Drug Interaction Report

GENERALLY AVOID: The use of alefacept with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids.

MANAGEMENT: Patients receiving other immunosuppressive or myelosuppressive agents or phototherapy should not be treated with alefacept because of the possibility of excessive immunosuppression. The duration of the period following treatment with alefacept before one should consider starting other immunosuppressive therapy has not been evaluated.

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.