Drug Interaction Report

MONITOR: Eribulin may cause prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In an uncontrolled, open-label electrocardiographic study consisting of 26 patients with solid tumors who received eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle, a delayed QTc prolongation was observed on day 8, independent of eribulin concentration. No QT prolongation was observed on day 1. The maximum mean QTcF change from baseline (95% upper confidence interval) was 11.4 (19.5) ms. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drugs involved and dosages of the drugs.

MANAGEMENT: Caution is recommended if eribulin is used in combination with other drugs that can prolong the QT interval. Baseline and periodic monitoring of electrocardiograms and serum electrolytes (potassium, magnesium) should be considered, and hypokalemia or hypomagnesemia corrected prior to initiating treatment with eribulin. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.