bor-TEZ-o-mib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: proteasome inhibitors

• Multiple myeloma (as initial therapy or after progression) (in combination with melphalan and prednisone).
• Mantle cell lymphoma.

• Inhibits proteasome, a regulator of intracellular protein catabolism, resulting in disruption of various intracellular processes.
• Cytotoxic to a variety of cancerous cells.

• Decreased progression and improved survival in multiple myeloma and mantle cell lymphoma.

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP2C19, CYP3A4, and CYP1A2 isoenzymes, and to a lesser extent by the CYP2D6 and CYP2C9 isoenzymes; excretion pathway unknown.

Half-life: 9–15 hr.

*Median time to response based on clinical parameters.

Contraindicated in:

• Hypersensitivity to bortezomib, boron, or mannitol
• Intrathecal administration (may cause death)
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Moderate to severe hepatic impairment
• History of or risk factors for HF
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: hypotension, HF.

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS.

EENT: blurred vision, diplopia.

GI: anorexia, constipation, diarrhea, nausea, vomiting, LIVER FAILURE.

Hemat: anemia, neutropenia, thrombocytopenia, BLEEDING, THROMBOTIC THROMBOCYTOPENIC PURPURA/HEMOLYTIC UREMIC SYNDROME.

Neuro: fatigue, malaise, peripheral neuropathy, weakness, dizziness, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), syncope.

Resp: pneumonia.

Misc: fever, tumor lysis syndrome.

Drug-Drug:

• Concurrent neurotoxic medications including amiodarone, some antivirals, nitrofurantoin, isoniazid, or HMG-CoA reductase inhibitors may ↑ risk of peripheral neuropathy.

Previously Untreated Multiple Myeloma

• IV, SC (Adults): 1.3 mg/m² twice weekly for Cycles 1–4 (days 1, 4, 8, 11, 22, 25, 29, and 32; no treatment during cycle 3), then once weekly for Cycles 5–9 (days 1, 8, 22, and 29; no treatment during Cycle 7); further cycles/doses depend on response and toxicity.

Previously Untreated Mantle Cell Lymphoma

• IV, SC (Adults): 1.3 mg/m² twice weekly on days 1, 4, 8, and 11, followed by a 10-day rest (days 12–21); repeat for 5 additional cycles; further cycles/doses depend on response and toxicity.

Relapsed Multiple Myeloma and Mantle Cell Lymphoma

• IV, SC (Adults): 1.3 mg/m² twice weekly for 2 wk (days 1, 4, 8, and 11), followed by a 10-day rest; further cycles/doses depend on response and toxicity. Patients with multiple myeloma who have previously responded to bortezomib therapy and who have relapsed 6 mo after prior bortezomib therapy can be started on their last tolerated dose; dose should be given twice weekly (days 1, 4, 8, and 11) every 3 wk for a maximum of 8 cycles.

(Generic available)

• Lyophilized powder for injection: 3.5 mg/vial;
• Solution for injection: 1 mg/mL; 2.5 mg/mL;

• Monitor vital signs frequently during therapy. May cause fever and orthostatic hypotension requiring adjustment of antihypertensives, hydration, or administration of mineralocorticoids.
• Monitor for GI adverse effects. May require antidiarrheals, antiemetics, and fluid and electrolyte replacement to prevent dehydration. Weigh weekly; modify diet as tolerated.
• Monitor for signs and symptoms of peripheral neuropathy (burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain, weakness) during therapy. If peripheral neuropathy is Grade 1 (paresthesia or loss of reflexes without pain or loss of function) continue prescribed dose. If paresthesia is Grade 1 with pain or Grade 2 (interfering with function but not with daily activities) reduce dose to 1.0 mg/m². If peripheral neuropathy is Grade 2 with pain or Grade 3 (interfering with activities of daily living) withhold dose until toxicity resolves, then reinitiate with a reduced dose of 0.7 mg/m² and decrease frequency to once/wk. If peripheral neuropathy is Grade 4 (permanent sensory loss that interferes with daily function) discontinue bortezomib.
• Monitor for signs and symptoms of tumor lysis syndrome (tachypnea, tachycardia, hypotension, pulmonary edema). Patients with high tumor burden prior to treatment are at increased risk.
• Monitor for signs of PRES (headache, seizure, lethargy, confusion, blindness). Hypertension may or may not be present. May occur within 16 hr to 1 yr of initiation of therapy. Treat hypertension if present and discontinue bortezomib therapy. Symptoms usually resolve within days.
• Monitor for signs and symptoms of thrombotic angiopathy (thrombocytopenia, microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, acute kidney injury). Discontinue therapy immediately if clinical or lab symptoms occur.

• Verify negative pregnancy test before starting therapy.Monitor CBC frequently during therapy. Assess platelet count before each dose. Dose modifications for hematologic toxicity are made based on indication and concurrent drug therapy; see manufacturer's recommendations. The nadir of thrombocytopenia is day 11 and recovery is usually by next cycle. Occurs more commonly in cycles 1 and 2, but may occur throughout therapy. May require discontinuation of therapy.
  • Monitor blood glucose levels closely in patients taking oral hypoglycemic agents; may require adjustment of antidiabetic agent dose.

• Should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.

IV Administration:

• SC: Reconstitution: Reconstitute each vial with 1.4 mL of 0.9% NaCl.Concentration: 2.5 mg/mL. Solution should be clear and colorless; do not administer solutions that are discolored or contain particulate matter. May inject into thigh or abdomen; rotate injection sites. Inject into sites at least 1 inch from other sites and avoid tender, bruised, erythematous, or indurated sites. If local injection site reactions occur, may inject a less concentrated (1 mg/mL) solution.
• IV Push: Reconstitution: Reconstitute each vial with 3.5 mL of 0.9% NaCl. Solution should be clear and colorless; do not administer solutions that are discolored or contain particulate matter.Concentration: 1 mg/mL. Administer reconstituted solution within 8 hr at room temperature; 3 of the 8 hr may be stored in a syringe.
• Rate: Administer as a 3–5 sec bolus injection twice weekly for 2 wk followed by a 10-day rest period. At least 72 hr should elapse between consecutive doses.

• Caution the patient that dehydration may occur with vomiting or diarrhea. Advise patient to maintain fluid intake and to notify health care professional if dizziness or fainting occurs.
• Instruct patient to contact health care professional if they experience new or worsening signs of peripheral neuropathy (tingling, numbness, pain, burning feeling in the feet or hands, weakness in the arms or legs), PML (progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; changes in thinking, memory, and orientation leading to confusion and personality changes), or if symptoms of dehydration (dizziness, fainting) due to vomiting or diarrhea; rash; shortness of breath; cough; swelling of feet, ankles, or legs; bleeding, infection, convulsions; persistent headache; reduced eyesight; increase in BP or blurred vision occur.
• May cause dizziness and blurred vision. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking Rx, OTC, or herbal products, especially St. John's wort.
• Advise diabetic patients taking oral hypoglycemic agents to monitor blood glucose frequently and notify health care professional of changes in blood sugar.
• Rep: Advise females of reproductive potential to use effective contraception during and for 7 mo after last dose and to avoid breastfeeding during therapy and for 2 mo after therapy. Advise males with female partner of reproductive potential to use effective contraception for 4 mo after last dose of bortezomib. Patient should notify health care professional immediately if pregnancy is suspected. May impair fertility for male and female patients.

• Decrease in serum and urine myeloma protein.
• Decrease in size and spread of malignancy.

Velcade

NDC Code^*

• 63020- Millennium Pharmaceuticals, Inc.
  • 63020-049- VELCADE
    • 63020-049-01- 1 VIAL in 1 CARTON (63020-049-01) > 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL (63020-049-04)

• 63323- Fresenius Kabi USA, LLC
  • 63323-721- Bortezomib
    • 63323-721-10- 1 VIAL, SINGLE-DOSE in 1 CARTON (63323-721-10) > 10 mL in 1 VIAL, SINGLE-DOSE