Drug Interaction Report

MONITOR: The concomitant or sequential use of epirubicin with agents known to induce hepatotoxicity may potentiate the risk of liver injury. Epirubicin undergoes elimination through the hepatobiliary system.

MANAGEMENT: Caution and clinical and laboratory monitoring for signs of liver injury are advisable before, during, or after use of epirubicin with other agents that are potentially hepatotoxic.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme, such as cobimetinib. However, the interaction seems to affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, 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 cobimetinib. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.