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Potential for Linezolid‐Related Blindness: A Review of Spontaneous Adverse Event Reports
Author(s) -
Brown Jack,
Aitken Samuel L.,
Manen Robbert P.
Publication year - 2011
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.31.6.585
Subject(s) - linezolid , medicine , adverse effect , retrospective cohort study , adverse event reporting system , intensive care medicine , pediatrics , vancomycin , biology , bacteria , genetics , staphylococcus aureus
Study Objective. To provide clinicians with an understanding of the comparative occurrence of linezolid and blindness, and to provide any clinically relevant characteristics that may be useful in identifying the patients at risk. Design. Retrospective cohort study. Data Source. Spontaneous reports in the United States Food and Drug Administration Adverse Event Reporting System (AERS) database generated between November 1, 1997, and December 21, 2008. Patients. Twenty‐nine patients who experienced blindness while receiving linezolid therapy. Measurements and Main Results. Available information related to each case of linezolid‐reported blindness in the AERS database was qualitatively and quantitatively reviewed. Optic nerve disorders, glaucoma, and treatment with linezolid for long durations were common characteristics in patients experiencing blindness. A limitation of AERS is the lack of a quantitative exposure estimate to put rare adverse events of the AERS, such as linezolid‐related blindness, into perspective. To overcome this limitation, disproportionality analysis with Bayesian correction methodology was used. Disproportionality analysis uses an adverse event relative reporting ratio (RRR) to compare the occurrence of a specific adverse event with an index drug of interest to the occurrence of the same adverse event with similar agents or with all other FDA‐approved prescription drugs. The disproportionality analysis was considered meaningful if the 5th percentile of the distribution of the RRR (RRR 05 ) was 2 or greater. Among the 29 reported cases of linezolid use and blindness, an RRR 05 of 2.1 was determined for linezolid‐related blindness compared with all other agents listed in the AERS. Also, RRR 05 values of 2.7 and 2.2 were found when linezolid was compared with all other systemic antibiotics and a select subgroup of antibiotics, respectively. Conclusion. Although disproportionality analyses suggested a quantitative signal for an association between linezolid use and blindness, causality cannot be inferred from the data. Thus, additional rigorous scientific analyses are warranted to explore these findings.