Bortezomib Kabi Dosage/Direction for Use

Bortezomib Kabi 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 Bortezomib Kabi.
Bortezomib retreatment may be considered for multiple myeloma patients who had previously responded to treatment with Bortezomib (see as follows and Pharmacology: Pharmacodynamics under Actions).
Monotherapy: Relapsed Multiple Myeloma and Relapsed Mantle Cell Lymphoma: Recommended Dosage: The recommended dose of BORTEZOMIB 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, BORTEZOMIB may be administered on the standard schedule or, for relapsed multiple myeloma, 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). At least 72 hours should elapse between consecutive doses of BORTEZOMIB.
Dose Modification and Reinitiation of Therapy: BORTEZOMIB 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, BORTEZOMIB 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 BORTEZOMIB-related neuropathic pain and/or peripheral sensory neuropathy (Table 15). Severe autonomic neuropathy resulting in treatment interruption or discontinuation has been reported. Patients with pre-existing severe neuropathy should be treated with BORTEZOMIB only after careful risk/benefit assessment. (See Table 15.)

Click on icon to see table/diagram/image

Administration: BORTEZOMIB is administered intravenously or subcutaneously. When administered intravenously, BORTEZOMIB 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 BORTEZOMIB injection subcutaneously, a less concentrated BORTEZOMIB 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: BORTEZOMIB (bortezomib) for Injection is administered in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles as shown in Table 16. In Cycles 1-4, BORTEZOMIB is administered twice weekly (Days 1, 4, 8, 11, 22, 25, 29 and 32). In Cycles 5-9, BORTEZOMIB is administered once weekly (Days 1, 8, 22 and 29). (See Table 16.)

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 BORTEZOMIB is administered in combination with melphalan and prednisone.
Prior to initiating a new cycle of therapy: Platelet counts should be ≥ 70 x 10⁹/l and the absolute neutrophils count should be ≥ 1.0 x 10⁹/l; Non-haematological toxicities should have resolved to Grade 1 or baseline. (See Table 17.)

Click on icon to see table/diagram/image

For additional information concerning melphalan and prednisone, see the corresponding Summary of Product Characteristics.
Previously Untreated Multiple Myeloma - Patients who are Eligible for Stem Cell Transplantation: Recommended Dosage: The recommended starting dose of BORTEZOMIB 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 BORTEZOMIB.
For BORTEZOMIB dosage adjustments for transplant eligible patients follow dose modification guidelines described under monotherapy (Table 15) as previously mentioned.
For dosing instructions for other medicinal products combined with BORTEZOMIB, see manufacturer's prescribing information.
Relapsed Multiple Myeloma: Recommended Dosage in Combination with Pegylated Liposomal-Doxorubicin: For BORTEZOMIB dosage and dose modifications, see Monotherapy as previously mentioned.
Pegylated liposomal doxorubicin is administered at 30 mg/m² on day 4 of the BORTEZOMIB 3 week regimen as a 1 hour intravenous infusion administered after the BORTEZOMIB injection.
For additional information concerning pegylated liposomal-doxorubicin, see manufacturer's prescribing information.
Recommended Dosage in Combination with Dexamethasone: For BORTEZOMIB dosage and dose modifications, see Monotherapy as previously mentioned.
Dexamethasone is administered orally at 20 mg on the day of, and the day after, BORTEZOMIB administration.
For additional information concerning dexamethasone, see manufacturer's prescribing information.
Retreatment for Multiple Myeloma: Patients who have previously responded to treatment with BORTEZOMIB (either alone or in combination) and who have relapsed should be started on retreatment at the last tolerated dose. Refer to Monotherapy as previously mentioned for dosing schedule.
Previously Untreated Mantle Cell Lymphoma: Recommended Dosage in Combination with Rituximab, Cyclophosphamide, Doxorubicin and Prednisone: For BORTEZOMIB dosage, see Monotherapy as previously mentioned. Six BORTEZOMIB cycles are administered.
For patients with a response first documented at Cycle 6, two additional BORTEZOMIB cycles are recommended.
The following medicinal products are administered on Day 1 of each BORTEZOMIB 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.
BORTEZOMIB treatment must be withheld at the onset of any Grade 3 non-hematological or Grade 3 hematological toxicities, excluding neuropathy (see also Precautions).
For dose adjustments, see Table 18 as follows.

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 BORTEZOMIB are not influenced by the degree of renal impairment. Therefore, dosing adjustments of BORTEZOMIB are not necessary for patients with renal insufficiency. Since dialysis may reduce BORTEZOMIB concentrations, the drug should be administered after the dialysis procedure (see Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: Patients with mild hepatic impairment do not require a dose adjustment and should be treated per the recommended dose. Patients with moderate or severe hepatic impairment see table 19 (also, see Pharmacology: Pharmacokinetics under Actions). (See Table 19.)

Click on icon to see table/diagram/image

Method of Administration: Bortezomib 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 BORTEZOMIB.
BORTEZOMIB IS FOR INTRAVENOUS OR SUBCUTANEOUS USE ONLY. Intrathecal administration has resulted in death.