dosing and admin

Reconstitution and dosing for subcutaneous and IV administration

FOR HEALTHCARE PROFESSIONALS ONLY

VELCADE® (bortezomib) is indicated for the treatment of patients with multiple myeloma. VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy.

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.

Please see Important Safety Information within theSafety tab and accompanying full Prescribing Information, also available at VELCADEHCP.com.

ABOUTVELCADE


DESCRIPTION▼ VELCADE (bortezomib) is an antineoplastic agent

▼ VELCADE is a reversible inhibitor of the chymotrypsin-like activityof the 26S proteasome in mammalian cells

▼ Procedures for proper handling and disposal should be considered.Please see the Storage and Disposal tab

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

STORAGE AND HANDLING▼ Store unopened vials of VELCADE at controlled room temperature 25°C (77°F); excursions are

permitted from 15°C to 30°C (59°F to 86°F). Retain vials in original package to protect from light

▼ Consider handling and disposal of VELCADE according to guidelines issued for cytotoxic drugs, including using gloves and other protective clothing to prevent skin contact1-4

About VELCADE® (bortezomib)

NDC 63020-049-01

A vial of VELCADE can beused for either subcutaneous

or IV administration, but reconstitution is different.

Please see Important Safety Information for VELCADE within the Safety tab.

SUBCUTANEOUSRECONSTITUTION


▼ VELCADE® (bortezomib) is an antineoplastic agent and should be administered under the supervision of a physician experienced in the use of antineoplastic therapy

▼ Procedures for proper handling and disposal should be considered

▼ Do not use VELCADE after the date stated on the vial and carton

▼ The volume of 0.9% sodium chloride used to reconstitute VELCADE for subcutaneous administration is less than the volume used 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 � nal concentration of 2.5 mg/mL VELCADE

— The reconstituted product should be a clear and colorlesssolution free of particulate matter

▼ Apply stickers to the vial and syringe that identify the intended route of administration

▼ VELCADE contains no antimicrobial preservative. Therefore, reconstitutedVELCADE should be administered within 8 hours of preparation (see Storageand Disposal tab for storage guidelines)

Please see Dose Modi� cation tab for dosing with hematologic toxicities, nonhematologic toxicities, peripheral neuropathy (PN), and moderate to severe hepatic impairment.

The reconstituted concentration of VELCADE forsubcutaneous administration (2.5 mg/mL) is greater than the reconstituted concentration for IV administration (1 mg/mL). Use caution when calculating the volume to be administered.

The recommended starting dose for both routes is 1.3 mg/m2.

Reconstitution for subcutaneous administration

0.9%NaCI

▼ Observe aseptic technique throughout handling of VELCADE

SUBCUTANEOUS INJECTION

1.4 mL0.9% sodium chloride

2.5 mg/mL� nal concentration

Add

To Make


IVRECONSTITUTION


▼ VELCADE® (bortezomib) is an antineoplastic agent and should be administered under the supervision of a physician experienced in the use of antineoplastic therapy

▼ Procedures for proper handling and disposal should be considered

▼ Do not use VELCADE after the date stated on the vial and carton

▼ The volume of 0.9% sodium chloride used to reconstitute VELCADE forIV administration is greater than the volume used for subcutaneous administration

— For IV reconstitution, add 3.5 mL of sterile 0.9% sodium chloridesolution to the powder contained in the vial of VELCADE

— This reconstitution will result in a � nal concentration of1 mg/mL VELCADE

— The reconstituted product should be a clear and colorlesssolution free of particulate matter

▼ Apply stickers to the vial and syringe that identify the intended route of administration

▼ VELCADE contains no antimicrobial preservative. Therefore, reconstituted VELCADE should be administered within 8 hours of preparation (see Storage and Disposal tab for storage guidelines)

Please see Dose Modi� cation tab for dosing with hematologic toxicities, nonhematologic toxicities, PN, and moderate to severe hepatic impairment.

The reconstituted concentration of VELCADE forIV administration (1 mg/mL) is less than the reconstituted concentration for subcutaneous administration (2.5 mg/mL). Use caution when calculating the volume to be administered.

The recommended starting dose for both routes is 1.3 mg/m2.

Reconstitution for IV administration

▼ Observe aseptic technique throughout handling of VELCADE

0.9%NaCI

INTRAVENOUS INJECTION

3.5 mL0.9% sodium chloride

1 mg/mL� nal concentration


Add

To Make

DOSING


▼ The recommended starting dose of VELCADE® (bortezomib) is 1.3 mg/m2 for both subcutaneous and IV administrations

▼ Please see Dose Modi� cation tab for dosing with hematologic and nonhematologic toxicities, PN, and moderate to severe hepatic impairment

▼ 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

▼ The drug quantity contained in one vial (3.5 mg) may exceed the doserequired. Use caution when calculating the dose to prevent overdose

OVERDOSAGE▼ There is no speci� c 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

Dosing

Please see section 2 of the full Prescribing Information for reconstitution,dosage, and administration instructions.

CALCULATING VELCADE VOLUME (mL)

Total VELCADE volume (mL) tobe administered

VELCADE dose (mg/m2) × patient BSA* (m2)

Reconstituted concentration†

=


† 2.5 mg/mL for subcutaneous administration and 1 mg/mL for IV administration.

BSA=square root of ([height in centimeters multiplied by body weight in kilograms] divided by 3600).5

BSA = Ht (cm) × Wt (kg)

3600

Because each route of administration has a different reconstituted concentration, use caution when calculating the volume to be administered.

*SAMPLE BSA CALCULATION:

1 4 8 11Day

Vc Vc Vc Vc

Rest 12-21

1 8Day

Vc Vc

Rest 9-21

1 4 8 11Day

Vc Vc Vc Vc

Rest 12-21

1 8Day

Vc Vc

Rest 9-21

DOSINGSCHEDULE

MP orally on days 1-4 every 6 weeks

MP† orally on days 1-4 every 6 weeks

3 WEEKS

x10

3 WEEKS

x8



Dosing schedule: previously untreated multiple myeloma (MM)

▼ Administer VELCADE® (bortezomib) (1.3 mg/m2) as a subcutaneous injection or a 3- to 5-second bolus IV injection in combination with oral MP (melphalan 9 mg/m2 and prednisone 60 mg/m2)

▼ Prior to initiating any cycle of therapy with VELCADE+MP: — Platelet count should be at least 70 × 109/L and absolute neutrophil count (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 renalinsuf� ciency. In patients undergoing dialysis, VELCADE should be administeredafter the dialysis procedure

▼ Please see Dose Modi� cation tab for guidelines for hematologic toxicities, nonhematologic toxicities, PN, and moderate to severe hepatic impairment

▼ In the VISTA trial, discontinuations due to adverse reactions (ARs) were 11% for VELCADE combination and 10% for MP alone6

▼ At least 72 hours should elapse between each VELCADE dose

*VELCADE.†Melphalan+prednisone.

*

TWICE-WEEKLY THEN WEEKLY DOSING FOR A TOTAL OF 54 WEEKS

TWICE WEEKLY

WEEKLY

Please see Trial Designs tab for clinical trial information.

1 4 8 11Day

Vc Vc Vc Vc

Rest 12-21

1 8Day

Vc Vc

Rest 9-21

1 8Day

Vc Vc

15

Vc

22

Vc

Rest 23-35

1 4 8 11Day

Vc Vc Vc Vc

Rest 12-21

1 8Day

Vc Vc

Rest 9-21

1 8Day

Vc Vc

15

Vc

22

Vc

Rest 23-35

1 4 8 11Day

Vc Vc Vc Vc

Rest 12-21

1 8Day

Vc Vc

Rest 9-21

1 8Day

Vc Vc

15

Vc

22

Vc

Rest 23-35

DOSINGSCHEDULE

FOR HEALTHCARE PROFESSIONALS ONLYFOR HEALTHCARE PROFESSIONALS ONLY

Dosing schedule: relapsed MM and mantle cell lymphoma (MCL)

FOR INITIAL THERAPYTWICE WEEKLY

FOR EXTENDED THERAPYWEEKLY MAINTENANCE SCHEDULE

TWICE-WEEKLY STANDARD SCHEDULE

OR3 WEEKS

x8

*

▼ In the APEX trial, responding patients received a medianof 31 weeks of therapy (39 planned) using twice-weekly followed by weekly dosing7

▼ Administer VELCADE® (bortezomib) (1.3 mg/m2) as a subcutaneous injection or a 3- to 5-second bolus IV injection

▼ Dosing adjustments of VELCADE are not necessary for patients with renal insuf� ciency. In patients undergoing dialysis, VELCADE should be administered after the dialysis procedure

▼ In the APEX trial, discontinuations due to ARs were 25% for VELCADE and 18% for dexamethasone. In the subcutaneous vs IV trial, discontinuations due to ARs were 18% vs 23%, respectively

▼ In the PINNACLE trial of MCL, 23% of patients discontinued VELCADE due to treatment-related ARs8

▼ At least 72 hours should elapse between each VELCADE dose

▼ Please see Dose Modi� cation tab for dosing with hematologictoxicities, nonhematologic toxicities, PN, and moderate to severe hepatic impairment



*VELCADE.

INITIAL THERAPY FOLLOWED BY EXTENDED THERAPY

Grade 3 or higher nonhematologic toxicities

Thrombocytopenia during a cycleIf platelet count is not above 30 × 109/Lor ANC is not above 0.75 × 109/L on aVELCADE dosing day (other than day 1)

Neutropenia/thrombocytopeniaIf 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

If several doses in consecutive cycles are withheld due to toxicity, reduce VELCADE dose by 1 dose level†

Withhold VELCADE dose until symptoms of the toxicity have resolved to grade 1 or baseline

Then VELCADE may be reinitiated with 1 dose-level reduction†

Withhold VELCADE dose

Once the symptoms of the toxicity have resolved, VELCADE therapy may be reinitiated at a dose reduced by 25%†

VELCADE therapy should be withheld at the onset of any grade 3 nonhematologic or grade 4 hematologic toxicities, excluding neuropathy

DOSEMODIFICATION


RELAPSED MM AND MCL

Dose Modification or DelayToxicity*

†From 1.3 mg/m2 to 1 mg/m2 or from 1 mg/m2 to 0.7 mg/m2.

*Please see subsequent pages for dose as well as modi� cation guidelines for neuropathic pain and/or PN related to therapy with VELCADE, and moderate to severe hepatic impairment.

Dose modi� cation: hematologic and nonhematologic toxicities

▼ Prior to initiating any therapy with VELCADE® (bortezomib)+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


PREVIOUSLY UNTREATED MM

MILDBilirubin 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

MODERATEBilirubin level more than 1.5–3 × ULN and any SGOT (AST) level

SEVEREBilirubin level more than 3 × ULN and any SGOT (AST) level

Reduce VELCADE® (bortezomib) to 0.7 mg/m2 in the first cycleConsider dose escalation to 1 mg/m2 or further dose reduction to 0.5 mg/m2 in subsequent cycles based on patient tolerability

None

DOSEMODIFICATION


Modification of Starting Dose

*Upper limit of normal range.†Serum glutamic oxaloacetic transaminase. ‡Aspartate aminotransferase.

Dose modi� cation: hepatic impairment Bilirubin and SGOT (AST) Levels


Please review all dosing guidelines for hematologic and nonhematologic toxicities, moderate to severe hepatic impairment, and PN throughout the Dose Modi� cation tab.

GRADE 1(asymptomatic; loss of deep tendon re� exes or paresthesia) without pain or loss of function

GRADE 1 WITH PAIN OR GRADE 2(moderate symptoms; limiting instrumental activities of daily living [ADL†])

GRADE 4(life-threatening consequences; urgent intervention indicated)

GRADE 2 WITH PAIN OR GRADE 3(severe symptoms; limiting self-care ADL‡)

Discontinue VELCADE

No action

Withhold VELCADE until toxicity resolves

Reduce VELCADE to 1 mg/m2

When toxicity resolves,reinitiate with a reduced dose of 0.7 mg/m2 once per week

DOSEMODIFICATION



Dose Modification or Delay

Dose modi� cation: peripheral neuropathy ▼ Early detection of PN is important in facilitating patient management

▼ Starting VELCADE® (bortezomib) subcutaneously may be considered for patients with preexisting PN or patients at high risk for PN

▼ Treatment-emergent PN is generally manageable and reversible with appropriate dose modification

— In VISTA, 79% of patients who received dose modification experienced improvement within a median of 1.9 months9

— In APEX, 64%§ of patients experienced resolution or improvement within a median of 3.6 months10

▼ Treatment with VELCADE may cause PN that is predominantly sensory. However, cases of severe sensory and motor PN have been reported

▼ Patients with preexisting symptoms or signs of PN may experience worsening PN. Patients with preexisting severe neuropathy should be treated with VELCADE only after careful risk-bene� t assessment

▼ Patients experiencing new or worsening PN during therapy with VELCADE may bene� t from dose modi� cation or discontinuation.

*Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.†Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using telephone, managing money, etc.‡Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not being bedridden.§Peripheral neuropathy grade ≥2 (n=91).10

Severity of PN Signs/Symptoms*

Please review all dosing guidelines for hematologic and nonhematologic toxicities, moderate to severe hepatic impairment, and PN throughout the Dose Modi� cation tab.

SUBCUTANEOUSADMINISTRATION


▼ Before VELCADE® (bortezomib) administration, visually inspect the 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

▼ Verify that the dose in the syringe is correct

INJECTION SITE REACTIONS▼ In the clinical trial, the most common reaction was redness, occurring in

57% of patients.11 Injection site reactions were reported in 6% of patients as an adverse reaction, with 1% being serious and leading to dose modi� cation 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 subcutaneously. Alternatively, consider the IV route of administration

▼ Use the abdomen or thighs as sitesfor subcutaneous injections

▼ Rotate injection sites

▼ Administer new injections at least 1 inch from an old site and never into areas where the skin is tender, bruised, erythematous, or indurated


For Patient Assistance Information or Reimbursement Assistance, call 1-866-VELCADE (835-2233), Option 2, or visit VELCADEHCP.com.

Please see Adverse Reactions tab for safety experience in the subcutaneous vs IV clinical trial.

Subcutaneous administration

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M

Y

CM

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CMY

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Flashcard_Art_HR.pdf 1 10/12/12 11:50 AM

SUBCUTANEOUSADMINISTRATION


RECOMMENDATIONS THAT MAY MINIMIZE INJECTION SITE REACTIONS▼ Before administration, make sure the needle used during preparation

has been changed to a new, clean, sharp, dry needle.12 This practice may reduce the chance of topical contact of medication with the skin

▼ Make sure there is adequate adipose tissue at the site of injection13

▼ Ensure that medication is deposited in the subcutaneous tissue13

— Generally, when using a 25-gauge needle that is 5/8 inch in length, insert needle at a 45-degree angle

— Generally, when using a 26- to 30-gauge needle that is 1/2 inchin length, insert needle at a 90-degree angle

▼ Inject slowly and steadily (≈1.0 mL for 10 seconds)12 allowing absorption by the surrounding tissue and avoiding � uid backtrack up the needle into the skin14

Subcutaneous administration continued



Please see Adverse Reactions tab for safety experience in the subcutaneous vs IV clinical trial.

IVADMINISTRATION


▼ Before VELCADE® (bortezomib) administration, visually inspect the 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

▼ Verify that the dose in the syringe is correct

INJECTION SITE REACTIONS▼ In clinical trials of VELCADE administered intravenously, local skin irritation

was reported in 5% of patients, but extravasation of VELCADE was not associated with tissue damage

IV administration

VELCADE can be administered intravenously as a 3- to 5-second bolus IV injection.



STORAGE ANDDISPOSAL


UNOPENED VIALS▼ Store unopened vials of VELCADE® (bortezomib) at 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

▼ Unopened vials of VELCADE are stable until the date indicated on the package when stored in the original package protected from light

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


Storage▼ 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

Disposal


TRIALDESIGNS


RELAPSED MULTIPLE MYELOMA: SUBCUTANEOUS VS IVA non-inferiority, phase 3, randomized (2:1), open-label trial that compared the ef� cacy and safety of VELCADE® (bortezomib) administered subcutaneously (n=148) with VELCADE administered intravenously (n=74) in patients with relapsed MM. 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 overall survival, and safety.

PREVIOUSLY UNTREATED MULTIPLE MYELOMA: VISTAA randomized, open-label, international phase 3 trial (N=682) evaluating the ef� cacy and safety of VELCADE administered intravenously in combination with MP vs MP in previously untreated MM. The primary endpoint was TTP. Secondary endpoints were CR, ORR, PFS, and overall survival. At a prespeci� ed interim analysis (median follow-up 16.3 months), VELCADE+MP resulted in signi� cantly superior results for TTP (median 20.7 months with VELCADE+MP vs 15.0 months with MP [p=0.000002]), PFS, overall survival, and ORR. Further enrollment was halted, and patients receiving MP were offered VELCADE in addition. Updated analyses were performed.

Trial designsRELAPSED MULTIPLE MYELOMA: APEXA randomized, open-label trial (N=669) evaluating the ef� cacy and safety of VELCADE administered intravenously vs dexamethasone in patients with relapsed/refractory MM. The primary endpoint was TTP. Secondary endpoints were overall survival, 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.

MANTLE CELL LYMPHOMA: PINNACLEA single-arm, multicenter, phase 2, open-label trial (N=155) evaluating the ef� cacy and safety of VELCADE in patients with MCL who had received at least 1 prior therapy. Primary endpoint was TTP and secondary endpoints were ORR, CR, DOR, and overall survival. 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 speci� ed in the protocol could not be performed.

CR: complete response; DOR: duration of response; ORR: overall response rate; PFS: progression-free survival; TTP: time to progression


ADVERSE REACTIONS


Adverse reactions: subcutaneous vs IV trial in patientswith relapsed multiple myeloma


Please see all safety experience throughout the Adverse Reactions tab.


Most Commonly Reported (≥20%) Adverse Reactions

Subcutaneous VELCADE® (bortezomib)(n=147) , %

IV VELCADE(n=74), %

AllEvents

Grade 3Events

Grade ≥4Events

AllEvents

Grade 3Events

Grade ≥4Events

Peripheral Neuropathies NEC 37 5 1 50 14 1

Thrombocytopenia 30 5 3 34 9 7

Neutropenia 23 10 3 27 14 4

Neuralgia 23 3 0 23 9 0

Anemia 19 5 0 23 4 0

Diarrhea 19 1 0 28 4 0

Leukopenia 18 5 0 20 5 1

ADVERSE REACTIONS IN RELAPSED MM: SUBCUTANEOUS AND IV

ADVERSE REACTIONS


Adverse reactions continuedRELAPSED MM AND MCL ▼ The most commonly reported ARs in the integrated safety analysis (N=1163)

of relapsed MM and relapsed MCL were nausea (49%), diarrhea (46%), fatigue (41%), peripheral neuropathies NEC (38%), thrombocytopenia (32%), vomiting (28%), constipation (25%), and pyrexia (21%)

▼ The most commonly reported serious ARs in the integrated safety analysis (N=1163) of relapsed MM and relapsed MCL included diarrhea, vomiting, and pyrexia (3% each); nausea, dehydration, and thrombocytopenia (2% each); and pneumonia, dyspnea, peripheral neuropathies NEC, and herpes zoster (1% each)

ADDITIONAL SAFETY CONSIDERATION ▼ Antiviral prophylaxis should be considered for patients treated with

VELCADE. Herpes zoster reactivation was more common in patientstreated with VELCADE

RELAPSED MM: SUBCUTANEOUS VS IV ▼ 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

PREVIOUSLY UNTREATED MM ▼ The most commonly reported ARs for VELCADE® (bortezomib)+MP (n=340)

vs MP alone (n=337) were thrombocytopenia (48% vs 42%), neutropenia (47% vs 42%), PN (46% vs 1%), nausea (39% vs 21%), diarrhea (35% vs 6%), neuralgia (34% vs <1%), anemia (32% vs 46%), and leukopenia (32% vs 28%)

▼ 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%)15



Please see all safety experience throughout the Adverse Reactions tab.

FAQs


Frequently asked questionsQ: The powder contained in the vial of VELCADE® (bortezomib) looks the same

for subcutaneous and IV. Is it the same vial?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 injections 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 use as a subcutaneous administration?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?

A: In a clinical trial, the most common reaction was redness, occurring in 57% of patients.11 Injection site reactions were reported in 6% of patients as an adverse reaction, with 1% being serious and leading to dose modi� cation 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.

Q: Is there any information on accidental overdosage of VELCADE? A: In the event of an overdosage, monitor the patient’s vital signs and give appropriate

supportive care. There is no speci� c 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

65 years or older and younger patients receiving VELCADE, but greater sensitivity of some older individuals cannot be ruled out.


SAFETY


Indications and important safety information for VELCADE® (bortezomib)INDICATIONS: VELCADE (bortezomib) is indicated for the treatment of patients with multiple myeloma. VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy.

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.

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.

▼ Peripheral neuropathy, including severe cases, may occur. Patients should be monitored for symptoms and managed with dose modi� cation 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 in� ltrative pulmonary disease of unknown etiology have occurred (sometimes fatal). Pulmonary hypertension, in the absence of left heart failure or signi� cant 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 � uid replacement. Interrupt VELCADE for severe symptoms.

▼ Thrombocytopenia/Neutropenia: Manage with dose and/or schedule modi� cations. Complete blood counts should be monitored frequently during treatment. There have been reports of gastrointestinal and intracerebral hemorrhage. Transfusions may be considered.

▼ Tumor lysis syndrome: Closely monitor patients with high tumor burden and take appropriate precautions.

Please see accompanying full Prescribing Information, also availableat VELCADEHCP.com.

VELCADE, MILLENNIUM and are registered trademarks of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners.

Millennium Pharmaceuticals, Inc., Cambridge, MA 02139Copyright © 2013, Millennium Pharmaceuticals, Inc.All rights reserved. Printed in USA V-12-0352 1/13

SAFETY


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

Please see Important Safety Information for VELCADE on the Safety tab.

Please see accompanying full Prescribing Information, also available at VELCADEHCP.com.

Indications and important safety information for VELCADE® (bortezomib)continued

FOR HEALTHCARE PROFESSIONALS ONLYPlease see accompanying full Prescribing Information, also availableat VELCADEHCP.com.

▼ Hepatic toxicity: Monitor hepatic enzymes during treatment. Upon occurrence, interrupt therapy with VELCADE (bortezomib) to assess reversibility.

▼ Embryo-fetal risk: Women should avoid breast-feeding or becoming pregnant while on VELCADE.

▼ Patients with diabetes may require close monitoring and adjustment of the antidiabetic medications.

DRUG INTERACTIONS: Closely monitor patients receiving VELCADE in combination with strong CYP3A4 inhibitors. Avoid concomitant use of strong CYP3A4 inducers.

ADVERSE REACTIONS Most commonly reported adverse reactions (incidence ≥20%) in clinical studies include nausea, diarrhea, thrombocytopenia, neutropenia, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, constipation, vomiting, lymphopenia, rash, pyrexia, and anorexia.

The most commonly reported serious adverse reactions in clinical trials were pneumonia, pyrexia, diarrhea, vomiting, nausea, dehydration, dyspnea, thrombocytopenia, peripheral neuropathy, herpes zoster, and anemia.16

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. Simpli� ed calculation of body-surface area. N Engl J Med. 1987;317(17):1098. 6. Data on � le 53, Millennium Pharmaceuticals, Inc. 7. Data on � le 12, Millennium Pharmaceuticals, Inc. 8. Data on � le 55, Millennium Pharmaceuticals, Inc. 9. 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. 10. 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-modi� cation guideline. Br J Haematol. 2009;144:895-903. 11. 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. 12. Workman B. Safe injection techniques. Nurs Standard. 1999;13(39):47-53. 13. Ostendorf W. Administration of Parenteral Medications. In: Perry A, Potter P, Elkin M. Nursing Interventions and Clinical Skills. 5th ed. St Louis, MO: Elsevier Mosby. 2012:541-583. 14. Hunter J. Subcutaneous injection technique. Nurs Standard. 2008;22(27):41-44. 15. Data on � le 48, Millennium Pharmaceuticals, Inc.16. Data on � le 56, Millennium Pharmaceuticals, Inc.

POCKET

Please see full Prescribing Information at

velcade.com/Files/PDFs/VELCADE_PRESCRIBING_INFORMATION.pdf

http://www.velcade.com/Files/PDFs/VELCADE_PRESCRIBING_INFORMATION.pdf

dosing and admin

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