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Drug Interactions between bortezomib and Emend for Injection

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

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Interactions between your drugs

Moderate

bortezomib fosaprepitant

Applies to: bortezomib and Emend for Injection (fosaprepitant)

MONITOR: Coadministration with aprepitant or its prodrug, fosaprepitant, may increase the plasma concentrations of chemotherapeutic agents that are primarily metabolized by CYP450 3A4. The proposed mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by aprepitant. In premarketing clinical studies, aprepitant was administered commonly with etoposide, vinorelbine or paclitaxel, although dosages of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies, aprepitant had no effect on the pharmacokinetics of docetaxel or vinorelbine, both of which are substrates of CYP450 3A4. However, an interaction has been demonstrated with the probe CYP450 3A4 substrate, midazolam. In general, the effect of aprepitant on the pharmacokinetics of CYP450 3A4 substrates is expected to be greater when the substrates are administered orally as opposed to intravenously and may be altered following prolonged administration.

MANAGEMENT: Caution is advised if aprepitant or fosaprepitant is administered with chemotherapeutic agents that are primarily metabolized by CYP450 3A4, particularly those that were not studied extensively in premarketing trials. The potential for increased systemic toxicities of these agents should be considered. Chronic, continuous use of aprepitant for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during long-term use.

References (6)
  1. Kivisto KT, Kroemer HK, Eichelbaum M (1995) "The role of human cytochrome p450 enzymes in the metabolism of anticancer agents: implications for drug interactions." Br J Clin Pharmacol, 40, p. 523-30
  2. Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R (1993) "Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions." Biochem Pharmacol, 45, p. 853-61
  3. Clarke SJ, Rivory LP (1999) "Clinical pharmacokinetics of docetaxel." Clin Pharmacokinet, 36, p. 99-114
  4. Charasson V, Haaz MC, Robert J (2002) "Determination of Drug Interactions Occurring with the Metabolic Pathways of Irinotecan." Drug Metab Dispos, 30, p. 731-733
  5. (2003) "Product Information. Emend (aprepitant)." Merck & Co., Inc
  6. (2008) "Product Information. Emend for Injection (fosaprepitant)." Merck & Co., Inc

Drug and food interactions

Moderate

bortezomib food

Applies to: 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 (3)
  1. Bannerman B, Xu L, Jones M, et al. (2011) "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, p. 1145-54
  2. Golden EB, Lam PY, Kardosh A, et al. (2009) "Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid–based proteasome inhibitors." Blood, 113, p. 5927-37
  3. Jia L, Liu FT (2013) "Why bortezomib cannot go with 'green'?" Cancer Biol Med, 10, p. 206-13

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.

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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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