DOSAGE AND ADMINISTRATION
The recommended dose of VELCADE is 1.3 mg/m2/dose administered as a 3 to 5 second bolus intravenous injection 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 for a description of dose administration during the trials). At least 72 hours should elapse between consecutive doses of VELCADE.
Dose Modification and Re-initiation of Therapy
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 PRECAUTIONS). 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 1.0 mg/m2/dose; 1.0 mg/m2/dose reduced to 0.7 mg/m2/dose).
Table 9 contains the recommended dose modification for the management of patients who experience VELCADE related neuropathic pain and/or peripheral neuropathy. Patients with preexisting severe neuropathy should be treated with VELCADE only after careful risk-benefit assessment.
Table 9: Recommended Dose Modification for VELCADE related Neuropathic Pain and/or Peripheral Sensory or Motor Neuropathy
|Severity of Peripheral Neuropathy Signs and Symptoms||Modification of Dose and Regimen|
|Grading based on NCI Common Toxicity Criteria CTCAE v3.0|
|Grade 1 (paresthesias, weakness and/or loss of reflexes) without pain or loss of function|| No action|
|Grade 1 with pain or Grade 2 (interfering with function but not with activities of daily living)||Reduce VELCADE to 1.0 mg/m2|
|Grade 2 with pain or Grade 3 (interfering with activities of daily living) ||Withhold VELCADE therapy until toxicity resolves. When toxicity resolves reinitiate with a reduced dose of VELCADE at 0.7 mg/m2 and change treatment schedule to once per week.|
|Grade 4 (Sensory neuropathy which is disabling or motor neuropathy that is life threatening or leads to paralysis)|| Discontinue VELCADE|
Administration Precautions: VELCADE is an antineoplastic. Caution should be used during handling and preparation including careful dose calculation to prevent overdose. The drug quantity contained in one vial (3.5 mg) may exceed the usual single dose required. Proper aseptic technique should be used. Use of gloves and other protective clothing to prevent skin contact is recommended. In clinical trials, local skin irritation was reported in 5% of patients, but extravasation of VELCADE was not associated with tissue damage.
Reconstitution/Preparation for Intravenous Administration: Prior to use, the contents of each vial must be reconstituted with 3.5 mL of normal (0.9%) saline, Sodium Chloride Injection, USP. The reconstituted product should be a clear and colorless solution.
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. When reconstituted as directed, VELCADE may be stored at 25°C (77°F). Reconstituted VELCADE should be administered within 8 hours of preparation. 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.