Fluvoxamine at 100 times therapeutic concentration prolonged the terminal repolarization phase in anesthetized dogs, indicating potential to directly induce long QT syndrome.
Does fluvoxamine prolong the QT interval and induce proarrhythmic effects in an in vivo canine model?
Fluvoxamine has the potential to directly induce long QT syndrome and proarrhythmic effects at supra-therapeutic concentrations by delaying repolarization in a reverse use-dependent manner.
Fluvoxamine is one of the typical selective serotonin-reuptake inhibitors. While its combined use with QT-prolonging drugs has been contraindicated because of the increase in plasma concentrations of such drugs, information is still limited whether fluvoxamine by itself may directly prolong the QT interval. We examined electropharmacological effects of fluvoxamine together with its pharmacokinetic profile by using the halothane-anesthetized dogs (n = 4). Fluvoxamine was intravenously administered in three escalating doses of 0.1, 1 and 10 mg/kg over 10 min with a pause of 20 min between the doses. The low dose provided therapeutic plasma drug concentration, whereas the middle and high doses attained approximately 10 and 100 times of the therapeutic ones, respectively. Supra-therapeutic concentration of fluvoxamine exerted the negative chronotropic, inotropic and hypotensive effects; and suppressed the atrioventricular nodal and intraventricular conductions, indicating inhibitory actions on Ca2+ and Na+ channels, whereas it delayed the repolarization in a reverse use-dependent manner, reflecting characteristics of rapidly activating delayed rectifier K+ current channel-blocking property. Fluvoxamine prolonged the terminal repolarization phase at 100 times higher concentration than the therapeutic, indicating its proarrhythmic potential. Thus, fluvoxamine by itself has potential to directly induce long QT syndrome at supra-therapeutic concentrations.
Yamazaki-Hashimoto et al. (Fri,) conducted a other in Long QT syndrome (n=4). Fluvoxamine was evaluated on Electropharmacological effects and pharmacokinetic profile. Fluvoxamine at 100 times therapeutic concentration prolonged the terminal repolarization phase in anesthetized dogs, indicating potential to directly induce long QT syndrome.