Drug Interaction Report

MONITOR: There are no data regarding the use of live, unattenuated Adenovirus Type 4 and Type 7 vaccine during treatment with immunosuppressive therapies, including alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, and long-term topical or inhaled corticosteroids. It is not known whether immunosuppressed patients may have an increased risk of adverse reactions or a decreased or suboptimal immunologic response to the vaccine.

MANAGEMENT: The safety and efficacy of live, unattenuated Adenovirus Type 4 and Type 7 vaccine have not been established in patients receiving immunosuppressive therapies. Caution is advised.

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.