Mechanism of action<unk>  works by selectively blocking the rapid component of the delayed rectifier outward potassium current (IKr). This causes the refractory period of atrial tissue to increase, hence its effectiveness in the treatment of atrial fibrillation and atrial flutter.<unk>  does not affect dV/dTmax (the slope of the upstroke of phase 0 depolarization), conduction velocity, or the resting membrane potential.<unk>  synthesis There is a dose-dependent increase in the QT interval and the corrected QT interval (QTc). Because of this, many practitioners will initiate<unk>  therapy only on individuals under telemetry monitoring or if serial EKG measurements of QT and QTc can be performed. Pharmacokinetics Peak plasma concentrations are seen two to three hours after oral dosing when fasting.<unk>  is well absorbed in its oral form, with a bioavailability of >90%. Intravenous administration of<unk>  is not available in the United States. The elimination half-life of<unk>  is roughly 10 hours; however, this varies based on many physiologic factors (most significantly creatinine clearance), and ranges from 4.8 to 13.5 hours. Due to the significant level of renal elimination (80% unchanged, 20% metabolites), the dose of<unk>  must be adjusted to prevent toxicity due to impaired renal function.<unk>  is metabolized predominantly by CYP3A4 enzymes predominantly in the liver and GI tract. This means that it is likely to interact with drugs that inhibit CYP3A4, such as erythromycin, clarithromycin, or ketoconazole, resulting in higher and potentially toxic levels of<unk> . Metabolism A steady-state plasma level of<unk>  is achieved in 2–3 days. 80% of<unk>  is excreted by the kidneys, so the dose of<unk>  should be adjusted in individuals with chronic kidney disease, based on creatinine clearance. In the kidneys,<unk>  is eliminated via cation exchange (secretion). 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<unk> . About 20 percent of<unk>  is metabolized in the liver via the CYP3A4 isoenzyme of the cytochrome P450 enzyme system. Drugs that interfere with the activity of the CYP3A4 isoenzyme can increase serum<unk>  levels. If the renal cation exchange system is interfered with (as with the medications listed above), a larger percentage of<unk>  is cleared via the CYP3A4 isoenzyme system.
Dofetilide
Ibutilide
Sotalol
Flecainide
Verapamil
Amiodarone
Nortilidine
Procainamide