Download Reconstitution and dosing for subcutaneous and IV administration

Reconstitution and dosing
for subcutaneous and IV
administration
INDICATIONS: VELCADE® (bortezomib) is indicated for the
treatment of patients with multiple myeloma and patients
with mantle cell lymphoma.
CONTRAINDICATIONS: VELCADE is contraindicated in
patients with hypersensitivity (not including local reactions)
to bortezomib, boron, or mannitol, including anaphylactic
reactions. VELCADE is contraindicated for intrathecal
administration. Fatal events have occurred with intrathecal
administration of VELCADE.
Please see Important Safety Information
within the Safety tab and accompanying full
Prescribing Information.
FOR HEALTHCARE PROFESSIONALS ONLY
Storage
DESCRIPTION
UNOPENED VIALS
▼ VELCADE (bortezomib) is an antineoplastic agent
▼ Store unopened vials of VELCADE® (bortezomib) at a controlled room temperature
of 25ºC (77ºF); excursions are permitted from 15ºC to 30ºC (59ºF to 86ºF). Retain
vials in original package to protect from light
▼ VELCADE is a reversible inhibitor of the chymotrypsin-like activity of the 26S
proteasome in mammalian cells
▼ Procedures for proper handling and disposal should be considered. Please see
the information on the following page
HOW SUPPLIED
▼ VELCADE is supplied as individually cartoned 10-mL vials containing 3.5 mg
of bortezomib as a white to off-white cake or powder
▼ Each carton of VELCADE contains a glass vial with a royal blue cap in a
transparent blister pack
▼ Unopened vials of VELCADE are stable until the date indicated on the package
when stored in the original package and protected from light
▼ Do not use VELCADE after the date stated on the vial and carton
RECONSTITUTED VELCADE
▼ VELCADE contains no antimicrobial preservative. Administer reconstituted
VELCADE within 8 hours of preparation
▼ When reconstituted as directed, VELCADE may be stored at 25ºC (77ºF). The
reconstituted material may be stored in the original vial and/or the syringe prior
to administration. The product may be stored for up to 8 hours in a syringe;
however, total storage time for the reconstituted material must not exceed
8 hours when exposed to normal indoor lighting
Disposal
▼ Each vial of VELCADE is for only a single use. Dispose of any unused product
or waste material in accordance with local requirements
▼ Consider handling and disposing of VELCADE according to guidelines issued
for cytotoxic drugs, including using gloves and other protective clothing to
prevent skin contact1-4
A vial of VELCADE can be used for either
subcutaneous or intravenous (IV) administration,
but reconstitution is different
NDC 63020-049-01
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
ABOUT VELCADE
About VELCADE® (bortezomib)
Dosing
▼ The recommended starting dose of VELCADE® (bortezomib) is 1.3 mg/m2
for both subcutaneous and IV administrations
▼ Please see the Dose Modifications tab for dosing with hematologic and
nonhematologic toxicities, moderate to severe hepatic impairment, and
peripheral neuropathy
▼ The drug quantity contained in 1 vial (3.5 mg) may exceed the dose required.
Use caution when calculating the dose to prevent overdose
OVERDOSAGE
▼ There is no specific antidote known for overdosage with VELCADE. In humans,
fatal outcomes following the administration of more than twice the recommended
therapeutic dose have been reported, which were associated with the acute onset
of symptomatic hypotension and thrombocytopenia
▼ The volume of 0.9% sodium chloride solution used to reconstitute VELCADE (bortezomib)
for subcutaneous administration is different from the volume for IV administration. Use
caution when calculating the volume to be administered
▼ The reconstituted concentration for subcutaneous administration is greater than the
reconstituted concentration for IV administration
– For subcutaneous reconstitution, add 1.4 mL of sterile 0.9% sodium chloride
solution to the powder contained in the vial of VELCADE. This reconstitution
will result in a final concentration of 2.5 mg/mL VELCADE
– For IV reconstitution, add 3.5 mL of sterile 0.9% sodium chloride solution to
the powder contained in the vial of VELCADE. This reconstitution will result
in a final concentration of 1 mg/mL VELCADE
– The reconstituted product should be a clear and colorless solution free of
particulate matter
▼ Apply stickers to the vial and syringe that identify the intended route of administration
▼ VELCADE contains no antimicrobial preservative
▼ Reconstituted VELCADE should be administered within 8 hours of preparation
BECAUSE EACH ROUTE OF ADMINISTRATION HAS A
DIFFERENT RECONSTITUTED CONCENTRATION, USE CAUTION
WHEN CALCULATING THE VOLUME TO BE ADMINISTERED
▼ VELCADE is for subcutaneous or IV use only. VELCADE should not be administered
by any other route
▼ Fatal events have occurred with intrathecal administration
SUBCUTANEOUS
injection only
IV
injection only
ADD
CALCULATING VELCADE VOLUME (mL)
VELCADE dose (mg/m2) × patient BSA* (m2)
Reconstituted concentration†
†
Total VELCADE
= volume (mL) to
be administered
2.5 mg/mL for subcutaneous administration and 1 mg/mL for IV administration.
*Sample BSA calculation:
BSA =
BSA=square root of ([height in
Ht (cm) × Wt (kg) centimeters multiplied by body weight
3600
in kilograms] divided by 3600).5
1.4 mL
0.9% sodium chloride
ADD
0.9%
NaCl
0.9%
NaCl
TO MAKE
2.5
mg/mL
final concentration
3.5 mL
0.9% sodium chloride
TO MAKE
1 mg/mL
final concentration
▼ The recommended starting dose of VELCADE is 1.3 mg/m2 for both subcutaneous
and IV administrations
▼ Please see the Dose Modifications tab for dosing with hematologic and nonhematologic
toxicities, moderate to severe hepatic impairment, and peripheral neuropathy
FOR ALL SUBCUTANEOUS INJECTIONS, IT IS
IMPORTANT TO USE PROPER ASEPTIC TECHNIQUE
Please see section 2 of the full Prescribing Information for dosage, reconstitution,
and administration instructions.
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
DOSING & RECONSTITUTION
▼ The amount (in mg) of VELCADE to be administered is based on body
surface area (BSA) calculations* using a standard nomogram5 or according
to institutional policy
Reconstitution of subcutaneous
VELCADE® (bortezomib) is different
Subcutaneous administration
INJECTION-SITE REACTIONS AS OBSERVED IN A CLINICAL TRIAL
▼ In a clinical trial of patients with relapsed multiple myeloma, the most common
reaction was redness, occurring in 57% of patients.6 Injection-site reactions were
reported in 6% of patients as an adverse reaction, with 1% being serious and leading
to dose modification or discontinuation. All events resolved in a median of 6 days
▼ If local injection-site reactions occur following administration of VELCADE® (bortezomib)
subcutaneously, a less concentrated VELCADE solution (1 mg/mL instead of 2.5 mg/mL)
may be administered subcutaneously. Alternatively, consider the IV route of administration
▼ Please see Administration Precautions (section 2.9) in the full Prescribing Information
Techniques that may minimize
injection-site reactions with
subcutaneous administration
START CLEAN
▼ Ensure a new, clean, sharp, dry needle before administration7
▼ Inspect solution for particulate matter and discoloration
▼ If any discoloration or particulate matter is observed, do not use the
reconstituted product. File a product complaint by calling 1-866-VELCADE
▼ VELCADE is for subcutaneous or IV use only. VELCADE should not be administered
by any other route
▼ Verify correct dose
▼ Fatal events have occurred with intrathecal administration
▼ Inject slowly and steadily (≈1.0 mL for 10 seconds)7
SLOW AND STEADY
▼ Allow absorption by the surrounding tissue8
▼ Avoid fluid backtrack up the needle into the skin8
ALWAYS FOLLOW BEST PRACTICES
▼ Wash hands before and following administration8
Rotate
injection
sites
Use the abdomen
or thighs as sites
for subcutaneous
injections
▼ Wear gloves; however, they may not protect from needlestick injuries8
▼ Carefully and immediately dispose of sharps at the point of administration8
Generally, when using a
25-gauge needle that is
5/8 inch in length, insert
needle at a 45-degree
angle9,10
Skin
Administer new injections at least 1 inch from
an old site and never into areas where the skin
is tender, bruised, erythematous, or indurated
Subcutaneous
tissue
Muscle
1/2-inch needle9
5/8-inch needle9
Generally, when using a 26- to 30-gauge
needle that is 1/2 inch in length, insert
needle at a 90-degree angle9,10
Please see the MM Trial Designs & Adverse Reactions tab for safety information
in the subcutaneous vs IV clinical trial.
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
Ensure that the medication
is deposited in the
subcutaneous tissue9
SUBCUTANEOUS
ADMINISTRATION
▼ Maintain aseptic procedures
In previously untreated multiple myeloma
In previously untreated multiple myeloma
Dosing schedule
TWICE-WEEKLY FOLLOWED BY WEEKLY DOSING FOR 1 YEAR
(54 WEEKS PLANNED)
Cycles 1-4
TWICE WEEKLY, 6-WEEK CYCLES
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MP orally on days 1 to 4 every 6 weeks.
VELCADE® (bortezomib)
Oral melphalan+prednisone (MP)
Administration of concomitant
medications
▼ In the VISTA trial, concomitant medications for certain conditions were permitted
for patients receiving VELCADE® (bortezomib)12
Condition
Concomitant treatment
Prophylaxis for herpes zoster
reactivation
Antiviral prophylaxis recommended. Acceptable
therapies include:
• Acyclovir (400 mg orally, 3 times daily)
• Famciclovir (125 mg orally, twice daily)
• Valacyclovir (500 mg orally, twice daily)
Hematologic-related events
• Colony-stimulating factors
• Erythropoietin
• Transfusion of platelets and red blood cells, per
standard practice
Prevention of myeloma-related
kidney disease
• Adequate hydration
Osteopenia or lytic destruction
of bone
• Bisphosphonates in accordance with ASCO clinical
practice guidelines
• Bisphosphonate therapy may be initiated within 1 week
of starting VELCADE for those patients who were not on
it previously
Constipation
• Adequate hydration
• High-fiber diet
• Stool softeners, if needed
Diarrhea
• Loperamide as needed, per standard practice. Prophylactic
loperamide was not recommended
Prevention of tumor lysis syndrome
• Allopurinol treatment, per standard practice
• Special attention should be given to ensure
adequate hydration
Cycles 5-9
ONCE WEEKLY, 6-WEEK CYCLES
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2
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8
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MP orally on days 1 to 4 every 6 weeks.
▼ Administer VELCADE (1.3 mg/m ) as a subcutaneous injection or as a 3- to 5-second
bolus IV injection in combination with oral MP (melphalan 9 mg/m2 and prednisone
60 mg/m2). VELCADE is contraindicated for intrathecal administration; fatal events
have occurred
2
▼ Prior to initiating any cycle with VELCADE in combination with MP, platelet count
should be at least 70 × 109/L and absolute neutrophil count (ANC) should be at least
1.0 × 109/L
▼ At least 72 hours should elapse between each VELCADE dose
▼ Dosing adjustments of VELCADE are not necessary for patients with renal insufficiency.
In patients undergoing dialysis, VELCADE should be administered after the dialysis procedure
The above medications and supportive therapies are examples of appropriate supportive care that were permitted in the
phase 3 trial.
▼ In the VISTA trial, discontinuations due to adverse reactions were 11% for VELCADE
combination and 10% for MP alone11
Please see the MM Trial Designs & Adverse Reactions tab for clinical trial information.
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
MM DOSING
SCHEDULES
▼ Please see the Dose Modifications tab for dosing with hematologic and nonhematologic
toxicities, moderate to severe hepatic impairment, and peripheral neuropathy
In relapsed multiple myeloma
In relapsed multiple myeloma
RETREAT TWICE WEEKLY AT THE LAST TOLERATED DOSE
INITIAL THERAPY FOLLOWED BY WEEKLY MAINTENANCE
SCHEDULE OR STANDARD SCHEDULE
Dosing schedule for retreatment
with VELCADE® (bortezomib)
Retreatment cycles 1-8
TWICE WEEKLY, 3 WEEKS x8 (MAXIMUM)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
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21
Dosing schedule for
VELCADE® (bortezomib)-naïve patients
FOR INITIAL THERAPY
Cycles 1-8
Patients may be retreated with
VELCADE (bortezomib) if they:
✓ Responded to prior
VELCADE-based therapy
✓ Relapsed ≥6 months after
completing that therapy
VELCADE
▼ Administer VELCADE (1.3 mg/m2) as a subcutaneous injection or as a 3- to 5-second
bolus IV injection. VELCADE is contraindicated for intrathecal administration; fatal
events have occurred
▼ VELCADE may be administered as a single agent or in combination
with dexamethasone
▼ At least 72 hours should elapse between each VELCADE dose
▼ Dosing adjustments of VELCADE are not necessary for patients with renal
insufficiency. In patients undergoing dialysis, VELCADE should be administered
after the dialysis procedure
▼ Please see the Dose Modifications tab for hematologic and nonhematologic
toxicities, moderate to severe hepatic impairment, and peripheral neuropathy
▼ In the RETRIEVE trial, adverse reactions leading to discontinuation occurred in
13% of patients
FOR EXTENDED THERAPY
TWICE WEEKLY, 3 WEEKS x8
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Cycle 9 and beyond
WEEKLY MAINTENANCE SCHEDULE
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2
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5
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VELCADE (bortezomib)
OR
TWICE-WEEKLY STANDARD SCHEDULE
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2
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11
12
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▼ At least 72 hours should elapse between each VELCADE dose
▼ Dosing adjustments of VELCADE are not necessary for patients with renal insufficiency.
In patients undergoing dialysis, VELCADE should be administered after the dialysis procedure
▼ Please see the Dose Modifications tab for dosing with hematologic and nonhematologic
toxicities, moderate to severe hepatic impairment, and peripheral neuropathy
▼ In the APEX trial, responding patients received a median of 31 weeks of
therapy (39 weeks planned) using twice-weekly followed by weekly dosing13
▼ In the APEX trial, discontinuations due to adverse reactions were 25% for VELCADE
and 18% for dexamethasone
Please see the MM Trial Designs & Adverse Reactions tab for clinical trial information.
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
MM DOSING
SCHEDULES
▼ Administer VELCADE (1.3 mg/m2) as a subcutaneous injection or as a 3- to 5-second
bolus IV injection. VELCADE is contraindicated for intrathecal administration; fatal
events have occurred
Multiple myeloma trial designs
Adverse reactions in multiple myeloma
PREVIOUSLY UNTREATED MULTIPLE MYELOMA: VISTA
PREVIOUSLY UNTREATED MULTIPLE MYELOMA
A randomized, open-label, international, phase 3 trial (N=682) evaluating the efficacy
and safety of VELCADE® (bortezomib) administered intravenously in combination with
melphalan+prednisone (MP) vs MP in previously untreated multiple myeloma. After
progressive disease was established, all patients were eligible to receive subsequent
therapies. The primary endpoint was time to progression (TTP). Secondary endpoints were
complete response (CR), objective response rate (ORR), progression-free survival (PFS), and
overall survival (OS). At a prespecified interim analysis (median follow-up: 16.3 months),
VELCADE+MP resulted in significantly superior results for TTP (median: 20.7 months
with VELCADE+MP vs 15.0 months with MP [p=0.000002]), PFS, OS, and ORR. Further
enrollment was halted, and patients receiving MP were offered VELCADE in addition.
Updated analyses were performed.
▼ The most commonly reported adverse reactions (ARs) for VELCADE® (bortezomib)+
melphalan+prednisone (MP) vs MP alone were thrombocytopenia (48% vs 42%),
neutropenia (47% vs 42%), peripheral neuropathy (46% vs 1%), nausea (39% vs 21%),
diarrhea (35% vs 6%), neuralgia (34% vs <1%), anemia (32% vs 46%), and leukopenia
(32% vs 28%)
RELAPSED MULTIPLE MYELOMA: SUBCUTANEOUS VS IV
A non-inferiority, phase 3, randomized (2:1), open-label trial that compared the efficacy
and safety of VELCADE administered subcutaneously (n=148) with VELCADE administered
intravenously (n=74) in patients with relapsed multiple myeloma. Patients who did not
obtain a CR after 4 cycles were allowed oral dexamethasone. The primary endpoint was
ORR at 4 cycles. Secondary endpoints included response rate at 8 cycles, median TTP,
and PFS (months), 1-year OS, and safety.
RELAPSED MULTIPLE MYELOMA (VELCADE-NAÏVE): APEX
A randomized, open-label trial (N=669) evaluating the efficacy and safety of VELCADE
administered intravenously vs dexamethasone in patients with relapsed/refractory multiple
myeloma. The primary endpoint was TTP. Secondary endpoints were OS, ORR, and safety.
The APEX trial was terminated at a preplanned interim analysis of TTP. All dexamethasone
patients were offered VELCADE. Median TTP was 6.2 months with VELCADE vs 3.5 months
with dexamethasone (p<0.0001). An updated analysis was performed.
RETREATMENT OF RELAPSED MULTIPLE MYELOMA: RETRIEVE
A single-arm, open-label study in patients with relapsed multiple myeloma (N=130).
Patients with multiple myeloma who had previously achieved ≥partial response (PR) on a
VELCADE-containing regimen (median of 2 prior lines of therapy [range: 1-7]) and progressed
≥6 months after completing that regimen were retreated with IV VELCADE±dexamethasone.
Patients received VELCADE on days 1, 4, 8, and 11 q 3 weeks for 24 weeks. The primary
endpoint was best confirmed response to treatment as assessed by the European Group
for Blood and Marrow Transplantation criteria. The secondary endpoints were duration of
response (DOR) and safety.
RELAPSED MULTIPLE MYELOMA: SUBCUTANEOUS VS IV
▼ In the phase 3 study of VELCADE administered subcutaneously vs intravenously in
relapsed multiple myeloma, safety data were similar between the two treatment groups.
The most commonly reported ARs in the subcutaneous vs IV treatment groups were
peripheral neuropathy (37% vs 50%) and thrombocytopenia (30% vs 34%). The incidence
of serious ARs was similar in the subcutaneous and IV treatment groups (20% vs 19%,
respectively). The most commonly reported serious ARs in the subcutaneous treatment
group were pneumonia and pyrexia (2% each); in the IV treatment group, pneumonia,
diarrhea, and peripheral sensory neuropathy (3% each)
▼ Dose reductions due to ARs occurred in 31% of patients in the subcutaneous group
vs 43% in the IV group
RELAPSED MULTIPLE MYELOMA
▼ The most commonly reported ARs with VELCADE vs dexamethasone were nausea
(52% vs 9%), diarrhea NOS (52% vs 11%), fatigue (39% vs 25%), PN NEC (35%
vs 4%), thrombocytopenia (33% vs 3%), and constipation (30% vs 8%)
▼ The most commonly reported serious ARs in the VELCADE treatment group were
diarrhea (3%), dehydration, herpes zoster, pyrexia, nausea, vomiting, dyspnea, and
thrombocytopenia (2% each). In the dexamethasone treatment group, the most
commonly reported serious ARs were pneumonia (4%), hyperglycemia (3%), and
pyrexia and psychotic disorder (2% each)
ADDITIONAL SAFETY CONSIDERATION
▼ Antiviral prophylaxis should be considered for patients treated with VELCADE.
Herpes zoster reactivation was more common in patients treated with VELCADE
FOR HEALTHCARE PROFESSIONALS ONLY
MM TRIAL DESIGNS
& ADVERSE REACTIONS
Please see Important Safety Information for VELCADE within the Safety tab.
▼ A total of 25% of patients in the treatment group receiving VELCADE+MP experienced
serious ARs vs 18% in the treatment group receiving MP. The most commonly reported
serious ARs with VELCADE+MP vs MP alone included pneumonia (5% vs 4%), diarrhea
(4% vs 0%), thrombocytopenia (3% vs 1%), vomiting (3% vs <1%), nausea (2% vs <1%),
anemia (2% vs 2%), herpes zoster (2% vs <1%), and dehydration (2% vs <1%)14
In previously untreated mantle cell lymphoma
Dosing schedule
Administration of concomitant
medications
REPLACE VINCRISTINE IN R-CHOP* WITH TWICE-WEEKLY
VELCADE® (bortezomib)
TWICE WEEKLY, 6-8 CYCLES
1
2
3
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5
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9
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VELCADE (bortezomib)
Rituximab, cyclophosphamide, and doxorubicin
▼ In the phase 3 trial, concomitant medications for certain conditions were permitted
for patients receiving VELCADE® (bortezomib)15
Condition
Concomitant treatment
Prophylaxis for herpes zoster
(mandated in the clinical trial)
Antiviral prophylaxis. Acceptable therapies include:
• Acyclovir (400 mg orally, 3 times daily)
• Famciclovir (125 mg orally, twice daily)
• Valacyclovir (500 mg orally, twice daily)
Prophylaxis for hepatitis B
re-activation
• Lamivudine (100 mg/day orally or equivalent prophylaxis)
recommended until 8 weeks after the last dose
of treatment
Thrombocytopenia
• Platelet transfusions as needed, per standard practice
Anemia
• Red blood cell transfusions as needed, per
standard practice
Prevention of neutropenia and
management of treatment-emergent
toxicities
• Colony-stimulating growth factors, per standard practice
Management of hematologic
toxicities associated with
cyclophosphamide or doxorubicin
• Granulocyte colony-stimulating factors
Prevention of hemorrhagic cystitis
• Mesna, as clinically indicated
Infusion reactions to rituximab
Premedication before each infusion as clinically indicated:
• Acetaminophen
• Diphenhydramine
• Steroids
Diarrhea
• Loperamide as needed, per standard practice. Prophylactic
loperamide was not recommended
Prevention of tumor lysis syndrome
• Allopurinol treatment, per standard practice
• Special attention should be given to ensure
adequate hydration
Prednisone
▼ Administer VELCADE (1.3 mg/m2) as a 3- to 5-second bolus IV injection in combination
with rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2),
and prednisone (100 mg/m2). VELCADE is contraindicated for intrathecal administration;
fatal events have occurred
▼ Prior to the first day of each VR-CAP cycle (other than cycle 1):
†
– Platelet count should be at least 100 × 109/L and absolute neutrophil count (ANC)
should be at least 1.5 × 109/L
– Hemoglobin should be at least 8 g/dL (at least 4.96 mmol/L)
– Nonhematologic toxicity should have recovered to grade 1 or baseline
▼ At least 72 hours should elapse between each VELCADE (bortezomib) dose
▼ Please see the Dose Modifications tab for dosing with hematologic and nonhematologic
toxicities, moderate to severe hepatic impairment, and peripheral neuropathy
▼ In a phase 3 study of VR-CAP vs R-CHOP in adult patients with previously untreated
mantle cell lymphoma
– For patients with a response first documented at cycle 6, two additional treatment
cycles were allowed. Median number of cycles received by patients in both treatment
arms was 6, with 17% of patients in the R-CHOP group and 14% of patients in the
VR-CAP group receiving up to 2 additional cycles
The above medications and supportive therapies are examples of appropriate supportive care that were permitted in the
phase 3 trial.
– Discontinuations due to adverse reactions were 8% with VR-CAP and 6% with R-CHOP
*R-CHOP=rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
†
VR-CAP=VELCADE, rituximab, cyclophosphamide, doxorubicin, and prednisone.
Please see the MCL Trial Designs & Adverse Reactions tab for clinical trial information.
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
MCL DOSING
SCHEDULES
In previously untreated mantle cell lymphoma
In relapsed mantle cell lymphoma
Dosing schedule for
VELCADE® (bortezomib) patients
Mantle cell lymphoma trial designs
INITIAL THERAPY FOLLOWED BY WEEKLY MAINTENANCE
SCHEDULE OR STANDARD SCHEDULE
A randomized, open-label, phase 3 study (N=487) evaluating the efficacy and safety of
VELCADE® (bortezomib) administered intravenously in combination with rituximab,
cyclophosphamide, doxorubicin, and prednisone (VR-CAP) vs rituximab, cyclophosphamide,
doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated
mantle cell lymphoma (stage II, III, or IV) who were ineligible or not considered for bone
marrow transplantation. The primary endpoint was progression-free survival (PFS).
FOR INITIAL THERAPY
FOR EXTENDED THERAPY
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RELAPSED MANTLE CELL LYMPHOMA: PINNACLE
Cycle 9 and beyond
WEEKLY MAINTENANCE SCHEDULE
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VELCADE® (bortezomib)
OR
TWICE-WEEKLY STANDARD SCHEDULE
1
2
3
4
5
6
7
8
9
10
11
12
13
14
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▼ Administer VELCADE (1.3 mg/m2) as a subcutaneous injection or as a
3- to 5-second IV injection. VELCADE is contraindicated for intrathecal administration;
fatal events have occurred
▼ At least 72 hours should elapse between each VELCADE dose
▼ Please see the Dose Modifications tab for dosing with hematologic and nonhematologic
toxicities, moderate to severe hepatic impairment, and peripheral neuropathy
▼ In the PINNACLE trial, 23% of patients discontinued VELCADE due to
treatment-related adverse reactions16
A single-arm, multicenter, phase 2, open-label trial (N=155) evaluating the efficacy and
safety of VELCADE in patients with mantle cell lymphoma who had received at least 1 prior
therapy. Primary endpoint was time to progression (TTP) and secondary endpoints were
objective response rate (ORR), complete response (CR), duration of response (DOR), and
overall survival (OS).
As an appropriate cohort of historical controls could not be found for comparison to the
results of this study, the formal statistical comparisons of TTP and survival specified in
the protocol could not be performed.
Adverse reactions in
mantle cell lymphoma
PREVIOUSLY UNTREATED MANTLE CELL LYMPHOMA
▼ The most commonly reported adverse reactions with VR-CAP vs R-CHOP were
neutropenia (87% vs 71%), thrombocytopenia (72% vs 17%), leukopenia (48%
vs 36%), anemia (44% vs 29%), peripheral neuropathy (30% vs 27%), lymphopenia
(28% vs 12%), diarrhea (25% vs 5%), nausea (23% vs 12%), and pyrexia (20%
vs 10%)
▼ A total of 38% of patients receiving VR-CAP experienced serious adverse reactions
vs 30% of patients receiving R-CHOP. The most commonly reported serious adverse
reactions included febrile neutropenia (11% vs 8%), pneumonia (8% vs 3%),
neutropenia (5% vs 5%), and pyrexia (4% vs 2%), respectively17
RELAPSED MANTLE CELL LYMPHOMA
▼ The most commonly reported adverse reactions were peripheral neuropathy NEC
(54%), fatigue (52%), diarrhea NOS (39%), nausea (36%), constipation (34%), and
vomiting and rash NOS (23% each)
▼ The most commonly reported serious adverse reactions were nausea, vomiting
NOS, abdominal pain NOS, and syncope (3% each); pyrexia, pneumonia NOS,
and sepsis NOS (2% each)18
▼ Treatment-related deaths were reported in 3% of patients19
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
MCL TRIAL DESIGNS
& ADVERSE REACTIONS
Cycles 1-8
TWICE WEEKLY
PREVIOUSLY UNTREATED MANTLE CELL LYMPHOMA: LYM-3002
Dose modifications for hematologic
and nonhematologic toxicities
Previously untreated multiple myeloma
Toxicity
Dose modification or delay
Neutropenia/thrombocytopenia
If prolonged grade 4 neutropenia or thrombocytopenia,
or thrombocytopenia with bleeding, is observed in the
previous cycle
Consider reduction of the melphalan dose by 25%
in the next cycle
Thrombocytopenia during a cycle
If platelet count is not above 30 × 109/L or absolute
neutrophil count (ANC) is not above 0.75 × 109/L on
a VELCADE dosing day (other than day 1)
VELCADE® (bortezomib) dose should be withheld
If several doses in consecutive cycles are withheld
due to toxicity, VELCADE dose should be reduced
by 1 dose level*
Grade 3 or higher nonhematologic toxicities
VELCADE therapy should be withheld until
symptoms of the toxicity have resolved to grade
1 or baseline
Then VELCADE may be reinitiated with 1 doselevel reduction*
Relapsed multiple myeloma
Once the symptoms of the toxicity have resolved,
VELCADE therapy may be reinitiated at a dose
reduced by 25%*
Dose modifications on days 4, 8, and 11 for previously untreated mantle cell lymphoma
Toxicity
Dose modification or delay
Grade 3 or higher neutropenia, or a
platelet count not at or above 25 × 109/L
Withhold VELCADE® (bortezomib) therapy for up to 2 weeks
until the patient has an absolute neutrophil count (ANC) at or above
0.75 × 109/L and a platelet count at or above 25 × 109/L
• If, after VELCADE has been withheld, the toxicity does not resolve,
discontinue VELCADE
• If toxicity resolves such that the patient has an ANC at or above
0.75 x 109/L and a platelet count at or above 25 × 109/L,
VELCADE dose should be reduced by 1 dose level*
Grade 3 or higher
nonhematologic toxicities
Withhold VELCADE therapy until symptoms of the toxicity have
resolved to grade 2 or better. Then, VELCADE may be reinitiated
with one dose level reduction*
For VELCADE-related neuropathic pain and/or peripheral
neuropathy, hold or modify VELCADE, as per guidelines
Relapsed mantle cell lymphoma
VELCADE therapy should be withheld at the onset of
any grade 3 nonhematologic or grade 4 hematologic
toxicities, excluding neuropathy
Once the symptoms of the toxicity have resolved,
VELCADE therapy may be reinitiated at a dose
reduced by 25%*
*From 1.3 mg/m2 to 1 mg/m2 or from 1 mg/m2 to 0.7 mg/m2.
*From 1.3 mg/m2 to 1 mg/m2 or from 1 mg/m2 to 0.7 mg/m2.
▼ Prior to initiating any cycle of therapy with VELCADE in combination with
melphalan+prednisone (MP):
— Platelet count should be at least 70 × 109/L and ANC should be at least 1.0 × 109/L
— Nonhematologic toxicities should have resolved to grade 1 or baseline
▼ Dosing adjustments of VELCADE are not necessary for patients with renal insufficiency
▼ In patients undergoing dialysis, VELCADE should be administered after the
dialysis procedure
▼ Prior to the first day of each VELCADE, rituximab, cyclophosphamide, doxorubicin, and
prednisone (VR-CAP) cycle (other than cycle 1):
– Platelet count should be at least 100 × 109/L and ANC should be at least 1.5 × 109/L
– Hemoglobin should be at least 8 g/dL (at least 4.96 mmol/L)
– Nonhematologic toxicity should have recovered to grade 1 or baseline
▼ Interrupt VELCADE treatment at the onset of any grade 3 hematologic or
nonhematologic toxicities
Please review all dosing guidelines for hematologic and nonhematologic
toxicities, moderate to severe hepatic impairment, and peripheral neuropathy
throughout the Dose Modifications tab.
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
DOSE
MODIFICATIONS
VELCADE therapy should be withheld at the onset of
any grade 3 nonhematologic or grade 4 hematologic
toxicities, excluding neuropathy
Dose modifications for hematologic
and nonhematologic toxicities (cont.)
Dose modifications for peripheral
neuropathy (PN)
Dose modifications for hepatic
impairment
Bilirubin and SGOT (AST) levels
Modification of starting dose
Severity of PN signs/symptoms*
Dose modification or delay
Mild
Bilirubin level less than or equal to 1.0× ULN* and SGOT† (AST‡)
levels more than ULN or bilirubin level more than 1.0-1.5× ULN
and any SGOT (AST) level
Grade 1
(asymptomatic; loss of deep tendon reflexes or
paresthesia without pain or loss of function)
No action
None
Grade 1 with pain or grade 2
(moderate symptoms; limiting instrumental activities of
daily living [ADL]†)
Reduce VELCADE® (bortezomib) to 1 mg/m2
Grade 2 with pain or grade 3
(severe symptoms; limiting self-care ADL‡)
• Withhold VELCADE therapy until toxicity resolves
• When toxicity resolves, reinitiate with a reduced
dose of 0.7 mg/m2 once per week
Grade 4
(life-threatening consequences; urgent intervention
indicated)
Discontinue VELCADE
Moderate
Bilirubin level more than 1.5-3× ULN and any SGOT (AST) level
Severe
Bilirubin level more than 3× ULN and any SGOT (AST) level
Reduce VELCADE (bortezomib) to
0.7 mg/m2 in the first cycle
Consider dose escalation to 1 mg/m2
or further dose reduction to 0.5 mg/m2
in subsequent cycles based on
patient tolerability
®
*Upper limit of normal range.
†
Serum glutamic oxaloacetic transaminase.
‡
Aspartate aminotransferase.
▼ Patients with mild hepatic impairment do not require a starting-dose adjustment
▼ Patients with moderate or severe hepatic impairment should be started on
VELCADE at a reduced dose of 0. 7 mg/m2 per injection during the first cycle
— Subsequent dose escalation to 1. 0 mg/m2 or further dose reduction to
0.5 mg/m2 may be considered based on patient tolerance
*Grading based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
†
Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.
‡
Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not
being bedridden.
▼ Treatment-emergent PN is generally manageable and reversible with VELCADE
dose modification
▼ Compromised hepatic function may occur in patients with multiple myeloma20
— In VISTA, 79% of patients who received a dose modification experienced
improvement within a median of 1.9 months21
▼ Cases of acute liver failure have been reported in patients receiving multiple
concomitant medications and with serious underlying medical conditions.
In such cases, interrupt therapy with VELCADE to assess reversibility
— In APEX, 64%§ of patients experienced resolution or improvement within a median
of 3.6 months22
▼ Patients with preexisting severe neuropathy should be treated with VELCADE only after
careful risk-benefit assessment
▼ Treatment with VELCADE may cause PN that is predominantly sensory. However, cases
of severe sensory and motor PN have been reported. Patients should be monitored
for symptoms of neuropathy, such as burning sensation, hyperesthesia, hypoesthesia,
paresthesia, discomfort, neuropathic pain, or weakness
▼ Patients experiencing new or worsening PN during therapy with VELCADE may require
a decrease in the dose, a less dose-intense schedule, or discontinuation
▼ Starting VELCADE subcutaneously may be considered for patients with preexisting PN
or patients at high risk for PN
▼ The long-term outcome of PN has not been studied in mantle cell lymphoma
§
Peripheral neuropathy grade ≥2 (n=91).22
Please review all dosing guidelines for hematologic and nonhematologic
toxicities, moderate to severe hepatic impairment, and peripheral neuropathy
throughout the Dose Modifications tab.
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
DOSE
MODIFICATIONS
▼ Monitor hepatic enzymes during treatment. Upon occurrence, interrupt therapy
with VELCADE to assess reversibility
GO
Frequently asked questions
Frequently asked questions (cont.)
Q: The powder contained in the vial of VELCADE looks the same for subcutaneous
and IV. Is it the same vial?
Q: Is there any information on accidental overdosage of VELCADE?
A: Yes, a vial of VELCADE can be used for either subcutaneous or IV administration.
VELCADE is available in individual vials, each containing 3.5 mg of powdered product.
However, the reconstitution of VELCADE for subcutaneous and IV administrations
differs. The reconstituted concentration of VELCADE for subcutaneous administration
(2.5 mg/mL) is greater than the reconstituted concentration for IV administration
(1 mg/mL). Stickers that indicate the route of administration are provided within
the carton.
Q: What do I add to the 3.5-mg vial of VELCADE to reconstitute it for subcutaneous
administration?
A: In the event of an overdosage, monitor the patient’s vital signs and give appropriate
supportive care. There is no specific antidote known for overdosage with VELCADE.
In humans, fatal outcomes following the administration of more than twice the
recommended therapeutic dose have been reported, which were associated with
the acute onset of symptomatic hypotension and thrombocytopenia.
Q: Is there any information on use in special populations, such as older patients?
A: No overall differences in safety or effectiveness were observed between patients aged
65 years or older and younger patients receiving VELCADE, but greater sensitivity of
some older individuals cannot be ruled out.
A: For subcutaneous reconstitution, add 1.4 mL of sterile 0.9% sodium chloride solution
to the powder contained in the vial of VELCADE.
Q: Not all of the reconstituted VELCADE was used. Can it be stored for future use?
A: Each vial of VELCADE is for only a single use. VELCADE contains no antimicrobial
preservative. Administer reconstituted VELCADE within 8 hours of preparation. When
reconstituted as directed, VELCADE may be stored at 25ºC (77ºF). The reconstituted
material may be stored in the original vial and/or the syringe prior to administration.
The product may be stored for up to 8 hours in a syringe; however, total storage time
for the reconstituted material must not exceed 8 hours when exposed to normal
indoor lighting. Dispose of any unused product or waste material in accordance with
local requirements.
Q: How far ahead of use can I reconstitute VELCADE for subcutaneous injection?
A: VELCADE contains no antimicrobial preservative. Administer reconstituted VELCADE
within 8 hours of preparation.
Q: How common are injection-site reactions with subcutaneous administration
of VELCADE® (bortezomib)?
Please see Important Safety Information for VELCADE within the Safety tab.
FOR HEALTHCARE PROFESSIONALS ONLY
FAQs
A: In a clinical trial, the most common reaction was redness, occurring in 57% of patients.6
Injection-site reactions were reported in 6% of patients as an adverse event, with 1%
being serious and leading to dose modification or discontinuation. All events resolved
in a median of 6 days. If local injection-site reactions occur following administration of
VELCADE subcutaneously, a less concentrated VELCADE solution (1 mg/mL instead of
2.5 mg/mL) may be administered. Alternatively, consider the IV route of administration.
References: 1. US Department of Health and Human Services. Preventing Occupational Exposures to Antineoplastic and
Other Hazardous Drugs in Health Care Settings. Cincinnati, OH: US Dept of Health and Human Services; 2004. DHHS (NIOSH)
publication 2004-165. 2. US Department of Labor. Controlling occupational exposure to hazardous drugs (section VI, chapter
2). In: US Dept of Labor. OSHA Technical Manual (OTM). Washington, DC: Occupational Safety and Health Administration;
1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html. 3. American Society of Health-System Pharmacists. ASHP
guidelines on handling hazardous drugs. Am J Health-Syst Pharmacists. 2006;63:1172-1191. 4. Polovich M, Whitford JM,
Olsen M, eds. Fundamentals of administration. In: Polovich M, Whitford JM, Olsen M, eds. Chemotherapy and Biotherapy
Guidelines and Recommendations for Practice. 3rd ed. Pittsburgh, PA: Oncology Nursing Society. 2009;73-104. http://ons.
metapress.com/content/r14224/?p= f24648586d21451f8fe672fed78a5511&pi=0. 5. Mosteller RD. Simplified calculation
of body-surface area. N Engl J Med. 1987;317(17):1098. 6. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus
intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority
study. Lancet Oncol. 2011;12(5):431-440. 7. Workman B. Safe injection techniques. Nurs Stand. 1999;13(39):47-53. 8. Hunter
J. Subcutaneous injection technique. Nurs Stand. 2007;22(21):41-44. 9. Ostendorf W. Administration of parenteral medications.
In: Perry AG, Potter PA, Elkin MK, eds. Nursing Interventions and Clinical Skills. 5th ed. St Louis, MO: Elsevier Mosby; 2012:541583. 10. Smith SF, Duell DJ, Martin BC. Parenteral medication administration. In: Clinical Nursing Skills Basic to Advanced
Skills. 8th ed. Upper Saddle River, NJ: Pearson Education, Inc; 2012:607-630. 11. Data on file 53, Millennium Pharmaceuticals,
Inc. 12. Data on file 72, Millennium Pharmaceuticals, Inc. 13. Data on file 12, Millennium Pharmaceuticals, Inc. 14. Data on
file 48, Millennium Pharmaceuticals, Inc. 15. Data on file 73, Millennium Pharmaceuticals, Inc. 16. Data on file 55, Millennium
Pharmaceuticals, Inc. 17. Data on file 66, Millennium Pharmaceuticals, Inc. 18. Data on file 51, Millennium Pharmaceuticals,
Inc. 19. Fisher RI, Bernstein SH, Kahl BS, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory
mantle cell lymphoma. J Clin Oncol. 2006;24(30):4867-4874. 20. Thomas FB, Clausen KP, Greenberger NJ. Liver disease in
multiple myeloma. Arch Intern Med. 1973;132(2):195-202. 21. Dimopoulos MA, Mateos M-V, Richardson PG, et al. Risk factors
for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients
with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol. 2011;86(1):23-31. 22. Richardson PG,
Sonneveld P, Schuster MW, et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX
trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol. 2009;144(6):895-903.
Indications and Important Safety
Information for VELCADE® (bortezomib)
Important Safety Information for
VELCADE® (bortezomib) (cont.)
INDICATIONS: VELCADE (bortezomib) is indicated for the treatment of patients with multiple
myeloma and patients with mantle cell lymphoma.
▼ Hepatic toxicity: Monitor hepatic enzymes during treatment. Upon occurrence,
interrupt therapy with VELCADE (bortezomib) to assess reversibility.
CONTRAINDICATIONS: VELCADE is contraindicated in patients with hypersensitivity (not
including local reactions) to bortezomib, boron, or mannitol, including anaphylactic reactions.
VELCADE is contraindicated for intrathecal administration. Fatal events have occurred with
intrathecal administration of VELCADE.
▼ Embryo-fetal risk: Women should avoid breast-feeding or becoming pregnant
while on VELCADE.
WARNINGS AND PRECAUTIONS: VELCADE is for subcutaneous or IV administration only.
Because each route of administration has a different reconstituted concentration, caution
should be used when calculating the volume to be administered.
DRUG INTERACTIONS: Closely monitor patients receiving VELCADE in combination
with strong CYP3A4 inhibitors. Avoid concomitant use of strong CYP3A4 inducers.
▼ Peripheral neuropathy, including severe cases, may occur. Patients should be
monitored for symptoms and managed with dose modification or discontinuation.
Patients with preexisting symptoms may experience worsening peripheral neuropathy
(including ≥Grade 3). Starting with VELCADE subcutaneously may be considered for
patients who either have preexisting or are at high risk for peripheral neuropathy.
▼ Hypotension: Caution should be used when treating patients receiving antihypertensives,
those with a history of syncope, and those who are dehydrated.
▼ Cardiac toxicity, including acute development or exacerbation of congestive heart failure
and new onset of decreased left ventricular ejection fraction, has occurred. Isolated cases
of QT-interval prolongation have been reported. Patients with risk factors for, or existing,
heart disease should be closely monitored.
▼ Pulmonary toxicity: Acute respiratory distress syndrome (ARDS) and acute diffuse
infiltrative pulmonary disease of unknown etiology have occurred (sometimes fatal).
Pulmonary hypertension, in the absence of left heart failure or significant pulmonary
disease, has been reported. In the event of new or worsening cardiopulmonary
symptoms, consider interrupting VELCADE until a prompt and comprehensive
diagnostic evaluation is conducted.
▼ Posterior reversible encephalopathy syndrome has occurred. Consider MRI imaging
for onset of visual or neurological symptoms; discontinue VELCADE if suspected.
▼ Gastrointestinal toxicity, including nausea, diarrhea, constipation, and vomiting,
has occurred and may require use of antiemetic and antidiarrheal medications or
fluid replacement. Interrupt VELCADE for severe symptoms.
▼ Thrombocytopenia/Neutropenia: Manage with dose and/or schedule modifications.
Complete blood counts should be monitored frequently during treatment. There have
been reports of gastrointestinal and intracerebral hemorrhage. Support with
transfusions and supportive care, according to published guidelines.
▼ Tumor lysis syndrome: Closely monitor patients with high tumor burden and
take appropriate precautions.
A vi
for e
but
▼ The
both
▼ Bec
conc
▼ Patients with diabetes may require close monitoring and adjustment of the
antidiabetic medications.
–V
–V
a
▼ Visit
and
ADVERSE REACTIONS
▼ Previously untreated multiple myeloma (MM): In the phase 3 study of VELCADE
administered intravenously with melphalan and prednisone (MP) vs MP alone, the most
commonly reported adverse reactions (ARs) were thrombocytopenia (48% vs 42%),
neutropenia (47% vs 42%), peripheral neuropathy (46% vs 1%), nausea (39% vs 21%),
diarrhea (35% vs 6%), neuralgia (34% vs <1%), anemia (32% vs 46%), and leukopenia
(32% vs 28%).
Please
Please
at VELC
▼ Relapsed MM subcutaneous vs IV: In the phase 3 study of VELCADE administered
subcutaneously vs intravenously in relapsed MM, safety data were similar between
the two treatment groups. The most commonly reported ARs in the subcutaneous vs IV
treatment groups were peripheral neuropathy (37% vs 50%) and thrombocytopenia (30%
vs 34%). The incidence of serious ARs was similar in the subcutaneous treatment group
(20%) and the IV treatment group (19%). The most commonly reported serious ARs were
pneumonia and pyrexia (each 2%) in the subcutaneous treatment group and pneumonia,
diarrhea, and peripheral sensory neuropathy (each 3%) in the IV treatment group.
▼ Previously untreated mantle cell lymphoma (MCL): In a phase 3 study of VELCADE
administered intravenously with rituximab, cyclophosphamide, doxorubicin, and
prednisone (VR-CAP) vs vincristine, rituximab, cyclophosphamide, doxorubicin, and
prednisone (R-CHOP), the most commonly reported ARs were neutropenia (87% vs 71%),
thrombocytopenia (72% vs 17%), leukopenia (48% vs 36%), anemia (44% vs 29%),
lymphopenia (28% vs 12%), peripheral neuropathy (30% vs 27%), diarrhea (25% vs 5%),
nausea (23% vs 12%), and pyrexia (20% vs 10%).
▼ Relapsed MM and MCL: In the integrated analysis of 1163 patients in phase 2 and 3
studies of VELCADE administered intravenously, the most commonly reported ARs were
nausea (49%), diarrhea NOS (46%), fatigue (41%), peripheral neuropathy NEC (38%),
and thrombocytopenia (32%). A total of 26% of patients experienced serious ARs. The
most commonly reported serious ARs included diarrhea, vomiting, and pyrexia (each
3%); nausea, dehydration, and thrombocytopenia (each 2%); and pneumonia, dyspnea,
peripheral neuropathies NEC, and herpes zoster (each 1%).
FOR HE
Please see accompanying full Prescribing Information, also available
at VELCADE-hcp.com.
SAFETY
FOR HEALTHCARE PROFESSIONALS ONLY
Takeda Oncol
Other tradem
Copyright © 2
All rights rese
A vial of VELCADE® (bortezomib) can be used
for either subcutaneous or IV administration,
but reconstitution is different
▼ The recommended starting dose of VELCADE (bortezomib) is 1.3 mg/m2 for
both subcutaneous and IV administrations
▼ Because each route of administration has a different reconstituted
concentration, use caution when calculating the volume to be administered
– VELCADE is administered subcutaneously at a concentration of 2.5 mg/mL
– VELCADE is administered intravenously at a concentration of 1 mg/mL as
a 3- to 5-second bolus IV injection
▼ Visit the VELCADE Nurse Portal at VELCADE-rn.com for educational tools
and resources to help support you and your patients
Please see Important Safety Information for VELCADE within the Safety tab.
Please see accompanying full Prescribing Information, also available
at VELCADE-hcp.com.
FOR FINANCIAL, TREATMENT, OR PERSONAL
SUPPORT FOR YOUR PATIENTS, CONTACT A CASE MANAGER
AT 1-866-VELCADE (OPTION 2)
FOR HEALTHCARE PROFESSIONALS ONLY
Takeda Oncology and
are registered trademarks of Takeda Pharmaceutical Company Limited.
Other trademarks are the property of their respective owners.
Copyright © 2014, Millennium Pharmaceuticals, Inc.
All rights reserved.
Printed in the USA
USO/BOR/14/0055
1/15
Please see full Prescribing Information at
velcade.com/Files/PDFs/VELCADE_PRESCRIBING_INFORMATION.pdf