Drug Interactions between cholera vaccine, live and cobimetinib

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.

ADJUST DOSING INTERVAL: Coadministration of oral cholera vaccine with food or an oral beverage may impair its efficacy. The formulations of both the inactivated and live, attenuated oral cholera vaccines (Dukoral and Vaxchora, respectively) are acid-labile, and must be administered with a buffer. According to the manufacturer, eating and drinking may interfere with the protective effect of the buffer. However, clinical data are not available.

MANAGEMENT: It is recommended that patients avoid eating or drinking for 60 minutes before and after administration of either Dukoral or Vaxchora oral cholera vaccines.