Drug Interaction Report

CONTRAINDICATED: Talimogene laherparepvec is a live, attenuated herpes simplex virus. Administration during immunosuppressant or intense antineoplastic therapy may be associated with a risk of potentially life-threatening disseminated herpetic infection due to enhanced virus replication in the presence of diminished immune competence. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, or long-term topical or inhaled corticosteroids.

MANAGEMENT: Talimogene laherparepvec should not be used in patients receiving immunosuppressive therapy or cancer chemotherapy. Treatment with talimogene laherparepvec may need to be deferred until after such therapy is discontinued and the patient's immune system has sufficiently recovered.

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.