Active Ingredient: Bortezomib
Bortezomib as monotherapy or in combination with pegylated liposomal doxorubicin or dexamethasone is indicated for the treatment of adult patients with progressive multiple myeloma who have received at least 1 prior therapy and who have already undergone or are unsuitable for
haematopoietic stem cell transplantation. Bortezomib in combination with melphalan and prednisone is indicated for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for high-dose chemotherapy with haematopoietic stem cell transplantation.
Bortezomib in combination with dexamethasone, or with dexamethasone and thalidomide, is indicated for the induction treatment of adult patients with previously untreated multiple myeloma who are eligible for high-dose chemotherapy with haematopoietic stem cell transplantation.
For this indication, competent medicine agencies globally authorize below treatments:
Intravenous
1.3 - 1.3 mg per m² of body surface area (BSA)
From 1.3 To 1.3 mg per m² of body surface area (BSA) once every 3 day(s)
bortezomib 3.5 mg powder for solution for injection is administered via intravenous injection at the recommended dose of 1.3 mg/m² body surface area twice weekly for two weeks on days 1, 4, 8, and 11 in a 21-day treatment cycle. This 3-week period is considered a treatment cycle. It is recommended that patients receive 2 cycles of bortezomib following a confirmation of a complete response. It is also recommended that responding patients who do not achieve a complete remission receive a total of 8 cycles of bortezomib therapy. At least 72 hours should elapse between consecutive doses of bortezomib.
Bortezomib treatment must be withheld at the onset of any Grade 3 non-haematological or any Grade 4 haematological toxicities, excluding neuropathy as discussed below. Once the symptoms of the toxicity have resolved, bortezomib treatment may be re-initiated at a 25% reduced dose (1.3 mg/m² reduced to 1.0 mg/m²; 1.0 mg/m² reduced to 0.7 mg/m²). If the toxicity is not resolved or if it recurs at the lowest dose, discontinuation of bortezomib must be considered unless the benefit of treatment clearly outweighs the risk.
Patients who experience bortezomib-related neuropathic pain and/or peripheral neuropathy are to be managed as presented in the following table. Patients with pre-existing severe neuropathy may be treated with bortezomib only after careful risk/benefit assessment.
Recommended* posology modifications for bortezomib-related neuropathy:
| Severity of neuropathy | Posology modification |
|---|---|
| Grade 1 (asymptomatic; loss of deep tendon reflexes or paresthesia) with no pain or loss of function | None |
| Grade 1 with pain or Grade 2 (moderate symptoms; limiting instrumental Activities of Daily Living (ADL)**) | Reduce bortezomib to 1.0 mg/m² or Change bortezomib treatment schedule to 1.3 mg/m² once per week |
| Grade 2 with pain or Grade 3 (severe symptoms; limiting self care ADL***) | Withhold bortezomib treatment until symptoms of toxicity have resolved. When toxicity resolves re-initiate bortezomib treatment and reduce dose to 0.7 mg/m² once per week. |
| Grade 4 (life-threatening consequences; urgent intervention indicated) and/or severe autonomic neuropathy | Discontinue bortezomib |
* Based on posology modifications in Phase II and III multiple myeloma studies and post-marketing experience. Grading based on NCI Common Toxicity Criteria CTCAE v 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 medicinal products, and not bedridden.
Bortezomib 3.5 mg powder for solution for injection is administered via intravenous injection at the recommended dose of 1.3 mg/m² body surface area twice weekly for two weeks on days 1, 4, 8, and 11 in a 21-day treatment cycle. This 3-week period is considered a treatment cycle. At least 72 hours should elapse between consecutive doses of bortezomib. Pegylated liposomal doxorubicin is administered at 30 mg/m² on day 4 of the bortezomib treatment cycle as a 1 hour intravenous infusion administered after the bortezomib injection.
Up to 8 cycles of this combination therapy can be administered as long as patients have not progressed and tolerate treatment. Patients achieving a complete response can continue treatment for at least 2 cycles after the first evidence of complete response, even if this requires treatment for more than 8 cycles. Patients whose levels of paraprotein continue to decrease after 8 cycles can also continue for as long as treatment is tolerated and they continue to respond.
Subcutaneous
1.3 - 1.3 mg per m² of body surface area (BSA)
From 1.3 To 1.3 mg per m² of body surface area (BSA) once every 3 day(s)
bortezomib 3.5 mg powder for solution for injection is administered via intravenous or subcutaneous injection at the recommended dose of 1.3 mg/m² body surface area twice weekly for two weeks on days 1, 4, 8, and 11 in a 21-day treatment cycle. This 3-week period is considered a treatment cycle. It is recommended that patients receive 2 cycles of bortezomib following a confirmation of a complete response. It is also recommended that responding patients who do not achieve a complete remission receive a total of 8 cycles of bortezomib therapy. At least 72 hours should elapse between consecutive doses of bortezomib.
Bortezomib treatment must be withheld at the onset of any Grade 3 non-haematological or any Grade 4 haematological toxicities, excluding neuropathy as discussed below. Once the symptoms of the toxicity have resolved, bortezomib treatment may be re-initiated at a 25% reduced dose (1.3 mg/m² reduced to 1.0 mg/m²; 1.0 mg/m² reduced to 0.7 mg/m²). If the toxicity is not resolved or if it recurs at the lowest dose, discontinuation of bortezomib must be considered unless the benefit of treatment clearly outweighs the risk.
Patients who experience bortezomib-related neuropathic pain and/or peripheral neuropathy are to be managed as presented in the following table. Patients with pre-existing severe neuropathy may be treated with bortezomib only after careful risk/benefit assessment.
Recommended* posology modifications for bortezomib-related neuropathy:
| Severity of neuropathy | Posology modification |
|---|---|
| Grade 1 (asymptomatic; loss of deep tendon reflexes or paresthesia) with no pain or loss of function | None |
| Grade 1 with pain or Grade 2 (moderate symptoms; limiting instrumental Activities of Daily Living (ADL)**) | Reduce bortezomib to 1.0 mg/m² or Change bortezomib treatment schedule to 1.3 mg/m² once per week |
| Grade 2 with pain or Grade 3 (severe symptoms; limiting self care ADL***) | Withhold bortezomib treatment until symptoms of toxicity have resolved. When toxicity resolves re-initiate bortezomib treatment and reduce dose to 0.7 mg/m² once per week. |
| Grade 4 (life-threatening consequences; urgent intervention indicated) and/or severe autonomic neuropathy | Discontinue bortezomib |
* Based on posology modifications in Phase II and III multiple myeloma studies and post-marketing experience. Grading based on NCI Common Toxicity Criteria CTCAE v 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 medicinal products, and not bedridden.
Bortezomib 3.5 mg powder for solution for injection is administered via intravenous or subcutaneous injection at the recommended dose of 1.3 mg/m² body surface area twice weekly for two weeks on days 1, 4, 8, and 11 in a 21-day treatment cycle. This 3-week period is considered a treatment cycle. At least 72 hours should elapse between consecutive doses of bortezomib. Pegylated liposomal doxorubicin is administered at 30 mg/m² on day 4 of the bortezomib treatment cycle as a 1 hour intravenous infusion administered after the bortezomib injection.
Up to 8 cycles of this combination therapy can be administered as long as patients have not progressed and tolerate treatment. Patients achieving a complete response can continue treatment for at least 2 cycles after the first evidence of complete response, even if this requires treatment for more than 8 cycles. Patients whose levels of paraprotein continue to decrease after 8 cycles can also continue for as long as treatment is tolerated and they continue to respond.
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