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Drug Interactions between atazanavir / cobicistat and bortezomib

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

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Interactions between your drugs

Moderate

bortezomib atazanavir

Applies to: bortezomib and atazanavir / cobicistat

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of bortezomib, which is primarily metabolized by the isoenzyme. In a study of 12 patients, administration of bortezomib with the potent inhibitor ketoconazole resulted in a 35% increase in mean bortezomib systemic exposure (AUC) compared to administration alone.

MANAGEMENT: Pharmacologic response to bortezomib should be monitored more closely whenever a potent CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the dosage adjusted as necessary. Patients should be monitored for the development of potential bortezomib toxicities such as peripheral neuropathy, orthostatic hypotension, thrombocytopenia, and neutropenia.

References

  1. (2003) "Product Information. Velcade (bortezomib)." Millennium Pharmaceuticals Inc
  2. Uttamsingh V, Lu C, Miwa GT, Gan LS (2005) "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, p. 1723-8
  3. Pekol T, Daniels JS, Labutti J, et al. (2005) "Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites." Drug Metab Dispos, 33, p. 771-7

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Moderate

bortezomib cobicistat

Applies to: bortezomib and atazanavir / cobicistat

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of bortezomib, which is primarily metabolized by the isoenzyme. In a study of 12 patients, administration of bortezomib with the potent inhibitor ketoconazole resulted in a 35% increase in mean bortezomib systemic exposure (AUC) compared to administration alone.

MANAGEMENT: Pharmacologic response to bortezomib should be monitored more closely whenever a potent CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the dosage adjusted as necessary. Patients should be monitored for the development of potential bortezomib toxicities such as peripheral neuropathy, orthostatic hypotension, thrombocytopenia, and neutropenia.

References

  1. (2003) "Product Information. Velcade (bortezomib)." Millennium Pharmaceuticals Inc
  2. Uttamsingh V, Lu C, Miwa GT, Gan LS (2005) "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, p. 1723-8
  3. Pekol T, Daniels JS, Labutti J, et al. (2005) "Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites." Drug Metab Dispos, 33, p. 771-7

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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

  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

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Moderate

atazanavir food

Applies to: atazanavir / cobicistat

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References

  1. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb

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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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