Borviz

Bortezomib

Monotherapy or in combination w/ pegylated lipos doxorubicin or dexamethasone in adults w/ progressive multiple myeloma who have received at least 1 prior therapy & undergone or are unsuitable for haematopoietic stem cell transplantation. In combination w/ melphalan & prednisone in adults w/ previously untreated multiple myeloma who are ineligible for high-dose chemotherapy w/ haematopoietic stem cell transplantation. In combination w/ dexamethasone, or dexamethasone & thalidomide in adults w/ previously untreated multiple myeloma who are eligible for high-dose chemotherapy w/ haematopoietic stem cell transplantation. In combination w/ rituximab, cyclophosphamide, doxorubicin & prednisone in adults w/ previously untreated mantle cell lymphoma who are unsuitable for haematopoietic stem cell transplantation.

IV/SC 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in 21-day treatment cycle in at least 72-hr interval. Progressive multiple myeloma as monotherapy 2 cycles following confirmation on complete response. Total of 8 cycles for patients who do not achieve complete remission. Dose adjustment: Reduce dose from 1.3 mg/m² to 1 mg/m² or from 1 mg/m² to 0.7 mg/m². Combination w/ pegylated lipos doxorubicin Bortezomib + pegylated lipos doxorubicin 30 mg/m² on day 4 as 1 hr IV infusion after bortezomib inj. Up to 8 cycles for patients who do not progress or tolerate treatment. Continue treatment for at least 2 cycles after 1st evidence of complete response. Combination w/ dexamethasone Bortezomib + dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11 & 12. Max: Additional 4 cycles in patients achieving response or stable disease after 4 cycles. Previously untreated multiple myeloma patients ineligible for haematopoietic stem cell transplantation In combination w/ melphalan & prednisone Cycles 1-4: 1.3 mg/m² twice wkly on days 1, 4, 8, 11, 22, 25, 29 & 32 for at least 72-hr interval in 6-wk period. Cycles 5-9: 1.3 mg/m² once wkly on days 1, 8, 22 & 29 for at least 72-hr interval in 6-wk period. Administer melphalan 9 mg/m² & prednisone 60 mg/m² orally on days 1-4 of the 1st wk of each of the 9 treatment cycles. Previously untreated multiple myeloma patients eligible for haematopoietic stem cell transplantation In combination w/ dexamethasone Bortezomib + dexamethasone 40 mg orally on days 1-4 & 8-11 for 4 cycles; in combination w/ dexamethasone & thalidomide Bortezomib + dexamethasone 40 mg orally on days 1-4 & 8-11 for 4 cycles & thalidomide 50 mg orally on days 1-14.  May be increased to 100 mg on days 15-28 & further increased to 200 mg daily from cycle 2 thereafter for 4 cycles. May receive 2 additional cycles for patients w/ at least partial response. Previously untreated mantle cell lymphoma in combination w/ rituximab, cyclophosphamide, doxorubicin & prednisone 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 followed by 10-day rest period on days 12-21 in 3-wk cycle for at least 72-hr interval for 6 cycles. Additional 2 cycles for patients w/ response 1st documented at cycle 6. Administer rituximab 375 mg/m², cyclophosphamide 750 mg/m² & doxorubicin 50 mg/m² as IV infusion on day 1 of each 3-wk treatment cycle + prednisone 100 mg/m² orally on days 1-5 of each treatment cycle. Moderate or severe hepatic impairment Initially 0.7 mg/m² on 1st treatment cycle, subsequently increase dose to 1 mg/m² or further reduce dose to 0.5 mg/m².

Hypersensitivity to bortezomib or boron. Acute diffuse infiltrative pulmonary & pericardial disease. Concomitant use w/ other medicinal products.

Not to be administered intrathecally. Discontinue if progressive multifocal leukoencephalopathy (PML) is diagnosed; posterior reversible encephalopathy syndrome develops; serious potentially immunocomplex-mediated reactions occur. GI & haematological toxicities; GI & intracerebral haemorrhage; HZV reactivation; QT-interval prolongation; pulmonary disorders; severe motor neuropathy w/ or w/o sensory peripheral neuropathy. Withhold treatment when platelet count is <25,000/μL or ≤30,000/μL in combination w/ melphalan & prednisone. Monitor patients who experience constipation; for signs & symptoms of infection; risk factors for or existing heart disease; for any new or worsening neurological symptoms or signs suggestive of PML; symptoms of neuropathy. Patients w/ risk factors for seizures; history of syncope receiving medicinal products associated w/ hypotension or who are dehydrated due to recurrent diarrhea or vomiting; at risk of tumour lysis syndrome w/ high tumour burden prior to treatment; patients receiving oral hypoglycemics. Monitor platelet counts prior to each dose; CBC throughout treatment. Consider prophylactic use of granulocyte colony stimulating factors in case of repeated delays of administration; antiviral prophylaxis. Early & regularly monitor for symptoms of treatment-emergent neuropathy w/ neurological evaluation in combination w/ medicinal products associated w/ neuropathy eg, thalidomide. Perform HBV screening prior to treatment in combination w/ rituximab in patients at risk of HBV infection. Concomitant use w/ thalidomide. Not recommended in concomitant use w/ high-dose cytarabine. Combination w/ potent CYP3A4 inhibitors; CYP3A4 or CYP2C19 substrates. May affect ability to drive & use machines. Renal impairment. Moderate or severe hepatic impairment & hepatic reactions. Males & females of childbearing potential must use effective contraception during & for 3 mth following treatment. Not to be used during pregnancy. Discontinue lactation during treatment. Childn <18 yr.

Nausea, diarrhoea, constipation, vomiting, fatigue, pyrexia, thrombocytopenia, anaemia, neutropenia, peripheral neuropathy (including sensory), headache, paraesthesia, decreased appetite, dyspnoea, rash, herpes zoster & myalgia.

Increased AUC w/ potent CYP3A4 inhibitor eg, ketoconazole, ritonavir. Reduced AUC w/ potent CYP3A4 inducer eg, rifampicin. Concomitant use w/ strong CYP3A4 inducers eg, rifampicin, carbamazepine, phenytoin, phenobarb & St. John's wort; oral hypoglycemics.

Targeted Cancer Therapy

L01XG01 - bortezomib ; Belongs to the class of proteasome inhibitors. Used in the treatment of cancer.

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