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Velcade (bortezomib)
Reversible inhibitor of 26S proteasome chymotrypsin-like activity preventing ubiquitinated protein degradation.
Bortezomib is a proteasome inhibitor approved for multiple myeloma and mantle cell lymphoma in adult patients. It reversibly inhibits 26S proteasome activity, disrupting protein homeostasis and inducing cancer cell death through multiple signaling pathways. Key risks include hypersensitivity reactions and increased toxicity with strong CYP3A4 inhibitors; intrathecal administration is contraindicated due to fatal outcomes. The drug demonstrates variable pharmacokinetics with half-lives of 40-193 hours and requires dose adjustment in moderate-to-severe hepatic impairment.
At a glance
| Generic name | bortezomib |
|---|---|
| Sponsor | Shilpa |
| Drug class | Proteasome inhibitor |
| Target | 26S proteasome chymotrypsin-like activity |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
| First approval | 2003 |
Mechanism of action
Bortezomib 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 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 and causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma.
Approved indications
- Mantle cell lymphoma
- Multiple myeloma
- Systemic AL amyloidosis
Common side effects
- Constipation
- Infections and infestations - Other, specify
- Nausea
- Neutropenia
- Insomnia
- Neutrophil count decreased
- Fatigue
- Febrile neutropenia
- Anorexia
- Diarrhoea
- Hypokalemia
- Cough
Drug interactions
- Strong CYP3A4 inducers
- Strong CYP3A4 inhibitors
- Dexamethasone, omeprazole, melphalan with prednisone
Key clinical trials
- Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (PHASE3)
- Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma (PHASE3)
- Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Multiple Myeloma (PHASE3)
- CARTITUDE-4 (PHASE3)
- A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis (PHASE3)
- A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy (PHASE3)
- (Mel/MelVel) (PHASE3)
- A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple Myeloma (PHASE1, PHASE2)
Patents
| Patent | Expiry | Type |
|---|---|---|
| 11752164 | 2042-09-23 | Method of Use |
| 11679119 | 2042-09-23 | Method of Use |
| 12005069 | 2042-09-23 | Formulation |
| 8962572 | 2032-11-03 | Formulation |
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
| FDA Orange Book | Patents + exclusivity |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Velcade CI brief — competitive landscape report
- Velcade updates RSS · CI watch RSS
- Shilpa portfolio CI