VELCADE is a proteasome inhibitor indicated for:

• treatment of patients with multiple myeloma (1.1)
• treatment of patients with mantle cell lymphoma (1.2)

• For subcutaneous or intravenous use only (2.1)
• The recommended starting dose of VELCADE is 1.3 mg/m2 administered either as a 3 to 5 second bolus intravenous injection or subcutaneous injection. (2.2, 2.4, 2.6)
• Retreatment for multiple myeloma: May retreat starting at the last tolerated dose. (2.6)
• Hepatic Impairment: Use a lower starting dose for patients with moderate or severe hepatic impairment. (2.8)
• Dose must be individualized to prevent overdose (2.10)

• Peripheral Neuropathy: Manage with dose modification or discontinuation. (2.7) Patients with preexisting severe neuropathy should be treated with VELCADE only after careful risk-benefit assessment. (2.7, 5.1)
• Hypotension: Use caution when treating patients taking anti-hypertensives, 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 heart disease. (5.3)
• Pulmonary Toxicity: Acute respiratory syndromes have occurred. Monitor closely for new or worsening symptoms. (5.4)
• Posterior Reversible Encephalopathy Syndrome: Consider MRI imaging for onset of visual or neurological symptoms; discontinue VELCADE if suspected. (5.5).
• Gastrointestinal Toxicity: Nausea, diarrhea, constipation, and vomiting may require use of antiemetic and antidiarrheal medications or fluid replacement. (5.6)
• Thrombocytopenia or Neutropenia: Monitor complete blood counts regularly throughout treatment. (5.7)
• Tumor Lysis Syndrome: Closely monitor patients with high tumor burden (5.8).
• Hepatic Toxicity: Monitor hepatic enzymes during treatment.(5.9).
• Embryo-fetal Risk: Women should avoid becoming pregnant while being treated with VELCADE. Advise pregnant women of potential embryo-fetal harm. (5.10)

Most commonly reported adverse reactions (incidence ≥ 20%) in clinical studies include nausea, diarrhea, thrombocytopenia, neutropenia, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, constipation, vomiting, lymphopenia, rash, pyrexia, and anorexia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Millennium Pharmaceuticals at 1-866 VELCADE or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Co-administration with strong CYP3A4 inhibitors can increase VELCADE exposure. Closely monitor patients receiving VELCADE in combination with strong CYP3A4 inhibitors. (7.1)
• Co-administration with strong CYP3A4 inducers can decrease VELCADE exposure. Avoid concomitant use of strong CYP3A4 inducers. (7.3)

• Patients with diabetes may require close monitoring of blood glucose and adjustment of anti-diabetic medication. (8.8)