Velcade Dosage
Generic name: bortezomib
Dosage form: injection, powder, lyophilized, for solution
This dosage information does not include all the information needed to use Velcade safely and effectively. See full prescribing information for Velcade.
The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.
The recommended starting dose of VELCADE is 1.3 mg/m2. VELCADE may be administered intravenously at a concentration of 1 mg/mL, or subcutaneously at a concentration of 2.5 mg/mL [see Reconstitution/Preparation for Intravenous and Subcutaneous Administration (2.8)]. When administered intravenously, VELCADE is administered as a 3 to 5 second bolus intravenous injection. VELCADE is for intravenous or subcutaneous use only. VELCADE should not be administered by any other route.
Because each route of administration has a different reconstituted concentration, caution should be used when calculating the volume to be administered.
Dosage in Previously Untreated Multiple Myeloma
VELCADE (bortezomib) for Injection is administered in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles as shown in Table 1. In Cycles 1-4, VELCADE is administered twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32). In Cycles 5-9, VELCADE is administered once weekly (days 1, 8, 22 and 29). At least 72 hours should elapse between consecutive doses of VELCADE.
| Twice Weekly VELCADE (Cycles 1-4) | ||||||||||||
| Week | 1 | 2 | 3 | 4 | 5 | 6 | ||||||
| VELCADE (1.3 mg/m2) |
Day 1 |
-- | -- | Day 4 |
Day 8 |
Day 11 |
rest period |
Day 22 |
Day 25 |
Day 29 |
Day 32 |
rest period |
| Melphalan(9 mg/m2) Prednisone(60 mg/m2) |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
-- | -- | rest period |
-- | -- | -- | -- | rest period |
| Once Weekly VELCADE (Cycles 5-9 when used in combination with Melphalan and Prednisone) | ||||||||||||
| Week | 1 | 2 | 3 | 4 | 5 | 6 | ||||||
| VELCADE (1.3 mg/m2) |
Day 1 |
-- | -- | Day 8 |
rest period |
Day 22 |
Day 29 |
rest period |
||||
| Melphalan(9 mg/m2) Prednisone(60 mg/m2) |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
-- | -- | rest period |
-- | -- | -- | -- | rest period |
Dose Modification Guidelines for Combination Therapy with VELCADE, Melphalan and Prednisone
Prior to initiating any cycle of therapy with VELCADE in combination with melphalan and prednisone:
- Platelet count should be at least 70 × 109/L and the absolute neutrophil count (ANC) should be at least 1.0 x 109/L
- Non-hematological toxicities should have resolved to Grade 1 or baseline
| Toxicity | Dose modification or delay | |
|---|---|---|
| For information concerning melphalan and prednisone, see manufacturer's prescribing information. | ||
| Hematological toxicity during a cycle: 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 | |
| If platelet count is not above 30 × 109/L or ANC is not above 0.75 × 109/L on a VELCADE dosing day (other than day 1) | VELCADE dose should be withheld | |
| If several VELCADE doses in consecutive cycles are withheld due to toxicity | VELCADE dose should be reduced by 1 dose level (from 1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 mg/m2) | |
| Grade 3 or higher non-hematological toxicities | VELCADE therapy should be withheld until symptoms of the toxicity have resolved to Grade 1 or baseline. Then, VELCADE may be reinitiated with one dose level reduction (from 1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 mg/m2). For VELCADE-related neuropathic pain and/or peripheral neuropathy, hold or modify VELCADE as outlined in Table 3. | |
For dose modifications guidelines for peripheral neuropathy see Management of Peripheral Neuropathy section (2.5).
Dosage in Relapsed Multiple Myeloma and Mantle Cell Lymphoma
VELCADE (1.3 mg/m2/dose) is administered twice weekly for 2 weeks (Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12-21). For extended therapy of more than 8 cycles, VELCADE may be administered on the standard schedule or on a maintenance schedule of once weekly for 4 weeks (Days 1, 8, 15, and 22) followed by a 13-day rest period (Days 23 to 35) [see Clinical Studies section (14) for a description of dose administration during the trials]. At least 72 hours should elapse between consecutive doses of VELCADE.
Dose Modification Guidelines for Relapsed Multiple Myeloma and Mantle Cell Lymphoma
VELCADE therapy should be withheld at the onset of any Grade 3 non-hematological or Grade 4 hematological toxicities excluding neuropathy as discussed below [see Warnings and Precautions (5)]. Once the symptoms of the toxicity have resolved, VELCADE therapy may be reinitiated at a 25% reduced dose (1.3 mg/m2/dose reduced to 1 mg/m2/dose; 1 mg/m2/dose reduced to 0.7 mg/m2/dose).
For dose modifications guidelines for peripheral neuropathy see Management of Peripheral Neuropathy section (2.5).
Management of Peripheral Neuropathy
​Starting VELCADE subcutaneously may be considered for patients with pre-existing or at high risk of peripheral neuropathy. Patients with pre-existing severe neuropathy should be treated with VELCADE only after careful risk-benefit assessment.
​Patients experiencing new or worsening peripheral neuropathy during VELCADE therapy may require a decrease in the dose and/or a less dose-intense schedule.
​For dose or schedule modification guidelines for patients who experience VELCADE-related neuropathic pain and/or peripheral neuropathy see Table 3.
| ​Severity of Peripheral Neuropathy Signs and Symptoms* | Modification of Dose and Regimen | |
|---|---|---|
|
||
| ​Grade 1 (asymptomatic; loss of deep tendon reflexes or paresthesia) without pain or loss of function | No action | |
| ​Grade 1 with pain or Grade 2 (moderate symptoms; limiting instrumental Activities of Daily Living (ADL)†) | Reduce VELCADE 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 VELCADE at 0.7 mg/m2 once per week. | |
| ​Grade 4 (life-threatening consequences; urgent intervention indicated) | Discontinue VELCADE | |
Dosage in Patients with Hepatic Impairment
Patients with mild hepatic impairment do not require a starting dose adjustment and should be treated per the recommended VELCADE dose. 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, and a subsequent dose escalation to 1.0 mg/m2 or further dose reduction to 0.5 mg/m2 may be considered based on patient tolerance (see Table 4). [see Warnings and Precautions (5.10), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]
| Bilirubin Level | SGOT (AST) Levels | Modification of Starting Dose | |
|---|---|---|---|
| Abbreviations: SGOT = serum glutamic oxaloacetic transaminase; AST = aspartate aminotransferase; ULN = upper limit of the normal range. |
|||
| Mild | Less than or equal to 1.0x ULN | More than ULN | None |
| More than 1.0x–1.5x ULN | Any | None | |
| Moderate | More than 1.5x–3x ULN | Any | Reduce VELCADE to 0.7 mg/m2 in the first cycle. Consider dose escalation to 1.0 mg/m2 or further dose reduction to 0.5 mg/m2 in |
| Severe | More than 3x ULN | Any | subsequent cycles based on patient tolerability. |
Administration Precautions
​The drug quantity contained in one vial (3.5 mg) may exceed the usual dose required. Caution should be used in calculating the dose to prevent overdose. [see Reconstitution/Preparation for Intravenous and Subcutaneous Administration (2.8)]
​When administered subcutaneously, sites for each injection (thigh or abdomen) should be rotated. New injections should be given at least one inch from an old site and never into areas where the site is tender, bruised, erythematous, or indurated.
​If local injection site reactions occur following VELCADE administration subcutaneously, a less concentrated VELCADE solution (1 mg/mL instead of 2.5 mg/mL) may be administered subcutaneously [see Reconstitution/Preparation for Intravenous and Subcutaneous Administration (2.8) and follow reconstitution instructions for 1 mg/mL]. Alternatively, the intravenous route of administration should be considered [see Reconstitution/Preparation for Intravenous and Subcutaneous Administration (2.8)]
VELCADE is an antineoplastic. Procedures for proper handling and disposal should be considered. [see How Supplied/Storage and Handling (16)]
​In clinical trials of VELCADE intravenous, local skin irritation was reported in 5% of patients, but extravasation of VELCADE was not associated with tissue damage. In a clinical trial of subcutaneous VELCADE, a local reaction was reported in 6% of patients as an adverse event, mostly redness.
Reconstitution/Preparation for Intravenous and Subcutaneous Administration
​Proper aseptic technique should be used. Reconstitute only with 0.9% sodium chloride. The reconstituted product should be a clear and colorless solution.
​Different volumes of 0.9% sodium chloride are used to reconstitute the product for the different routes of administration. The reconstituted concentration of bortezomib for subcutaneous administration (2.5 mg/mL) is greater than the reconstituted concentration of bortezomib for intravenous administration (1 mg/mL). Because each route of administration has a different reconstituted concentration, caution should be used when calculating the volume to be administered [see Administration Precautions (2.7)]
​For each 3.5 mg single-use vial of bortezomib reconstitute with the following volume of 0.9% sodium chloride based on route of administration (Table 5):
| ​Route of administration | Bortezomib (mg/vial) |
Diluent (0.9% Sodium Chloride) |
Final Bortezomib concentration (mg/mL) |
|---|---|---|---|
| Intravenous | 3.5 mg | 3.5 mL | 1 mg/mL |
| Subcutaneous | 3.5 mg | 1.4 mL | 2.5 mg/mL |
After determining patient body surface area (BSA) in square meters, use the following equations to calculate the total volume (mL) of reconstituted VELCADE to be administered:
- ​Intravenous Administration [1 mg/mL concentration]
​
- ​Subcutaneous Administration [2.5 mg/mL concentration]
​
​Stickers that indicate the route of administration are provided with each VELCADE vial. These stickers should be placed directly on the syringe of VELCADE once VELCADE is prepared to help alert practitioners of the correct route of administration for VELCADE.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. If any discoloration or particulate matter is observed, the reconstituted product should not be used.
Stability: Unopened vials of VELCADE are stable until the date indicated on the package when stored in the original package protected from light.
VELCADE contains no antimicrobial preservative. Reconstituted VELCADE should be administered within 8 hours of preparation. When reconstituted as directed, VELCADE may be stored at 25°C (77°F). 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.
