Names and pronunciation
(bor-tez′oh-mib) Velcade
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Drug reference
(bor-tez′oh-mib) Velcade
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Func. class.: Antineoplastic— miscellaneous
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Chem. class.: Proteasome inhibitor
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ACTION: Reversible inhibitor of chy- motrypsin-like activity; causes delay in tumor growth by disrupting normal homeostatic mechanisms
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USES: Multiple myeloma previously untreated or when at least 2 other treat- ments have failed; mantle cell lymphoma in patients who have received ≥1 prior therapy
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CONTRAINDICATIONS: Preg- nancy, breastfeeding; hypersensitivity to product, boron, mannitol Precautions: Children, geriatric patients, peripheral neuropathy, cardiac/ hepatic disease, hypotension, tumor lysis syndrome, thrombocytopenia, infection, diabetes mellitus, bone marrow suppres- sion, intracranial bleeding, injection site irritation
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SIDE EFFECTS CNS: Posterior reversible encephalopathy syndrome (PRES), progressive multifocal leukoencephalopathy (PML), dizziness, headache, peripheral neuropathy, fever, headache, fatigue, malaise, weakness CV: Hypotension, edema GI: Abdominal pain, constipation, diar- rhea, nausea, vomiting, anorexia, hepatotoxicity HEMA: Anemia, neutropenia, thrombo- cytopenia MISC: Tumor lysis syndrome RESP: Cough, pneumonia, dyspnea
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INTERACTIONS Increase: risk for bleeding—anticoagu- lants, NSAIDs, platelet inhibitors, salicylates, thrombolytics Increase: peripheral neuropathy— amiodarone, antivirals (amprenavir, atazanavir, didanosine, lamiVUDine, 3TC, ritonavir, stavudine, zidovudine), chloramphenicol, CISplatin, colchi- cine, cycloSPORINE, dapsone, disulfi- ram, DOCEtaxel, gold salts, HMG-CoA reductase inhibitors, iodoquinol, INH, metroNIDAZOLE, nitrofurantoin, oxali- platin, PACLitaxel, penicillamine, phe- nytoin, sulfaSALAzine, thalidomide, vinBLAStine, vinCRIStine, zalcitabine ddc, isoniazid, statins, others Drug/Herb Increase: toxicity or decrease efficacy— St. John’s wort Drug/Lab Increase: LFTs, glucose Decrease: platelets
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DOSAGE AND ROUTES Multiple myeloma (previously untreated) • Adult: IV BOL/SUBCUT Give for nine 6-wk cycles; cycles 1-4, 1.3 mg/m2/dose given on days 1, 4, 8, 11, then a 10-day rest period (days 12-21), then give again on days 22, 25, 29, 32, then a 10-day rest pe- riod (days 33-42); given with melphalan (9 mg/m2/day on days 1-4) and predniSONE (60 mg/m2/day on days 1-4); during cycles 5-9, give bortezomib 1.3 mg/m2/dose on days 1, 8, 22, 29 with melphalan (9 mg/m2/ day on days 1-4) and predniSONE (60 mg/ m2/day on days 1-4); this 6-wk cycle is considered 1 course; at least 72 hr should elapse between consecutive doses Mantle cell lymphoma in combination (previously untreated) • Adult: IV BOL/SUBCUT 1.3 mg/m2/ dose on days 1, 4, 8, 11 followed by a 10-day rest period (days 12-21); ×6 (3- wk) cycles with rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, DOXOru- bicin 50 mg/m2 all on day 1, and predni- SONE 100 mg/m2 daily on days 1-5, give bortezomib before rituximab Relapsed multiple myeloma or mantle cell lymphoma • Adult: IV BOL/SUBCUT 1.3 mg/m2/2 × per wk on days 1, 4, 8, 11 followed by a 10-day rest period Hepatic dose • Adult: IV bilirubin >1.5 × ULN, reduce to 0.7 mg/m2 during cycle 1; consider dose escalation to 1 mg/m2 or further re- duction to 0.5 mg/m2 during next cycles based on tolerability
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Available forms: Lyophilized powder for injection 3.5 mg
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Administer: • IV and SUBCUT concentrations are dif- ferent IV bolus route • Reconstitute each vial with 3.5 mL of 0.9% NaCl (1 mg/mL); solution should be clear/colorless; inject as bolus over 3-5 sec • Store unopened product at room tem- perature, protect from light • Wear protective clothing during han- dling, preparation; avoid contact with skin • Check for extravasation at injection site SUBCUT route • Reconstitute with 1.4 mL of NS to a fi- nal concentration of 2.5 mg/mL; if injec- tion site reaction occurs, reconstitute vial with 3.5 mL of NS to a final concentration of 1 mg/mL or consider IV administra- tion; use within 8 hr • Administer calculated dose into the thigh or abdomen; rotate sites with each injec- tion; inject at least 1 inch from old sites • Space apart consecutive doses by at least 72 hr. Consider SUBCUT in patients with preexisting peripheral neuropathy or at high risk for the condition
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Assess: • VS baseline and frequently, hypoten- sion may occur, patients who are dehy- drated are at greater risk • GI toxicity: nausea, vomiting, diarrhea, constipation, may require antiemetics, antidiarrheals • Thrombocytopenia, neutropenia: CBC baseline and periodically, platelets before each dose, dose adjustment may be required (nadir 11 platelets) • Peripheral neuropathy: discomfort, burning, stinging in extremities; may use SUBCUT in those at risk • Pregnancy/breastfeeding: do not use in pregnancy, breastfeeding during or for 2 mo after last dose • Fatal pulmonary toxicity: assess for risk factors or new or worsening pulmo- nary symptoms • Tumor lysis syndrome: usually in patients with a high tumor burden (hyper- kalemia, hyperuricemia, hyperphosphate- mia, renal failure) • PRES: headache, malaise, confusion, seizures, blindness, hypertension, usually occurs within a few hours up to 1 yr after starting treatment, most symptoms do not need treatment, MRI confirms • PML: for new infections of the brain
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Evaluate: • Therapeutic response: improvement of multiple myeloma symptoms
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To monitor blood glucose levels if diabetic • To contact prescriber about new or wors- ening peripheral neuropathy, severe vomiting, diarrhea, easy bruising, bleeding, infection • To avoid driving, operating machinery until effect is known • To avoid using other medications un- less approved by prescriber • About bleeding risk; to report bruis- ing, bleeding • To immediately report headache, confu- sion, lethargy (PRES) • Pregnancy/breastfeeding: To use contraception while taking this product and for 2 mo after last dose; not to breast- feed during and for 2 mo after last dose
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PHARMACOKINETICS Half-life 9-15 hr, protein binding 83%, metabolized by CYP450 enzymes (3A4, 2D6, 2C19, 2C9, 1A2), onset, peak, duration unknown
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• Adult: IV BOL/SUBCUT Give for nine 6-wk cycles; cycles 1-4, 1.3 mg/m2/dose given on days 1, 4, 8, 11, then a 10-day rest period (days 12-21), then give again on days 22, 25, 29, 32, then a 10-day rest pe- riod (days 33-42); given with melphalan (9 mg/m2/day on days 1-4) and predniSONE (60 mg/m2/day on days 1-4); during cycles 5-9, give bortezomib 1.3 mg/m2/dose on days 1, 8, 22, 29 with melphalan (9 mg/m2/ day on days 1-4) and predniSONE (60 mg/ m2/day on days 1-4); this 6-wk cycle is considered 1 course; at least 72 hr should elapse between consecutive doses Mantle cell lymphoma in combination (previously untreated)
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• Adult: IV BOL/SUBCUT 1.3 mg/m2/ dose on days 1, 4, 8, 11 followed by a 10-day rest period (days 12-21); ×6 (3- wk) cycles with rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, DOXOru- bicin 50 mg/m2 all on day 1, and predni- SONE 100 mg/m2 daily on days 1-5, give bortezomib before rituximab Relapsed multiple myeloma or mantle cell lymphoma
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• Adult: IV BOL/SUBCUT 1.3 mg/m2/2 × per wk on days 1, 4, 8, 11 followed by a 10-day rest period Hepatic dose
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• Adult: IV bilirubin >1.5 × ULN, reduce to 0.7 mg/m2 during cycle 1; consider dose escalation to 1 mg/m2 or further re- duction to 0.5 mg/m2 during next cycles based on tolerability
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