Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is generally administered by intravenous bolus or subcutaneous injection and functions as a reversible inhibitor of the 26S proteasome via a boronic acid pharmacophore that binds the chymotrypsin-like active site of the beta5 subunit, leading to accumulation of polyubiquitinated proteins, disruption of NF-kappaB signaling, induction of endoplasmic reticulum stress and apoptotic pathways in malignant plasma cells. The drug is formulated as a sterile lyophilized powder for reconstitution, undergoes extensive hepatic metabolism primarily via cytochrome P450 isoenzymes to inactive metabolites, displays high plasma protein binding and a multi-phasic disposition profile, and is dosed according to body surface area or fixed-dose schedules within combination regimens guided by hematologic monitoring.
Parent: Bortezomib
Parent: Bortezomib
Parent: Bortezomib
Parent: Bortezomib
Parent: Bortezomib
Parent: Bortezomib
The impurity profile for bortezomib active substance and finished injection is defined by controlled related substances and degradation products arising from synthesis, handling and storage, including deboronation products, epimeric isomers, oxidized species and hydrolytic fragments; typical regulatory specifications set individual related-substance limits commonly in the range of not more than 0.5 to 1.5 percent by weight for single impurities and a total impurities limit commonly not more than 2.0 to 3.0 percent by weight, with lower reporting thresholds for specified genotoxic or unknown degradants; identification, quantification and allowable limits are established by validated stability-indicating methods and must comply with ICH Q3A and pharmacopeial requirements for purity, residual solvents and elemental impurities.
Bortezomib injection is used to treat multiple myeloma and mantle cell lymphoma; it is indicated both for patients who are treatment-naive and those previously treated, usually as part of combination chemotherapy regimens or as single-agent therapy depending on clinical protocol.
Bortezomib reversibly inhibits the 26S proteasome by binding the chymotrypsin-like active site of the beta5 subunit via its boronic acid moiety, causing accumulation of misfolded and ubiquitinated proteins, disruption of proteostasis, inhibition of NF-kappaB signaling, induction of endoplasmic reticulum stress and activation of apoptotic cascades in malignant plasma cells.
Another name for bortezomib is Velcade, which is a commonly used brand name; the substance is also referred to by its generic name bortezomib and by research identifiers used in regulatory filings.
Bortezomib can be administered either by intravenous bolus injection into a peripheral or central vein using aseptic technique, or by subcutaneous injection into the abdominal wall, thigh or upper arm subcutaneous tissue; local site rotation and proper injection technique are recommended to reduce injection site reactions.
