Version May 2024
Dosage guidance:
Dosing: Consecutive doses should be separated by at least 72 hours.
Dosage form information: The reconstituted concentrations for IV and SUBQ administration are different; use caution when calculating the volume for each route and dose.
Clinical considerations: 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 preexisting neuropathy (Ref).
Antibody-mediated rejection, treatment (off-label use): 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, mycosis fungoides, relapsed or 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, kidney transplantation (adjunctive) (off-label use): 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 (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, previously untreated (first-line therapy): Note: 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).
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: IV, SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle for up to 17 cycles or for 4 cycles beyond initial complete response; discontinue for disease progression or unacceptable toxicity (Ref) or 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).
Multiple myeloma, previously untreated (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: Note: Platelets should be ≥70,000/mm3, ANC should be ≥1,000/mm3, and nonhematologic toxicities should resolve to grade 1 or baseline prior to initiation of any cycle of therapy. 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 1.3 mg/m2 on days 1, 8, 15, and 22 every 35 days for 2 consolidation cycles (in combination with thalidomide and dexamethasone) beginning 3 months after second transplant (Ref) or 1.3 mg/m2 on days 1, 4, 8, and 11 of a 28-day treatment cycle (in combination with thalidomide and dexamethasone) for 6 induction cycles followed by hematopoietic cell transplant and maintenance (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 (in combination with cyclophosphamide 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, 11 of a 28-day treatment cycle (in combination with cyclophosphamide and dexamethasone) for up to 4 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 (in combination with doxorubicin and dexamethasone) for 3 cycles, 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).
VTD-PACE regimen:
Induction: SUBQ: 1 mg/m2 on days 1, 4, 8, and 11 (in combination with thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) for 2 cycles administered ≤8 weeks apart, followed by autologous hematopoietic cell transplant (HCT) (Ref).
Consolidation: SUBQ: 1 mg/m2 on days 1, 4, 8, and 11 (in combination with thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) for 2 cycles. Consolidation cycle 1 is to begin 6 weeks to 4 months following last autologous HCT and cycle 2 is to begin 2 to 4 months following cycle 1 (Ref).
Maintenance: SUBQ: 1 mg/m2 on days 1, 4, 8, and 11 of a 28-day cycle (in combination with thalidomide and dexamethasone) for 1 year. Maintenance is to begin 1 to 4 months following cycle 2 of consolidation (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 or 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 (in combination with lenalidomide and dexamethasone) for up to 8 cycles, 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 (in combination with pomalidomide and dexamethasone) for 8 cycles, followed by 1.3 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with pomalidomide and dexamethasone) until disease progression or unacceptable toxicity (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 (in combination with liposomal doxorubicin) for at least 8 cycles or until disease progression or unacceptable toxicity (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 (in combination with bendamustine and dexamethasone) for 4 cycles (if no response) or for up to a maximum of 8 cycles (Ref).
Peripheral T-cell lymphoma, relapsed or 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 (off-label use):
Single-agent therapy: IV: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day treatment cycle (with or without dexamethasone) for up to 8 cycles (Ref) or 1.6 mg/m2 on days 1, 8, 15, and 22 of a 35-day cycle for up to 8 cycles (Ref).
Combination therapy: Note: Refer to protocols for dosage adjustment details.
CyBorD (or VCD or CVD) regimen: IV: 1 mg/m2 on days 1, 4, 8, and 11 (in combination with cyclophosphamide and dexamethasone) for a maximum of 8 cycles; bortezomib dose could be increased to 1.3 mg/m2 if well-tolerated (Ref).
Daratumumab-CyBorD (or VCD) regimen: SUBQ: 1.3 mg/m2 on days 1, 8, 15, and 22 of a 28-day cycle (in combination with daratumumab hyaluronidase, cyclophosphamide, and dexamethasone) for 6 cycles (Ref).
Bortezomib/melphalan/dexamethasone regimen: IV or SUBQ: 1.3 mg/m2 on days 1, 4, 8, and 11 of a 28-day cycle (in combination with melphalan and dexamethasone) for 2 cycles, followed by 1.3 mg/m2 on days 1, 8, 15, and 22 of a 35-day cycle (in combination with melphalan and dexamethasone) for 6 additional cycles (Ref).
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).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV, SUBQ: No dosage adjustment necessary for any degree of kidney impairment (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV, SUBQ: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzability unknown but likely minimal given large Vd (Ref):
IV, SUBQ: No dosage adjustment is necessary; when scheduled dose falls on a dialysis day, administer after dialysis (Ref).
Peritoneal dialysis: Dialyzability unknown but likely minimal given large Vd (Ref): IV, SUBQ: No dosage adjustment necessary (Ref).
CRRT: IV, SUBQ: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV, SUBQ:No dosage adjustment necessary; when scheduled dose falls on a PIRRT day, administer after PIRRT (Ref).
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).
Acute 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).
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).
Note: Hematologic toxicity may also require platelet transfusion, supportive care, and/or myeloid growth factors as clinically indicated.
Multiple myeloma (previously untreated, in combination with melphalan and prednisone): Note: Refer to protocol for specific dosage modifications for melphalan and prednisone.
|
Adverse reaction |
Severity |
Bortezomib dosage modification |
|---|---|---|
|
Hematologic toxicity | ||
|
Neutropenia |
ANC <750/mm3 on bortezomib dosing day (except day 1) |
Withhold bortezomib. If several bortezomib doses in consecutive cycles are withheld due to toxicity, reduce bortezomib dose by one dose level (1.3 mg/m2/dose reduced to 1 mg/m2/dose; 1 mg/m2/dose reduced to 0.7 mg/m2/dose). |
|
Thrombocytopenia |
Platelets ≤30,000/mm3 on bortezomib dosing day (except day 1) |
Withhold bortezomib. If several bortezomib doses in consecutive cycles are withheld due to toxicity, reduce bortezomib dose by one dose level (1.3 mg/m2/dose reduced to 1 mg/m2/dose; 1 mg/m2/dose reduced to 0.7 mg/m2/dose). |
|
Nonhematologic toxicity | ||
|
Other nonhematologic adverse reactions (excluding neuropathy) |
≥ Grade 3 |
Withhold bortezomib until toxicity resolves to grade 1 or baseline; may reinitiate with one 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). |
Mantle cell lymphoma (previously untreated, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone): Note: Refer to protocol for specific dosage modifications for rituximab, cyclophosphamide, doxorubicin, and prednisone.
|
Adverse reaction |
Severity |
Bortezomib dosage modification |
|---|---|---|
|
Hematologic toxicity | ||
|
Neutropenia |
≥ Grade 3 |
Withhold bortezomib for up to 2 weeks until ANC ≥750/mm3. ANC ≥750/mm3 within 2 weeks of interruption: Resume bortezomib with one 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). Resolution of ANC ≥750/mm3 does not occur within 2 weeks of interruption: Discontinue bortezomib. |
|
Thrombocytopenia |
Platelets <25,000/mm3 on bortezomib dosing day |
Withhold bortezomib for up to 2 weeks until platelets ≥25,000/mm3. Platelets ≥25,000/mm3 within 2 weeks of interruption: Resume bortezomib with one 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). Resolution of platelets ≥25,000/mm3 does not occur within 2 weeks of interruption: Discontinue bortezomib. |
|
Nonhematologic toxicity | ||
|
Other nonhematologic adverse reactions (excluding neuropathy) |
≥ Grade 3 |
Withhold bortezomib until toxicity resolves to ≤grade 2; may reinitiate with one 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). |
Relapsed multiple myeloma and relapsed mantle cell lymphoma: Note: Refer to protocol for specific dosage modifications for other concomitant anticancer therapies.
|
Hematologic toxicity |
Grade 4 |
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) |
|
Nonhematologic toxicity (excluding neuropathy) |
Grade 3 |
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) |
Other nonhematologic toxicities including neuropathic pain and/or peripheral sensory, motor, or autonomic neuropathy (all indications):
|
Adverse reaction |
Severity |
Bortezomib dosage modification |
|---|---|---|
|
Nonhematologic toxicity | ||
|
a PRES = Posterior reversible leukoencephalopathy syndrome; TTP/HUS = Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome | ||
|
Cardiopulmonary toxicity |
Any |
Promptly evaluate with new or worsening symptoms; therapy interruption may be required. |
|
GI toxicity |
Any |
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) |
Any |
May require adjustment of diabetes medications. |
|
Hypotension (orthostatic or postural) |
Any |
May require adjustment of antihypertensive medication, hydration, and mineralocorticoids and/or sympathomimetics. |
|
Neuropathic pain and/or peripheral sensory, motor, or autonomic neuropathy |
Any |
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 dose modification required. | |
|
Grade 1 with pain or Grade 2 (moderate symptoms; limiting instrumental activities of daily living) |
Reduce bortezomib dose to 1 mg/m2. | |
|
Grade 2 with pain or Grade 3 (severe symptoms; limiting self-care activities of daily living) |
Withhold bortezomib until toxicity resolves; upon resolution, resume bortezomib at a reduced dose of 0.7 mg/m2. | |
|
Grade 4 (life-threatening consequences with urgent intervention indicated and/or severe autonomic neuropathy) |
Discontinue bortezomib. | |
|
PRESa |
Suspected |
Evaluate promptly any new onset or worsening neurologic symptoms. Perform MRI to confirm diagnosis. |
|
Confirmed |
Discontinue bortezomib. The safety of reinitiating bortezomib in patients previously experiencing PRES is unknown. | |
|
Thrombotic microangiopathy (including TTP/HUSa) |
Suspected |
Withhold bortezomib and evaluate promptly; may resume bortezomib if diagnosis of TTP/HUS is excluded. |
|
Confirmed |
Discontinue bortezomib. The safety of reinitiating bortezomib in patients previously experiencing TTP/HUS is unknown. | |
Refer to adult dosing.
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 generic products), mannitol (Velcade, some generic products), 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). Patients with a history of syncope, receiving medications associated with hypotension, and those who are dehydrated may be at increased risk of hypotension.
• 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 (TTP/HUS), 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.
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)
Yes
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): $42.00 - $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
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.
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: Reconstituted solution 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 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); 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 or refractory; Desensitization, kidney transplantation; Follicular lymphoma, relapsed or refractory; Peripheral T-cell lymphoma, relapsed or refractory; Systemic light-chain amyloidosis; Waldenström macroglobulinemia
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.
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
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
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
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. 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
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. 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
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
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
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. 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
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). 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
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
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
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
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
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). 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
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
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
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
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
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
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
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
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
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
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
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
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 7 months following bortezomib treatment. Patients with partners who could become pregnant should use effective contraception during and for 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, in utero exposure to bortezomib may cause fetal harm.
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); kidney 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]).
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.
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