ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Bortezomib: Drug information

Bortezomib: Drug information
(For additional information see "Bortezomib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Velcade
Brand Names: Canada
  • ACT Bortezomib;
  • Bortezomib SDZ;
  • PMS-Bortezomib;
  • TARO-Bortezomib;
  • Velcade
Pharmacologic Category
  • Antineoplastic Agent, Proteasome Inhibitor
Dosing: Adult

Note: Consecutive doses should be separated by at least 72 hours. Consider antiviral prophylaxis for herpes virus infection during therapy. Consider initiating via the SUBQ route in patients at risk for or with pre-existing neuropathy (Ref).

Antibody-mediated rejection, treatment

Antibody-mediated rejection, treatment: Note: Optimal dose, frequency, and duration of therapy have not been established and vary based on institutional protocols. Administer as part of an appropriate combination regimen.

Cardiac transplantation (off-label use): IV: 1.3 to 1.5 mg/m2 typically given on days 1, 4, 8, and 11 (treatment frequency varies) for a total of 4 doses (treatment duration may vary) (Ref).

Kidney transplantation (off-label use): Note: Use in patients with early antibody-mediated rejection; benefit is not demonstrated in patients with late antibody-mediated rejection (Ref).

IV, SUBQ: 1.3 mg/m2 every 3 to 4 days for 4 doses; administer after plasmapheresis (Ref).

Liver transplantation (off-label use): IV, SUBQ: 1.3 mg/m2 once to twice weekly for up to 4 doses (Ref).

Lung transplantation (off-label use): IV, SUBQ: 1.3 mg/m2 once every 3 to 4 days for a total of 4 doses (Ref).

Cutaneous T-cell lymphoma, relapsed/refractory

Cutaneous T-cell lymphoma (mycosis fungoides), relapsed/refractory (off-label use): IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for up to 6 cycles (Ref).

Desensitization

Desensitization (adjunctive) (off-label): Note: Optimal dose, frequency, and duration of therapy have not been established and vary based on institutional protocols. Administer as part of an appropriate combination regimen (eg, following intravenous immunoglobulin and rituximab). Appropriate antiviral and antimicrobial prophylaxis should be employed during and following treatment (Ref).

Kidney transplantation (off-label use): IV: 1.3 mg/m2 every 3 days for 4 doses (Ref).

Follicular lymphoma, relapsed or refractory

Follicular lymphoma, relapsed or refractory (off-label use): IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 28-day treatment cycle, in combination with bendamustine and rituximab for 6 cycles (Ref) or 1.6 mg/m2 on days 1, 8, 15, and 22 of a 35-day treatment cycle, in combination with bendamustine and rituximab for 5 cycles (Ref).

Mantle cell lymphoma, first-line therapy

Mantle cell lymphoma, first-line therapy: VR-CAP (or VcR-CAP) regimen: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for 6 cycles (in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone). If response first documented at cycle 6, treatment for an additional 2 cycles is recommended (Ref).

Mantle cell lymphoma, relapsed

Mantle cell lymphoma, relapsed: IV, SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for up to 17 cycles (Ref).

Multiple myeloma, first-line therapy

Multiple myeloma, first-line therapy: Note: Bortezomib regimens also containing melphalan should be avoided in patients who are potential candidates for hematopoietic cell transplantation (Ref).

VMP regimen: IV, SUBQ: 1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day treatment cycle for 4 cycles, followed by 1.3 mg/m2 on days 1, 8, 22, and 29 of a 42-day treatment cycle for 5 cycles (in combination with melphalan and prednisone). Retreatment may be considered for patients who had previously responded to bortezomib (either as monotherapy or in combination) and who have relapsed at least 6 months after completing prior bortezomib therapy; initiate at the last tolerated dose (Ref).

First- line therapy, other dosing/combinations: Note: Refer to protocol for dosage adjustment details.

VRd (or RVd) regimen: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with lenalidomide and dexamethasone) for 8 cycles (Ref) or 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with lenalidomide and dexamethasone) for up to 8 induction cycles, followed by 1.3 mg/m2 on days 1, 8, 15, and 22 of a 42-day treatment cycle (as a single agent) for 4 maintenance cycles (Ref) or 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with lenalidomide and dexamethasone) for 3 cycles, followed by conditioning/transplant, followed (after hematologic recovery in patients without progression) by 1.3 mg/m2 (or last tolerated dose from cycle 3) on days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with lenalidomide and dexamethasone) for 2 cycles (Ref).

VRd (or RVd) regimen: SUBQ: 1.3 mg/m2 on days 1, 8, 15, and 22 of a 35-day treatment cycle (in combination with lenalidomide and dexamethasone) for 9 induction cycles, followed by 1.3 mg/m2 (or last tolerated dose from cycle 9) on days 1 and 15 of a 28-day treatment cycle (in combination with lenalidomide) for 6 consolidation cycles (Ref) or 1.3 mg/m2 on days 1, 4, 8, and 11 of a 28-day treatment cycle (in combination with lenalidomide and dexamethasone) for 6 induction cycles (with mobilization after the third induction cycle), followed by conditioning/transplant, followed by 2 additional consolidation cycles 3 months after transplant (Ref).

VTd regimen: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for 3 induction cycles (in combination with thalidomide and dexamethasone), followed by tandem transplant, followed by (3 months after second transplant) 1.3 mg/m2 on days 1, 8, 15, and 22 every 35 days for 2 consolidation cycles (in combination with thalidomide and dexamethasone) (Ref).

VTd regimen: SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with thalidomide and dexamethasone) for 4 induction cycles, followed by conditioning/transplant (Ref).

CyBorD (or VCd) regimen: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for up to 8 induction cycles (in combination with cyclophosphamide and dexamethasone), followed by 1.3 mg/m2 on days 1, 8, 15, and 22 of a 42-day treatment cycle (as a single agent) for 4 maintenance cycles (Ref) or 1.5 mg/m2 on days 1, 8, 15, and 22 of a 28-day treatment cycle for 4 cycles (may continue beyond 4 cycles) in combination with cyclophosphamide and dexamethasone (Ref).

PAD regimen: IV: Induction: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 28-day treatment cycle for 3 cycles (in combination with doxorubicin and dexamethasone), followed by conditioning/transplantation, and then maintenance bortezomib 1.3 mg/m2 once every 2 weeks for 2 years (Ref).

Daratumumab-containing regimens: SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle (in combination with daratumumab, lenalidomide, and dexamethasone; DVRd regimen) for 4 induction cycles and 2 post-transplant consolidation cycles (Ref) or 1.3 mg/m2 on days 1, 4, 8, and 11 of a 28-day cycle (in combination with daratumumab, thalidomide, and dexamethasone; DVTd regimen) for up to 4 pretransplant induction cycles and 2 posttransplant consolidation cycles (Ref) or 1.3 mg/m2 two times a week during weeks 1, 2, 4, and 5 of the first 6-week cycle (cycle 1; 8 doses/cycle), followed by 1.3 mg/m2 once a week during weeks 1, 2, 4, and 5 for eight 6-week cycles (cycles 2 to 9; 4 doses/cycle) in combination with daratumumab, melphalan, and prednisone; after cycle 9, daratumumab is continued as a single agent (Ref).

VD regimen: IV: Induction: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with dexamethasone) for 4 cycles, followed by autologous cell transplantation (Ref).

Patients ≥65 years of age: IV: 1.3 mg/m2 on days 1, 8, 15, and 22 of a 35-day treatment cycle for 9 cycles, in combination with either melphalan and prednisone or melphalan, prednisone, and thalidomide (Ref).

Maintenance therapy in transplant-eligible patients (following induction and transplant; in patients intolerant to or unable to receive maintenance therapy with lenalidomide): IV: 1.3 mg/m2 once every 2 weeks for 2 years (Ref). For high-risk patients, maintenance therapy with a proteosome inhibitor ± lenalidomide may be considered (Ref).

Multiple myeloma, relapsed/refractory

Multiple myeloma, relapsed/refractory:

Single-agent therapy: IV, SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle. Therapy extending beyond 8 cycles may be administered by the standard schedule or may be given once weekly for 4 weeks (days 1, 8, 15, and 22), followed by a 13-day rest (days 23 through 35). Retreatment may be considered for patients who had previously responded to bortezomib (either as monotherapy or in combination) and who have relapsed at least 6 months after completing prior bortezomib therapy; initiate at the last tolerated dose. Administer twice weekly for 2 weeks on days 1, 4, 8, and 11 of a 21-day treatment cycle (either as a single agent or in combination with dexamethasone) for a maximum of 8 cycles (Ref).

Relapsed or refractory disease, other dosing/combinations: Note: Refer to protocol for dosage adjustment details.

VRd (or RVd) regimen: IV: 1 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for up to 8 cycles (in combination with lenalidomide and dexamethasone), followed by maintenance therapy (if response or stable disease) of 1 mg/m2 (or the dose tolerated in cycle 8) on days 1 and 8 of a 21-day treatment cycle (± lenalidomide and/or dexamethasone) until disease progression or unacceptable toxicity (Ref).

DVd regimen: SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 every 21 days (in combination with daratumumab and dexamethasone) for up to 8 cycles (Ref).

VPd regimen: IV, SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for 8 cycles, followed by 1.3 mg/m2 on days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity (in combination with pomalidomide and dexamethasone) (Ref).

SVd regimen: SUBQ: 1.3 mg/m2 on days 1, 8, 15, and 22 every 35 days (in combination with selinexor and dexamethasone) until disease progression or unacceptable toxicity (Ref).

Bortezomib/Doxorubicin (liposomal) regimen: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for at least 8 cycles or until disease progression or unacceptable toxicity (in combination with liposomal doxorubicin) (Ref).

CyBorD (or VCD) regimen: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for up to 8 cycles, followed by 1.3 mg/m2 on days 1, 8, 15, and 22 of a 35-day treatment cycle for up to 3 cycles (in combination with cyclophosphamide and dexamethasone) (Ref).

Bendamustine/Bortezomib/Dexamethasone regimen: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 28-day treatment cycle for 4 cycles (if no response) or for up to a maximum of 8 cycles (in combination with bendamustine and dexamethasone) (Ref).

Peripheral T-cell lymphoma, relapsed/refractory

Peripheral T-cell lymphoma, relapsed/refractory (off-label use): IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for up to 6 cycles (Ref).

Systemic light chain amyloidosis

Systemic light chain amyloidosis (off-label use): IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (with or without dexamethasone) (Ref).

Waldenström macroglobulinemia

Waldenström macroglobulinemia (off-label use): Note: The Tenth International Workshop on Waldenström Macroglobulinemia prefers administering bortezomib SUBQ (if possible) (IWWM [Castillo 2020]). Refer to protocols for dosage adjustment details.

Initial therapy: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with dexamethasone and rituximab) for 4 cycles, followed by a 12-week rest, then an additional 4 cycles for a total of 8 cycles (Ref) or 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for 1 cycle, followed by 1.6 mg/m2 on days 1, 8, 15, and 22 of a 35-day treatment cycle for 4 cycles; cycles 2 and 5 also included dexamethasone and rituximab (Ref) or 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (as a single agent); continue until disease progression or until 2 cycles after achieving a complete response (Ref).

Relapsed or refractory disease: IV: 1.6 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle for 6 cycles (in combination with rituximab) (Ref) or 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (as a single agent); continue until disease progression or until 2 cycles after achieving a complete response (Ref).

Dosing: Kidney Impairment: Adult

No dosage adjustment is necessary (Ref). The International Myeloma Working Group (IMWG) recommendations suggest that bortezomib may be safely administered to patients with renal impairment, including those on dialysis (Ref). The IMWG recommends the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (preferred) or the Modification of Diet in Renal Disease (MDRD) formula to evaluate renal function estimation in patients with multiple myeloma with a stable serum creatinine. Dialysis may reduce bortezomib concentrations; administer postdialysis (Ref).

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment initiation:

Mild impairment (bilirubin ≤ ULN and AST >ULN or bilirubin >1 to 1.5 times ULN and any AST): No initial dose adjustment is necessary (Ref).

Moderate (bilirubin >1.5 to 3 times ULN and any AST) and severe impairment (bilirubin >3 times ULN and any AST): Reduce initial dose to 0.7 mg/m2 in the first cycle; based on patient tolerance, may consider dose escalation to 1 mg/m2 or further dose reduction to 0.5 mg/m2 in subsequent cycles (Ref).

Hepatotoxicity during treatment: Interrupt bortezomib treatment (to assess reversibility) if acute liver failure, hepatitis, increased transaminases, and/or hyperbilirubinemia occur; information on bortezomib rechallenge is limited (Ref).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).

Dosing: Adjustment for Toxicity: Adult

Note: Hematologic toxicity may also require platelet transfusion, supportive care, and/or myeloid growth factors as clinically indicated.

Multiple myeloma (first-line therapy):

Platelets should be ≥70,000/mm3, ANC should be ≥1000/mm3, and nonhematologic toxicities should resolve to grade 1 or baseline prior to therapy initiation.

Platelets ≤30,000/mm3 or ANC ≤750/mm3 on bortezomib day(s) (except day 1): Withhold bortezomib; if several bortezomib doses in consecutive cycles are withheld, reduce dose 1 level (1.3 mg/m2/dose reduced to 1 mg/m2/dose; 1 mg/m2/dose reduced to 0.7 mg/m2/dose)

Grade ≥3 nonhematological toxicity (other than neuropathy): Withhold bortezomib until toxicity resolves to grade 1 or baseline. May reinitiate bortezomib at 1 dose level reduction (1.3 mg/m2/dose reduced to 1 mg/m2/dose; 1 mg/m2/dose reduced to 0.7 mg/m2/dose).

Neuropathic pain and/or peripheral sensory or motor neuropathy: See "Neuropathic pain and/or peripheral sensory, motor, or autonomic neuropathy" toxicity adjustment guidelines below.

Mantle cell lymphoma (first-line therapy):

Platelets should be ≥100,000/mm3, ANC should be ≥1,500/mm3, hemoglobin should be ≥8 g/dL, and nonhematologic toxicities should resolve to grade 1 or baseline prior to each cycle (cycle 2 and beyond).

Platelets <25,000/mm3 or ≥ grade 3 neutropenia on bortezomib day(s) (except day 1): Withhold bortezomib for up to 2 weeks until platelets are ≥25,000/mm3 and/or ANC ≥750/mm3, then reduce dose 1 level (1.3 mg/m2/dose reduced to 1 mg/m2/dose; 1 mg/m2/dose reduced to 0.7 mg/m2/dose). If hematologic toxicity does not resolve after withholding therapy, discontinue bortezomib.

Grade ≥3 nonhematological toxicity (other than neuropathy): Withhold bortezomib until toxicity resolves to ≤ grade 2. May reinitiate bortezomib at 1 dose level reduction (1.3 mg/m2/dose reduced to 1 mg/m2/dose; 1 mg/m2/dose reduced to 0.7 mg/m2/dose).

Neuropathic pain and/or peripheral sensory or motor neuropathy: See "Neuropathic pain and/or peripheral sensory or motor neuropathy" toxicity adjustment guidelines below.

Relapsed multiple myeloma and mantle cell lymphoma:

Grade 3 nonhematological (excluding neuropathy) or grade 4 hematological toxicity: Withhold until toxicity resolved; may reinitiate with a 25% dose reduction (1.3 mg/m2/dose reduced to 1 mg/m2/dose; 1 mg/m2/dose reduced to 0.7 mg/m2/dose)

Neuropathic pain and/or peripheral sensory, motor, or autonomic neuropathy:

Note: Consider SUBQ administration in patients with preexisting or at high risk for peripheral neuropathy.

Grade 1 (asymptomatic; deep tendon reflex loss or paresthesia) without pain or loss of function: No action needed

Grade 1 with pain or grade 2 (moderate symptoms; limiting instrumental activities of daily living): Reduce dose to 1 mg/m2

Grade 2 with pain or grade 3 (severe symptoms; limiting self-care activities of daily living): Withhold until toxicity resolved, may reinitiate at 0.7 mg/m2 once weekly

Grade 4 (life-threatening consequences with urgent intervention indicated) and/or severe autonomic neuropathy: Discontinue therapy.

Other adverse reactions:

Cardiopulmonary symptoms: Promptly evaluate with new or worsening symptoms; therapy interruption may be required.

GI symptoms (eg, nausea, vomiting, diarrhea, constipation): GI symptoms may require antiemetics or antidiarrheals. Administer fluid and electrolytes to prevent dehydration; interrupt therapy for severe symptoms.

Hyper- or hypoglycemia in patients with diabetes: May require adjustment of diabetes medications.

Hypotension (orthostatic or postural): May require adjustment of antihypertensive medication, hydration, and mineralocorticoids and/or sympathomimetics.

Posterior reversible leukoencephalopathy syndrome (PRES): Discontinue bortezomib if PRES occurs; confirm diagnosis with MRI. The safety of reinitiating bortezomib in patients previously experiencing PRES is unknown.

Progressive multifocal leukoencephalopathy: Evaluate promptly any new onset or worsening neurologic symptoms.

Thrombotic microangiopathy: Discontinue and further evaluate if thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is suspected; may resume bortezomib if diagnosis of TTP/HUS is excluded. The safety of reinitiating bortezomib therapy in patients previously experiencing TTP/HUS is unknown.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Dermatologic: Skin rash (12% to 23%)

Gastrointestinal: Abdominal pain (11%), anorexia (14% to 21%), constipation (24% to 34%), decreased appetite (11%), diarrhea (19% to 52%; grade 3: 1% to 7%; grades ≥3: 7%), nausea (14% to 52%; grade 3: 2%; grades ≥3: 3%), vomiting (9% to 29%; grade 3: 2%; grades ≥3: 3% to 4%)

Hematologic & oncologic: Anemia (12% to 23%; grades ≥3: ≤6%), leukopenia (18% to 20%; grade 3: 5%; grade 4: 1%), neutropenia (5% to 27%; grades ≥3%: 2% to 18%), thrombocytopenia (16% to 52%; grades ≥3%: 3% to 28%)

Infection: Herpes zoster infection (herpes zoster infection and reactivation: 6% to 11%)

Nervous system: Dizziness (10% to 18%), fatigue (7% to 52%), headache (10% to 19%), malaise (≤59%), neuralgia (23%), paresthesia (7% to 19%), peripheral neuropathy (including peripheral motor neuropathy and peripheral sensory neuropathy: 28% to 54%; grades ≥2: 24% to 39%; grades ≥3: 6% to 15%; grade 4: <1%)

Neuromuscular & skeletal: Asthenia (7% to 16%)

Respiratory: Dyspnea (11%)

Miscellaneous: Fever (8% to 23%)

1% to 10%:

Cardiovascular: Cardiac disorder (treatment emergent: 8%), cardiogenic shock (≤1%), heart failure (≤1%), hypotension (including orthostatic hypotension: 8% to 9%)

Hematologic & oncologic: Hemorrhage (grades ≥3: 2%)

Infection: Herpes simplex infection (1% to 3%)

Local: Injection site reaction (mostly redness: 6%), irritation at injection site (5%)

Respiratory: Acute pulmonary edema (≤1%), pulmonary edema (≤1%)

<1%: Cardiovascular: Syncope

Frequency not defined (reported reactions may have occurred with either monotherapy or combination therapy):

Cardiovascular: Acute myocardial infarction, aggravated atrial fibrillation, angina pectoris, atrial flutter, atrioventricular block, bradycardia, cerebrovascular accident, decreased left ventricular ejection fraction, deep vein thrombosis, edema, facial edema, hemorrhagic stroke, hypersensitivity angiitis, hypertension, ischemic heart disease, limb embolism, pericardial effusion, pericarditis, peripheral edema, portal vein thrombosis, prolonged QT interval on ECG, pulmonary embolism, septic shock, sinoatrial arrest, subdural hematoma, torsades de pointes, transient ischemic attacks, ventricular tachycardia

Dermatologic: Pruritus, urticaria

Endocrine & metabolic: Amyloid heart disease, dehydration, hyperkalemia, hypernatremia, hyperuricemia, hypocalcemia, hypokalemia, hyponatremia, weight loss

Gastrointestinal: Acute pancreatitis, cholestasis, duodenitis (hemorrhagic), dysgeusia, dyspepsia, dysphagia, fecal impaction, gastritis (hemorrhagic), gastroenteritis, gastroesophageal reflux disease, hematemesis, intestinal obstruction, intestinal perforation, melena, oral candidiasis, paralytic ileus, peritonitis, stomatitis

Genitourinary: Bladder spasm, hematuria, hemorrhagic cystitis, urinary incontinence, urinary retention, urinary tract infection

Hematologic & oncologic: Disseminated intravascular coagulation, febrile neutropenia, lymphocytopenia, oral mucosal petechiae

Hepatic: Ascites, hepatic failure, hepatic hemorrhage, hepatitis, hyperbilirubinemia, increased liver enzymes

Hypersensitivity: Anaphylaxis, angioedema, drug-induced hypersensitivity reaction, hypersensitivity reaction, type III hypersensitivity reaction

Infection: Aspergillosis, bacteremia, listeriosis, toxoplasmosis

Local: Catheter complication, catheter infection, erythema at injection site, pain at injection site

Nervous system: Agitation, anxiety, ataxia, cerebral hemorrhage, chills, coma, confusion, cranial nerve palsy, dysarthria, dysautonomia, dysesthesia, encephalopathy, insomnia, mental status changes, motor dysfunction, paralysis, postherpetic neuralgia, psychosis, seizure (tonic-clonic), spinal cord compression, suicidal ideation, vertigo

Neuromuscular & skeletal: Arthralgia, back pain, bone fracture, limb pain, myalgia, ostealgia

Ophthalmic: Blurred vision, conjunctival infection, diplopia, eye irritation

Otic: Auditory impairment

Renal: Bilateral hydronephrosis, nephrolithiasis, proliferative glomerulonephritis, renal failure syndrome (including acute kidney injury and chronic renal failure)

Respiratory: Acute respiratory distress syndrome, aspiration pneumonia, atelectasis, bronchitis, cough, dyspnea on exertion, epistaxis, exacerbation of chronic obstructive pulmonary disease, hemoptysis, hypoxia, interstitial pneumonitis, laryngeal edema, nasopharyngitis, pleural effusion, pneumonia, pneumonitis, pulmonary hypertension, pulmonary infiltrates (including diffuse), respiratory distress, respiratory tract infection, sinusitis

Postmarketing:

Cardiovascular: Cardiac tamponade

Dermatologic: Stevens-Johnson syndrome, Sweet’s syndrome, toxic epidermal necrolysis

Gastrointestinal: Ischemic colitis

Hematologic & oncologic: Hemolytic-uremic syndrome, thrombotic microangiopathy, thrombotic thrombocytopenic purpura, tumor lysis syndrome

Nervous system: Guillain-Barre syndrome, herpes meningoencephalitis, peripheral demyelinating polyneuropathy, progressive multifocal leukoencephalopathy, reversible posterior leukoencephalopathy syndrome

Ophthalmic: Blepharitis, blindness, chalazion (Fraunfelder 2016), ocular herpes simplex, optic neuropathy

Otic: Deafness (bilateral)

Contraindications

Hypersensitivity (excluding local reactions) to bortezomib, boron, boric acid (generic product), glycine (some generics), mannitol (Velcade, some generics), or any component of the formulations; administration via the intrathecal route.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Hematologic toxicity, including grade 3 and 4 neutropenia and thrombocytopenia may occur; risk is increased in patients with pretreatment platelet counts <75,000/mm3. Nadirs generally occur following the last dose of a cycle and recover prior to the next cycle. Hemorrhage (GI and intracerebral) due to low platelet count has been observed. Neutropenic fever has been observed.

• Cardiovascular effects: Acute development or exacerbation of HF and new onset decreased left ventricular ejection fraction (LVEF) have been reported with bortezomib; some cases have occurred in patients without risk factors for HF and/or decreased LVEF. Isolated case of QTc prolongation have been reported with bortezomib.

• GI effects: Nausea, vomiting, diarrhea, constipation, or ileus may occur.

• Hepatotoxicity: Acute liver failure has been reported (rarely) in patients receiving multiple concomitant medications and with serious underlying conditions. Hepatitis, transaminase increases, and hyperbilirubinemia have also been reported. Limited data exist for patients that have been rechallenged.

• Herpes reactivation: Herpes (zoster and simplex) reactivation has been reported with bortezomib.

• Hypersensitivity: Anaphylactic reaction, drug hypersensitivity, immune complex mediated hypersensitivity, angioedema, and laryngeal edema have been reported with bortezomib.

• Hypotension: Bortezomib may cause hypotension (including postural and orthostatic).

• Peripheral neuropathy: Bortezomib may cause or worsen peripheral neuropathy (usually sensory but may be mixed sensorimotor); risk may be increased with previous use of neurotoxic agents or preexisting peripheral neuropathy (in patients with preexisting neuropathy, use only after risk versus benefit assessment). The incidence of grades 2 and 3 peripheral neuropathy may be lower with SUBQ route (compared to IV). The majority of patients with ≥ grade 2 peripheral neuropathy have improvement in or resolution of symptoms with dose adjustments or discontinuation. In a study of patients ≥65 years of age receiving a weekly bortezomib schedule with combination chemotherapy, the incidence of peripheral neuropathy was significantly reduced without an effect on outcome (Palumbo 2010).

• Posterior reversible leukoencephalopathy syndrome: Posterior reversible leukoencephalopathy syndrome (PRES, formerly RPLS) has been reported (rarely). Symptoms of PRES include confusion, headache, hypertension, lethargy, seizure, blindness and/or other vision, or neurologic disturbances.

• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy has been rarely observed; symptoms may include confusion, loss of balance, vision disturbances, reduced strength or weakness in an arm/leg.

• Pulmonary toxicity: Pulmonary disorders (some fatal) including pneumonitis, interstitial pneumonia, lung infiltrates, and acute respiratory distress syndrome (ARDS) have been reported. Pulmonary hypertension (without left heart failure or significant pulmonary disease) has been reported rarely.

• Thrombotic microangiopathy: Cases (some fatal) of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, have been reported.

• Tumor lysis syndrome: Tumor lysis syndrome has been reported with bortezomib; risk is increased in patients with high tumor burden prior to treatment.

Disease-related concerns:

• Diabetes: Hyper- and hypoglycemia may occur in patients with diabetes receiving oral hypoglycemics.

Other warnings/precautions:

• Appropriate administration: For SUBQ or IV administration only. Intrathecal administration is contraindicated; inadvertent intrathecal administration has resulted in death. Bortezomib should NOT be prepared during the preparation of any intrathecal medications. After preparation, keep bortezomib in a location away from the separate storage location recommended for intrathecal medications. Bortezomib should NOT be delivered to the patient at the same time with any medications intended for central nervous system administration. The reconstituted concentrations for IV and SUBQ administration are different; use caution when calculating the volume for each route and dose. The manufacturers provide stickers to facilitate identification of the route for reconstituted vials. Some bortezomib products may not be approved for SUBQ administration; refer to specific product labeling for approved administration routes.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Generic: 3.5 mg/1.4 mL (1.4 mL)

Solution Reconstituted, Injection:

Generic: 3.5 mg (1 ea)

Solution Reconstituted, Injection [preservative free]:

Velcade: 3.5 mg (1 ea)

Generic: 1 mg (1 ea); 2.5 mg (1 ea); 3.5 mg (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 3.5 mg (1 ea)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Bortezomib Intravenous)

3.5MG/1.4ML (per mL): $102.86

Solution (reconstituted) (Bortezomib Injection)

1 mg (per each): $97.40

2.5 mg (per each): $230.41

3.5 mg (per each): $50.40 - $1,827.42

Solution (reconstituted) (Bortezomib Intravenous)

3.5 mg (per each): $1,923.58

Solution (reconstituted) (Velcade Injection)

3.5 mg (per each): $1,923.60

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection:

Velcade: 3.5 mg (1 ea)

Generic: 2.5 mg (1 ea); 3.5 mg (1 ea)

Administration: Adult

Note: The reconstituted concentrations for IV and SUBQ administration are different; use caution when calculating the volume for each route and dose. Consider SUBQ administration in patients with preexisting or at high risk for peripheral neuropathy. Some bortezomib products may not be approved for SUBQ administration; refer to specific product labeling for approved administration routes.

IV: Administer via rapid IV push (3 to 5 seconds). When administering in combination with rituximab for first-line therapy of mantle cell lymphoma, administer bortezomib prior to rituximab.

SUBQ: SUBQ administration of bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle has been studied in patients with relapsed multiple myeloma; doses were administered SUBQ (concentration of 2.5 mg/mL) into the thigh or abdomen, rotating the injection site with each dose; injections at the same site within a single cycle were avoided (Ref). Response rates were similar to IV administration; decreased incidence of grade 3 or higher adverse events were observed with SUBQ administration. Administer at least 1 inch from an old site and never administer to tender, bruised, erythematous, or indurated sites. If injection site reaction occurs, the more dilute 1 mg/mL concentration may be used SUBQ (or IV administration of 1 mg/mL concentration may be considered).

For SUBQ or IV administration only; fatalities have been reported with inadvertent intrathecal administration. Bortezomib should NOT be delivered to the patient at the same time with any medications intended for central nervous system administration.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Mantle cell lymphoma: Treatment of mantle cell lymphoma in adults.

Multiple myeloma: Treatment of multiple myeloma in adults.

Use: Off-Label: Adult

Antibody-mediated rejection in cardiac transplantation (treatment); Antibody-mediated rejection, kidney transplantation (treatment); Antibody-mediated rejection, liver transplantation (treatment, refractory); Antibody-mediated rejection, lung transplantation (treatment); Cutaneous T-cell lymphoma (mycosis fungoides), relapsed/refractory; Desensitization, kidney transplantation; Follicular lymphoma, relapsed/refractory; Peripheral T-cell lymphoma, relapsed/refractory; Systemic light-chain amyloidosis; Waldenström macroglobulinemia

Medication Safety Issues
Sound-alike/look-alike issues:

Bortezomib may be confused with bosutinib, carfilzomib, ixazomib.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Administration issues:

The reconstituted concentrations for IV and SUBQ administration are different; use caution when calculating the volume for each route and dose. The manufacturers provide stickers to facilitate identification of the route for reconstituted vials.

For SUBQ or IV administration only. Intrathecal administration is contraindicated; inadvertent intrathecal administration has resulted in death. Bortezomib should NOT be prepared during the preparation of any intrathecal medications. After preparation, keep bortezomib in a location away from the separate storage location recommended for intrathecal medications. Bortezomib should NOT be delivered to the patient at the same time with any medications intended for intrathecal administration.

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Antidiabetic Agents: Bortezomib may enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Bortezomib. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Bortezomib. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Bortezomib. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Bortezomib. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Green Tea: May diminish the antineoplastic effect of Bortezomib. Management: Advise patients to avoid concurrent use of green tea extract and other green tea products, particularly at higher doses or amounts, during treatment with bortezomib when possible. Risk D: Consider therapy modification

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Multivitamins/Fluoride (with ADE): May diminish the therapeutic effect of Bortezomib. Specifically, the vitamin C (ascorbic acid) found in many multivitamins may impair the clinical effects of bortezomib. Management: Patients should avoid taking extra vitamin C supplements and vitamin C-containing multivitamins during their bortezomib therapy. It is likely unnecessary, though, to advise patients to avoid dietary sources of vitamin C. Risk D: Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): May diminish the therapeutic effect of Bortezomib. Management: Patients should avoid taking extra vitamin C supplements and vitamin C-containing multivitamins with bortezomib. It is probably unnecessary to restrict or limit vitamin C-containing foods/beverages. Risk D: Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May diminish the therapeutic effect of Bortezomib. Specifically, vitamin C may decrease bortezomib therapeutic effects. Management: Patients should avoid taking extra vitamin C supplements and vitamin C-containing multivitamins during their bortezomib therapy. It is likely unnecessary, though, to advise patients to avoid dietary sources of vitamin C. Risk D: Consider therapy modification

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Reproductive Considerations

Evaluate pregnancy status prior to initiating therapy in patients who could become pregnant. Patients who could become pregnant should avoid becoming pregnant during bortezomib treatment and use effective contraception during therapy and for at least 7 months following bortezomib treatment. Patients with partners who could become pregnant should use effective contraception during and for at least 4 months following bortezomib treatment.

Bortezomib may potentially affect male or female fertility (based on the mechanism of action).

Pregnancy Considerations

Based on the mechanism of action and on findings in animal reproduction studies, bortezomib may cause fetal harm if administered during pregnancy.

Breastfeeding Considerations

It is not known if bortezomib is present in breast milk. The manufacturer recommends lactating patients avoid breastfeeding during and for 2 months following bortezomib treatment.

Dietary Considerations

Green tea and green tea extracts may diminish the therapeutic effect of bortezomib and should be avoided (Golden 2009). Avoid grapefruit juice. Avoid additional, nondietary sources of ascorbic acid supplements, including multivitamins containing ascorbic acid (may diminish bortezomib activity) during treatment, especially 12 hours before and after bortezomib treatment (Perrone 2009).

Monitoring Parameters

CBC with differential and platelets (monitor frequently throughout therapy); liver function tests (in patients with existing hepatic impairment); renal function. Monitor blood glucose (in patients with diabetes). Verify pregnancy status prior to therapy initiation in patients who could become pregnant. Monitor BP. Monitor for signs/symptoms of peripheral neuropathy (consider SUBQ administration in patients with preexisting or at high risk for peripheral neuropathy), dehydration, hypotension (use with caution in patients with dehydration, history of syncope, or taking medications associated with hypotension), posterior reversible leukoencephalopathy syndrome, progressive multifocal leukoencephalopathy, tumor lysis syndrome, or hyper-/hypoglycemia. Monitor baseline chest x-ray and then periodic pulmonary function testing (with new or worsening pulmonary symptoms). Monitor closely in patients with risk factors for heart failure or existing heart disease.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017], (ESC [Lyon 2022]). Assess BP at baseline and each clinical visit (also consider weekly home monitoring for initial 3 months, then monthly thereafter); assess natriuretic peptide at baseline for high and very high-risk patients and consider at each cycle for the first 6 cycles; consider checking natriuretic peptide at baseline for low- and moderate-risk patients; obtain a baseline echocardiography in all patients (ESC [Lyon 2022]).

Mechanism of Action

Bortezomib inhibits proteasomes, enzyme complexes which regulate protein homeostasis within the cell. Specifically, it reversibly inhibits chymotrypsin-like activity at the 26S proteasome, leading to activation of signaling cascades, cell-cycle arrest, and apoptosis.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: ~498 to 1,884 L/m2; distributes widely to peripheral tissues.

Protein binding: ~83%.

Metabolism: Hepatic primarily via CYP2C19, CYP3A4, and CYP1A2 and to a lesser extent CYP2D6 and CYP2C9; forms metabolites (inactive) via deboronization followed by hydroxylation.

Half-life elimination: Single dose: IV: 9 to 15 hours; Multiple dosing: 1 mg/m2: 40 to 193 hours; 1.3 mg/m2: 76 to 108 hours.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Dose-normalized mean AUC levels were increased by ~60% in patients with moderate or severe hepatic impairment.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Bortezomib spc | Bortezon;
  • (AR) Argentina: Biliodim | Borater | Bortezomib everex | Bortezomib Sandoz | Bortmex | Bozob | Bromadene | Egidon | Eugene | Gysaty | Miasoma | Multizom | Ninib | Simbiote | Zefra;
  • (AT) Austria: Bortezomib accord | Velcade;
  • (AU) Australia: Bortezomib juno | Velcade;
  • (BE) Belgium: Bortezomib ab | Bortezomib accord | Bortezomib mylan | Bortezomib Sandoz | Bortezomib teva | Velcade;
  • (BG) Bulgaria: Bortega | Bortezocon | Bortezomib actavis | Bortezomib Sandoz | Vortemyel;
  • (BR) Brazil: Bortezomibe | Bortyz | Bozored | Mielocade | Tovar | Velcade | Verazo;
  • (CH) Switzerland: Bortezomib accord | Bortezomib Sandoz;
  • (CI) Côte d'Ivoire: Egybort;
  • (CL) Chile: Bicavan | Bozix;
  • (CN) China: Velcade;
  • (CO) Colombia: Borteleg | Bortemix | Borten | Bortesun | Bortezomib Sandoz | Bortezomseven | Botemib | Bozib | Nubortez | Rebtyk | Tenimib | Tizob | Velcade | Vortyz;
  • (CZ) Czech Republic: Bortega | Bortezomib accord | Bortezomib actavis | Bortezomib adamed | Bortezomib ebewe | Bortezomib fresenius kabi | Bortezomib glenmark | Bortezomib zentiva | Zegomib;
  • (DE) Germany: Bortezom accord bb farma | Bortezomib accord | Bortezomib beta | Bortezomib hexal | Bortezomib ratiopharm | Bortezomib ribosepharm | Bortezomib zentiva | Velcade;
  • (DO) Dominican Republic: Velcade;
  • (EC) Ecuador: Botemib | Bozob;
  • (EE) Estonia: Bortezomib accord | Bortezomib actavis | Bortezomib hospira | Bortezomib sun | Bortezomib teva | Velcade;
  • (EG) Egypt: Velcade;
  • (ES) Spain: Bortezomib accord | Bortezomib aurovitas | Bortezomib dr. reddys | Bortezomib kern | Bortezomib mylan | Bortezomib teva | Bortezomib tillomed | Velcade;
  • (ET) Ethiopia: Bortenat | Bortezomib msn;
  • (FI) Finland: Velcade;
  • (FR) France: Bortezomib ohre pharma | Bortezomib reddy pharma | Bortezomib zentiva | Velcade;
  • (GB) United Kingdom: Bortezomib accord | Bortezomib mylan | Bortezomib reddys | Velcade;
  • (GR) Greece: Velcade;
  • (HR) Croatia: Bortezomib pliva | Velcade;
  • (HU) Hungary: Bortezomib accord | Bortezomib actavis | Bortezomib msn | Bortezomib Sandoz | Bortezomib teva | Velcade | Vortemyel | Zegomib;
  • (ID) Indonesia: Velcade;
  • (IE) Ireland: Bortezomib accord;
  • (IN) India: Biocure | Bortecad | Bortemib | Bortenat | Bortero | Bortesam | Bortetor | Bortetrust | Bortezom | Bortiad | Bortirel | Bortrac | Borviz | Egybort | Mibor | Myezom | Mylosome | MyZomib | Ortez | Rolcade | Velcade | Zortemib;
  • (IT) Italy: Bortezomib Hikma | Bortezomib medac | Bortezomib reddys | Bortezomib zentiva | Velcade;
  • (JO) Jordan: Brotex | Veelbore;
  • (JP) Japan: Velcade;
  • (KE) Kenya: Bortemib | Bortesun | Bortimore;
  • (KR) Korea, Republic of: Belzomib | Bortevel | Protezomib | Tezobel | Tezobell | Tezomin | Velcade | Velkin | Velzomib;
  • (KW) Kuwait: Velcade;
  • (LB) Lebanon: Borcade | Velcade;
  • (LT) Lithuania: Bortezomib accord | Bortezomib sun | Sangrel | Vortemyel;
  • (LV) Latvia: Bortezomib accord | Bortezomib fresenius kabi | Bortezomib sun | Velcade | Vortemyel;
  • (MA) Morocco: Velcade;
  • (MX) Mexico: Bemoncaz | Bizmi | Bomib | Elomaziv | Exfucikanet | Misecade | Rebtyk | Velcade | Zuricade;
  • (MY) Malaysia: Accord bortezomib | Bortero | Myborte | Velcade;
  • (NL) Netherlands: Bortezomib accord | Velcade;
  • (NO) Norway: Bortezomib accord | Bortezomib mylan | Velcade;
  • (NZ) New Zealand: Bortezomib dr. reddys | Velcade;
  • (PE) Peru: Botemib | Mibor | Velcade | Velcord;
  • (PH) Philippines: Bezom | Bortesum | Bortether | Mylocure | Velcade | Zyocade;
  • (PK) Pakistan: Bortezomib pharmidea | Egybort;
  • (PL) Poland: Bortezomib accord | Bortezomib actavis | Bortezomib adamed | Bortezomib medac | Bortezomib sun | Velcade | Vortemyel;
  • (PR) Puerto Rico: Velcade;
  • (PT) Portugal: Bortezomib accord | Bortezomib krka | Bortezomib teva | Velcade;
  • (PY) Paraguay: Borater | Bortezomib bauel top | Bortezomib bioteng | Bortezomib catedral | Bortezomib cellofarm | Bortezomib gemepe | Bortezomib imedic | Bortezomib indufar | Bortezomib libra | Bortezomib prosalud | Bortezomib Sandoz | Botemib | Bozob;
  • (RO) Romania: Bortega | Bortezomib accord | Bortezomib actavis | Bortezomib glenmark | Bortezomib hospira | Bortezomib reddys | Bortezomib Sandoz | Bortezomib sun | Bortezomib zentiva | Vortemyel;
  • (RU) Russian Federation: Bartizar | Boramilan | Boramilan fs | Bortezol | Bortezomib canon | Milanfore | Milatib | Myborte | Velcade | Velmib | Verozomib;
  • (SA) Saudi Arabia: Bortezomib spc | Veelbore;
  • (SE) Sweden: Velcade;
  • (SG) Singapore: Velcade;
  • (SI) Slovenia: Bortezomib accord | Bortezomib actavis | Bortezomib mylan | Bortezomib Sandoz | Bortezomib teva | Velcade;
  • (SK) Slovakia: Bortega | Bortezomib accord | Bortezomib actavis | Bortezomib glenmark | Bortezomib mylan | Bortezomib pharmevid | Bortezomib Sandoz | Velcade | Zegomib;
  • (TH) Thailand: Bortero | Myborte | Tevazomib | Velcade;
  • (TN) Tunisia: Bortezomib neapoli | Velcade;
  • (TR) Turkey: Biemib | Boractib | Borcade | Velcade | Veltezo;
  • (TW) Taiwan: Velcade;
  • (UA) Ukraine: Bortenat | Bortero | Bortezomib Alvogen | Bortezovista | Brecer | Namibor;
  • (UY) Uruguay: Botemib;
  • (VE) Venezuela, Bolivarian Republic of: Botemib;
  • (ZA) South Africa: Bortrac | Valtib
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Agathocleous A, Rohatiner A, Rule S, et al. Weekly Versus Twice Weekly Bortezomib Given in Conjunction With Rituximab, in Patients With Recurrent follicular Lymphoma, Mantle Cell Lymphoma and Waldenström Macroglobulinaemia. Br J Haematol. 2010;151(4):346-353. [PubMed 20880120]
  3. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. [PubMed 27918725]
  4. Andre P, Cisternino S, Chiadmi F, et al. Stability of Bortezomib 1-mg/mL Solution in Plastic Syringe and Glass Vial. Ann Pharmacother. 2005;39(9):1462-1466. [PubMed 15985470]
  5. Arnulf B, Pylypenko H, Grosicki S, et al. Updated survival Analysis of a Randomized, Phase 3 Study of Subcutaneous versus Intravenous Bortezomib in Patients With Relapsed Multiple Myeloma. Haematologica. 2012;97(12):1925-1928. [PubMed 22689676]
  6. Baradaran H, Dashti-Khavidaki S, Taher M, Talebian M, Nasiri-Toosi M, Jafarian A. Antibody-mediated rejection in adult liver transplant recipients: a case series and literature review. J Clin Pharmacol. 2022;62(2):254-271. doi:10.1002/jcph.1963 [PubMed 34480762]
  7. Bortezomib 1 or 2.5 mg injection [prescribing information]. Lake Forest, IL: Hospira Inc; December 2022.
  8. Bortezomib 3.5 mg injection [prescribing information]. Lake Zurich, IL: Fresenius Kabi; September 2021.
  9. Bringhen S, Larocca A, Rossi D, et al. Efficacy and Safety of Once-Weekly Bortezomib in Multiple Myeloma Patients. Blood. 2010;116(23):4745-4753. [PubMed 20807892]
  10. Castillo JJ, Advani RH, Branagan AR, et al. Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia. Lancet Haematol. 2020;7(11):e827-e837. doi:10.1016/S2352-3026(20)30224-6 [PubMed 33091356]
  11. Cavo M, Pantani L, Petrucci MT, et al. Bortezomib-Thalidomide-Dexamethasone Is Superior to Thalidomide-Dexamethasone as Consolidation Therapy After Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma. Blood. 2012;120(1):9-19. [PubMed 22498745]
  12. Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376(9758):2075-2085. doi:10.1016/S0140-6736(10)61424-9 [PubMed 21146205]
  13. Chan KM, Lee CS, Wu TJ, Lee CF, Chen TC, Lee WC. Clinical perspective of acute humoral rejection after blood type-compatible liver transplantation. Transplantation. 2011;91(5):e29-e30. doi:10.1097/TP.0b013e318208138c [PubMed 21336085]
  14. Chanan-Khan AA, Kaufman JL, Mehta J, et al. Activity and Safety of Bortezomib in Multiple Myeloma Patients With Advanced Renal Failure: A Multicenter Retrospective Study. Blood. 2006;109(9):2604-2606. [PubMed 17138816]
  15. Chanan-Khan A, Sonneveld P, Schuster MW, et al. Analysis of Herpes Zoster Events Among Bortezomib-Treated Patients in the Phase III APEX Study. J Clin Oncol. 2008;26(29):4784-4790. [PubMed 18711175]
  16. Chen CI, Kouroukis CT, White D, et al. Bortezomib is Active in Patients With Untreated or Relapsed Waldenström's Macroglobulinemia: A Phase II Study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(12):1570-1575. doi:10.1200/JCO.2006.07.8659 [PubMed 17353550]
  17. Colvin MM, Cook JL, Chang P, et al. American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiopulmonary Critical Care, Perioperative and Resuscitation; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Disease in the Young; et al. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2015;131(18):1608-1639. [PubMed 25838326]
  18. Dimopoulos MA, Mateos MV, Richardson PG, et al. Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol. 2011;86(1):23-31. doi:10.1111/j.1600-0609.2010.01533.x [PubMed 20874823]
  19. Dimopoulos MA, García-Sanz R, Gavriatopoulou M, et al. Primary therapy of Waldenstrom macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN). Blood. 2013;122(19):3276-3782. doi:10.1182/blood-2013-05-503862 [PubMed 24004667]
  20. Dimopoulos MA, Richardson PG, Schlag R, et al. VMP (Bortezomib, Melphalan, and Prednisone) is Active and Well Tolerated in Newly Diagnosed Patients With Multiple Myeloma With Moderately Impaired Renal Function, and Results in Reversal of Renal Impairment: Cohort Analysis of the Phase III VISTA Study. J Clin Oncol. 2009;27(36):6086-6093. [PubMed 19858394]
  21. Dimopoulos MA, Sonneveld P, Leung N, et al. International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016;34(13):1544-1557. [PubMed 26976420]
  22. Durie BG, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-527. doi:10.1016/S0140-6736(16)31594-X [PubMed 28017406]
  23. Durie BGM, Hoering A, Sexton R, et al. Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT). Blood Cancer J. 2020;10(5):53. doi:10.1038/s41408-020-0311-8 [PubMed 32393732]
  24. Eskandary F, Bond G, Schwaiger E, et al. Bortezomib in late antibody-mediated kidney transplant rejection (BORTEJECT Study): study protocol for a randomized controlled trial. Trials. 2014;15:107. doi:10.1186/1745-6215-15-107 [PubMed 24708575]
  25. Eskandary F, Regele H, Baumann L, et al. A randomized trial of bortezomib in late antibody-mediated kidney transplant rejection. J Am Soc Nephrol. 2018;29(2):591-605. doi:10.1681/ASN.2017070818 [PubMed 29242250]
  26. Fisher RI, Bernstein SH, Kahl BS, et al. Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma. J Clin Oncol. 2006;24(30):4867-4874. [PubMed 17001068]
  27. Flechner SM, Fatica R, Askar M, et al. The role of proteasome inhibition with bortezomib in the treatment of antibody-mediated rejection after kidney-only or kidney-combined organ transplantation. Transplantation. 2010;90(12):1486-1492. doi:10.1097/TP.0b013e3181fdd9b0 [PubMed 21042239]
  28. Fowler N, Kahl BS, Lee P, et al. Bortezomib, Bendamustine, and Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma: The Phase II VERTICAL Study. J Clin Oncol. 2011;29(25):3389-3395. [PubMed 21810687]
  29. Fraunfelder FW, Yang HK. Association Between Bortezomib Therapy and Eyelid Chalazia. JAMA Ophthalmol. 2016;134(1):88-90. doi:10.1001/jamaophthalmol.2015.3963 [PubMed 26469392]
  30. Friedberg JW, Vose JM, Kelly JL, et al. The Combination of Bendamustine, Bortezomib, and Rituximab for Patients With Relapsed/Refractory Indolent and Mantle Cell Non-Hodgkin Lymphoma. Blood. 2011;117(10):2807-2812. [PubMed 21239695]
  31. Ghobrial IM, Hong F, Padmanabhan S, et al. Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010;28(8):1422-1428. doi:10.1200/JCO.2009.25.3237 [PubMed 20142586]
  32. Gilbar PJ, Seger AC. Fatalities Resulting From Accidental Intrathecal Administration of Bortezomib: Strategies for Prevention. J Clin Oncol. 2012;30(27):3427-3428. [PubMed 22851559]
  33. Golden EB, Lam PY, Kardosh A, et al. Green Tea Polyphenols Block the Anticancer Effects of Bortezomib and Other Boronic Acid-Based Proteasome Inhibitors. Blood. 2009;113(23):5927-5937. [PubMed 19190249]
  34. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
  35. Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3 [PubMed 33189178]
  36. Harousseau JL, Attal M, Avet-Loiseau H, et al. Bortezomib Plus Dexamethasone is Superior to Vincristine Plus Doxorubicin Plus Dexamethasone as Induction Treatment Prior to Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: Results of the IFM 2005-01 Phase III Trial. J Clin Oncol. 2010;28(30):4621-4629. [PubMed 20823406]
  37. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  38. Iwamoto T, Ishibashi M, Fujieda A, et al. Drug Interaction Between Itraconazole and Bortezomib: Exacerbation of Peripheral Neuropathy and Thrombocytopenia Induced by Bortezomib. Pharmacotherapy. 2010;30(7):661-665. [PubMed 20575631]
  39. Jacobson JO, Polovich M, McNiff KK, et al. American Society of Clinical Oncology/ Oncology Nursing Society Chemotherapy Administration Safety Standards. J Clin Oncol. 2009;27(32):5469-5475. [PubMed 19786650]
  40. Jagannath S, Barlogie B, Berenson JR, et al .Bortezomib in Recurrent and/or Refractory Multiple Myeloma; Initial Clinical Experience in Patients With Impaired Renal Function. Cancer. 2005;103(6):1195-1200. [PubMed 15690325]
  41. Jeong JC, Jambaldorj E, Kwon HY, et al. Desensitization using bortezomib and high-dose immunoglobulin increases rate of deceased donor kidney transplantation. Medicine (Baltimore). 2016;95(5):e2635. doi:10.1097/MD.0000000000002635 [PubMed 26844479]
  42. Kastritis E, Wechalekar AD, Dimopoulos MA, et al. Bortezomib With or Without Dexamethasone in Primary Systemic (Light Chain) Amyloidosis. J Clin Oncol. 2010;28(6):1031-1037. [PubMed 20085941]
  43. Khan ML, Reeder CB, Kumar SK, et al. A Comparison of Lenalidomide/Dexamethasone versus Cyclophosphamide/Lenalidomide/Dexamethasone versus Cyclophosphamide/Bortezomib/Dexamethasone in Newly Diagnosed Multiple Myeloma. Br J Haematol. 2012;156(3):326-333. [PubMed 22107129]
  44. Kim DG, Lee J, Park Y, et al. Transplant outcomes in positive complement-dependent cytotoxicity- versus flow cytometry-crossmatch kidney transplant recipients after successful desensitization: a retrospective study. BMC Nephrol. 2019;20(1):456. doi:10.1186/s12882-019-1625-2 [PubMed 31818254]
  45. Kolonko A, Słabiak-Błaż N, Karkoszka H, Więcek A, Piecha G. The preliminary results of bortezomib used as a primary treatment for an early acute antibody-mediated rejection after kidney transplantation-a single-center case series. J Clin Med. 2020;9(2):529. doi:10.3390/jcm9020529 [PubMed 32075220]
  46. Koslik MA, Friebus-Kardash J, Heinemann FM, Kribben A, Bräsen JH, Eisenberger U. Differential treatment effects for renal transplant recipients with DSA-positive or DSA-negative antibody-mediated rejection. Front Med (Lausanne). 2022;9:816555. doi:10.3389/fmed.2022.816555 [PubMed 35174191]
  47. Kropff M, Bisping G, Schuck E, et al; Deutsche Studiengruppe Multiples Myelom. Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol. 2007;138(3):330-337. doi:10.1111/j.1365-2141.2007.06656.x [PubMed 17614819]
  48. Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119(19):4375-4382. doi:10.1182/blood-2011-11-395749 [PubMed 22422823]
  49. Lamm W, Willenbacher W, Lang A, et al. Efficacy of the Combination of Bortezomib and Dexamethasone in Systemic AL Amyloidosis. Ann Hematol. 2011;90(2):201-206. [PubMed 20821326]
  50. Leal TB, Remick SC, Takimoto CH, et al. Dose-Escalating and Pharmacological Study of Bortezomib in Adult Cancer Patients With Impaired Renal Function: A National Cancer Institute Organ Dysfunction Working Group Study. Cancer Chemother Pharmacol. 2011;68(6):1439-1447. [PubMed 21479634]
  51. LoRusso PM, Venkatakrishnan K, Ramanathan RK, et al. Pharmacokinetics and Safety of Bortezomib in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase I NCI Organ Dysfunction Working Group Study NCI-6432. Clin Cancer Res. 2012;18(10):2954-2963. doi:10.1158/1078-0432.CCR-11-2873 [PubMed 22394984]
  52. Ludwig H, Kasparu H, Leitgeb C, et al. Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood. 2014;123(7):985-991. doi:10.1182/blood-2013-08-521468 [PubMed 24227817]
  53. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
  54. Mateos MV, Dimopoulos MA, Cavo M, et al; ALCYONE Trial Investigators. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518-528. doi:10.1056/NEJMoa1714678 [PubMed 29231133]
  55. Mateos MV, Richardson PG, Schlag R, et al. Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-up and Impact of Subsequent Therapy in the Phase III VISTA Trial. J Clin Oncol. 2010;28(13):2259-2266. [PubMed 20368561]
  56. Mikhael J, Ismaila N, Cheung MC, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol. 2019;37(14):1228-1263. doi:10.1200/JCO.18.02096 [PubMed 30932732]
  57. Mikhael JR, Belch AR, Prince HM, et al. High Response Rate to Bortezomib With or Without Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma: Results of a Global Phase 3b Expanded Access Program. Br J Haematol. 2009;144(2):169-175. [PubMed 19036114]
  58. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study [published correction appears in Lancet. Lancet. 2019;394(10192):29-38. doi:10.1016/S0140-6736(19)31240-1 [PubMed 31171419]
  59. Moreau P, Coiteux V, Hulin C, et al. Prospective Comparison of Subcutaneous Versus Intravenous Administration of Bortezomib in Patients With Multiple Myeloma. Haematologica. 2008;93(12):1908-1911. [PubMed 18768528]
  60. Moreau P, Hulin C, Macro M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood. 2016;127(21):2569-2574. doi:10.1182/blood-2016-01-693580 [PubMed 27002117]
  61. Moreau P, Karamanesht II, Domnikova N, et al. Pharmacokinetic, pharmacodynamic and covariate analysis of subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma. Clin Pharmacokinet. 2012;51(12):823-829. doi:10.1007/s40262-012-0010-0 [PubMed 23018466]
  62. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous Versus Intravenous Administration of Bortezomib in Patients With Relapsed Multiple Myeloma: A Randomised, Phase 3, Non-Inferiority Study. Lancet Oncol. 2011;12(5):431-440. [PubMed 21507715]
  63. Neuhaus K, Hohlfelder B, Bollinger J, Haug M 3rd, Torbic H. Antibody-mediated rejection management following lung transplantation. Ann Pharmacother. 2022;56(1):60-64. doi:10.1177/10600280211012410 [PubMed 33899550]
  64. Neumann J, Tarrasconi H, Bortolotto A, et al. Acute humoral rejection in a lung recipient: reversion with bortezomib. Transplantation. 2010;89(1):125-126. doi:10.1097/TP.0b013e3181c280f9 [PubMed 20061929]
  65. O'Connor OA, Wright J, Moskowitz C, et al. Phase II Clinical Experience With the Novel Proteasome Inhibitor Bortezomib in Patients With Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma. J Clin Oncol. 2005;23(4):676-684. [PubMed 15613699]
  66. O'Donnell EK, Laubach JP, Yee AJ, et al. A phase 2 study of modified lenalidomide, bortezomib and dexamethasone in transplant-ineligible multiple myeloma. Br J Haematol. 2018;182(2):222-230. doi:10.1111/bjh.15261 [PubMed 29740809]
  67. Orlowski RZ, Nagler A, Sonneveld P, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007;25(25):3892-3901. [PubMed 17679727]
  68. Palumbo A, Bringhen S, Rossi D, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010;28(34):5101-5109. doi:10.1200/JCO.2010.29.8216 [PubMed 20940200]
  69. Palumbo A, Chanan-Khan A, Weisel K, et al; CASTOR Investigators. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754-766. doi:10.1056/NEJMoa160 [PubMed 27557302]
  70. Paterno F, Shiller M, Tillery G, et al. Bortezomib for acute antibody-mediated rejection in liver transplantation. Am J Transplant. 2012;12(9):2526-2531. doi:10.1111/j.1600-6143.2012.04126.x [PubMed 22681986]
  71. Pekol T, Daniels JS, Labutti J, et al. Human Metabolism of the Proteasome Inhibitor Bortezomib: Identification of Circulating Metabolites. Drug Metab Dispos. 2005;33(6):771-777. [PubMed 15764713]
  72. Perrone G, Hideshima T, Ikeda H, et al. Ascorbic Acid Inhibits Activity of Bortezomib in vivo. Leukemia. 2009;23(9):1679-1686. [PubMed 19369963]
  73. Philogene MC, Sikorski P, Montgomery RA, Leffell MS, Zachary AA. Differential effect of bortezomib on HLA class I and class II antibody. Transplantation. 2014;98(6):660-665. doi:10.1097/TP.0000000000000132 [PubMed 24798311]
  74. Pratt G, El-Sharkawi D, Kothari J, et al; Diagnosis and management of Waldenström macroglobulinaemia- a British Society for Haematology guideline. Br J Haematol. 2022;197(2):171-187. doi:10.1111/bjh.18036 [PubMed 35020191]
  75. Reece DE, Hegenbart U, Sanchorawala V, et al. Efficacy and Safety of Once-Weekly and Twice-Weekly Bortezomib in Patients With Relapsed Systemic AL Amyloidosis: Results of a Phase 1/2 Study. Blood. 2011;118(4):865-873. doi:10.1182/blood-2011-02-334227 [PubMed 21562045]
  76. Reeder CB, Reece DE, Kukreti V, et al. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood. 2010;115(16):3416-3417. doi:10.1182/blood-2010-02-271676 [PubMed 20413666]
  77. Refer to manufacturer's labeling.
  78. Richardson PG, Oriol A, Beksac M, et al; OPTIMISMM trial investigators. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(6):781-794. doi:10.1016/S1470-2045(19)30152-4 [PubMed 31097405]
  79. Richardson PG, Sonneveld P, Schuster M, et al. Extended Follow-up of a Phase 3 Trial in Relapsed Multiple Myeloma: Final Time-to-Event Results of the APEX Trial. Blood. 2007;110(10):3557-3560. [PubMed 17690257]
  80. Richardson PG, Sonneveld P, Schuster MW, et al. Reversibility of Symptomatic Peripheral Neuropathy With Bortezomib in the Phase III APEX Trial in Relapsed Multiple Myeloma: Impact of a Dose-Modification Guideline. Br J Haematol. 2009;144(6):895-903. [PubMed 19170677]
  81. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or High-Dose Dexamethasone for Relapsed Multiple Myeloma. N Engl J Med. 2005;352(24):2487-249824429336 [PubMed 15958804]
  82. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116(5):679-686. doi:10.1182/blood-2010-02-268862 [PubMed 20385792]
  83. Richardson PG, Xie W, Jagannath S, et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014;123(10):1461-1469. doi:10.1182/blood-2013-07-517276 [PubMed 24429336]
  84. Robak T, Huang H, Jin J, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015;372(10):944-953. doi:10.1056/NEJMoa1412096 [PubMed 25738670]
  85. Robak T, Jin J, Pylypenko H, et al; LYM-3002 investigators. Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. Lancet Oncol. 2018;19(11):1449-1458. doi:10.1016/S1470-2045(18)30685-5 [PubMed 30348538]
  86. Roila F, Molassiotis A, Herrstedt J, et al; participants of the MASCC/ESMO Consensus Conference Copenhagen 2015. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(suppl 5):v119-v133. doi:10.1093/annonc/mdw270 [PubMed 27664248]
  87. Rosiñol L, Oriol A, Rios R, et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood. 2019;134(16):1337-1345. doi:10.1182/blood.2019000241 [PubMed 31484647]
  88. Roussel M, Lauwers-Cances V, Robillard N, et al. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014;32(25):2712-2717. doi:10.1200/JCO.2013.54.8164 [PubMed 25024076]
  89. Sadaka B, Ejaz NS, Shields AR, et al. A Banff Component Scoring-based histologic assessment of bortezomib-based antibody-mediated rejection therapy. Transplantation. 2015;99(8):1691-1699. doi:10.1097/TP.0000000000000694 [PubMed 25803498]
  90. San Miguel JF, Schlag R, Khuageva NK, et al. Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol. 2013;31(4):448-455. doi:10.1200/JCO.2012.41.6180 [PubMed 23233713]
  91. Sonneveld P, Chanan-Khan A, Weisel K, et al. Overall survival with daratumumab, bortezomib, and dexamethasone in previously treated multiple myeloma (CASTOR): a randomized, open-label, phase III trial. J Clin Oncol. 2023;41(8):1600-1609. doi:10.1200/JCO.21.02734 [PubMed 36413710]
  92. Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/ GMMG-HD4 Trial. J Clin Oncol. 2012;30(24):2946-2955. doi:10.1200/JCO.2011.39.6820 [PubMed 22802322]
  93. Stuckey LJ, Kamoun M, Chan KM. Lung transplantation across donor-specific anti-human leukocyte antigen antibodies: utility of bortezomib therapy in early graft dysfunction. Ann Pharmacother. 2012;46(1):e2. doi:10.1345/aph.1Q509 [PubMed 22202499]
  94. Taro-Bortezomib (bortezomib for injection) [product monograph]. Brampton, Ontario, Canada: Taro Pharmaceuticals Inc; October 2021.
  95. Timofeeva OA, Choe J, Alsammak M, et al. Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study. Transpl Int. 2021;34(4):700-708. doi:10.1111/tri.13825 [PubMed 33469943]
  96. Treon SP, Ioakimidis L, Soumerai JD, et al. Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180. J Clin Oncol. 2009;27(23):3830-3835. doi:10.1200/JCO.2008.20.4677 [PubMed 19506160]
  97. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 5, 2016.
  98. Uttamsingh V, Lu C, Miwa G, et al. Relative Contributions of the Five Major Hyman Cytochromes P450, 1A2, 2C9, 2C19, and 3A4, to the Hepatic Metabolism of the Proteosome Inhibitor Bortezomib. Drug Metab Dispos. 2005;33(11):1723-1728. [PubMed 16103134]
  99. Vacha M, Chery G, Hulbert A, et al. Antibody depletion strategy for the treatment of suspected antibody-mediated rejection in lung transplant recipients: does it work? Clin Transplant. 2017;31(3). doi:10.1111/ctr.12886 [PubMed 27988971]
  100. Vanderloo JP, Pomplun ML, Vermeulen LC, et al. Stability of Unused Reconstituted Bortezomib in Original Manufacturer Vials. J Oncol Pharm Pract. 2011;17(4):400-402. [PubMed 20926455]
  101. Velcade (bortezomib) [prescribing information]. Lexington, MA: Takeda Pharmaceuticals America Inc; August 2022.
  102. Velcade (bortezomib) [product monograph]. Toronto, Ontario, Canada: Janssen Inc; February 2022.
  103. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288 [PubMed 32325490]
  104. Waiser J, Budde K, Schütz M, et al. Comparison between bortezomib and rituximab in the treatment of antibody-mediated renal allograft rejection. Nephrol Dial Transplant. 2012;27(3):1246-1251. doi:10.1093/ndt/gfr465 [PubMed 21852274]
  105. Walsh RC, Everly JJ, Brailey P, et al. Proteasome inhibitor-based primary therapy for antibody-mediated renal allograft rejection. Transplantation. 2010;89(3):277-284. doi:10.1097/TP.0b013e3181c6ff8d [PubMed 20145517]
  106. Woodle ES, Shields AR, Ejaz NS, et al. Prospective iterative trial of proteasome inhibitor-based desensitization. Am J Transplant. 2015;15(1):101-118. doi:10.1111/ajt.13050 [PubMed 25534446]
  107. Zinzani PL, Musuraca G, Tani M, et al. Phase II Trial of Proteasome Inhibitor Bortezomib in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma. J Clin Oncol. 2007;25(27):4293-4297. [PubMed 17709797]
Topic 8509 Version 401.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟