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FDA issues alert after repackaged bevacizumab causes endophthalmitis infections in Florida
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The U.S. Food and Drug Administration has warned physicians that repackaged intravitreal injections of Avastin have caused a cluster of sight-threatening endophthalmitis infections in the Miami area, according to an FDA news release.
The Florida Department of Health reported a cluster of Streptococcus endophthalmitis infections at three clinics. The contaminated injections were traced to one pharmacy in Hollywood, Fla., that repackaged Avastin (bevacizumab, Genentech) from sterile injectable 100 mg/4 mL single-use, preservative-free vials into individual 1 mL single-use syringes, the release said.
The pharmacy distributed the bevacizumab to several eye clinics. At least 12 patients treated at the clinics sustained eye infections. Some reportedly lost remaining vision because of endophthalmitis, the release said.
"The agency and Florida health officials continue to investigate the cause of the infection," the release said. "While the investigation is not yet complete, the common link for the infections is the pharmacy that repackaged the Avastin and the single lot of Avastin used in the repackaging."
The FDA advised health care professionals to be aware that repackaging sterile drugs without taking aseptic measures may diminish drug sterility and increase patients' risk of infection.
"Health care professionals should ensure that drug products are obtained from appropriate, reliable sources and property administered," the release said.
Intravenous infusion of bevacizumab is approved for the treatment of some types of cancer. Bevacizumab is prescribed off label for the treatment of wet age-related macular degeneration.
Adverse events, side effects and quality issues related to repackaged intravitreal injections of bevacizumab should be reported to the FDA's MedWatch Safety Information and Adverse Event Reporting program at www.fda.gov/MedWatch/report.htm.
Endophthalmitis is the most concerning complication of an intravitreal injection. Patients who develop endophthalmitis can go on to lose a significant amount of vision or even all vision in the affected eye. Fortunately, it is an uncommon occurrence with a frequency of once every several thousand injections. The benefits of injecting intravitreal anti-VEGF agents far outweigh the small chance of endophthalmitis, such that ophthalmologists perform this procedure routinely.
Thus, when we hear that there is a cluster of cases in Miami from a compounding pharmacy using one particular lot of repackaged Avastin, we should all be very concerned. The New York Times just reported on a cluster of endophthalmitis cases related to repackaged Avastin in Tennessee and California as well. The exact details of these events have not yet been made public. We will have to leave up to the health authorities to determine the exact cause of these endophthalmitis cases. In my opinion, it is most likely contamination at the level of the compounding pharmacies, although further investigation will bear out the exact facts.
Avastin has been used commonly since the initial reports of its use in 2005. It has been estimated that millions of injections, for a variety of on-label and off-label indications, have been done since then and countless patients have had their vision saved by repackaged Avastin injections. Regardless of these recent events, intravitreal Avastin injections will likely continue to play a major therapeutic role in ophthalmologists’ offices for years to come. However, these recent events underscore the need for careful selection of a compounding pharmacy, monitoring for endophthalmitis cases that are clustered and to be vigilant about the use of any drugs that are compounded, period.
– Michael S. Ip, MD
Associate professor,
University of Wisconsin, Fundus Photograph Reading Center, Madison, Wisc.
Disclosure: Dr. Ip is a consultant for Allergan, Genentech, NicOx, Regeneron,
Alimera and EyeTech.
The series of 12 cases of endophthalmitis following intravitreal injection of contaminated bevacizumab is disturbing for both patients and ophthalmologists who rely upon compounding pharmacies to provide safe drugs. This event represents a process failure, and perhaps a system failure, at one compounding pharmacy. Nonetheless, it illustrates the potential vulnerability of the bevacizumab supply chain. Although the details of this event remain unknown, supplying bevacizumab for intravitreal injection is a relatively low margin business and it is therefore reasonable to consider whether some compounding pharmacies may be tempted to neglect appropriate quality control. Despite this event, it is important to recognize that compounding pharmacies have provided literally millions of safe and effective doses of bevacizumab for intravitreal injection since 2005. I trust this anomaly will result in even better safety systems for all compounding pharmacies.
– George A. Williams, MD
OSN
Retina/Vitreous Board Member
Disclosure: Dr. Williams is an investigator
in the CATT.