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

Route/Dosage

· Previously Untreated Multiple Myeloma

· Previously Untreated Mantle Cell Lymphoma

· Relapsed Multiple Myeloma and Mantle Cell Lymphoma

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. For 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) q 3 wk for a maximum of 8 cycles.

Hepatic Impairment

· IV (Adults): Moderate or severe hepatic impairment — 0.7 mg/m2 per injection for the first cycle, then may to 1 mg/m2 per injection or further to 0.5 mg/m2 per injection, based on tolerability.

Implementation

· 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: 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: 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 second bolus injection twice weekly for 2 wk followed by a 10-day rest period. At least 72 hr should elapse between consecutive doses.

· 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 re-initiate 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.

US Brand Names

Velcade

Pregnancy Category

Category D

Classifications

Therapeutic Classification: antineoplastics

Pharmacologic Classification: proteasome inhibitors

Availability

· Lyophilized powder for injection (requires reconstitution): 3.5 mg/vial;

Time/Action Profile

ROUTE	ONSET	PEAK	DURATION
IV	unknown	38 days*	unknown

*Median time to response based on clinical parameters.

Assessment

· 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 tumor lysis syndrome (tachypnea, tachycardia, hypotension, pulmonary edema). Patients with high tumor burden prior to treatment are at increased risk.

· Monitor for signs of RPLS (headache, seizure, lethargy, confusion, blindness). Hypertension may or may not be present. May occur with in 16 hr to 1 yr of initiation of therapy. Treat hypertension if present and discontinue bortezomib therapy. Symptoms usually resolve within days.

· Assess for any new signs or symptoms that may be suggestive of PML, an opportunistic infection of the brain caused by the JC virus, that leads to death or severe disability; withhold dose and notify health care professional promptly. PML symptoms may begin gradually but usually worsen rapidly. Symptoms vary depending on which part of brain is infected (mental function declines rapidly and progressively, causing dementia; speaking becomes increasingly difficult; partial blindness; difficulty walking; rarely, headaches and seizures occur). Diagnosis is usually made via gadolinium-enhanced MRI and CSF analysis. Risk of PML increases with the number of infusions. Withhold bortezomib at first sign of PML.

Lab Test Considerations:

· 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.

Pot. Nursing Diagnoses

· Risk for injury (Adverse Reactions).

Patient/Family Teaching

· 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; 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.

· Advise patient of the need for contraception and to avoid breast feeding during therapy. Patient should notify health care professional immediately if pregnancy is suspected.

Evaluation

· Decrease in serum and urine myeloma protein.

· Decrease in size and spread of malignancy.