BORTEZOMIB

BORTEZOMIB (bor-te-zo'mib) Velcade Classifications: antineoplastic agent; biologic response modifier; proteosome inhibitor; Therapeutic: antineoplastic agent; biologic response modifier Pregnancy Category: D

Availability

3.5 mg powder for injection

Action

Bortezomib is a reversible inhibitor of proteasome, which is responsible for regulation of protein expression and degradation of damaged or obsolete proteins within the cell; its activity is critical to activation or suppression of cellular functions including the cell cycle, oncogene expression, and apoptosis. Malignant cells are much more sensitive to the effects of proteasome inhibition than normal cells.

Therapeutic Effect

Proteasome inhibition may reverse some of the changes that allow proliferation of malignant cells and suppress apoptosis (programmed cell death) in malignant cells.

Uses

Treatment of relapsed or refractory multiple myeloma or mantle cell lymphoma in patients who have failed one prior therapy.

Contraindications

Hypersensitivity to bortezomib, boron, or mannitol; pregnancy (category D); lactation. Safety and effectiveness in children are not established.

Cautious Use

Peripheral neuropathy; history of syncope, dehydration, hypotension; concurrent antihypertensive drugs; history of allergies, asthma; preexisting electrolyte or acid-base disturbances, especially hypokalemia or hyponatremia; liver disease; myelosuppression, renal impairment; history of peripheral neuropathy or other neurologic disorders; GI toxicities.

Route & Dosage

Multiple Myeloma/Mantle Cell Lymphoma Adult: IV 1.3 mg/m2 twice weekly for 2 wk (days 1, 4, 8, and 11) followed by a 10-d rest period; at least 72 h should elapse between consecutive doses; 3 wk period is a treatment cycle Toxicity Adjustment Withhold dose with grade 3 or 4 hematologic toxicity, when symptoms resolve dose may be reduced 25% and restarted.

Administration

Intravenous Wear protective gloves and prevent contact with skin. PREPARE: Direct: Reconstitute 3.5 mg vial with 3.5 mL of NS for injection to yield 1 mg/mL. Discard if not clear and colorless. Give within 8 h of reconstitution.   ADMINISTER: Direct: Give as a bolus dose over 3–5 sec. Flush before/after with NS. • Store unopened vials at 15°–30° C (59°–86° F). Protect from light.• Store reconstituted vials at 15°–30° C (59°–86° F). Give within 8 h of reconstitution. May store up to 3 h in a syringe; however, total storage time must not exceed 8 h when exposed to normal indoor lighting.  INCOMPATIBILITIES Solution/additive: No data available. Do not recommend mixing or injecting with any other drugs.

Adverse Effects (≥1%)

Body as a Whole: Asthenia, weakness, fatigue, malaise, fever, dehydration, peripheral neuropathy, rigors, herpes zoster. CNS: Insomnia, headache, paresthesia, dizziness, anxiety. CV: Edema, hypotension, orthostatic hypotension. GI: Nausea, vomiting, diarrhea, anorexia, abdominal pain, constipation, dyspepsia, dysphagia. Hematologic: Thrombocytopenia, neutropenia, anemia. Musculoskeletal: Arthralgia, musculoskeletal pain, bone pain, myalgia, back pain, muscle cramps. Respiratory: Dyspnea, cough, upper respiratory infection. Skin: Rash, pruritus. Special Senses: Blurred vision, diplopia.

Interactions

Drug: Hypoglycemia and hyperglycemia have been reported with antidiabetic agents; antihypertensive agents may exacerbate hypotension; anticoagulants, antithymocyte globulin, nsaids, platelet inhibitors, aspirin, thrombolytic agents may increase risk of bleeding. Food: Grapefruit juice may increase drug levels.

Pharmacokinetics

Metabolism: In the liver primarily by CYP3A4. Half-Life: 9–15 h.

Nursing Implications

Assessment & Drug Effects

• Monitor for and report S&S of neuropathy (e.g., hyperesthesia, hypoesthesia, paresthesia, discomfort or neuropathic pain).
• Monitor postural vital signs for orthostatic hypotension.
• Monitor I&O and assess for S&S of dehydration or electrolyte imbalance if vomiting and/or diarrhea develop.
• Lab tests: Frequent CBC with platelet count; baseline and periodic LFTs; frequent blood glucose in diabetics.

Patient & Family Education

• Report promptly any of the following: dizziness, light-headedness or fainting spells; numbness, tingling, or other unusual sensations; signs of infection (e.g., fever, chills, cough, sore throat); bruising, pinpoint red spots on the skin; black, tarry stools, nosebleeds, or any other sign of bleeding.
• Do not drive or engage in other hazardous activities until reaction to drug is known.
• Females should use reliable methods of contraception to avoid pregnancy while on this drug.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug