Bortecade Special Precautions

Bortezomib should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.
Peripheral Neuropathy: Bortezomib treatment causes peripheral neuropathy that is predominantly sensory. However, cases of severe motor neuropathy with or without sensory peripheral neuropathy have been reported. Patients with pre-existing 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) during treatment with Bortezomib, Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require a change in the dose and schedule of Bortezomib (see Dosage & Administration).
Hypotension: Caution should be used when treating patients with 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 (see Adverse Reactions).
Cardiac Disorders: Acute development or exacerbation of congestive heart failure, and/or new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with few or no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing heart diseases should be closely monitored.
Hepatic Events: Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic events include increases in liver enzymes, hyperbilirubinemia, and hepatitis. Such changes may be reversible upon discontinuation of Bortezomib. There is limited re-challenge information in these patients.
Pulmonary Disorders: There have been rare 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. A higher proportion of these events have been reported in Japan. In the event of new or worsening pulmonary symptoms, a prompt diagnostic evaluation should be performed and patients treated appropriately.
Laboratory Tests: Complete blood counts (CBC) should be frequently monitored throughout treatment with Bortezomib.
Thrombocytopenia: Bortezomib is associated with thrombocytopenia (see Adverse Reactions). Platelets were lowest at Day 11 of each cycle of Bortezomib treatment and typically recovered to baseline by the next cycle. The cyclical pattern of platelet count decrease and recovery remained consistent over the 8 cycles of twice weekly dosing, and there was no evidence of cumulative thrombocytopenia. Platelet counts should be monitored prior to each dose of Bortezomib. Bortezomib therapy should be held when the platelet count is <25,000/uL and reinitiated at reduced dose, (see Dosage & Administration and Adverse Reactions). There have been reports of gastrointestinal and intracerebral hemorrhage in association with Bortezomib. Transfusion may be considered.
Gastrointestinal Adverse Events: Bortezomib treatment can cause nausea, diarrhea, constipation, and vomiting (see Adverse Reactions) sometimes requiring use of anti-emetics and antidiarrheal medications. Fluid and electrolyte replacement should be administered to prevent dehydration. Since patients receiving Bortezomib therapy may experience vomiting and/or diarrhea, patients should be advised regarding appropriate measures to avoid dehydration. Patients should be instructed to seek medical advice if they experience symptoms of dizziness, lightheadedness or fainting spells.
Tumor Lysis Syndrome: Because Bortezomib is a cytotoxic agent and can rapidly kill malignant cells the complications of tumor lysis syndrome may occur. The patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.
Patients with Hepatic Impairment: Bortezomib is metabolized by liver enzymes and bortezomib's clearance may decrease in patients with hepatic impairment. These patients should be closely monitored for toxicities when treated with Bortezomib.
Patients with Renal Impairment: No clinical information is available on the use of Bortezomib in patients with creatinine clearance values less than 13 mL/min and patients on hemodialysis. These patients should be closely monitored for toxicities when treated with Bortezomib.
Effects on Ability to Drive and Use Machines: Bortezomib may cause tiredness, dizziness, fainting, or blurred vision. Patients should be advised not to drive or operate machinery if they experience these symptoms.