TY - JOUR
TI - Brand-to-generic levetiracetam switch in patients with epilepsy in a routine clinical setting
AU - Markoula, S.
AU - Chatzistefanidis, D.
AU - Gatzonis, S.
AU - Siatouni, A.
AU - Siarava, E.
AU - Verentzioti, A.
AU - Kyritsis, A.P.
AU - Patsalos, P.N.
JO - Seizure
PY - 2017
VL - 48
TODO - null
SP - 1-6
PB - W.B. Saunders Ltd
SN - 1059-1311
TODO - 10.1016/j.seizure.2017.03.012
TODO - bromazepam;  carbamazepine;  citalopram;  clobazam;  clonazepam;  ferrous sulfate;  generic drug;  haloperidol;  lacosamide;  levetiracetam;  omeprazole;  oxcarbazepine;  phenobarbital;  pregabalin;  ramipril;  topiramate;  valproic acid;  zonisamide;  anticonvulsive agent;  etiracetam;  generic drug;  piracetam, adult;  aged;  anticonvulsant therapy;  area under the curve;  Article;  bioequivalence;  blood sampling;  clinical article;  concentration at steady-state;  drug blood level;  drug efficacy;  drug substitution;  drug tolerability;  drug withdrawal;  epilepsy;  female;  follow up;  human;  liquid chromatography-mass spectrometry;  male;  maximum plasma concentration;  middle aged;  open study;  plasma concentration-time curve;  priority journal;  prospective study;  time to maximum plasma concentration;  treatment duration;  unspecified side effect;  young adult;  analogs and derivatives;  clinical trial;  drug substitution;  epilepsy;  therapeutic equivalence;  treatment outcome, Adult;  Anticonvulsants;  Drug Substitution;  Drugs, Generic;  Epilepsy;  Female;  Humans;  Male;  Piracetam;  Prospective Studies;  Therapeutic Equivalency;  Treatment Outcome
TODO - Purpose The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution. Methods A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4 ± 16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded. Results Patients had epilepsy for a mean period of 14.1 ± 10.6 years and the mean daily LEV dose was 2583.3 ± 763.7 mg. The mean AUC ± SD and Cmax ± SD was 288.4 ± 86.3 (mg/L) h and 37.8 ± 10.4 mg/L respectively for brand LEV and 319.2 ± 104.7 (mg/L) h and 41.6 ± 12.3 mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded. Conclusions In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV. © 2017 British Epilepsy Association
ER -