Generic Name and Formulations:
Bortezomib 3.5mg/vial; lyophilized pwd for IV or SC inj after reconstitution; contains mannitol.
Takeda Pharmaceutical Company
Indications for VELCADE:
Multiple myeloma. Mantle cell lymphoma.
Give as a 3–5 second IV bolus inj or as SC inj into thigh or abdomen (rotate sites). Previously untreated multiple myeloma: Treat for nine 6-week cycles in combination with oral melphalan and oral prednisone. Cycles 1–4: 1.3mg/m2 twice weekly (Days 1, 4, 8, 11, 22, 25, 29, 32); Cycles 5–9: 1.3mg/m2 once weekly (Days 1, 8, 22, 29). Previously untreated mantle cell lymphoma: Treat for six 3-week cycles in combination with IV rituximab, cyclophosphamide, doxorubicin, and oral prednisone. 1.3mg/m2 twice weekly for 2 weeks (Days 1, 4, 8, 11) then 10 day rest period (Days 12–21); if response first documented at Cycle 6, two more cycles are recommended. Relapsed multiple myeloma or mantle cell lymphoma: Standard schedule: 1.3mg/m2 twice weekly for 2 weeks (Days 1, 4, 8, 11) then 10 day rest period (Days 12–21); Extended therapy (if using >8 cycles): may use standard schedule, or maintenance schedule: 1.3mg/m2 once weekly for 4 weeks (Days 1, 8, 15, 22) then 13-day rest period (Days 23–35). Multiple myeloma patients who have previously responded to bortezomib (alone or in combination) and have relapsed at least 6 months after completing prior bortezomib therapy: may retreat starting at last tolerated dose, given twice weekly every 3 weeks (Days 1, 4, 8, 11); max 8 cycles. Allow at least 72hrs between consecutive doses. May be given as a single agent or in combination with dexamethasone. Dose modifications: see full labeling. Moderate-to-severe hepatic impairment: reduce to 0.7mg/m2 in 1st cycle; may consider dose increase to 1mg/m2 or further decrease to 0.5mg/m2 in subsequent cycles based on tolerance.
Boron or mannitol sensitivity. Intrathecal administration.
Pre-existing or at high-risk of peripheral neuropathy: consider SC inj; if severe, treat only after careful risk-benefit assessment. Monitor for development or worsening of peripheral neuropathy; consider dose and/or schedule adjustment. History of syncope. Dehydration; replace fluids and electrolytes. Heart disease; monitor for CHF. Interrupt therapy and evaluate if new or worsening cardiopulmonary symptoms develop. High tumor burden: monitor for tumor lysis syndrome. Diabetes; closely monitor blood glucose. Hepatic impairment. Monitor CBC frequently during therapy and platelets prior to each dose; adjust dose/schedule for thrombocytopenia (see full labeling). Embryo-fetal toxicity; use effective contraception during and for 2 months after treatment. Pregnancy; avoid. Nursing mothers: not recommended.
May be antagonized by concomitant strong CYP3A4 inducers (eg, rifampin, St. John's Wort): not recommended. Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir); consider reducing bortezomib dose. Caution with hypotensives and hypoglycemics.
GI toxicity (eg, nausea, diarrhea, constipation, vomiting; interrupt therapy if severe), thrombocytopenia, neutropenia, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, lymphopenia, rash, pyrexia, anorexia; hypotension, CHF, decreased LVEF, ARDS, diffuse infiltrative lung disease, hepatotoxicity; rare: posterior reversible encephalopathy syndrome (discontinue if occurs).