Biogen Idec, the world’s fourth largest biopharmaceutical company, has notified healthcare professionals of a significant revision to BOXED WARNINGS, WARNINGS, and ADVERSE REACTIONS sections of the Prescribing Information for the cancer drug Zevalin.
The alert and warning revision (http://www.fda.gov/medwatch/safety/2005/ZevalinPI.pdf) describe severe cutaneous or mucocutaneous reactions, some with fatal outcome, that have been reported in association with the Zevalin therapeutic regimen in the post-marketing experience.
Patients experiencing a severe cutaneous or mucocutaneous reaction should not receive any further components of the Zevalin therapeutic regimen and should seek prompt medical evaluation.
Similar events have been associated with Rituxan (rituximab), a component of the Zevalin therapeutic regimen according to the senior director of drug safety and risk management for Biogen Idec, in its advisory letter.
The Zevalin “regimen” combines the anti-CD20 monoclonal antibodies Zevalin (ibritumomab tiuxetan) and Rituxan with indium-111- and yttrium-90 labeled radioisotopes. The regimen is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL), including patients with follicular B-cell NHL that is refractory to Rituxan.
"Deaths have occurred within 24 hours of rituximab infusion, an essential component of the Zevalin therapeutic regimen," reads a boxed warning in the Zevalin package insert. "These fatalities were associated with an infusion reaction symptom complex that included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Approximately 80% of fatal infusion reactions occurred in association with the first rituximab infusion."
In September Biogen Idec changed the Zevalin product labeling to include a black-box warning about post-marketing reports of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, and exfoliative dermatitis in patients who received the Zevalin therapeutic regimen. Some of the cases resulted in death.
Onset of the reactions was variable; in some cases occurring within only days of administration, while in other cases the reactions occurred at three to four months.
Serious adverse events associated with the use of Zevalin should be reported to Biogen Idec at 1-877-866-4332 or to the FDA’s MedWatch reporting system (1-800-FDA-1088).