Drug Interactions between miconazole and Tikosyn

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 including azole antifungal agents may increase the plasma concentrations of dofetilide, which is partially metabolized by the isoenzyme. The use of dofetilide has been associated with dose-related prolongation of the QT interval, thus elevated plasma levels of the drug may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes as well as cardiac arrest and sudden death. The interaction has not been studied with miconazole buccal tablets. Although systemic absorption following mucous membrane exposure is limited, the potential for interaction with drugs metabolized by CYP450 3A4 such as dofetilide cannot be ruled out.

MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of dofetilide, caution is advised during coadministration with miconazole mucous membrane preparations. Coadministration of dofetilide and miconazole is considered to be contraindicated by some authorities (GB, AU). Patients should be cautioned about the potential for interaction and advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.