Zomod 1/Zomod 3.5

Monotherapy or in combination w/ pegylated lipos doxorubicin or dexamethasone for treatment of progressive multiple myeloma in adults who have received at least 1 prior therapy & who have already undergone or are unsuitable for hematopoietic stem cell transplantation. In combination w/ melphalan & prednisone for treatment of previously untreated multiple myeloma in adults who are not eligible for high-dose chemotherapy w/ hematopoietic stem cell transplantation. In combination w/ dexamethasone or w/ dexamethasone & thalidomide for induction treatment of adults w/ previously untreated multiple myeloma who are eligible for high-dose chemotherapy w/ hematopoietic stem cell transplantation. Zomod 1 In combination w/ rituximab, cyclophosphamide, doxorubicin & prednisone for treatment of adults w/ previously untreated mantle cell lymphoma who are unsuitable for hematopoietic stem cell transplantation.

Zomod 1 IV/Zomod 3.5 IV/SC Adult Monotherapy for treatment of progressive multiple myeloma (patient who received at least 1 prior therapy) 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle. Patient is recommended to receive 2 cycles following confirmation of complete response; a total of 8 cycles in patients who do not achieve complete remission. At least 72 hr should elapse between consecutive doses. Combination therapy w/ pegylated lipos doxorubicin for treatment of progressive multiple myeloma (patient who received at least 1 prior therapy) 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle + pegylated lipos doxorubicin at 30 mg/m² on day 4 of bortezomib treatment cycle as 1-hr IV infusion after bortezomib inj. Up to 8 cycles can be administered if patient has not progressed & tolerated treatment. At least 72 hr should elapse between consecutive bortezomib doses. Patient achieving complete response can continue treatment for at least 2 cycles after 1st evidence of complete response. Combination therapy w/ dexamethasone for treatment of progressive multiple myeloma (patient who received at least 1 prior therapy) 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle + dexamethasone 20 mg PO on days 1, 2, 4, 5, 8, 9, 11 & 12 of bortezomib treatment cycle. At least 72 hr should elapse between consecutive bortezomib doses. Patient achieving response or stable disease after 4 cycles of combination therapy can continue to receive the same combination for max 4 additional cycles. Combination therapy w/ melphalan & prednisone for previously untreated multiple myeloma in patient not eligible for hematopoietic stem cell transplantation 1.3 mg/m² for 6 wk. Cycles 1-4: Administer bortezomib twice wkly on days 1, 4, 8, 11, 22, 25, 29 & 32. Cycles 5-9: Administer bortezomib once wkly on days 1, 8, 22 & 29. At least 72 hr should elapse between consecutive bortezomib doses. Melphalan & prednisone should both be given PO on days 1, 2, 3 & 4 of the 1st wk of each bortezomib treatment cycle. Combination therapy w/ dexamethasone for induction therapy in previously untreated multiple myeloma patient eligible for haematopoietic stem cell transplantation 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8, & 11 in a 21-day treatment cycle + dexamethasone 40 mg PO on days 1, 2, 3, 4, 8, 9, 10 & 11 of bortezomib treatment cycle. Administer 4 treatment cycles. At least 72 hr should elapse between consecutive bortezomib doses. Combination therapy w/ dexamethasone & thalidomide for induction therapy in previously untreated multiple myeloma patient eligible for haematopoietic stem cell transplantation 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 28-day treatment cycle + dexamethasone 40 mg PO on days 1, 2, 3, 4, 8, 9, 10 & 11 of bortezomib treatment cycle, & thalidomide 50 mg daily PO on days 1-14, may increase to 100 mg on days 15-28 & to 200 mg daily from cycle 2 if dose is well tolerated. Administer 4 treatment cycles, & 2 additional cycles in patients w/ at least partial response. Combination therapy w/ rituximab, cyclophosphamide, doxorubicin & prednisone for treatment of previously untreated mantle cell lymphoma 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. Administer on day 1 of each 3-wk treatment cycle as IV infusions: Rituximab at 375 mg/m², cyclophosphamide at 750 mg/m² & doxorubicin at 50 mg/m². Prednisone is administered at 100 mg/m² PO on days 1, 2, 3, 4 & 5 of each bortezomib treatment cycle. 6 bortezomib cycles are recommended; 2 additional bortezomib cycles may be given for patients w/ response 1st documented at cycle 6. At least 72 hr should elapse between consecutive bortezomib doses. Patient w/ moderate or severe hepatic impairment Start w/ 0.7 mg/m² per inj during 1st treatment cycle, may be increased to 1 mg/m² or reduced to 0.5 mg/m² based on patient tolerability.

Hypersensitivity to bortezomib or boron. Acute diffuse infiltrative pulmonary & pericardial disease.

Do not administer intrathecally. Risk of GI toxicity including nausea, diarrhoea, vomiting & constipation; hematological toxicities (thrombocytopenia, neutropenia & anaemia); peripheral neuropathy, which is predominantly sensory; orthostatic/postural hypotension; HZV or HBV reactivation; complications of tumour lysis syndrome. Reports of GI & intracerebral haemorrhage; seizures in patients w/o previous history of seizure or epilepsy; acute development or exacerbation of CHF &/or new onset of decreased left ventricular ejection fraction; isolated cases of QT interval prolongation; acute diffuse infiltrative pulmonary disease (rare); hepatic failure (rare) w/ concomitant medicinal products & in patients w/ serious underlying medical conditions. Closely monitor patients who experience constipation. Monitor platelet counts prior to each dose of bortezomib; w/hold treatment when platelet count is <25,000/microliter or, in case of combination w/ melphalan & prednisone, when platelet count is ≤30,000/microliter. Frequently monitor CBC w/ differential including platelet counts throughout treatment. Perform HBV screening in patients at risk of HBV infection before treatment initiation. Discontinue treatment in case of progressive multifocal leukoencephalopathy; posterior reversible encephalopathy syndrome; potentially immunocomplex-mediated reactions eg, serum-sickness-type reaction, polyarthritis w/ rash & proliferative glomerulonephritis. Concomitant use w/ potent CYP3A4 inhibitors; CYP3A4 or CYP2C19 substrates; oral hypoglycemics. Moderate influence on the ability to drive & use machines. Closely monitor patients w/ renal impairment & patients w/ moderate or severe hepatic impairment. Male & female patients of childbearing potential must use effective contraceptive measures during & for 3 mth following treatment. Should not be used during pregnancy unless clinical condition of the woman requires treatment w/ bortezomib. Discontinue breast-feeding during treatment. Safety & efficacy in childn <18 yr have not been established.

Thrombocytopenia, neutropenia, anaemia; decreased appetite; peripheral sensory neuropathy, dysaesthesia, neuralgia; nausea & vomiting symptoms, diarrhoea, constipation; pyrexia, fatigue, asthenia. Herpes zoster (including disseminated & ophth), herpes simplex, fungal infection; hypokalaemia, hyponatraemia, abnormal blood glucose; sleep disorders & disturbances; motor neuropathy, loss of consciousness (including syncope), dizziness, dysgeusia; abnormal vision; hypotension, orthostatic hypotension, HTN; dyspnoea, upper/lower resp tract infection, cough; GI haemorrhage (including mucosal), dyspepsia, abdominal distension, oropharyngeal pain, abdominal pain (including GI & splenic pain), oral disorder; rash, pruritus; muscle spasms, pain in extremity; oedema (including peripheral), chills, malaise; decreased wt. Multiple myeloma: Neuropathies; musculoskeletal pain. Pneumonia; leukopenia, lymphopenia; dehydration, hypocalcaemia, enzyme abnormality; mood disorders & disturbances, anxiety disorder; lethargy, headache; eye swelling, conjunctivitis; vertigo; epistaxis; stomatitis, flatulence; hepatic enzyme abnormality; erythema, dry skin; muscular weakness; renal impairment; pain. Mantle cell lymphoma: Pneumonia; febrile neutropenia, leukopenia, lymphopenia; stomatitis; hair disorder. Sepsis (including septic shock), herpes virus infection, bacterial infections; hypersensitivity; DM, fluid retention; neuropathies, encephalopathy, peripheral sensorimotor neuropathy, autonomic neuropathy; dysacusis (including tinnitus); cardiac fibrillation (including atrial), arrhythmia, cardiac failure (including left & right ventricular), myocardial ischaemia, ventricular dysfunction; hiccups; gastritis, oral ulceration, abdominal discomfort, dysphagia, GI inflammation; hepatotoxicity (including liver disorder); dermatitis; musculoskeletal pain; UTI; inj site reaction; hyperbilirubinaemia, abnormal protein analyses, increased wt.

Increased AUC w/ potent CYP3A4 inhibitors (eg, ketoconazole, ritonavir). Reduced AUC & efficacy w/ strong CYP3A4 inducers (eg, rifampicin, carbamazepine, phenytoin, phenobarb & St. John's wort). Reports of hypoglycemia & hyperglycemia in diabetic patients taking oral hypoglycaemics.

Targeted Cancer Therapy

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

Rx