Drug Interaction Report

MONITOR: Coadministration with berotralstat may increase the plasma concentrations and effects of drugs that are substrates of the efflux transporter P-glycoprotein (P-gp). The mechanism is decreased clearance due to inhibition of P-gp activity by berotralstat. The administration of a 300 mg dose of berotralstat (twice the recommended daily dose) increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of the sensitive P-gp substrate digoxin, by approximately 1.6-fold and 1.5-fold, respectively. Clinical data are not available.

MANAGEMENT: Caution is advised when berotralstat is coadministered with drugs that are substrates of P-gp, particularly those with a narrow therapeutic index. This interaction has only been reported at twice the recommended daily dose of berotralstat. Clinical and laboratory monitoring should be considered following the initiation or discontinuation of berotralstat, and the individual dosage of the concomitant agents adjusted as needed.

ADJUST DOSING INTERVAL: Oral cladribine may increase the bioavailability of other drugs, which may increase the risk or severity of adverse reactions. Cladribine tablets may contain hydroxypropyl betadex, which could form a complex with the active ingredients of other drugs, especially agents with low solubility. The clinical relevance of this interaction remains unknown.

MANAGEMENT: Administration of oral cladribine should be separated from any other oral drug by at least 3 hours.