Velcade

Multiple myeloma — in combination with other agents for newly diagnosed and relapsed/refractory disease; Mantle cell lymphoma — in patients who have received at least one prior therapy

Standard schedule: 1.3 mg/m² as IV bolus (3-5 seconds) or SC injection on Days 1, 4, 8, and 11 of a 21-day cycle, for up to 8 cycles
Retreatment: May reinitiate at last tolerated dose for patients who previously responded
SC administration: Inject in thigh or abdomen; rotate injection sites. Preferred route to reduce peripheral neuropathy risk.
Dose reduction: 1.0 mg/m², then 0.7 mg/m² for toxicities

For injection: 3.5 mg lyophilized powder in single-dose vial for reconstitution (IV or subcutaneous)

Hypersensitivity to bortezomib, boron, or mannitol. Intrathecal administration is contraindicated (fatal events reported).

• Peripheral Neuropathy: Reported in 37% of patients. Primarily sensory; may be painful. Dose-modify at first sign of Grade 2 neuropathy with pain or Grade 3.
• Hypotension: Orthostatic/postural hypotension in 12%. Use caution with antihypertensives; ensure adequate hydration.
• Cardiac Toxicity: Acute heart failure, conduction abnormalities, and pericardial disease reported.
• Pulmonary Toxicity: Acute pulmonary infiltrates/ARDS reported (rare, fatal cases).
• Posterior Reversible Encephalopathy Syndrome (PRES)
• GI Toxicity: Nausea, diarrhea, constipation, and vomiting common; ileus may occur.
• Thrombocytopenia/Neutropenia: Thrombocytopenia in 43%; typically cyclical with nadir on Day 11. Monitor CBCs frequently.
• Tumor Lysis Syndrome: Monitor patients with high tumor burden.
• Hepatotoxicity: Cases of acute liver failure reported. Monitor LFTs.

Nausea (55%), diarrhea (52%), thrombocytopenia (43%), fatigue (41%), peripheral neuropathy (37%), constipation (34%), vomiting (33%), neutropenia (24%), anorexia (21%), pyrexia (21%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome, a large protein complex that degrades ubiquitinated proteins. Proteasome inhibition disrupts multiple cell signaling cascades, including NF-κB pathway, resulting in cell cycle arrest and apoptosis in malignant cells. Bortezomib also inhibits angiogenesis and modulates the bone marrow microenvironment.

Mean elimination half-life: 40-193 hours after multiple dosing. Vd: 498-1884 L/m². Metabolized primarily by CYP3A4, CYP2C19, and CYP1A2. Protein binding: 83%. SC bioavailability: 100% relative to IV.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• APEX — Bortezomib vs. dexamethasone in relapsed multiple myeloma. Phase III, n=669.
  🔬 NCT00048230 ↗ 📄 Primary Publication ↗
• VISTA — Bortezomib + melphalan/prednisone vs. MP in newly diagnosed MM not eligible for transplant. Phase III, n=682.
  🔬 NCT00111319 ↗ 📄 Primary Publication ↗

Velcade has FDA-approved indications across the following cancer types covered on PipelineEvidence: