Drug Interactions between cobimetinib and Metamucil

ADJUST DOSING INTERVAL: Bulk-forming laxatives such as guar gum, psyllium, polycarbophil, or methylcellulose may affect the bioavailability of concomitantly administered substances due to their effect on the rate of gastrointestinal transit and gastric emptying.

MANAGEMENT: In general, oral medications should be administered at least 2 hours before or 2 hours after dosing of the bulk-forming laxative.

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.