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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.