Myborte Special Precautions

Peripheral neuropathy: Bortezomib treatment causes a peripheral neuropathy that is predominantly sensory. However, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with preexisting symptoms (numbness, pain, or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including grade 3 or higher) during treatment with bortezomib. Monitor patients for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypesthesia, paresthesia, discomfort, neuropathic pain, or weakness. In the phase 3 relapsed multiple myeloma trial comparing bortezomib subcutaneous versus IV, the incidence of grade 2 or more peripheral neuropathy events was 24% for subcutaneous and 39% for IV. Grade 3 or more peripheral neuropathy occurred in 6% of patients in the subcutaneous treatment group compared with 15% in the IV treatment group. Starting bortezomib subcutaneously may be considered for patients with preexisting or at high risk of peripheral neuropathy. Patients experiencing new or worsening peripheral neuropathy during bortezomib therapy may benefit from a decrease in the dose and/or a less dose-intense schedule. In the phase 3 relapsed multiple myeloma study of bortezomib versus dexamethasone following dose adjustments or interruptions, improvement in or resolution of peripheral neuropathy was reported in 48% of patients with at least grade 2 peripheral neuropathy. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued because of grade 2 neuropathy or who had at least grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.
Hypotension: The incidence of hypotension (postural, orthostatic, and hypotension not otherwise specified) was 8%. These reactions are observed throughout therapy. Use caution when treating patients who have a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensive medication, hydration, or administration of mineralocorticoids and/or sympathomimetics. (See Adverse Reactions.)
Cardiac effects: Acute development or exacerbation of congestive heart failure (CHF) and new onset of decreased left ventricular ejection fraction have been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Closely monitor patients with risk factors for heart disease and those with existing heart disease. In the relapse multiple myeloma study, the incidence of any treatment- emergent cardiac disorder was 8% and 5% in the bortezomib and dexamethasone groups, respectively. The incidence of adverse reactions suggestive of heart failure (eg, acute pulmonary edema, cardiac failure, CHF, cardiogenic shock, pulmonary edema) was 1% or less for each individual reaction in the bortezomib group. In the dexamethasone group, the incidence was 1% or less for cardiac failure and CHF; there were no reported reaction of acute pulmonary edema, pulmonary edema, or cardiogenic shock. There have been isolated cases of QT interval prolongation in clinical studies; causality has not been established.
Pulmonary disorder: There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown aetiology (eg, pneumonitis, interstitial pneumonia, lung infiltration) and acute respiratory distress syndrome (ARDS) in patients receiving bortezomib. Some of these events have been fatal. In the event of new or worsening cardiopulmonary symptoms, consider interrupting bortezomib until a prompt comprehensive diagnostic evaluation is conducted.
Posterior Reversible Encephalopathy Syndrome: Posterior reversible encephalopathy syndrome (formerly reversible posterior leukoencephalopathy syndrome) has occurred in patients receiving bortezomib. Posterior reversible encephalopathy syndrome is a rare, reversible neurological disorder that can present with seizure, hypertension, headache, lethargy, confusion, blindness and other visual and neurological disturbances.
Brain imaging, preferably magnetic resonance imaging, is used to confirm the diagnosis.
Discontinue bortezomib in patients developing posterior reversible encephalopathy syndrome. The safety of reinitiating bortezomib therapy in patients previously experiencing posterior reversible encephalopathy syndrome is not known.
GI effects: Bortezomib treatment can cause constipation, diarrhea, nausea, and vomiting, sometimes requiring use of antiemetics and antidiarrheal medications. Ileus can occur. Administer fluid and electrolyte replacement to prevent dehydration. Interrupt bortezomib for severe symptoms.
Thrombocytopenia/Neutropenia: Bortezomib is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases and recovery remained consistent over the 8 cycles of twice-weekly dosing, and there was no evidence of cumulative thrombocytopenia or neutropenia. The mean platelet count nadir measured was approximately 40% of baseline. In the relapsed multiple myeloma study of bortezomib versus dexamethasone, the incidence of bleeding (grade 3 or higher) was 2% in the bortezomib arm and was less than 1% in the dexamethasone arm. Monitor complete blood cell counts (CBC) frequently during treatment. Monitor platelet counts prior to each dose of bortezomib. Patients experiencing thrombocytopenia may require a change in the dose and schedule of bortezomib.
Tumor lysis syndrome: Tumor lysis syndrome has been reported. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. Monitor patients closely and take appropriate precautions.
Hepatic effects: Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and those with serious underlying medical conditions. Other reported hepatic reactions include increases in liver enzymes, hyperbilirubinemia, and hepatitis. Interrupt bortezomib therapy to excess reversibility.