Bortezomib for injection is a proteasome inhibitor indicated for:

• Treatment of adult patients with multiple myeloma. (1.1)
• Treatment of adult patients with mantle cell lymphoma. (1.2)

• For subcutaneous or intravenous use only. Each route of administration has a different reconstituted concentration. Exercise caution when calculating the volume to be administered. (2.1, 2.10)
• The recommended starting dose of bortezomib for injection 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)

For injection: Single-dose vial contains 3.5 mg of bortezomib as lyophilized powder for reconstitution and withdrawal of the appropriate individual patient dose. (3)

• Patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol, including anaphylactic reactions. (4)
• Contraindicated for intrathecal administration. (4)

• Peripheral Neuropathy: Manage with dose modification or discontinuation. (2.7) Patients with pre-existing severe neuropathy should be treated with bortezomib for injection 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 heart disease. (5.3)
• Pulmonary Toxicity: Acute respiratory syndromes have occurred. Monitor closely for new or worsening symptoms and consider interrupting bortezomib for injection therapy. (5.4)
• Posterior Reversible Encephalopathy Syndrome: Consider MRI imaging for onset of visual or neurological symptoms; discontinue bortezomib for injection 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 and 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. Interrupt bortezomib for injection therapy to assess reversibility. (5.9)
• Thrombotic Microangiopathy: Monitor for signs and symptoms. Discontinue bortezomib for injection if suspected. (5.10)
• Embryo-Fetal Toxicity: Bortezomib for injection can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.11)

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 Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Strong CYP3A4 Inhibitors: Closely monitor patients with concomitant use. (7.1)
• Strong CYP3A4 Inducers: Avoid concomitant use. (7.1)

Patients with diabetes may require close monitoring of blood glucose and adjustment of antidiabetic medication. (8.8)