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Bortezomib Intravenous and Equetro

Determining the interaction of Bortezomib Intravenous and Equetro and the possibility of their joint administration.

Check result:
Bortezomib Intravenous <> Equetro
Relevance: 20.08.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

CarBAMazepine may reduce the blood levels of bortezomib, which may make the medication less effective in treating your condition. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects 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. Because the study was not designed to exert the maximum effect of rifampin on bortezomib pharmacokinetics, greater decreases may be possible. In the same study, 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. In a phase I trial to determine the dose-limiting toxicities and maximum tolerated dose (MTD) of bortezomib in patients with recurrent high-grade gliomas, patients who received concomitant enzyme-inducing antiepileptic drugs (primarily phenytoin, but also carbamazepine, oxcarbazepine, phenobarbital, and primidone) were found to tolerate a higher dosage of bortezomib compared to those who either did not receive antiepileptic medications or received ones that did not significantly induce hepatic microsomal enzymes. Bortezomib doses were escalated to 2.5 mg/m2 without reaching the MTD in the former group, whereas MTD was found to be 1.7 mg/m2 in the latter group. Moreover, maximum proteasome inhibition was reached at a higher dosage of bortezomib in the former group relative to the latter group. Although pharmacokinetics of bortezomib were not examined in the trial, these results suggest enhanced clearance of bortezomib in the presence of enzyme-inducing antiepileptic drugs.

MANAGEMENT: Given the potential for diminished pharmacologic effects of bortezomib in the presence of potent CYP450 3A4 inducers, concomitant use is not recommended.

References
  • "Product Information. Velcade (bortezomib)." Millennium Pharmaceuticals Inc, Cambridge, MA.
  • 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
  • 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
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  • 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
  • Phuphanich S, Supko JG, Carson KA, et.al "Phase 1 clinical trial of bortezomib in adults with recurrent malignant glioma." J Neurooncol 100 (2010): 95-103
Bortezomib Intravenous

Generic Name: bortezomib

Brand name: Velcade

Synonyms: Bortezomib (Intravenous)

Equetro

Generic Name: carbamazepine

Brand name: Carbatrol, Epitol, Equetro, Tegretol, Tegretol XR, Tegretol, Tegretol XR

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

Interaction with food and lifestyle
Disease interaction