Levetiracetam vs. Fosphenytoin for Second-Line Treatment of Status Epilepticus: Propensity Score Matching Analysis Using a Nationwide Inpatient Database

Abstract

Objective: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam vs. fosphenytoin. We compare the safety of intravenous levetiracetam and fosphenytoin as a second-line treatment in patients with status epilepticus using a nationwide database. Methods: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from March 1, 2011 to March 31, 2018. Patients who received intravenous levetiracetam on the day of admission were defined as the levetiracetam group and those who received intravenous fosphenytoin on the day of admission were defined as the fosphenytoin group. Propensity score matching was performed to compare outcomes obtained for the levetiracetam and fosphenytoin groups. Results: The analysis examined data of 5,667 patients. Overall, 1,403 (25%) patients received levetiracetam; 4,264 (75%) received fosphenytoin. One-to-one propensity score matching created 1,363 matched pairs. No significant difference was found in in-hospital mortality (5.2 vs. 5.1%; odds ratio, 1.03; 95% confidence interval, 0.73-1.46). The proportion of vasopressor use on the day of admission was significantly lower for the levetiracetam group than for the fosphenytoin group (3.2 vs. 4.9%; odds ratio, 0.63; 95% confidence interval, 0.43-0.92). No significant difference was found in other secondary outcomes including total hospitalization cost. Conclusion: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for fosphenytoin, in adult status epilepticus.

Challenges of Delirium Management in Patients with Traumatic Brain Injury: From Pathophysiology to Clinical Practice

“…The first-line therapy for status epilepticus in this context is a fast-acting benzodiazepine such as lorazepam or midazolam, to be given intravenously. Accepted second-line therapies include intravenous phenytoin, fosphenytoin (a phenytoin pro-drug with lower risk of cardiac and subcutaneous adverse effects [ 282 ]), valproate [ 283 ] or levetiracetam [ 284 , 285 ]. Pharmacologic coma, e.g .…”

Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for adult convulsive status epilepticus: a multicentre non-inferiority randomised control trial

“…Our nationwide database analysis showed the more frequent use of intravenous LEV than intravenous FPHT to treat adult SE despite the lack of coverage by the national health insurance system, 20 and revealed the higher efficacy and safety of intravenous LEV. 21 To establish intravenous LEV for the treatment of SE, we herein conducted a multicentre non-inferiority RCT, in which adult patients with convulsive SE transported to an emergency room were randomised into LEV and FPHT groups as a secondline treatment after the administration of diazepam, a typical benzodiazepine and their efficacies were compared. Since the participating facilities were recruited around Ibaraki in Japan, this study was entitled the Ibaraki Emergency room NEtwork Epilepsy Control Trial with LevetIracetam versus FosphEnytoine; IENE ECT with LIFE.…”

“…Our nationwide database analysis showed the more frequent use of intravenous LEV than intravenous FPHT to treat adult SE despite the lack of coverage by the national health insurance system, 20 and revealed the higher efficacy and safety of intravenous LEV. 21 …”

Treating Status Epilepticus: Phenytoin Versus Levetiracetam

“…Despite the similar efficacies of the two drugs in treating SE, numerous studies have demonstrated that levetiracetam is a safer AED to administer than phenytoin [ 15 , 18 , 23 , 25 , 26 , 63 ]. Four of the studies in Table 1 reported a significantly greater incidence of adverse effects associated with phenytoin treatment than levetiracetam, with the most common being acute hypotension [ 18 , 23 , 25 , 26 ].…”

“…Four of the studies in Table 1 reported a significantly greater incidence of adverse effects associated with phenytoin treatment than levetiracetam, with the most common being acute hypotension [ 18 , 23 , 25 , 26 ]. Another clinical study showed that IV fosphenytoin was associated with significantly greater vasopressor usage than levetiracetam when treating SE, primarily due to the hypotension induced [ 63 ]. Since maintaining cerebral blood perfusion is vital in helping to prevent neuronal injury in SE, the risk of hypotension associated with IV phenytoin and fosphenytoin could lead to worse patient outcomes [ 64 ].…”