Drug Interactions between berotralstat and sodium phenylbutyrate / taurursodiol

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of berotralstat. Berotralstat is a substrate of both P-gp and BCRP. Coadministration with the potent P-gp and BCRP inhibitor cyclosporine increased berotralstat peak plasma concentration (Cmax) and total systemic drug exposure (AUC 0-inf) by 25% and 69%, respectively. However, other regulatory bodies reported that cyclosporine decreased the Cmax of a single 150 mg dose of berotralstat by 7% and increased the AUC by 24-27%. Increased plasma concentrations of berotralstat may increase the risk of adverse effects, including the potential for QT prolongation. Berotralstat may cause concentration-dependent prolongation of the Fridericia-corrected QT interval (QTcF). A mean increase in the QTcF interval of 15.9 milliseconds has been reported at 3-times the recommended dose of berotralstat; however, berotralstat has not been shown to prolong the QT interval to any clinically relevant extent when administered at the recommended daily dose of 150 mg. Data are not available for other, less potent P-gp and/or BCRP inhibitors.

MANAGEMENT: No dose adjustments of berotralstat are recommended; however, monitoring for adverse events may be advisable during concomitant use of berotralstat with P-gp and/or BCRP inhibitors. Patients should be advised to contact their physician if they experience undue adverse effects of berotralstat such as abdominal pain, vomiting, or diarrhea. Patients should seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath, or syncope.