Drug Interaction Report

MONITOR CLOSELY: Dofetilide can cause dose- and concentration-related QT interval prolongation. Theoretically, coadministration with agents that can produce hypokalemia and/or hypomagnesemia (e.g., potassium-wasting diuretics, amphotericin B, cation exchange resins, stimulant laxatives) may result in elevated risk of ventricular arrhythmias, including ventricular tachycardia and torsade de pointes, because of additive arrhythmogenic potential.

MANAGEMENT: Caution is advised if dofetilide must be used concomitantly with medications that can cause potassium and/or magnesium disturbances. Serum electrolytes should be evaluated and any abnormalities corrected prior to initiating therapy with dofetilide. During therapy, potassium concentrations should be kept above 4 mEq/dL and magnesium concentrations above 1.8 mg/dL. Patients should also have frequent ECGs and be monitored for serious arrhythmias when QT intervals are prolonged. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.