Transient Risk of Breakthrough Seizures Associated with Phenytoin Refilling and Switching

Epilepsy;Breakthrough seizures;Phenytoin;Drug Safety.;Epidemiology

He, MengdongSegal, Jodi Beth ;

Johns Hopkins University

关键词: Epilepsy;    Breakthrough seizures;    Phenytoin;    Drug Safety.;    Epidemiology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/38110/HE-THESIS-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

BackgroundGeneric substitution is prevalent in the U.S.; however, clinicians and patients remain wary of use of generic products for drugs with narrow therapeutic indices. Epileptic seizure control is an example of a condition which requires consistent blood concentrations of medications; this cannot be assured when patients switch among medications from different manufacturers and even between product lots. ObjectiveWe aimed to quantify the transient risk of seizure activity attributable to refills and switches of phenytoin from same and different manufacturers.MethodsWe conducted a case-crossover study using administrative claims from the Truven MarketScan Commercial Claims and Encounters database in 2010-2012. We identified individuals who had at least 1 emergency room visit or hospitalization with a primary diagnosis of epilepsy or seizure. We required the cases to have epilepsy and at least 2 phenytoin prescription dispensed during the 6-months enrollment in their insurance plan before the first observed emergency room visit or hospitalization (index date). The case period was defined as the 7 days prior to the index date and the control period as 7 days prior to the case period. We used conditional logistic regression to estimate the odds ratio.ResultsWe identified 717 eligible individuals and 143 were discordant cases contributing to the analysis. 38% were females and the median age was 48 years old (interquartile range (IQR) 18 years). Individuals, who refilled phenytoin of the exact same dosage form and strength by the same manufacturer, had a 67% higher odds [odds ratio (OR) 1.67; 95% confidence interval (CI) (1.14-2.44)] of seizure-related events, when the prescription was filled in the 7 days prior to the index date rather than earlier. Individuals who switched phenytoin products had a non-significant 21% increased odds [OR 1.21; 95% CI (0.60-2.46)] of an event. The refill-adjusted risk for switching was close to the null [OR 0.73; 95% CI (0.33-1.63)].ConclusionsOur results suggest that the period after refills and switches may be a high risk period for epileptic patients. Equal attention should be given to the cautious monitoring after refilling and switching and longer days of supply should be encouraged.