Methods: Adverse drug reactions (ADRs) reported to the U.S. Food and Drug Administration (FDA) from January 1, 2015 to September 30, 2017 were extracted from the FDA's Adverse Event Reporting System (FAERS). The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify preferred terms that were subsequently used to create a neurotoxicity composite ADR. Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) were calculated for the neurotoxicity composite ADR and for common preferred terms associated with neurotoxicity. An association was considered to be statistically significant if the 95% CI did not include 1.0.
Results: The neurotoxicity composite ADR (consisting of 40+ MedDRA preferred terms) occurred in 13.9% (n=209/1504) of cefepime reports. Cefepime was three times more likely to have a report of the neurotoxicity composite ADR as compared to other drugs in the FDA's FAERS database (ROR, 2.90; 95%CI, 2.51-3.36). The most frequent individual MedDRA preferred terms for the neurotoxicity composite ADR included (in descending order): “confusional state” (3.1%, 46/1504), “mental status changes” (2.8%, 42/1504), “encephalopathy” (2.3%, 35/1504), “seizure” (2.3%, 34/1504), “myoclonus” (1.8%, 27/1504), and “neurotoxicity” (1.2%, 18/1504). The highest RORs with cefepime vs. other drugs were (in descending order): “myoclonus” 45.0 (30.6-66.1), “encephalopathy” 29.7 (21.2-41.6), “mental status changes” 27.8 (20.4-37.8), “neurotoxicity” 26.7 (16.7-42.6), “confusional state” 4.3 (3.2-5.7), and “seizure” 3.5 (2.5-4.9).
Conclusion: Cefepime was associated with significantly higher odds of myoclonus, encephalopathy, mental status changes, neurotoxicity, confusional state, seizure, and a neurotoxicity composite ADR as compared to other drugs. Practitioners should use caution in initiating cefepime in those patients at risk of neurotoxicity and monitor closely for ADRs.
V. Encarnacion, None
H. Razzack, None
O. Obodozie-Ofoegbu, None
C. R. Frei, None