Generic Name and Formulations:
Bortezomib 3.5mg/vial; pwd for IV or SC inj after reconstitution; contains mannitol.
Millennium Pharmaceuticals, Inc.
Multiple myeloma. Mantle cell lymphoma in patients who have received at least one prior therapy.
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). 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). Allow at least 72 hours between consecutive doses. Adjust dose if toxicity develops: see literature. SC inj may be considered for patients with pre-existing or at high-risk of peripheral neuropathy. Moderate-to-severe hepatic impairment: reduce to 0.7mg/m2 in 1st cycle; may consider dose increase to 1mg/m2 or decrease to 0.5mg/m2 in subsequent cycles based on tolerance.
Boron or mannitol sensitivity. Intrathecal administration.
Hepatic impairment. Pre-existing severe neuropathy; treat only after careful risk-benefit assessment. Monitor for development or worsening of peripheral neuropathy; consider dose or schedule adjustment. Diabetes. History of syncope. Avoid dehydration; give fluids and electrolytes. Heart disease (monitor for CHF). Monitor CBC and platelets and for toxicities. High tumor burden (monitor for tumor lysis syndrome). Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.
Concomitant strong CYP3A4 inducers (eg, rifampin): not recommended; efficacy may be reduced. Avoid St. John's Wort. Potentiated by ketoconazole, other potent CYP3A inhibitors. Increased risk of peripheral neuropathy with other agents that can cause neuropathy (eg, amiodarone, antivirals, isoniazid, metronidazole, statins, nitrofurantoin, or previous neurotoxic agents). Caution with hypotensives and hypoglycemics.
Asthenia, GI upset, peripheral neuropathy, decreased appetite, thrombocytopenia, anemia, orthostatic hypotension, pyrexia, headache, insomnia, psychiatric disorders, arthralgia, neutropenia, hypercalcemia, pain, edema, paresthesia, dysesthesia, dyspnea, cough, pruritus, dizziness, blurred vision, pneumonia, CHF, decreased LVEF, herpes reactivation, hepatotoxicity; rare: pulmonary disorders, reversible posterior leukoencephalopathy syndrome (discontinue if occurs).