Bortero

Bortero Special Precautions

bortezomib

Manufacturer:

Camber

Distributor:

Camber
Full Prescribing Info
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 41% for IV. Grade 3 or more peripheral neuropathy occurred in 6% of patients in the subcutaneous treatment group, compared with 16% 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 single agent phase 3 relapsed multiple myeloma study of bortezomib versus dexamethasone, following dose adjustments, improvement in or resolution of peripheral neuropathy was reported in 51% of patients with at least grade 2 peripheral neuropathy in the relapsed multiple myeloma study. 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 13%. 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 medications, hydration, or administration of mineralocorticoids and/or sympathomimetics.
Cardiac effects: Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have been reported, including reported 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 relapsed multiple myeloma study, the incidence of any treatment-emergent cardiac disorder was 15% and 13% in the bortezomib and dexamethasone groups, respectively. The incidence of heart failure events (eg, acute pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock, pulmonary edema) was similar in the bortezomib and dexamethasone groups (5% and 4%, respectively). There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established.
Pulmonary effects: There have been reports of acute diffuse infiltrative pulmonary disease of unknown etiology, such as pneumonitis, interstitial pneumonia, lung infiltration, and acute respiratory distress syndrome (ARDS) in patients receiving bortezomib. Some of these events have been fatal.
There have been reports of pulmonary hypertension associated with bortezomib administration in the absence of left heart failure or significant pulmonary disease.
In the event of new or worsening cardiopulmonary symptoms, consider conducting a prompt comprehensive diagnostic evaluation.
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.
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 were 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 significant bleeding events (grade 3 or higher) was similar on the bortezomib (4%) and dexamethasone (5%) arms. 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: Because bortezomib is a cytotoxic agent and can rapidly kill malignant cells, the complications of tumor lysis syndrome may occur. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. Monitor these patients closely and take appropriate precautions.
Hepatic effects: Causes of acute liver failure have been reported in patients receiving multiple concomitant medications and those with serious underlying medical conditions. Other reported hepatic events include increase in liver enzymes, hyperbilirubinemia, and hepatitis. Such changes may be reversible upon discontinuation of bortezomib. There is limited rechallenge information in these patients.
Diabetes: During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving bortezomib treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication.
Renal function impairment: Because dialysis may reduce bortezomib concentrations, administer the drug after the dialysis procedure.
Hepatic function impairment: Bortezomib exposure is increased in patients with moderate or severe hepatic impairment; treat these patients with bortezomib at reduced starting doses and closely monitor for toxicities.
Use in Children: The safety and efficacy of bortezomib in children have not been established.
Use in the Elderly: No overall differences in safety or efficacy were observed between patients 65 years of age and older and younger patients receiving bortezomib; however, greater sensitivity of some older patients cannot be ruled out.
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