Drug Interaction Report

Coadministration with inhibitors of CYP450 2C19 may increase the plasma concentrations of brivaracetam, which is partially metabolized by the isoenzyme. Blood level of brivaracetam is increased by 22% or 42%, respectively, in human subjects possessing genetic variations in CYP450 2C19 with one or both mutated alleles, while production of the hydroxy metabolite is decreased by 2-fold or 10-fold, respectively. The risk of a clinically relevant CYP450 2C19-mediated interaction is considered to be low according to the manufacturer.

GENERALLY AVOID: Data from in vitro and animal (mice) studies suggest that green tea may antagonize the cytotoxic effects of bortezomib. Polyphenols in green tea such as (-)-epigallocatechin gallate (EGCG) have been shown to block the proteasome inhibitory action of bortezomib in multiple myeloma and glioblastoma cancer cell lines. The mechanism appears to involve a direct chemical reaction between the boronic acid moiety of bortezomib and the 1,2-benzenediol groups present in certain polyphenols leading to inactivation of bortezomib. However, one group of investigators reported that no antagonism of bortezomib was observed in preclinical in vivo experiments where EGCG plasma concentrations are commensurate with dietary or supplemental intake.

MANAGEMENT: Until more data are available, it may be advisable to avoid or limit consumption of green tea and green tea products during treatment with bortezomib. The interaction has not been demonstrated for other, non-boronic acid proteasome inhibitors.