Association of compounded bevacizumab with postinjection endophthalmitis.
OBJECTIVE
Current draft guidelines set forth by the US Food and Drug Administration for compounded or repackaged medications would greatly limit the availability and use of bevacizumab by ophthalmologists across the country. Little evidence beyond highly publicized case reports exists for or against the need for additional regulation of compounded bevacizumab.


OBJECTIVE
To determine whether the distribution of bevacizumab through compounding pharmacies increases the risk for endophthalmitis compared with the distribution of single-use vials of ranibizumab from the manufacturer.


METHODS
A retrospective cohort study using medical claims data from ambulatory care centers across the United States that were submitted to a large, national US insurer. Cohorts were created using information on 530 382 intravitreal injections administered from January 1, 2005, through December 31, 2012. Any individual from this data set who received an intravitreal injection of bevacizumab or ranibizumab (n=383 810) and had at least 6 months of data before and 1 month after the injection was eligible. After exclusions (any previous diagnosis of endophthalmitis, multiple injected drugs given on the index day, or intraocular surgery within 15 days of the injection or between the injection and a diagnosis of endophthalmitis), our analysis involved 383 810 intravitreal injections given to 58 612 patients. Data collection and analysis occurred from February 16 through April 7, 2015.


METHODS
The odds of developing endophthalmitis after an intravitreal injection of bevacizumab compared with ranibizumab.


RESULTS
In total, 296 565 injections of bevacizumab were given to 51 116 patients and 87 245 injections of ranibizumab were given to 7496 patients. We found 71 cases of endophthalmitis (49 in the bevacizumab cohort and 22 in the ranibizumab cohort) for an endophthalmitis rate of 0.017% (95% CI, 0.012%-0.021%; 1 case per 6061 injections) for bevacizumab and 0.025% (95% CI, 0.015%-0.036%; 1 case per 3968 injections) for ranibizumab. After controlling for age, race, sex, injection-related diagnosis, and year of injection, we found no significant association with development of endophthalmitis after a bevacizumab injection compared with ranibizumab (odds ratio, 0.66 [95% CI, 0.39-1.09]; P = .11).


CONCLUSIONS
The results of this study suggest bevacizumab as currently used across the United States does not increase the risk for endophthalmitis; therefore, additional regulations on the use of repackaged bevacizumab may be unnecessary.
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia2Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman S.
Brian L
BL
VanderBeek
currently a medical student at Lake Erie College of Osteopathic Medicine, Bradenton, Florida.
Sarah G
SG
Bonaffini
Leonard Davis Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Liyuan
L
Ma
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000737:chemistry; D000068258:Bevacizumab / Q000009:adverse effects* / Q000737:chemistry; D016208:Databases, Factual; D004339:Drug Compounding / Q000009:adverse effects*; D004349:Drug Packaging; D009877:Endophthalmitis / Q000453:epidemiology* / Q000209:etiology; D015818:Eye Infections, Bacterial / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D007880:Legislation, Drug; D008297:Male; D016017:Odds Ratio; D012164:Retinal Diseases / Q000188:drug therapy; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D042461:Vascular Endothelial Growth Factor A
D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab