Angioedema Risk Evaluated for Levetiracetam Versus Phenytoin

"The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin," wrote the researchers.

The risk of angioedema with levetiracetam, an anti-epileptic drug (AED), is similar to and possibly lower than the risk with phenytoin, according to a study conducted by the Observational Health Data Sciences and Informatics Research Network.

Jon Duke and colleagues conducted a retrospective observational new-user study of 10 databases consisting of 276,665 patients with seizure disorder. The researchers used patients treated with phenytoin (n=74,682) as a comparator group.The analysis consisted of propensity score-matching and computed hazard ratios (HR) for angioedema events by per-protocol and (ITT) analyses. 

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The researchers found that angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in ITT). When they examined each database, they found no significant increase in angioedema risk with levetiracetam (HRs ranging from 0.43 to 1.31).

Meta-analysis showed a summary HR 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 ITT 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,” the researchers write, adding that “further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.”


Duke JD, Ryan PB, Suchard MA, et al. Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research network. Epilepsia. 2017 Jul 6. [Epub ahead of print]