Optimización posológica de levetiracetam en pacientes con epilepsia

Abstract

Levetiracetam (LEV) is a newer-generation antiepileptic drug extensively used in Neurology and Psychiatry over the past 10 years because of its wide range of action, few adverse effects and good tolerance. Due to the fact that there is a general perception that LEV is safe, rarely undertake dose adjustments based on renal function or concomitant medication. The aim of this study was to analyze different aspects such as co-medication or the influence of certain demographic or anthropometric variables on pharmacokinetics of LEV. In addition, the effectiveness and toxicity of this drug have been studied in a naturalistic setting. Sex is a conditioning factor in apparent oral levetiracetam clearance (LEV CL/F). This influence is principally due to the anatomo-physiological changes of each sex. The lower LEV CL/F in women could be explained by the fact that their weight and creatinine clearance (CCr) are generally diminished compared to those of men. Age affects the elimination of LEV, showing a progressive reduction with the advance of age and in a proportion similar to the decline in renal function. There were no significant differences in LEV CL/F, expressed in L/h, between normal weight range, overweight and obese patients. However, when LEV CL/F is expressed in mL/h/Kg, a progressive reduction of this parameter is observed as the weight increased (p=0.000) The important role of the renal function on LEV CL/F has been confirmed. There is a positive and statistically significant correlation between CCr and LEV CL/F (p=0.000). Data showed that LEV CL/F is increased by more than 40% in patients prescribed concomitant enzyme-inducing antiepileptic drugs (EIAEDs). Such an increase would be expected to have clinical consequences. These data suggest that monitoring LEV serum concentrations during polytherapy with EIAEDs is indicated. The results confirmed the effectiveness of LEV as monotherapy and as add-on therapy. Most of patients who started treatment during the study showed complete responses (85%). LEV was effective in the treatment of partial seizures and generalized seizures. Adverse events were reported in 34% of patients. The most frequent were somnolence (40%), headache (27.5%) and psychiatric disorders (22.5%). Most of the patients (77.8%) in who dose optimization were performed after pharmacokinetic monitoring, obtained clinical benefit. These results emphasized the need to monitor LEV.