RECENT MAJOR CHANGES

INDICATIONS AND USAGE

VELCADE is a proteasome inhibitor indicated for:

• treatment of patients with multiple myeloma (1.1)
• treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy (1.2)

DOSAGE AND ADMINISTRATION

The recommended dose of VELCADE is 1.3 mg/m2 administered as a 3 to 5 second bolus intravenous injection. (2.1, 2.3)

DOSAGE FORMS AND STRENGTHS

• 1 single-use vial contains 3.5 mg of bortezomib. Dose must be individualized to prevent overdose. (3)

CONTRAINDICATIONS

• VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. (4)

WARNINGS AND PRECAUTIONS

• Peripheral neuropathy, including severe cases, may occur - manage with dose modification or discontinuation. (2.5) Patients with preexisting severe neuropathy should be treated with VELCADE only after careful risk-benefit assessment. (2.2, 2.4, 5.1)
• Hypotension can occur. Use caution when treating patients receiving antihypertensives, those with a history of syncope, and those who are dehydrated. (5.2)
• Closely monitor patients with existing heart disease or risk factors for heart disease. (5.3)
• Acute diffuse infiltrative pulmonary disease has been reported. (5.4)
• Nausea, diarrhea, constipation, and vomiting have occurred and may require use of antiemetic and antidiarrheal medications or fluid replacement. (5.6)
• Thrombocytopenia or neutropenia can occur; complete blood counts should be regularly monitored throughout treatment. (5.7)
• Tumor Lysis Syndrome (5.8), Reversible Posterior Leukoencephalopathy Syndrome (5.5), and acute hepatic failure (5.9) have been reported.
• Women should avoid becoming pregnant while being treated with VELCADE. Pregnant women should be apprised of the potential harm to the fetus. (5.11, 8.1)

ADVERSE REACTIONS

Most commonly reported adverse reactions (incidence ≥ 30%) in clinical studies include asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, psychiatric disorders, anorexia and decreased appetite, neutropenia, neuralgia, leukopenia and anemia. (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.

DRUG INTERACTIONS

• Closely monitor patients receiving VELCADE in combination with strong CYP3A4 inhibitors. (7.1)
• Concomitant use of strong CYP3A4 inducers is not recommended. (7.3)

USE IN SPECIFIC POPULATIONS

• Patients with diabetes may require close monitoring of blood glucose and adjustment of anti-diabetic medication. (8.8)
• Hepatic Impairment: Use a lower starting dose for patients with moderate or severe hepatic impairment.(2.5, 5.10, 8.7, 12.3)