Velcade

Bortezomib

Multiple myeloma. Mantle cell lymphoma.

IV/SC Recommended starting dose: 1.3 mg/m², may be administered IV at 1 mg/mL for 3-5 sec bolus inj or SC at 2.5 mg/mL. Previously untreated multiple myeloma In combination w/ oral melphalan & prednisone for 9, 6-wk treatment cycles. Cycles 1-4, Velcade twice wkly (Days 1, 4, 8, 11, 22, 25, 29 & 32). Cycles 5-9, Velcade once wkly (Days 1, 8, 22 & 29). At least 72 hr should elapse between consecutive doses of Velcade. Previously untreated multiple myeloma eligible for haematopoietic stem cell transplantation (induction therapy) W/ dexamethasone IV/SC 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in 21-day treatment cycle. Dexamethasone 40 mg orally on days 1, 2, 3, 4, 8, 9, 10 & 11. 4-treatment cycles are administered. W/ dexamethasone & thalidomide IV/SC 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in 28-day treatment cycle. Dexamethasone 40 mg orally on days 1, 2, 3, 4, 8, 9, 10 & 11. Thalidomide 50 mg daily orally on days 1-14 & if tolerated, increase dose to 100 mg on days 15-28, thereafter may be further increased to 200 mg daily from cycle 2. 4-treatment cycles are administered. Previously untreated mantle cell lymphoma 1.3mg/m² IV in combination w/ IV rituximab, cyclophosphamide, doxorubicin & oral prednisone for 6 3-wk treatment cycles. Velcade is administered 1st followed by rituximab. Velcade is administered twice wkly for 2 wk (days 1, 4, 8 & 11) followed by 10-day rest period on Days 12-21. Dose modification might be required if hematological toxicity &/or peripheral neuropathy occurs.

Hypersensitivity to bortezomib, boron or mannitol.

Not for intrathecal administration. Peripheral neuropathy, to change dose schedule or route of administration to SC. Hypotension. Cardiac disorders, monitor patients w/ risk factors/existing heart disease. Hepatic events. Pulmonary disorders. Lab tests, monitor CBC frequently. Thrombocytopenia/neutropenia, monitor platelet count prior to each dose. GI adverse events, fluid & electrolyte replacement should be administered to prevent dehydration, advise patient regarding appropriate measures to avoid dehydration. Tumour lysis syndrome, monitor closely. Hepatic impairment, exposure is increased, to reduce starting doses & monitor closely for toxicities. Posterior reversible encephalopathy syndrome, discontinue if develop. May affect ability to drive & use machines. Renal & hepatic impairment. Women of childbearing potential should use effective contraception during treatment. Avoid use during pregnancy & lactation.

Thrombocytopenia, anemia, neutropenia, leucopenia, lymphopenia, pancytopenia, febrile neutropenia; arrhythmias, tachycardia, atrial fibrillation, palpitations, acute development or exacerbation of cardiac failure including CHF, pulmonary edema, cardiogenic shock, new onset of decreased left ventricular ejection fraction, atrial flutter, bradycardia; hearing impairment; blurred vision, conjunctival infection & irritation; constipation, diarrhea, nausea, vomiting, GI & abdominal pain, dyspepsia, pharyngolaryngeal pain, gastroesophageal reflux, eructation, abdominal distension, stomatitis & mouth ulceration, dysphagia, GI & rectal hemorrhage, tongue ulceration, retching, upper GI hemorrhage, hematemesis, oral mucosal petechiae, paralytic ileus; asthenic conditions, weakness, fatigue, lethargy, malaise, pyrexia, rigors, lower limb oedema, neuralgia, chest pain, inj site pain & irritation, inj site phlebitis; hyperbilirubinemia, abnormal LFTs, hepatitis; drug hypersensitivity; nasopharyngitis, upper & lower resp tract & lung infections, pneumonia, herpes zoster & simplex, bronchitis, post-herpetic neuralgia, sinusitis, pharyngitis, oral candidiasis, UTI, catheter-related infection, sepsis & bacteremia, gastroenteritis; catheter-related complications; increased ALT, AST, alkaline phosphatase, GGT; decreased appetite & anorexia, dehydration, hyper- & hypoglycemia, hyponatremia, tumour lysis syndrome; limb pain, myalgia, arthralgia; peripheral neuropathy; paresthesia & dysesthesia, dizziness, headache, dysgeusia, polyneuropathy, syncope, convulsions, loss of consciousness, ageusia; anxiety; renal impairment & failure, difficulty in micturition, hematuria; epistaxis, cough, dyspnea, exertional dyspnea, pleural effusion, rhinorrhoea, hemoptysis; skin rash, urticaria; hypotension, orthostatic/postural hypotension, petechiae, cerebral hemorrhage.

Increased mean AUC w/ potent CYP3A4 inhibitors eg, ketoconazole, ritonavir. Reduced mean AUC w/ potent CYP3A4 inducers eg, rifampicin & other potent CYP3A4 inducers eg, carbamazepine, phenytoin, phenobarb, St. John's wort. Close monitoring of blood glucose levels w/ oral antidiabetic agents & dose adjustments of antidiabetics. Concomitant use w/ medications associated w/ peripheral neuropathy (eg, amiodarone, antivirals, INH, nitrofurantoin or statins) or w/ decreased BP.

Targeted Cancer Therapy

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

B