Drug Interactions between bortezomib and valoctocogene roxaparvovec

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.

GENERALLY AVOID: Coadministration with other hepatotoxic agents such as alcohol may increase the risk of liver injury and decrease the therapeutic efficacy of valoctocogene roxaparvovec, a liver-directed adeno-associated virus (AAV) vector designed to help replace missing coagulation factor VIII. Most of the patients treated with valoctocogene roxaparvovec in clinical studies experienced ALT elevations, presumably due to immune-mediated injury of transduced hepatocytes, which may decrease the therapeutic efficacy of valoctocogene roxaparvovec. In a clinical trial of adults with severe hemophilia (n=134) receiving a single dose of valoctocogene roxaparvovec (6 x 10[13] vector genomes [vg]/kg), 107 patients (96%) experienced increased ALT levels greater than or equal to 1.5 times baseline or greater than the upper limit of normal (ULN), while 12 patients (9%) experienced increased ALT levels greater than 5 to 20 times ULN. Some of the ALT elevations were associated with decreased factor VIII activity, and some were attributed to alcohol consumption. Most patients treated with valoctocogene roxaparvovec required immunosuppressive medications, including corticosteroids, to control elevations in transaminases and prevent loss of transgene expression.

MANAGEMENT: After administration of valoctocogene roxaparvovec, alcohol consumption should be avoided for at least 1 year and limited thereafter.