VELCADE

Following intravenous administration of 1 mg/m 2 and 1.3 mg/m 2 doses, the mean maximum plasma concentrations of bortezomib (C max ) after the first dose (Day 1) were 57 and 112 ng/mL, respectively. When administered twice weekly, the mean maximum observed plasma concentrations ranged from 67 to 106 ng/mL for the 1 mg/m 2 dose and 89 to 120 ng/mL for the 1.3 mg/m 2 dose. Following an intravenous bolus or subcutaneous injection of a 1.3 mg/m 2 dose to patients with multiple myeloma, the total sys...

14.1 Multiple Myeloma Randomized, Open-Label Clinical Study in Patients with Previously Untreated Multiple Myeloma A prospective, international, randomized (1:1), open-label clinical study ( NCT00111319 ) of 682 patients was conducted to determine whether VELCADE administered intravenously (1.3 mg/m 2 ) in combination with melphalan (9 mg/m 2 ) and prednisone (60 mg/m 2 ) resulted in improvement in time to progression (TTP) when compared to melphalan (9 mg/m 2 ) and prednisone (60 mg/m 2 ) in patients with previously untreated multiple myeloma. Treatment was administered for a maximum of nine ...

The following clinically significant adverse reactions are also discussed in other sections of the labeling: Peripheral Neuropathy [see Warnings and Precautions (5.1) ] Hypotension [see Warnings and Precautions (5.2) ] Cardiac Toxicity [see Warnings and Precautions (5.3) ] Pulmonary Toxicity [see Warnings and Precautions (5.4) ] Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions (5.5) ] Gastrointestinal Toxicity [see Warnings and Precautions (5.6) ] Thrombocytopeni...

VELCADE is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol. Reactions have included anaphylactic reactions [see Adverse Reactions (6.1) ] . VELCADE is contraindicated for intrathecal administration. Fatal events have occurred with intrathecal administration of VELCADE. Patients with hypersensitivity (not including local reactions)...

Peripheral Neuropathy: Manage with dose modification or discontinuation. ( 2.7 ) Patients with pre-existing severe neuropathy should be treated with VELCADE only after careful risk-benefit assessment. ( 2.7 , 5.1 ) Hypotension: Use caution when treating patients taking antihypertensives, with a history of syncope, or with dehydration. ( 5.2 ) Cardiac Toxicity: Worsening of and development of cardiac failure has occurred. Closely monitor patients with existing heart disease or risk factors for he...

7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Closely monitor patients with concomitant use. ( 7.1 ) Strong CYP3A4 Inducers: Avoid concomitant use. ( 7.1 ) 7.1 Effects of Other Drugs on VELCADE Strong CYP3A4 Inducers Coadministration with a strong CYP3A4 inducer decreases the exposure of bortezomib [see Clinical Pharmacology (12.3) ] which may decrease VELCADE efficacy. Avoid coadministration with...