Velcade Dosage/Direction for Use

VELCADE may be administered: Intravenously (at a concentration of 1 mg/mL) as a 3 to 5 second bolus injection or; Subcutaneously (at a concentration of 2.5 mg/mL).
Because each route of administration has a different reconstituted concentration, caution should be used when calculating the volume to be administered.
At least 72 hours should elapse between consecutive doses of VELCADE.
VELCADE IS FOR INTRAVENOUS OR SUBCUTANEOUS USE ONLY. Intrathecal administration has resulted in death.
VELCADE retreatment may be considered for multiple myeloma patients who had previously responded to treatment with VELCADE (see discussion as follows, and Pharmacology: Pharmacodynamics under Actions).
Monotherapy: Relapsed Multiple Myeloma and Relapsed Mantle Cell Lymphoma: Recommended Dosage: The recommended dose of VELCADE is 1.3 mg/m²/dose 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, for relapse multiple myeloma, on 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). At least 72 hours should elapse between consecutive doses of VELCADE.
Dose Modification and Reinitiation 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 as follows (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).
The following table contains the recommended dose modification for the management of patients who experience VELCADE-related neuropathic pain and/or peripheral sensory neuropathy (see Table 14). Severe autonomic neuropathy resulting in treatment interruption or discontinuation has been reported. Patients with pre-existing severe neuropathy should be treated with VELCADE only after careful risk/benefit assessment. (See Table 14.)

Click on icon to see table/diagram/image

Administration: VELCADE is administered intravenously or subcutaneously. When administered intravenously, VELCADE is administered as a 3-5 second bolus intravenous injection through a peripheral or central intravenous catheter followed by a flush with 0.9% sodium chloride solution for injection. For subcutaneous administration, the reconstituted solution is injected into the thighs (right or left) or abdomen (right or left). Injection sites should be rotated for successive injections.
If local injection site reactions occur following VELCADE injection subcutaneously, a less concentrated VELCADE solution (1 mg/mL instead of 2.5 mg/mL) may be administered subcutaneously, or changed to IV injection.
Combination Therapy: Previously Untreated Multiple Myeloma-Patients who are Not Eligible for Stem Cell Transplantation: Recommended Dosage in Combination with Melphalan and Prednisone: VELCADE (bortezomib) for Injection is administered in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles as shown in Table 15. 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). (See Table 15.)

Click on icon to see table/diagram/image

Dose Management Guidelines for Combination Therapy with Melphalan and Prednisone: Dose modification and re-initiation of therapy when VELCADE is administered in combination with melphalan and prednisone.
Prior to initiating a new cycle of therapy: Platelet count should be ≥ 70 x 10⁹/l and the ANC should be ≥ 1.0 x 10⁹/l; Non-hematological toxicities should have resolved to Grade 1 or baseline. (See Table 16.)

Click on icon to see table/diagram/image

For additional information concerning melphalan and prednisone, see manufacturer's prescribing information.
Previously Untreated Multiple Myeloma-Patients who are Eligible for Stem Cell Transplantation: Recommended Dosage: The recommended starting dose of VELCADE in combination with other medicinal products used for the treatment of multiple myeloma is 1.3 mg/m² to be administered twice weekly on Days 1, 4, 8, and 11, followed by a rest period of 10-18 days, which is considered a treatment cycle. Three to 6 cycles should be administered. At least 72 hours should elapse between consecutive doses of VELCADE.
For VELCADE dosage adjustments for transplant eligible patients follow dose modification guidelines described previously under monotherapy (Table 14).
For dosing instructions for other medicinal products combined with VELCADE, see manufacturer's prescribing information.
Relapsed Multiple Myeloma: Recommended Dosage in Combination with Pegylated Liposomal-Doxorubicin: For VELCADE dosage and dose modifications, see previous discussion on Monotherapy.
Pegylated liposomal doxorubicin is administered at 30 mg/m² on day 4 of the VELCADE 3 week regimen as a 1 hour intravenous infusion administered after the VELCADE injection.
For additional information concerning pegylated liposomal-doxorubicin, see manufacturer's prescribing information.
Recommended Dosage in Combination with Dexamethasone: For VELCADE dosage and dose modifications, see previous discussion on Monotherapy.
Dexamethasone is administered orally at 20 mg on the day of, and the day after, VELCADE administration.
For additional information concerning dexamethasone, see manufacturer's prescribing information.
Retreatment for Multiple Myeloma: Patients who have previously responded to treatment with VELCADE (either alone or in combination) and who have relapsed should be started on retreatment at the last tolerated dose. Refer to Monotherapy for dosing schedule.
Previously Untreated Mantle Cell Lymphoma: Recommended Dosage in Combination with Rituximab, Cyclophosphamide, Doxorubicin and Prednisone: For VELCADE dosage, see Monotherapy. Six VELCADE cycles are administered. For patients with a response first documented at Cycle 6, two additional VELCADE cycles are recommended.
The following medicinal products are administered on Day 1 of each VELCADE 3 week treatment cycle as intravenous infusions: rituximab at 375 mg/m², cyclophosphamide at 750 mg/m², and doxorubicin at 50 mg/m². Prednisone is administered orally at 100 mg/m² on Days 1, 2, 3, 4 and 5 of each treatment cycle.
Dose Adjustments during Treatment for Patients with Previously Untreated Mantle Cell Lymphoma: Prior to the first day of each cycle (other than Cycle 1): Platelet count should be ≥100 x 10⁹/L and absolute neutrophil count (ANC) should be ≥1.5 x 10⁹/L; Hemoglobin should be ≥8 g/dL (≥4.96 mmol/L); Non-hematologic toxicity should have recovered to Grade 1 or baseline.
VELCADE treatment must be withheld at the onset of any Grade 3 non hematological or Grade 3 hematological toxicities, excluding neuropathy (see Precautions). For dose adjustments, see Table 17.

Click on icon to see table/diagram/image

For dosing instructions for rituximab, cyclophosphamide, doxorubicin, or prednisone, see manufacturer's prescribing information.
Special Populations: Patients with Renal Impairment: The pharmacokinetics of VELCADE are not influenced by the degree of renal impairment. Therefore, dosing adjustments of VELCADE are not necessary for patients with renal insufficiency. Since dialysis may reduce VELCADE concentrations, the drug should be administered after the dialysis procedure (see Pharmacology: Pharmacokinetics under Actions).
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. For patients with moderate or severe hepatic impairment, see Table 18 (see also Pharmacology: Pharmacokinetics under Actions).

Click on icon to see table/diagram/image