Label Changes for:

Velcade (bortezomib) for Injection

October 2014

Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
 

October 2014

5 WARNINGS AND PRECAUTIONS

5.7 Thrombocytopenia/Neutropenia
  • ...section updated

 

October 2012

ADVERSE REACTIONS

Postmarketing Experience
  • 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)…

 

November 2011

ADVERSE REACTIONS

Postmarketing Experience
  • optic neuropathy, blindness

PRECAUTIONS

Drug Interactions
  • 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 
 
December 2010

 

ADVERSE REACTIONS

Postmarketing Experience
  • 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.

June 2008 

Summary View

 

Sections Modified Summary of Changes to Contraindications and Warnings

WARNINGS AND PRECAUTIONS

  • Use in Pregnancy
  • Peripheral Neuropathy
  • Cardiac Disorders
  • Gastrointestinal Adverse Events
  • Thrombocytopenia/Neutropenia
    • Table 4

ADVERSE REACTIONS

  • Clinical Trials Safety Experience
    • Summary of Clinical Trial in Patients with Previously Untreated Multiple Myeloma (new subsection)
      • Table 5 (new)
    • Description of Selected Adverse Events from the Phase 2 and 3 Relapsed Multiple Myeloma and Phase 2 Mantle Cell Lymphoma Studies
      • Herpes Virus Infection

DRUG INTERACTIONS

  • Ketoconazole
  • Melphalan-Prednisone
  • Omeprazole

USE IN SPECIFIC POPULATIONS

  • Pregnancy
  • Patients with Renal Impairment

PATIENT COUNSELING INFORMATION

  • Dehydration/Hypotension
  • Pregnancy/Nursing
  • Concomitant Medications
  • Diabetic Patients
  • Peripheral Neuropathy
  • Other

WARNINGS AND PRECAUTIONS

Use in Pregnancy

...Bortezomib administered to rabbits during organogenesis caused post-implantation loss and a decreased number of live fetuses...

Peripheral Neuropathy

...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...

Cardiac Disorders

...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...

Thrombocytopenia/Neutropenia

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...

 

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