Names and pronunciation
(bor-tez′oh-mib) Velcade
Source page 179
Loading InternPractice…
Individual generic drug information
Extracted information for bortezomib only.
(bor-tez′oh-mib) Velcade
Source page 179
Func. class.: Antineoplastic— miscellaneous
Source page 179
Chem. class.: Proteasome inhibitor
Source page 179
ACTION: Reversible inhibitor of chy- motrypsin-like activity; causes delay in tumor growth by disrupting normal homeostatic mechanisms
Source page 179
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
Source page 179
Extracted information for bortezomib only.
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
Source page 179
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
Source page 180
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
Source page 180
Extracted information for bortezomib only.
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
Source pages 179, 180
Available forms: Lyophilized powder for injection 3.5 mg
Source page 180
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
Source page 180
Extracted information for bortezomib only.
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
Source pages 180, 181
Evaluate: • Therapeutic response: improvement of multiple myeloma symptoms
Source page 181
CLINICAL CONSIDERATIONS
Source page 180
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
Source page 181
Extracted information for bortezomib only.
PHARMACOKINETICS Half-life 9-15 hr, protein binding 83%, metabolized by CYP450 enzymes (3A4, 2D6, 2C19, 2C9, 1A2), onset, peak, duration unknown
Source page 180
Filter the extracted dose blocks for this individual drug.
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)
Candidate age grouping · source pages 179, 180
Multiple myeloma (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
Candidate age grouping · source pages 179, 180
Multiple myeloma (previously untreated)
• 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
Candidate age grouping · source pages 179, 180
Multiple myeloma (previously untreated)
• 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
Candidate age grouping · source pages 179, 180