title: Topiramate: a prospective study on the relationship between concentration, dosage and adverse events in epileptic patients on combination therapy.
abstract: BACKGROUND
  The relationship between topiramate (TPM) concentration, dosage and adverse events in patients with epilepsy is still controversial. We therefore performed a prospective study in patients with poorly controlled epilepsy treated with TPM, predominantly in combination with other antiepileptic drugs. The goal of the study was to investigate the relationship between the occurrence of adverse events due to TPM and its serum concentration or dosage, respectively.
  
  
  METHODS
  The relationship between the occurrence of adverse events and TPM serum concentration or dosage, respectively, was examined in a group of 42 young adult and adult patients with poorly controlled epilepsy. Within 22 months, all patients treated with TPM had been included in the study. The 8 adverse events occurring most frequently (difference > or = 10%) in TPM-treated patients in 5, double-blind, placebo-controlled, parallel group studies, were checked regularly. This side effect profile has been presented by Reife et al. (1995a). Other possible or probable adverse events were also documented.
  
  
  RESULTS
  The difference in TPM serum concentrations and TPM dosages (mg/kg) for patients without an adverse event, and patients with a given adverse event was statistically significant for "abnormal thinking, impaired concentration, weight loss, dizziness, speech problems, somnolence, ataxia, increased seizure frequency and paresthesia". To avoid adverse events, we recommend an initial "maintenance serum concentration" of below 4 microg/mL. As regards the TPM dosage, our results suggest initial maintenance dosages of 100 TPM or lower, 1.5 mg/kg or lower, respectively. These conclusions are limited by the relatively small number of patients.
authors.affiliation: Department of Neurology and Epileptology, the Epilepsy Center Bodensee, Die Weissenau, Germany. w.froescher@arcor.de
authors.forename: Walter
authors.initials: W
authors.lastname: Fröscher
authors.forename: Katja R
authors.initials: KR
authors.lastname: Schier
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer
authors.forename: Theodor W
authors.initials: TW
authors.lastname: May
authors.forename: Bernhard
authors.initials: B
authors.lastname: Rambeck
authors.forename: Johannes
authors.initials: J
authors.lastname: Rösche
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose