Abstracts

Levetiracetam is a novel anticonvulsant with a side-effect and pharmacokinetic profile which recommends it use in a number of clinical settings,including the patient who presents to the emergency room with acute onset siezures. Levetiracetam is particularly useful if patients are taking multiple other medications since it is renally excreted, non-protein-bound and neither inhibits nor induces hepatic enxzymes. An intravenous formulation of levetiracetam is not yet available for general use and many physicians have concerns regarding oral loading of anticonvulsants in the acute setting. Concerns regarding the need to achieve a rapid therapeutic level of an anticonvulsant were addressed by means of simultaneous intravenous loading of fosphenytoin or phenytoin combined with oral loading of levetiracetam, followed by levetiracetam monotherapy., Several patients were managed in the manner described above in the acute hospital setting, mainly emergency room admissions and but also some inpatients who suffered seizures in other clinical settings. Intravenous fosphenytoin was given at doses of 15-20 mgs/kg and combined with oral loading doses of levetiracetam ranging from 1000 - 1500mgs.
A retrospective chart review was carried out to assess the efficacy of this approach in terms of short-term seizure control and side effect profile., A total of 20 patients were identified who were treated according to this protocol.
No adverse events were reported related to the use of oral levetiracetam dosing (1000-1500mgs oral loading dose) although one patient suffered purple-glove syndrome due to phenytoin infusion.
All patients remained seizure free over the 72 hours following combined loading, by which time levetiracetam concentrations had acheived steady-state concentrations. The majority were discharged on levetiracteam monotherapy and these patients were followed-up on an out-patient basis to assess long-term efficacy and side-effect profile., An intravenous preparation of levetiracetam will be available in the near future, however approval for intravenous loading as a first line therapy in the acute setting is unlikely to be obtained in the short-term. The approach outlined in this study combines the safety and experience of intravenous fosphenytoin loading with the pharmacokinetic advantages of maintenance LEV therapy. The use of one loading dose of fosphenytoin addresses the main concern of clinicians in the acute setting, namely the acheivement of immediate theraputic anticonvulsant levels, this is combined with the pharmacokinetic advantages of levetiracetam maintenance therapy.
Based on the limited data available in this retrospective analysis, this approach appears to be safe and effective in terms of immediate seizure control and long-term maintenance therapy., (Supported by UCB Pharmal.)