Drug Interaction Report

GENERALLY AVOID: Concomitant use of landiolol with negative inotropes, medications that slow heart rate or cardiac conduction should be done with caution. Coadministration may result in additive suppression of cardiac function, atrioventricular (AV) conduction abnormalities, prolonged PR interval, and potentially additive heart-rate and blood pressure lowering effects. Landiolol alone is associated with increased risk of bradycardia and heart block, and therefore coadministration with these agents may potentiate these effects.

MANAGEMENT: If coadministration is clinically necessary, careful titration of the landiolol infusion and close hemodynamic monitoring is advised. Consultation with package labeling and relevant institutional protocols may be advisable for further guidance.

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.