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Drug Interactions between Dexasone LA and Velcade

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Minor

dexAMETHasone bortezomib

Applies to: Dexasone LA (dexamethasone) and Velcade (bortezomib)

Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of bortezomib, which is primarily metabolized by the isoenzyme with secondary contribution from CYP450 2C19. In a study of patients with relapsed or refractory multiple myeloma or non-Hodgkin's lymphoma treated with intravenous bortezomib (1.3 mg/m2 on days 1, 4, 8 and 11 of each 21-day cycle) for 3 cycles, six patients who were coadministered the potent CYP450 3A4 inducer rifampin (600 mg once daily on days 4 to 10 of cycle 3) had an approximately 23% decrease in bortezomib peak plasma concentration (Cmax) and 45% decrease in systemic exposure (AUC) compared to 12 patients treated with bortezomib alone. However, seven patients who were coadministered the weaker CYP450 3A4 inducer dexamethasone (40 mg once daily on days 1 to 4 and 9 to 12 of cycle 3) did not demonstrate significant changes in the pharmacokinetics of bortezomib compared to patients administered bortezomib alone. Based on available data, no particular precaution appears necessary when bortezomib is coadministered with weak or moderate CYP450 3A4 inducers.

References

  1. "Product Information. Velcade (bortezomib)." Millennium Pharmaceuticals Inc (2003):
  2. Uttamsingh V, Lu C, Miwa GT, Gan LS "Relative contributions of the five major human cytochromes P450, 1A2, 2C9, 2C19, 2D6, and 3A4 to the hepatic metabolism of teh protosome inhibitor bortezomib." Drug Metab Dispos 33 (2005): 1723-8
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Pekol T, Daniels JS, Labutti J, et al. "Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites." Drug Metab Dispos 33 (2005): 771-7
  5. Hellmann A, Rule S, Walewski J, et al. "Effect of cytochrome P450 3A4 inducers on the pharmacokinetic, pharmacodynamic and safety profiles of bortezomib in patients with multiple myeloma or Non-Hodgkin's lymphoma." Clin Pharmacokinet 50 (2011): 781-91
View all 5 references

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Drug and food interactions

Moderate

bortezomib food

Applies to: Velcade (bortezomib)

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.

References

  1. Bannerman B, Xu L, Jones M, et al. "Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea." Cancer Chemother Pharmacol 68 (2011): 1145-54
  2. Golden EB, Lam PY, Kardosh A, et al. "Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid–based proteasome inhibitors." Blood 113 (2009): 5927-37
  3. Jia L, Liu FT "Why bortezomib cannot go with 'green'?" Cancer Biol Med 10 (2013): 206-13

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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