Dofetilide is a class III antiarrhythmic agent. It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 μg of dofetilide. It is not available in Europe or Australia. Mechanistically, dofetilide prolongs cardiac action potential duration and the effective refractory period by selectively inhibiting the rapid component of the delayed rectifier potassium current IKr, with limited direct effects on sodium or calcium currents. The drug is well absorbed after oral dosing with Tmax typically within a few hours and systemic bioavailability sufficient for predictable plasma exposure. Renal excretion is a major elimination route and dosing is adjusted according to renal function to limit accumulation. Clinically relevant properties include dose-dependent QT interval prolongation, a modest volume of distribution, and the need for ECG monitoring at treatment initiation and during dose adjustment. Analytical characterization for quality control commonly uses reversed phase HPLC and LC-MS for potency and impurity profiling.
Parent: Dofetilide
Parent: Dofetilide
Parent: Dofetilide
Parent: Dofetilide
Parent: Dofetilide
Parent: Dofetilide
Parent: Dofetilide
Parent: Dofetilide
Parent: Dofetilide
Parent: Dofetilide
Known related substances associated with dofetilide manufacture and degradation include N-dealkylated species, N-oxide derivatives, low level ring-modified species, and residual synthetic intermediates. Typical manufacturer specifications and pharmacopeial monographs set limits to control patient exposure and to meet ICH Q3A/Q3B expectations for low dose drugs. Typical acceptance criteria used in technical specifications are individual known or unknown impurities at or below 0.05 to 0.10 percent of the active substance, and total impurities controlled below 0.30 to 0.50 percent, with tighter limits applied for identified genotoxic impurities if present. Quantitation and identification methods include validated HPLC with photodiode array detection, LC-MS for confirmation of mass and structure, and where required, preparative isolation followed by NMR. Stability studies guide allowable impurity levels over shelf life and inform specification limits for related compounds and degradation products.
Dofetilide is used to treat and maintain normal sinus rhythm in patients with atrial fibrillation and atrial flutter. It is prescribed when cardioversion is indicated or when rhythm control is preferred, and initiation requires in-hospital monitoring in many jurisdictions because of proarrhythmic risk.
Dofetilide selectively blocks the cardiac rapid delayed rectifier potassium current IKr, which prolongs action potential duration and the myocardial effective refractory period. This electrophysiological effect reduces the likelihood of reentrant arrhythmias in the atria and can restore and maintain sinus rhythm.
Dofetilide carries a significant safety risk relative to many other medications because it can prolong the QT interval and precipitate torsades de pointes, a potentially life threatening ventricular arrhythmia. Risk is higher with renal impairment, drug interactions that increase plasma levels, electrolyte abnormalities, or excessive dosing, so careful patient selection, dosing based on renal function, and ECG monitoring are required.
Yes, dofetilide is a potassium channel blocker that acts selectively on the rapid component of the delayed rectifier potassium current known as IKr. This selective blockade underlies its class III antiarrhythmic classification and its effect on repolarization and QT interval.
