levetiracetam and Arrhythmias--Cardiac

Nonantiarrhythmic drugs may have the potential to prolong the QT interval, leading to potentially fatal ventricular tachycardias, including torsades de pointes.. This study evaluated the potential of the newer-generation, multiple-action antiepileptic drug levetiracetam, which binds to the synaptic vesicle protein SV2A, to affect cardiac repolarization, as detected by prolongation of the QT/corrected QT (QTc) interval.. This was a single-dose, randomized, placebo- and active-controlled, 4-way crossover study in healthy subjects. Subjects were randomly allocated to 1 of 4 different administration sequences. Each sequence included 3 double-blind treatments (levetirace-tam 1000 mg, levetiracetam 5000 mg, and placebo) and 1 open-label treatment (moxifloxacin 400 mg). Triplicate electrocardiograms (ECGs) were obtained at baseline and at various time points over 24 hours after each treatment using continuous Holter monitoring. ECGs were read centrally in a blinded manner. Blood samples for the determination of plasma concentrations of levetiracetam and moxifloxacin were collected before dosing and at 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours after dosing, within 5 minutes after the ECG recordings. The QT interval was corrected for heart rate using a sex- and study-specific correction (QTc(ss)) as the primary outcome measure and Fridericia's correction (QTc(F))as a secondary outcome measure. The primary analysis was performed on the time-matched, baseline-subtracted QTc(ss) (DeltaQTc(ss)). The maximum DeltaQTc(ss) difference between each active treatment and placebo (DeltaDeltaTc(ss)) was derived from a mixed-effect analysis of variance. Clinical laboratory tests, standard 12-lead ECGs, and vital signs were monitored at regular intervals. Spontaneously reported adverse events were recorded throughout the study.. Fifty-two healthy, nonsmoking subjects (26 men, 26 women; 37 white, 9 black, 3 Hispanic, and 3 Asian/Pacific Islander) with a mean (SD) age of 28.4 (7.5) years (range, 18-45 years) and a mean weight of 71.5 (12.6) kg (range, 49-103 kg) participated in the study. Levetiracetam did not significantly prolong the QTc(ss). The upper bound of the 1-sided 95% CI for the maximum DeltaDeltaTc(ss) was 8.0 milliseconds for levetiracetam 1000 mg and 8.1 milliseconds for levetiracetam 5000 mg, with mean estimates of 4.0 and 4.1 milliseconds, respectively; similar results were obtained for the maximum DeltaDeltaQTc(F). Moxifloxacin significantly prolonged the QTc(ss), with a lower bound of the 1-sided 95% CI for the maximum DeltaDeltaQTc(ss) of 3.7 milliseconds and a mean estimate of 7.7 milliseconds. There was no statistically significant relationship between measured DeltaQTc(ss) and the levetiracetam plasma concentration, whereas a significant linear relationship was observed between measured DeltaQTc(ss) and the moxifloxacin plasma concentration (slope estimate: 4.4 milliseconds/[microg/mL]); 95% CI, 3.2-5.7; P < 0.001). No unexpected safety concerns arose based on reported adverse events, clinical laboratory evaluations, physical examinations, vital signs, or ECG monitoring during the course of the study.. This randomized, placebo- and active-controlled study in healthy adult subjects found no clinically relevant changes in the QTc interval after a single levetiracetam dose of 1000 or 5000 mg.

Topics: Action Potentials; Adolescent; Adult; Anticonvulsants; Arrhythmias, Cardiac; Aza Compounds; Cross-Over Studies; Double-Blind Method; Electrocardiography, Ambulatory; Female; Fluoroquinolones; Heart Conduction System; Heart Rate; Humans; Levetiracetam; Male; Middle Aged; Moxifloxacin; Piracetam; Quinolines; Risk Assessment; Young Adult

To evaluate P-wave dispersion before and after antiepileptic drug (AED) treatment as well as to investigate the risk of ventricular repolarization using the Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio in patients with epileptic disorder.. A total of 63 patients receiving AED therapy and 35 healthy adults were included. ECG recordings were obtained before and 3 months after anti-epileptic treatment among patients with epilepsy. For both groups, Tp-e and Tp-e/QT ratio were measured using a 12-lead ECG device.. Tp-e interval, Tpe/QT and Tp-e/QTc ratios were found to be higher in the patient group than in the control group (p<0.05, for all), while QTmax ratio was significantly lower in the patient group. After 3 months of AED therapy, significant increases in QT max, QTc max, QTcd, Tp-e, Tp-e/QT, and Tp-e/QTc were found among the patients (p<0.05). When the arrhythmic effects of the drugs before and after treatment were compared, especially in the valproic acid group, there were significant increases in Tp-e interval, Tp-e/QT and Tp-e/QTc values after three months of treatment (p<0.05). Carbamazepine and levetiracetam groups were not statistically significant in terms of pre- and post-treatment values.. It was concluded that an arrhythmogenic environment may be associated with the disease, and patients who received AED monotherapy may need to be followed up more closely for arrhythmia.. A P-hullám-diszperzió értékelése antiepileptikus kezelés (AETh) előtt és után, valamint a ventricularis repolarizáció kockázatának vizsgálata a Tpeak-Tend (Tp-e) intervallum és a Tp-e/QT arány használatával epilepsziás betegek körében.. Hatvanhárom, AETh-ban részesülő beteget és 35 egészséges kontrollszemélyt vontunk be a vizsgálatba. Az epilepsziás betegek körében az EKG-vizsgálatot az AETh előtt és utána három hónappal végeztük. A Tp-e intervallumot és a Tp-e/QT arányt mindkét csoport esetében 12 elvezetéses EKG-berendezéssel mértük.. A Tp-e intervallum hosszabbnak, a Tp-e/QT és a Tp-e/QTc arányok magasabbnak bizonyultak a betegcsoportban, mint a kontrollok között (p < 0,05, mind­egyik esetében), ugyanakkor a QTmax-arány szignifikánsan alacsonyabb volt a betegcsoportban. Három hónap AETh után a betegek körében szignifikáns mértékben növekedett a QTmax, a QTcmax, a QTcd, a Tp-e, a Tp-e/QT és a Tp-e/QTc (p < 0,05). Miután értékelték az AETh arrhythmiás hatását, három hónapos kezelés után különösen a valproinsavval kezeltek esetében észlelték a Tp-e intervallum, a Tp-e/QT és a Tp-e/QTc arányok szignifikáns növekedését (p < 0,05). A carbamazepinnel és a levetiracetammal kezeltek esetében nem különböztek szignifikáns mértékben a terápia előtti és utáni értékek.. Az epilepszia arrhythmogen környezettel társulhat, és az AETh-ban részesülő betegeket szorosan monitorozni érdemes az arrhythmia kiszűrése érdekében.

Topics: Adult; Anticonvulsants; Arrhythmias, Cardiac; Carbamazepine; Case-Control Studies; Electrocardiography; Epilepsy; Heart Conduction System; Heart Ventricles; Humans; Levetiracetam; Valproic Acid

We previously demonstrated that insulin-induced severe hypoglycemia-associated sudden death is largely mediated by fatal cardiac arrhythmias. In the current study, a pharmacological approach was taken to explore the potential contribution of hypoglycemic seizures and the sympathoadrenergic system in mediating severe hypoglycemia-associated sudden death. Adult Sprague-Dawley rats were randomized into one of four treatment groups: 1) saline (SAL), 2) anti-arrhythmic (β

Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Anti-Arrhythmia Agents; Anticonvulsants; Arrhythmias, Cardiac; Atenolol; Death, Sudden, Cardiac; Drug Therapy, Combination; Electrocardiography; Hypoglycemia; Levetiracetam; Male; Rats; Rats, Sprague-Dawley; Seizures

Antiepileptic medications have been reported to cause disturbances in cardiac conduction. Lacosamide decreases seizure burden by modulating sodium channels. Although it has been demonstrated to have few side effects, there have been reports of clinically significant cardiac conduction disturbances. We report the case of a child with hypoplastic left-heart syndrome and well-controlled multifocal atrial tachycardia who developed haemodynamically significant atrial tachycardia after receiving two doses of lacosamide.

Topics: Acetamides; Anticonvulsants; Arrhythmias, Cardiac; Child, Preschool; Comorbidity; Humans; Hypoplastic Left Heart Syndrome; Isoxazoles; Lacosamide; Levetiracetam; Male; Piracetam; Seizures; Tachycardia, Sinus; Treatment Outcome; Zonisamide