Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration of berotralstat with drugs that are both substrates of the isoenzyme CYP450 3A4 as well as inhibitors of the efflux transporters P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) may lead to an increase in the plasma concentrations and effects of both drugs. Berotralstat is considered a moderate CYP450 3A4 inhibitor and has been reported in drug interaction studies to increase the peak plasma concentration (Cmax) and systemic exposure (AUC) of the sensitive CYP450 3A4 substrate midazolam by approximately 1.5-fold and 2.25-fold, respectively. In addition, 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. 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 three 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.

MANAGEMENT: During concomitant use of berotralstat with drugs that are substrates of CYP450 3A4, particularly those with a narrow therapeutic index, clinical and laboratory monitoring for patient response and tolerance and individual dose adjustments as needed are recommended. Conversely, while no dose adjustments of berotralstat are recommended, monitoring for adverse events may be advisable during concomitant use of berotralstat with drugs that are also P-gp and/or BCRP inhibitors. Patients should be advised to contact their physician if they experience any undue adverse effects from their medications. 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. In addition, the prescribing information for concomitant medications should be consulted and dosages adjusted as needed.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 including grapefruit or grapefruit juice may increase the plasma concentrations of leniolisib, which undergoes extensive CYP450 3A4-mediated first-pass metabolism in the gut wall and liver. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of leniolisib. Some authorities recommend to avoid grapefruit products during leniolisib treatment (UK).