((C-040)) (C-040) Levetiracetam and the Risk of Thrombocytopenia: Active-comparator restricted disproportionality analysis

Background: Levetiracetam, an anticonvulsant medication, is frequently prescribed for the management of epilepsy and other seizure disorders. One potential side effect associated with levetiracetam is thrombocytopenia, a condition characterized by a low platelet count, which can lead to increased risk of bleeding. Given the potential severity of this side effect, we aimed to assess the reporting frequency of thrombocytopenia associated with levetiracetam in comparison to other anticonvulsants, such as gabapentin and pregabalin.

Objectives: To determine the risk of levetiracetam-associated thrombocytopenia compared to gabapentin and pregabalin using data from the FDA Adverse Event Reporting System (FAERS).

Methods: Design and Setting: An active comparator-restricted disproportionality analysis of FAERS data from 2015Q3 to 2023Q3, utilizing MedDRA-v27.1 preferred terms and restricting the analysis to primary suspect cases. Exposures and Outcome: Levetiracetam was compared to gabapentin and pregabalin as active comparators. The primary outcome was the frequency of thrombocytopenia reports. Statistical Analysis: The Reporting Odds Ratios (RORs) were calculated, adjusting for age, sex, epilepsy, and pain.

Results: A total of 207,434 individual case safety reports (ICSRs) were analyzed: 45,441 reports for levetiracetam (21.9%), 56,158 for gabapentin (27.1%), and 105,835 for pregabalin (51.0%). Disproportionality analyses revealed that reports of levetiracetam-associated thrombocytopenia were 12- to 14-fold higher than those linked to gabapentin (627/45,441[1.38%] vs 98/56,158 [0.18%], aROR 11.59, 95% CI [8.49 to 15.03]) and pregabalin (627/45,441[1.38%] vs 142/105,835[0.13%], aROR 13.88, 95% CI [11.07to 17.39]).

Conclusions: Our analysis indicated that levetiracetam is significantly associated with a higher risk of thrombocytopenia compared to gabapentin and pregabalin. These findings underscore the importance of monitoring platelet levels in patients using levetiracetam, particularly for those at higher risk of bleeding. Further pharmacoepidemiological studies are warranted to investigate the clinical significance and mechanisms of this association.