Trade name Tikosyn

Bioavailability 96% orally

Protein binding 60% -70%

Elimination half-life 10 hours due  to the significant level of renal elimination-80% unchanged, 20% metabolites.

Dofetilide is a class III antiarrhythmic agent.

Dofetilide is used for the maintenance of sinus rhythm in individuals prone to the occurrence of atrial fibrillation and flutter arrhythmias, and for chemical cardioversion to sinus rhythm from atrial fibrillation and flutter.

It has clinical advantages over other class III antiarrhythmics in chemical cardioversion of atrial fibrillation, and maintenance of sinus rhythm.

It does not have the pulmonary or hepatotoxicity of amiodarone, however atrial fibrillation is not generally considered life-threatening, and dofetilide causes an increased rate of potentially life-threatening arrhythmias in comparison to other therapies.

Prior to administration of the first dose, the corrected QT (QTc) must be determined. 

If the QTc is greater than 440 msec, or 500 msec in patients with ventricular conduction abnormalities, dofetilide is contraindicated. 

After each subsequent dose of dofetilide, QTc should be determined and dosing should be adjusted. 

If at any time after the second dose of dofetilide the QTc is greater than 500 msec (550 msec in patients with ventricular conduction abnormalities), dofetilide should be discontinued. 

Torsades de pointes is the most serious side effect of dofetilide therapy. 

The incidence of torsades de pointes is 0.3-10.5%. 

The incidence of torsades de pointes is 

dose-related, with increased incidence associated with higher doses. 

The majority of episodes of torsades de pointes have occurred within the first three days of initial dosing, while being monitored.

It works by selectively blocking the rapid component of the delayed rectifier outward potassium current (IKr), causing the refractory period of atrial tissue to increase, hence its effectiveness in the treatment of atrial fibrillation and atrial flutter.

Dofetilide does not affect the slope of the upstroke of phase 0 depolarization, conduction velocity, or the resting membrane potential.

Peak plasma concentrations are seen two to three hours after oral dosing when fasting. 

Intravenous administration of dofetilide is not available.

The elimination half-life of dofetilide is roughly 10 hours, but varies based on creatinine clearance, and ranges from 4.8 to 13.5 hours. 

The dose of dofetilide must be adjusted to prevent toxicity due to impaired renal function.

Dofetilide is metabolized predominantly by CYP3A4 enzymes predominantly in the liver and GI tract. 

Drugs that inhibit CYP3A4, such as erythromycin, clarithromycin, or ketoconazole, result in higher and potentially toxic levels of dofetilide. 

A steady-state plasma level of dofetilide is achieved in 2–3 days.

80% of dofetilide is excreted by the kidneys, the dose of dofetilide should be adjusted in individuals with chronic kidney disease, based on creatinine clearance.

Agents that interfere with the renal cation exchange system, such as verapamil, cimetidine, hydrochlorothiazide, itraconazole, ketoconazole, prochlorperazine, and trimethoprim should not be administered to individuals taking dofetilide.

About 20 percent of dofetilide is metabolized in the liver via the CYP3A4 isoenzyme of the cytochrome P450 enzyme system. 

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