Drug Interactions between bortezomib and pravastatin

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.

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.