#高警訊藥品

多發性骨髓瘤 Multiple myeloma; Mantle cell lymphoma

Antineoplastic Agent, Proteasome Inhibitor
Bortezomib inhibits proteasomes, enzyme complexes which regulate protein homeostasis within the cell. Specifically, it reversibly inhibits chymotrypsin-like activity at the 26S proteasome, leading to activation of signaling cascades, cell-cycle arrest, and apoptosis.

Distribution:
1. Vd: ~498 to 1,884 L/m2; distributes widely to peripheral tissues.
2. Protein binding: ~83%.
Metabolism:
1. Hepatic primarily via CYP2C19, CYP3A4, and CYP1A2 and to a lesser extent CYP2D6 and CYP2C9; forms metabolites (inactive) via deboronization followed by hydroxylation.
2. Half-life elimination: (Single dose) IV: 9 to 15 hours; (Multiple dosing) 1 mg/m2: 40 to 193 hours.

Hypersensitivity to bortezomib, boron or mannitol.

D; Fetal risk cannot be ruled out

The manufacturer recommends lactating patients avoid breastfeeding during and for 2 months following bortezomib treatment.

Asthenic conditions (including fatigue, malaise, and weakness), nausea, vomiting, diarrhea, appetite decreased, peripheral neuropathy, thrombocytopenia, anemia, neutropenia, hepatic events, hypotension, fever

Multiple myeloma
1. First-line therapy (in combination with melphalan and prednisone):
IV, SUBQ 1.3 mg/m2 days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day treatment cycle for 4 cycles, followed by 1.3 mg/m2 days 1, 8, 22, and 29 of a 42-day treatment cycle for 5 cycles.
2. Relapsed/refractory:
IV, SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle. Therapy extending beyond 8 cycles may be administered by the standard schedule or may be given once weekly for 4 weeks (days 1, 8, 15, and 22), followed by a 13-day rest (days 23 through 35).
Mantle cell lymphoma
1. First-line therapy (VcR-CAP regimen):
IV 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for 6 cycles (in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone). If response first documented at cycle 6, treatment for an additional 2 cycles is recommended.
2. Mantle cell lymphoma, relapsed:
IV, SUBQ 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for up to 17 cycles.

1. No dosage adjustment is necessary.
2. Dialysis may reduce bortezomib concentrations; administer postdialysis.

Hepatic impairment prior to treatment initiation:
1. Mild impairment (bilirubin 1 times ULN and AST >ULN or bilirubin >1 to 1.5 times ULN and any AST): No initial dose adjustment is necessary.
2. Moderate (bilirubin >1.5 to 3 times ULN and any AST) and severe impairment (bilirubin >3 times ULN and any AST): Reduce initial dose to 0.7 mg/m2 in the first cycle; based on patient tolerance, may consider dose escalation to 1 mg/m2 or further dose reduction to 0.5 mg/m2 in subsequent cycles.
Hepatotoxicity during treatment:
Hepatitis, transaminase increases, and hyperbilirubinemia: Interrupt therapy to assess reversibility.

Prior to use, the contents of each vial must be reconstituted with 3.5 ml of normal (0.9%) saline. Reconstituted Velcade should be administered within 8 hours of preparation.