Bortez
Generic Name: Bortezomib
Therapeutic Class:Therapeutic Class
Indications
Bortez is a proteasome inhibitor indicated for:
- Treatment of adult patients with multiple myeloma
- Treatment of adult patients with mantle cell lymphoma
Pharmacology
Bortezomib for Injection is an antineoplastic agent available for intravenous (IV) and subcutaneous injection use. It is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that Bortezomib is cytotoxic to a variety of cancer cell types in vitro. Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma.
Distribution: The distribution volume of Bortezomib as a single agent was not assessed at the recommended dose in patients with multiple myeloma.The binding of Bortezomib to human plasma proteins averaged 83% over the concentration range of 100 to 1000 ng/mL.
Metabolism: Bortezomib is primarily oxidatively metabolized via cytochrome P450 enzymes 3A4, 2C19, and 1 A2. Bortezomib metabolism by CYP 2D6 and 2C9 enzymes is minor. The major metabolic pathway is deboronation to form 2 deboronated metabolites that subsequently undergo hydroxylation to several metabolites. Deboronated Bortezomib metabolites are inactive as 26S proteasome inhibitors.
Elimination: The mean elimination half-life of Bortezomib after first dose ranged from 9 to 15 hours at doses ranging from 1.45 to 2.00 mg/m2 in patients with advanced malignancies. The pathways of elimination of Bortezomib have not been characterized in humans.
Dosage & Administration
The recommended dose of Bortezomib is 1.3 mg/m2/dose administered as a 3 to 5 second bolus intravenous and subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12-21). For extended therapy of more than 8 cycles, Bortezomib may be administered on the standard schedule or on a maintenance schedule of once weekly for 4 weeks (Days 1, 8, 15, and 22) followed by a 13-day rest period (Days 23 to 35).
Bortezomib retreatment may be considered for patients with multiple myeloma who has previously responded to treatment with Bortezomib and who has relapsed at least 6 months after completing prior Bortezomib treatment. Treatment may be started at the last tolerated dose. Bortezomib is for intravenous or subcutaneous use only. Bortezomib should not be administered by any other route.
