Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2017 Aug;58(8):e101-e106.
doi: 10.1111/epi.13828. Epub 2017 Jul 6.

Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research network

Jon D Duke  1   2 , Patrick B Ryan  1   3   4 , Marc A Suchard  1   5 , George Hripcsak  1   4 , Peng Jin  1   4 , Christian Reich  1   6 , Marie-Sophie Schwalm  1   6 , Yuriy Khoma  1   7   8 , Yonghui Wu  1   9 , Hua Xu  1   9 , Nigam H Shah  1   10 , Juan M Banda  1   10 , Martijn J Schuemie  1   3
Affiliations
Observational Study

Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research network

Jon D Duke et al. Epilepsia. 2017 Aug.

Abstract

Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.

Keywords: Adverse drug reactions; Angioedema; Anticonvulsant hypersensitivity syndrome; Levetiracetam; Observational research; Pharmacovigilance.

PubMed Disclaimer

Conflict of interest statement

DISCLOSURE OF CONFLICT OF INTEREST

One of the authors (JD) changed institutions after the protocol had been completed and at his new institution joined an ongoing unrelated informatics project funded by Union Chimique Belge (UCB), a brand manufacturer of levetiracetam. The remaining authors have no conflicts of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

Figure 1.
Figure 1.
Forest plots showing the HRs for angioedema with exposure to levetiracetam compared with phenytoin in patients with seizure disorder across multiple databases, as well as combined estimate, for the per-protocol and intent-to-treat analyses.
Figure 2.
Figure 2.
Kaplan-Meier plots showing angioedema events in levetiracetam (red) and phenytoin (blue) cohorts from four claims datasets in the per-protocol analysis. Shaded areas indicate 95% CI.
See this image and copyright information in PMC

References

    1. FDA Adverse Event Reporting System (FAERS) (formerly AERS). Available at: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveil.... Accessed October 25,2013.
    1. Research C for DE. FDA Adverse Events Reporting System (FAERS) - Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS) between October–December 2015. Available at: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveil.... Accessed February 12, 2017.
    1. Vittorio CC, Muglia JJ. Anticonvulsant hypersensitivity syndrome. ArchInternMed 1995;155:2285. - PubMed
    1. Leyva L, Torres MJ, Posadas S, et al. Anticonvulsant-induced toxic epidermal necrolysis: monitoring the immunologic response. J Allergy Clin Immunol 2000;105:157–165. - PubMed
    1. Lerch M Drug-induced angioedema. Chem Immunol Allergy 2012;97:98–105. - PubMed

Publication types