Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
USE IN SPECIAL POPULATIONS
- *updated based on the pediatric study report for Study AALL07P1, entitled “A Phase II Pilot Trial of Bortezomib in Combination with Intensive Re-Induction Therapy for Children with Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL).”
5 WARNINGS AND PRECAUTIONS
- ...section updated
- Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:...progressive multifocal leukoencephalopathy (PML)…
- optic neuropathy, blindness
- Bortezomib is a substrate of cytochrome P450 enzyme 3A4, 2C19 and 1A2.
- CYP3A4 inhibitors: Co-administration of ketoconazole, a strong CYP3A4 inhibitor, increased the exposure of bortezomib by 35% in 12 patients. Therefore, patients should be closely monitored when given bortezomib in combination with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir).
- CYP2C19 inhibitors: Co-administration of omeprazole, a strong inhibitor of CYP2C19, had no effect on the exposure of bortezomib in 17 patients.
- CYP3A4 inducers: Co-administration of rifampin, a strong CYP3A4 inducer, is expected to decrease the exposure of bortezomib by at least 45%. Because the drug interaction study (n=6) was not designed to exert the maximum effect of rifampin on bortezomib PK, decreases greater than 45% may occur.
- Efficacy may be reduced when VELCADE is used in combination with strong CYP3A4 inducers; therefore, concomitant use of strong CYP3A4 inducers is not recommended in patients receiving Velcade.
- St. John’s Wort (Hypericum perforatum) may decrease bortezomib exposure unpredictably and should be avoided.
- Dexamethasone: Co-administration of dexamethasone, a weak CYP3A4 inducer, had no effect on the exposure of bortezomib in 7 patients
- acute frebrile neutrophilic dermatosis (Sweet syndrome).
- reversible posterior leukoencephalopathy syndrome (RPLS)
|The detailed view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, or PATIENT PACKAGE INSERT/MEDICATION GUIDE sections. Deletions or editorial revisions made to these sections are not included in this summary.|
|Sections Modified||Summary of Changes to Contraindications and Warnings|
WARNINGS AND PRECAUTIONS
USE IN SPECIFIC POPULATIONS
PATIENT COUNSELING INFORMATION
WARNINGS AND PRECAUTIONS
Use in Pregnancy
...Bortezomib administered to rabbits during organogenesis caused post-implantation loss and a decreased number of live fetuses...
...Following dose adjustments, improvement in or resolution of peripheral neuropathy was reported in 51% of patients with >Grade 2 peripheral neuropathy in the relapsed multiple myeloma study...
...In the relapsed multiple myeloma study, the incidence of any treatment-emergent cardiac disorder was 15% and 13% in the Velcade and dexamethasone groups, respectively...
Gastrointestinal Adverse Events
...Ileus can occur...
Velcade 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...
...In the relapsed multiple myeloma study, the incidence of significant bleeding events (>Grade 3) was similar on both the Velcade (4%) and dexamethasone (5%) arms. Platelet count should be monitored prior to each dose of Velcade. Patients experiencing thrombocytopenia may require change in the dose and schedule of Velcade...