Dofetilide prolongs the action potential and QTC in a concentration-related manner. Dofetilide exerts its effects solely by inhibition of the rapid component of the delayed rectifier potassium current Ikr.

Dofetilide has stronger evidence in its favor for acute cardioversion of atrial fibrillation than for maintenance thereafter, according to a meta-analysis.

It can be given to patients with depressed function but needs to be initiated while being continuously monitored on telemetry for the first 3 days of therapy since this too has a risk of proarrhythmia-like ibutilide.

The risk of torsades de pointes can be reduced by normal serum potassium and magnesium levels, predose adjustment of renal function, and postdose reduction based on QTC (ideally baseline QTC below 429 milliseconds).

Administration of dofetilide requires that the hospital and the prescriber be trained as confirmed administrators.

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