Note: Consecutive doses should be separated by at least 72 hours. Consider antiviral prophylaxis for herpes virus infection during therapy.
Antibody-mediated rejection in cardiac transplantation, treatment (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) (AHA [Colvin 2015]).
Cutaneous or 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 (Zinzani 2007).
Follicular lymphoma, relapsed/refractory (off-label use): IV: 1.3 mg/m2 days 1, 4, 8, and 11 of a 28-day treatment cycle, in combination with bendamustine and rituximab for 6 cycles (Friedberg 2011) or 1.6 mg/m2 days 1, 8, 15, and 22 of a 35-day treatment cycle, in combination with bendamustine and rituximab for 5 cycles (Fowler 2011).
Mantle cell lymphoma, first-line therapy: 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 (Roback 2015).
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 (Fisher 2006).
Multiple myeloma, first-line therapy; in combination with melphalan and prednisone: IV, SUBQ: 1.3 mg/m2 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 days 1, 8, 22, and 29 of a 42-day treatment cycle for 5 cycles.
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.
First-line therapy off-label dosing/combinations:
CyBorD regimen: IV: 1.5 mg/m2 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 (Khan 2012).
Daratumumab-containing regimens: SUBQ: 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 (Moreau 2019) 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 (Mateos 2018).
PAD regimen: IV: Induction: 1.3 mg/m2 days 1, 4, 8, and 11 of a 28-day treatment cycle for 3 cycles (in combination with doxorubicin and dexamethasone), followed by conditioning/stem cell transplantation, and then maintenance bortezomib 1.3 mg/m2 once every 2 weeks for 2 years (Sonneveld 2012).
VD regimen: IV: Induction: 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with dexamethasone) for 4 cycles, followed by autologous stem cell transplantation (Harousseau 2010).
VRd regimen: IV: 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day treatment cycle for 8 cycles (in combination with lenalidomide and dexamethasone) (Durie 2017).
VTd regimen: IV: 1.3 mg/m2 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, then (3 months after second transplant) 1.3 mg/m2 days 1, 8, 15, and 22 every 35 days for 2 consolidation cycles (in combination with thalidomide and dexamethasone) (Cavo 2010).
Patients ≥65 years of age: IV: 1.3 mg/m2 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 (Bringhen 2010; Palumbo 2010).
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 (ASCO [Mikhael 2019]; Sonneveld 2012). For high-risk patients, maintenance therapy with a proteosome inhibitor ± lenalidomide may be considered (ASCO [Mikhael 2019]).
Multiple myeloma, relapsed/refractory: 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.
Off-label dosing/combinations for relapsed/refractory disease:
DVd regimen: SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 every 21 days (in combination with daratumumab and dexamethasone) for 8 cycles (Palumbo 2016).
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 (Grosicki 2020).
VRd regimen: IV: 1 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for 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 (Richardson 2014).
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) (Ludwig 2014).
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) (Orlowski 2007).
CyBorD 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) (Kropff 2007).
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) (Richardson 2019).
Systemic light-chain amyloidosis (off-label use): IV: 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day treatment cycle (with or without dexamethasone) (Kastritis 2010).
Waldenström's macroglobulinemia, relapsed/refractory (off-label use): IV: 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day treatment cycle; continue until disease progression or until 2 cycles after achieving a complete response (Chen 2007) or 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day treatment cycle (in combination with dexamethasone and rituximab) (Treon 2009) or 1.6 mg/m2 days 1, 8, and 15 of a 28-day treatment cycle for 6 cycles (in combination with rituximab) (Ghobrial 2010). The Tenth International Workshop on Waldenström Macroglobulinemia prefers administering bortezomib SUBQ (if possible) (IWWM [Castillo 2020]).
No dosage adjustment is necessary. The International Myeloma Working Group (IMWG) recommendations suggest that bortezomib may be safely administered to patients with renal impairment, including those on dialysis (Dimopoulos 2016). 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 (Leal 2011).
Hepatic impairment prior to treatment initiation:
Mild impairment (bilirubin ≤1 times ULN and AST >ULN or bilirubin >1 to 1.5 times ULN and any AST): No initial dose adjustment is necessary (LoRusso 2012).
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 (LoRusso 2012) or further dose reduction to 0.5 mg/m2 in subsequent cycles.
Hepatotoxicity during treatment:
Hepatitis, transaminase increases, and hyperbilirubinemia: Interrupt therapy to assess reversibility.
Refer to adult dosing.
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 (full 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 (ASCO [Griggs 2021]).
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection [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)
Yes
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)
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. Not all bortezomib products are 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 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 (Moreau 2011). 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 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).
Mantle cell lymphoma: Treatment of mantle cell lymphoma in adults.
Multiple myeloma: Treatment of multiple myeloma in adults.
Antibody-mediated rejection in cardiac transplantation (treatment); Cutaneous T-cell lymphomas (mycosis fungoides), relapsed/refractory; Follicular lymphoma, relapsed/refractory; Peripheral T-cell lymphoma, relapsed/refractory; Systemic light-chain amyloidosis; Waldenström macroglobulinemia, relapsed/refractory
Bortezomib may be confused with bosutinib, carfilzomib, ixazomib.
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.
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.
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)
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.
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. Not all bortezomib products are approved for SUBQ administration; refer to specific product labeling for approved administration routes.
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
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
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-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. 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
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).
Based on the mechanism of action and on findings in animal reproduction studies, bortezomib may cause fetal harm if administered during pregnancy.
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.
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).
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.
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.
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.
Hepatic function impairment: Dose-normalized mean AUC levels were increased by ~60% in patients with moderate or severe hepatic impairment.
Solution (Bortezomib Injection)
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): $90.00 - $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
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