Serious adverse events with tedizolid and linezolid: pharmacovigilance insights through the FDA adverse event reporting system

ABSTRACT

Background

To investigate the adverse event (AE) profile of tedizolid and linezolid in post-marketing surveillance.

Research design and methods

We queried the worldwide FDA Adverse Event Reporting System and selected all records where tedizolid and linezolid were reported as suspect by removing potential duplicates. Disproportionality analysis was performed investigating designated medical events (DMEs) and specific AEs of clinical interest reported with tedizolid. The reporting odds ratios (RORs) were calculated, deemed significant by a lower limit of the 95% confidence interval (LL95%CI)>1, using linezolid as comparator. Case-by-case assessment of AEs reported in at least three cases with tedizolid was performed.

Results

Overall, 271 and 11,259 reports mentioning respectively tedizolid and linezolid were recorded, of which respectively 59 and 4,473 patients with DMEs or selected AEs were found. No difference emerged for the selected AEs except for increased reporting of hepatic failure (N = 3; LL95%CI = 1.06) with tedizolid considering reports collected after 2014. Extensive off-label use in terms of therapeutic indications (83.6%) and treatment duration was reported with tedizolid.

Conclusions

Similar AE reporting between the two oxazolidinones was found. Considering limitations of pharmacovigilance, this hypothesis of comparable safety profile should be tested prospectively through dedicated real-world studies.

KEYWORDS:

• Tedizolid
• linezolid
• disproportionality analysis
• hepatic failure
• lactic acidosis
• myelotoxicity
• serotonin syndrome

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

MG made substantial contribution to study conception and design, acquisition and analysis of data, and was involved in drafting the manuscript. MF made substantial contribution to acquisition of data. ER made substantial contribution to study design and interpretation of data. All authors revised the manuscript critically for important intellectual content. All authors approved the final version of the manuscript.

Ethics approval

Under current legislation, institutional review board approval is not required when performing analysis of the publicly available FAERS database, because it contains anonymized data that cannot allow patients’ identification.

Availability of data and material

Data supporting the findings of this study were derived from the following resource available in the public domain: https://www.fda.gov/drugs/questions-andanswers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard

Additional information

Funding

This study was supported by Institutional Funds of the University of Bologna granted to E Raschi, E Poluzzi and F De Ponti. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.