Bortezomib
for Injection

Bortezomib for injection is a proteasome inhibitor indicated for:

• treatment of adult patients with multiple myeloma

• treatment of adult patients with mantle cell lymphoma

• For subcutaneous or intravenous use only. Each route of administration has a different reconstituted concentration. Exercise caution when calculating the volume to be administered

• 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.

• Retreatment for Multiple Myeloma: May retreat starting at the last tolerated dose.

• Hepatic Impairment: Use a lower starting dose for patients with moderate or severe hepatic impairment.

• Dose must be individualized to prevent overdose.

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

• Patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol, including anaphylactic reactions.

• Contraindicated for intrathecal administration.

• Peripheral Neuropathy:
  Manage with dose modification or discontinuation. Patients with pre-existing severe neuropathy should be treated with bortezomib only after careful risk-benefit assessment.

• Hypotension:
  Use caution when treating patients taking antihypertensives, with a history of syncope, or with dehydration.

• Cardiac Toxicity:
  Worsening of and development of cardiac failure has occurred. Closely monitor patients with existing heart disease or risk factors for heart disease.

• Pulmonary Toxicity:
  Acute respiratory syndromes have occurred. Monitor closely for new or worsening symptoms and consider interrupting bortezomib therapy.

• Posterior Reversible Encephalopathy Syndrome:
  Consider MRI imaging for onset of visual or neurological symptoms; discontinue bortezomib if suspected.

• Gastrointestinal Toxicity:
  Nausea, diarrhea, constipation, and vomiting may require use of antiemetic and antidiarrheal medications or fluid replacement.

• Thrombocytopenia or Neutropenia:
  Monitor complete blood counts regularly throughout treatment.

• Tumor Lysis Syndrome:
  Closely monitor patients with high tumor burden.

• Hepatic Toxicity:
  Monitor hepatic enzymes during treatment. Interrupt bortezomib therapy to assess reversibility.

• Thrombotic Microangiopathy:
  Monitor for signs and symptoms. Discontinue bortezomib if suspected.

• Embryo-Fetal Toxicity:
  Bortezomib 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.

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.

Strong CYP3A4 Inhibitors:
Closely monitor patients with concomitant use.

Strong CYP3A4 Inducers:
Avoid concomitant use.

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