Drug Interaction Report

MONITOR: Bortezomib can cause peripheral neuropathy, and concurrent use of other agents that are also associated with this adverse effect can potentiate the risk and/or severity of nerve damage. Bortezomib treatment causes a peripheral neuropathy that is predominantly sensory, although cases of mixed sensorimotor neuropathy have also been reported. During clinical trials, 37% of the patients experienced treatment emergent neuropathy. Of these, more than 70% had previously been treated with neurotoxic agents and more than 80% of these patients had signs or symptoms of peripheral neuropathy at baseline. The incidence of grade 3 neuropathy (i.e., that which interferes with activities of daily life) was 5% in patients without baseline neuropathy.

MANAGEMENT: Caution is advised if bortezomib is used with other neurotoxic agents. Patients should be closely monitored for symptoms of neuropathy such as visual disturbances or burning, tingling, pain, numbness, and/or weakness in the extremities. Patients experiencing new or worsening peripheral neuropathy may require an adjustment in the dosage and schedule of bortezomib in accordance with the product labeling. Symptoms may improve or return to baseline in some patients upon discontinuation of bortezomib, although the complete time course of this toxicity has not been fully characterized.

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.