Drug Interactions between PC-CAP and tebentafusp

MONITOR: It is uncertain whether tebentafusp causes clinically significant prolongation of the QT interval. According to the manufacturer, cases of QT interval prolongation were reported following tebentafusp treatment. 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 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, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Some authorities recommend caution if tebentafusp is coadministered with other agents known to prolong the QT interval. An ECG should be obtained before and after tebentafusp administration during the first 3 weeks of treatment and subsequently as clinically indicated. If the Fridericia-corrected QT interval (QTcF) exceeds 500 ms or increases by 60 ms or more from baseline, tebentafusp should be withheld and patients should be treated for any underlying precipitating factors (e.g., electrolyte abnormalities). Tebentafusp should be resumed once QTcF is less than 500 ms or less than 60 ms above baseline. Patients should be advised to seek prompt medical attention if they experience symptoms that 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.