A comparison of approaches to identify possible cases of local anesthetic systemic toxicity in the FDA Adverse Event Reporting System (FAERS) database

ABSTRACT

Background: Local anesthetic systemic toxicity (LAST) is a rare but potentially serious adverse event .

Methods: Data from the US Food and Drug Administration Adverse Event Reporting System were examined for liposomal bupivacaine (LB), bupivacaine, or other injectable local anesthetics. Possible LAST cases were identified based on MedDRA system organ classes (Approach 1), a recent publication (Approach 2), and a novel approach based on LAST literature (Approach 3). Disproportionality analyses compared possible LAST cases for LB and bupivacaine with other injectable local anesthetics.

Results: Approaches 1, 2, and 3 identified 75, 42, and 29 possible LAST cases associated with LB, respectively, compared with 9,595, 3,422, and 549 for other injectable local anesthetics. The proportional reporting ratios (95% CI) for LB versus other injectable local anesthetics for the 3 approaches were 1.9 (1.6–2.3), 2.9 (2.2–3.9), and 1.6 (1.1–2.2), respectively. Based on sales data, the estimated incidence of possible LAST with LB was 0.1 per 10,000 uses; literature estimates for LAST with other injectable local anesthetics were 0 to 18 per 10,000 uses.

Conclusions: Our findings suggest the estimated incidence of possible LAST cases with LB is similar to, or less than, the reported incidence with other injectable local anesthetics.

KEYWORDS:

• Bupivacaine
• disproportionality analysis
• FAERS
• local anesthetic systemic toxicity
• liposomal bupivacaine
• pharmacovigilance

Acknowledgments

The authors wish to acknowledge assistance provided by Brian Faley, PharmD, and Aaron Shiraz, MD, when developing some of the methods used in this manuscript. Editorial support for development of this manuscript was provided by Vandana Sharma, PhD, at C4 MedSolutions, LLC (Yardley, PA), a CHC Group company, and was funded by Pacira Pharmaceuticals, Inc.

Author Contributions

All authors participated in the study conception and design and interpretation of the data, were responsible for review and critical revision of the manuscript for intellectual content, gave final approval of the version to be published, and agree to be accountable for all aspects of the work. ARJ and CCV collected and analyzed the data.

Declaration of interest

S Dagenais and R Scranton are employees of Pacira Pharmaceuticals, Inc. AR Joyce and CC Vick are Principals at Venebio Group, LLC, and served as consultants to Pacira Pharmaceuticals, Inc. The authors have no other 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 apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary data

Supplementary data can be accessed here.

Additional information

Funding

This paper has been funded by Pacira pharmaceuticals.