Drug Interactions between eribulin and PC-CAP

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.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.