Dofetilide

Dofetilide is a prescription antiarrhythmic medication in the class III category. It is used to maintain sinus rhythm in adults with atrial fibrillation or atrial flutter after cardioversion. Dofetilide is sold under the brand name Tikosyn and is available in oral and intravenous forms. Because of the risk of dangerous heart rhythm disturbances, initiation of therapy is tightly controlled in many countries.

Mechanism of action and effects: Dofetilide is a pure blocker of the rapid component of the delayed rectifier potassium current (Ikr) in cardiac tissue. By inhibiting this current, it prolongs the action potential duration and the QT interval, reducing the likelihood of recurrent atrial arrhythmias but increasing the risk of torsades de pointes, a form of ventricular tachycardia.

Pharmacokinetics and dosing: Dofetilide is primarily eliminated by the kidneys, so dosing is adjusted according to renal function. Because of QT prolongation risk, initiation and dose adjustment are performed in a hospital setting with continuous ECG monitoring. In many treatment guidelines, the dose ranges from lower to higher levels based on creatinine clearance and potential drug interactions, with the aim of achieving a safe QT interval.

Contraindications and precautions: It is contraindicated in patients with congenital or acquired long QT syndrome, significant electrolyte disturbances (such as hypokalemia or hypomagnesemia), severe renal impairment, or a history of torsades de pointes. Caution is advised when combining dofetilide with other drugs that prolong the QT interval or with medications that affect renal excretion, as these can elevate the risk of QT prolongation and torsades de pointes.

Adverse effects: The most serious risks are QT prolongation and torsades de pointes. Other possible effects include bradycardia, headaches, dizziness, and abdominal discomfort. Monitoring and patient selection are essential to minimize these risks.