluate the mechanism of tachycardia inducibility after isoproterenol and the value of isoproterenol challenge as a predictor of spontaneous arrhythmia recurrence. Seventeen patients underwent electrophysiologic study before and after oral flecainide administration and after the addition of isoproterenol to flecainide. No patient had inducible sustained supraventricular tachycardia after flecainide alone. Two patients had inducible sustained and six had inducible nonsustained tachycardia after isoproterenol was added to flecainide. The patients were then followed up on the same flecainide dose they received at the time of the electrophysiologic study. FINDINGS: 1) Flecainide treatment prolonged HV and VA intervals, and the addition of isoproterenol did not affect these variables. 2) Isoproterenol shortened anterograde and retrograde block cycle length and the refractory period of the accessory pathway and the AV node. It also decreased the tachycardia cycle length, an effect that was due solely to shortening of AV node conduction time. 3) Flecainide treatment prevented tachycardia induction by affecting retrograde conduction over the accessory pathway. Isoproterenol allowed for tachycardia induction and for more sustained episodes of tachycardia by reversing the effect of flecainide on retrograde accessory pathway conduction. 4) Tachycardia recurred during follow-up in all three patients in whom tachycardia of greater than or equal to 10 s duration was induced after isoproterenol but in no patient who had no or shorter episodes of induced tachycardia (and who did not have a change in medical regimen). CONCLUSIONS: 1) Isoproterenol reverses flecainide-induced prolongation of block cycle length and refractory periods of the accessory pathway and AV node. 2) Isoproterenol reverses flecainide-induced prevention of tachycardia induction through reversal of the effects of flecainide on the retrograde accessory pathway. 3) The addition of isoproterenol during flecainide restudy is valuable in predicting long-term drug efficacy.

Cardiac Pacing, Artificial↗

PubMed1989

Stereoselective disposition of flecainide in relation to the sparteine/debrisoquine metaboliser phenotype.

1. The disposition of the enantiomers of the antiarrhythmic drug flecainide has been studied in five extensive (EM) and five poor (PM) metabolisers of sparteine/debrisoquine after administration of 50 mg of racemic flecainide acetate under conditions of high urinary flow rate and acidic urinary pH. 2. In the EM subjects there were no significant differences in the oral clearance, half-life or urinary excretion of (+)-S- and (-)-R-flecainide. 3. In the PM subjects differences in the pharmacokinetics of S- and R-flecainide were observed. The oral clearance of R-flecainide (467 +/- 109 ml min-1) was less (P less than 0.03) than that of the S-enantiomer (620 +/- 172 ml min-1). The half-life of R-flecainide (12.9 h) was longer (P less than 0.03) than that of S-flecainide (9.8 h). The renal clearance of the two enantiomers was, however, comparable and similar to that observed in the EM subjects. The urinary recovery of R-flecainide (15.6 +/- 3.7 mg) was greater (P less than 0.03) than that of the S-enantiomer (12.0 +/- 3.7 mg). The enantioselective disposition observed in PMs is therefore due to greater impairment in the metabolism of R- than S-flecainide. 4. The urinary recoveries of two major metabolites of flecainide, meta-O-dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of flecainide (MODLF) were lower (P less than 0.05) in PMs, 12.0% +/- 3.1% and 8.2% +/- 3.2% of the dose administered, respectively, than in EMs of 17.7% +/- 3.3% and 16.5% +/- 3.3%, respectively. 5. One PM subject had a greatly diminished flecainide metabolic capacity and a rare genotype, as assigned by Xbal RFLP analysis.

Debrisoquin↗

PubMed1991

Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group.

The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease.

Anilides↗

PubMed1991

Electrophysiological effects of the combination of mexiletine and flecainide in guinea-pig ventricular fibres.

1. The effects of flecainide alone, mexiletine alone and their combination at the Na+ channel level were studied in guinea-pig papillary muscles. The maximum upstroke velocity (Vmax) was used as an indirect index of the magnitude of the fast inward Na+ current (INa). 2. In muscles driven at 0.02 Hz, neither mexiletine (10(-5) M) nor flecainide (10(-6) M) nor the combination of both drugs modified the action potential characteristics. Mexiletine, but not flecainide, increased the effective refractory period/action potential duration ratio; this enhancement was greater when flecainide was also present. 3. Mexiletine or flecainide alone produced a frequency-dependent Vmax block. Although at 0.5 Hz the blockade induced by the combination of flecainide and mexiletine was similar to that produced by flecainide alone, in muscles driven at 1 and 2 Hz the combination increased the magnitude and the onset rate of the Vmax block. 4. The time constant of recovery of Vmax block was similar in the presence of flecainide or the combination mexiletine plus flecainide (tau re = 16.4 +/- 2.3 s and 16.7 +/- 2.7 s, respectively), but the combination decreased the magnitude of the slow component of reactivation induced by flecainide (93.8 +/- 1.5% versus 68.9 +/- 1.7%). Moreover, the combination of both drugs was more effective in inhibiting the Vmax of early test stimuli than either drug alone. 5. It is concluded that the combination of mexiletine and flecainide is synergistic at driving rates faster than 0.5 Hz without detracting from the characteristics of flecainide.

Action Potentials↗

PubMed1990

Flecainide excretion in human breast milk.

Healthy human volunteers who intended not to breast feed were placed on a regimen of 100 mg oral flecainide every 12 hours for 5 1/2 days beginning 1 day after parturition. Milk and blood samples were collected during the dosing period and for 2 days after the last dose. Concentrations of flecainide in milk and plasma were assayed by HPLC. Apparent steady-state levels of flecainide in both milk and plasma were achieved in most cases by day 4 of the study. Highest daily average concentration of flecainide in milk ranged from 270 to 1529 ng/ml for the 11 subjects. Mean +/- SD milk to plasma flecainide ratios were 3.7 +/- 3.5, 3.2 +/- 2.3, 3.5 +/- 2.1, and 2.6 +/- 0.7 on study days 2, 3, 4, and 5, respectively. After the last dose of flecainide, peak milk levels of the drug occurred at 3 to 6 hours and then declined monoexponentially. The half-life for elimination of flecainide from milk was 14.7 +/- 3.5 hours and is very similar to the plasma elimination half-life of flecainide in healthy human subjects. The mean milk to plasma ratios for flecainide after the last dose were 2.3 +/- 1.0 and 2.9 +/- 1.1 at 24 and 48 hours after the dose, respectively. Based on the pharmacokinetics of flecainide in infants, the expected average steady-state plasma concentration of flecainide in a newborn infant consuming all of the milk production of its mother (approximately 700 ml/day) would not be expected to exceed about 62 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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↗

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↗

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↗

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↗

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↗