Drug Interaction Report

MONITOR: Coadministration of momelotinib may increase the plasma concentrations and effects of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The proposed mechanism is increased exposure of the P-gp substrate due to inhibition of intestinal P-gp efflux transporter. However, clinical data are not available.

MANAGEMENT: Caution is recommended with the concomitant use of momelotinib and P-gp substrates, particularly those with a narrow therapeutic index. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever momelotinib is added to or withdrawn from therapy with these drugs. Individual product labeling for the coadministered drug may also be consulted for specific guidance.

GENERALLY AVOID: The concurrent use of levomethadyl acetate and alcohol may result in additive CNS and respiratory depression, hypotension, sedation, or coma. Grapefruit juice may increase the plasma concentrations of orally administered drugs which are substrates of the CYP450 3A4 isoenzyme, such as levomethadyl acetate. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who are known to abuse alcohol should be warned of the risk of potentially fatal overdose if these substances are taken concurrently. Patients who regularly consume grapefruits and grapefruit juice should be monitored for adverse effects and altered plasma concentrations of levomethadyl acetate. A 12-lead ECG should be performed before initiating therapy, 12 to 14 days after initiating therapy, and periodically thereafter. Patients should be advised to immediately seek medical attention if they experience palpitations, dizziness, lightheadedness, fainting, or seizures. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.