Indications: Mantle cell lymphoma: Treatment of mantle cell lymphoma in patients who have received at least 1 prior therapy Multiple myeloma: Treatment of multiple myeloma.

Cautions: cardiovascular disease; pulmonary disease (chest x-ray recommended before treatment—discontinue if interstitial lung disease develops); consider antiviral prophylaxis for herpes zoster infection; risk factors for seizures; amyloidosis; history of syncope and concurrent use of medication which may cause hypotension; dehydration; risk of neuropathy—; monitor blood-glucose concentration in patients on oral antidiabetics; monitor for symptoms of progressive multifocal leucoencephalopathy (presenting as new or worsening neurological signs or symptoms)—discontinue treatment if diagnosed.

Note: High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Contra-indications: Hypersensitivity (excluding local reactions) to bortezomib, boron, mannitol, or any component of the formulation; administration via the intrathecal route.

Renal impairment: No dosage adjustment necessary.

Dialysis may reduce bortezomib concentrations; administer post dialysis.

Hepatic impairment: Mild impairment (bilirubin ≤1 times ULN and AST >ULN or bilirubin >1-1.5 times ULN): No initial dose adjustment is necessary. Moderate (bilirubin >1.5-3 times ULN) and severe impairment (bilirubin >3 times ULN): Reduce initial dose to 0.7 mg/m2 in the first cycle; based on patient tolerance, may consider dose escalation to 1 mg/m2 (LoRusso, 2012) or further dose reduction to 0.5 mg/m2 in subsequent cycles Obesity: ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen- related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved.

Side Effects: MOST COMMON: Central nervous system: Fatigue, peripheral neuropathy neuralgia, headache, paresthesia, dizziness (excludes vertigo) Dermatologic: Skin rash. Gastrointestinal: Diarrhea, nausea, constipation, vomiting, anorexia, abdominal pain, decreased appetite. Hematologic & oncologic: Thrombocytopenia, neutropenia anemia, leukopenia.

Neuromuscular & skeletal: Weakness Respiratory: Dyspnea. Miscellaneous: Fever. LESS COMMON: Cardiovascular: Cardiac disease, hypotension, cardiac failure (includes acute pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock) Endocrine & metabolic: Dehydration. Hematologic & oncologic: Hemorrhage. Infection: Herpes zoster. Local: Irritation at injection site. Respiratory: Pneumonia. Miscellaneous: Herpes zoster. RARE (Limited to important or life- threatening): Acute ischemic stroke, adult respiratory distress syndrome, aggravated atrial fibrillation, amyloid heart disease, amyloidosis, anaphylaxis, angina pectoris, angioedema, arthralgia, ascites, aspergillosis, ataxia, atelectasis, atrial flutter, atrioventricular block, auditory impairment, back pain, bacteremia, blindness, blurred vision, bone fracture, bradycardia, brain disease, bronchitis, cardiac arrest, cardiac tamponade, cardiorespiratory arrest, catheter infection, cerebral hemorrhage, cerebrovascular accident, chills, cholestasis, coma, confusion, conjunctival infection, conjunctival irritation, cranial nerve palsy, decreased left ventricular ejection fraction, deep vein thrombosis, diplopia, disseminated intravascular coagulation, duodenitis (hemorrhagic), dysarthria, dysautonomia, dysgeusia, dyspepsia, dysphagia, edema, embolism, epistaxis, febrile neutropenia, fecal impaction, gastritis (hemorrhagic), gastroenteritis, gastroesophageal reflux disease, glomerulonephritis, hematemesis, hematuria, hemoptysis, hemorrhagic cystitis, hemorrhagic stroke, hepatic failure, hepatic hemorrhage, hepatic injury, hepatitis, herpes meningoencephalitis, hyperbilirubinemia, hyperglycemia, hyperkalemia, hypernatremia, hypersensitivity, hypersensitivity angiitis, hyperuricemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, hypoxia, increased gamma-glutamyl transferase, increased serum alkaline phosphatase, increased serum transaminases, interstitial pneumonitis, intestinal obstruction, intestinal perforation, ischemic colitis, ischemic heart disease, laryngeal edema, limb pain, listeriosis, lymphocytopenia, malaise, melena, mental status changes, myalgia, myocardial infarction, nasopharyngitis, nephrolithiasis, ocular herpes simplex, optic neuritis, oral candidiasis, oral mucosal petechiae, ostealgia, pancreatitis, paralytic ileus, pericardial effusion, pericarditis, peritonitis, phlebitis, pleural effusion, pneumonitis, portal vein thrombosis, proliferative glomerulonephritis, prolonged Q-T interval on ECG, pruritus, psychosis, pulmonary embolism, pulmonary hypertension, pulmonary infiltrates (including diffuse), renal failure, respiratory failure, respiratory insufficiency, respiratory tract infection, reversible posterior leukoencephalopathy syndrome, seizure, sepsis, septic shock, SIADH, sinoatrial arrest, sinusitis, spinal cord compression, Stevens-Johnson syndrome, stomatitis, subarachnoid hemorrhage, subdural hematoma, suicidal ideation, Sweet's syndrome, syncope, tachycardia, torsades de pointes, toxic epidermal necrolysis, toxoplasmosis, transient ischemic attacks, tumor lysis syndrome, urinary incontinence, urinary retention, urinary tract infection, urticaria, ventricular tachycardia, vertigo, weight loss.

Dose: Note: Consecutive doses should be separated by at least 72 hours. Multiple myeloma (first-line therapy; in combination with melphalan and prednisone): IV, SubQ: 1.3 mg/m2 days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day treatment cycle for 4 cycles, followed by 1.3 mg/m2 days 1, 8, 22, and 29 of a 42-day treatment cycle for 5 cycles. Retreatment may be considered for multiple myeloma patients who had previously responded to bortezomib (either as monotherapy or in combination) and who have relapsed at least 6 months after completing prior bortezomib therapy; initiate at the last tolerated dose.

Alternative first-line therapy (unlabeled dosing): CyBorD regimen: IV: 1.5 mg/m2 days 1, 8, 15, and 22 of a 28-day treatment cycle for 4 cycles (may continue beyond 4 cycles) in combination with cyclophosphamide and dexamethasone.

PAD regimen (IV Induction): 1.3 mg/m2 days 1, 4, 8, and 11 of a 28-day treatment cycle for 3 cycles (in combination with doxorubicin and dexamethasone), followed by conditioning/stem cell transplantation, and then maintenance bortezomib 1.3 mg/m2 once every 2 weeks for 2 years.

VRd regimen (IV): 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day treatment cycle for 8 cycles (in combination with lenalidomide and dexamethasone).

Patients ≥65 years (IV): 1.3 mg/m2 days 1, 8, 15, and 22 of a 35-day treatment cycle, in combination with either melphalan and prednisone or melphalan, prednisone, and thalidomide.

Multiple myeloma (relapsed): IV, SubQ: 1.3 mg/m2 twice weekly for 2 weeks on days 1, 4, 8, and 11 of a 21-day treatment cycle. Therapy extending beyond 8 cycles may be administered by the standard schedule or may be given once weekly for 4 weeks (days 1, 8, 15, and 22), followed by a 13-day rest (days 23 through 35).

Retreatment may be considered for multiple myeloma patients who had previously responded to bortezomib (either as monotherapy or in combination) and who have relapsed at least 6 months after completing prior bortezomib therapy; initiate at the last tolerated dose.

Administer twice weekly for 2 weeks on days 1, 4, 8, and 11 of a 21-day treatment cycle (either as a single-agent or in combination with dexamethasone) for a max. of 8 cycles.

Alternative relapsed therapy (unlabeled dosing): IV: 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day treatment cycle for at least 8 cycles or until disease progression or unacceptable toxicity (in combination with liposomal doxorubicin).

Mantle cell lymphoma: IV, SubQ: 1.3 mg/m2 twice weekly for 2 weeks on days 1, 4, 8, and 11 of a 21-day treatment cycle. Therapy extending beyond 8 cycles may be administered by the standard schedule or may be given once weekly for 4 weeks (days 1, 8, 15, and 22), followed by a 13-day rest (days 23 through 35).

Cutaneous or peripheral T-cell lymphoma, relapsed/refractory (unlabeled use): IV: 1.3 mg/m2 twice weekly for 2 weeks on days 1, 4, 8, and 11 of a 21-day treatment cycle (Zinzani, 2007); additional data may be necessary to further define the role of bortezomib in this condition.

Follicular lymphoma, relapsed/refractory (unlabeled use): IV: 1.3 mg/m2 days 1, 4, 8, and 11 of a 28-day treatment cycle, in combination with bendamustine and rituximab for 6 cycles (Friedberg, 2011) or 1.6 mg/m2 days 1, 8, 15, and 22 of a 35-day treatment cycle, in combination with bendamustine and rituximab for 5 cycles (Fowler, 2011) Systemic light-chain amyloidosis (unlabeled use): IV:

1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day treatment cycle (with or without dexamethasone) (Kastritis, 2010)