Use of Levetiracetam plasma levels monitoring in the management of patients with epilepsy.

Rationale: The aim of this study was to evaluate if monitoring lev- etiracetam (LEV) plasma levels can be useful in the management of patients with epilepsy. Methods: This study includes 30 patients with epilepsy, 20 females and 10 males, mean age 39.4 yrs, 25 with Focal Epilepsy and 5 with Generalized Epilepsy, all already treated with two or more appropriate AEDs. LEV was used as adjunctive treatment of refractory seizures in 28 patients; in the remaining 2, already seizure free, LEV was added with the goal of successively reducing concomitant AEDs. After stabilization of the new therapeuthic regimen, with LEV daily oral dosages ranging between 2–3 g, LEV plasma concentrations were evaluated before carrying out further changes of AED treatment. LEV quantitation was performed by a HPLC method (ES/IS) and detected using a PDA. Plasma levels between 10–40 µg/mL were considered in therapeutical range. Patients were considered responders to add on LEV therapy when a reduction of seizures ≥50% in respect to baseline was observed. Results: At the time of LEV plasma levels evaluation: 5 patients were seizure free; they were candidate to reduction of concomitant AEDs, which caused side effects in most cases. In 3 of these subjects LEV plasma levels were at the mid of the therapeutical range, and withdrawal of concomitant AEDs was started without any change of LEV oral dosage. In the other 2, inwhomLEVplasma levelswere at the lowest end of the range, withdrawal of concomitant AEDs was accompanied by an increase in LEV oral dosages. All these 5 patients remained seizure free after reduction/withdrawal of concomitant AED therapy. 13 patients were responders with a ≥50% reduction of seizure frequency. In most of them LEV plasma levels were at the lowest end of the therapeutical range, with the remaining showing plasma levels at the mid/high end of the range. In all these 13 subjects LEV oral dosages were increased, resulting in a further reduction of seizure frequency in 8 patients (3 becoming seizure free and 5 reaching a ≥75% seizure reduction). 12 patients were non responders, having shown no change or a < 50% reduction in seizure frequency. In 2 of themLEV plasma levels were found below the therapeutical range: these patients admitted non compliance to LEV therapy. In the remaining, LEV plasma levels were at the lowest end of the therapeuthical range in 8 and at the mid/high end in 2. In these 10 patients LEV oral dosage was increased, resulting in ≥50%reduction of seizure frequency in 5 cases. Conclusions: In our sample of polytherapy patients, in whom further increase of LEV oral dosage or tapering of concomitant AEDs could have been problematic, evaluation of LEV plasma levels was extremely useful, resulting in increase of responders.