title: Systematic Adverse Drug Reaction Monitoring of Patients Under Newer Antiepileptic Drugs Using Routine Clinical Data of Inpatients.
abstract: BACKGROUND
  Based on data of clinical trials, new agents are receiving approval to the pharmaceutical market, for which information concerning safety issues under real-life conditions is not yet available.
  
  
  OBJECTIVE
  The aim was to evaluate the tolerability of newer antiepileptic drugs (AEDs), such as topiramate, levetiracetam, zonisamide, pregabalin, extended-release oxcarbazepine, lacosamide and eslicarbazepine, under real-life conditions by means of an assessment of routine clinical data of inpatients.
  
  
  METHODS
  Over 2.75 years data of all inpatients receiving one of the newer AEDs were documented. Occurring adverse drug reactions (ADRs) were classified according to the WHO-UMC Causality Assessment concerning their likely relationship to the prescribed AEDs. For each AED, the total number of patients without and with ADRs, assessed as at least possibly related to the particular drug, was calculated and corresponding incidences compared with reference data provided in the Summary of Product Characteristics (SmPC). For statistical evaluation Spearman correlation (rs), estimated relative risk and logistic regression analysis were used.
  
  
  RESULTS
  In total, the data of 562 patients were assessed, of which 90 % received up to six different AEDs. The proportion of off-label use with regard to dosage varied between 6.4 and 64.7 %. Levetiracetam and oxcarbazepine as an extended-release formulation were most commonly used, and levetiracetam showed the best tolerance. By using logistic regression, the occurrence of ADRs was significantly associated with the number of AEDs (p< 0.001) as well as the defined daily doses (p= 0.003). In total, ADRs of AEDs were documented for 318 patients (56.6 %). The most common referred to electrolyte imbalance, e.g., low sodium (n= 79, 14.1 %) and potassium (n= 25, 4.4 %) levels, the central nervous system, including dizziness (n= 61, 10.9 %), disturbed vision (n= 47, 8.4 %), fatigue (n= 40, 7.1 %), nystagmus (n= 36, 6.4 %) and ataxia (n= 29, 5.2 %), or cognitive deficits, especially disturbance of speech (n= 37, 6.6 %), memory impairment (n= 36, 6.4 %) and mental slowing (n= 32, 5.7 %). By comparing the assessed ADR incidences with specification data, for some ADRs, a probable underestimation by the SmPC of respective risk could be assumed.
  
  
  CONCLUSIONS
  During inpatient treatment, valuable data are generated, which are currently rarely utilized for pharmacoepidemiologic or pharmacovigilance purposes. A systematic evaluation of these data can increase the probability of detecting ADRs and can promote real-life-related drug surveillance.
authors.affiliation: Ev. Krankenhaus Bielefeld gGmbH, Bethesdaweg 10, 33617 Bielefeld, Germany ; Epilepsiezentrum Bethel, Krankenhaus Mara gGmbH, 33617 Bielefeld, Germany ; Charité Universitätsmedizin Berlin, Institut für klinische Pharmakologie, 10115 Berlin, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Hilgers
authors.affiliation: Charité Universitätsmedizin Berlin, Institut für klinische Pharmakologie, 10115 Berlin, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Schaefer