Drug Interactions between bortezomib and rufinamide

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: Alcohol may potentiate some of the pharmacologic effects of rufinamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.