title: Levetiracetam versus phenytoin for seizure prophylaxis during and early after craniotomy for brain tumours: a phase II prospective, randomised study.
abstract: OBJECTIVE
  Phenytoin (PHT) is routinely used for seizure prophylaxis in patients with brain tumours during and after craniotomy, despite incomplete evidence. We performed a prospective, randomised study to investigate the significance of prophylactic use of levetiracetam (LEV), in comparison with PHT, for patients with supratentorial tumours in the perioperative period.
  
  
  METHODS
  Patients were randomised to receive LEV, 500 mg/body every 12 h until postoperative day 7, or PHT, 15-18 mg/kg fosphenytoin followed by 125 mg PHT every 12 h until postoperative day 7. The primary end point was the occurrence of seizures, and secondary end points included the occurrence of haematological and non-haematological adverse events.
  
  
  RESULTS
  One hundred and forty-six patients were randomised to receive LEV (n=73) or PHT (n=73). The incidence of seizures was significantly less in the LEV group (1.4%) compared with the PHT group (15.1%, p=0.005), suggesting benefit of LEV over PHT. The observed OR for being seizure free in the LEV prophylaxis group relative to the PHT group was 12.77 (95% CI 2.39 to 236.71, p=0.001). In a subgroup analysis of patients who did not have seizures before craniotomy, similar results were demonstrated: the incidence of seizures was 1.9% (LEV) and 13.8% (PHT, p=0.034), and OR was 8.16 (95% CI 1.42 to 154.19, p=0.015). LEV was completed in all cases, although PHT was withdrawn in five patients owing to liver dysfunction (1), skin eruption (2) and atrial fibrillation (2).
  
  
  CONCLUSIONS
  Prophylactic use of LEV in the perioperative period is recommended because it is safe and significantly reduces the incidence of seizures in this period.
  
  
  BACKGROUND
  UMIN13971.
authors.affiliation: Division of Neurological Surgery, Chiba Cancer Centre, Chiba, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iuchi
authors.affiliation: Division of Pharmacy, Chiba Cancer Centre, Chiba, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kuwabara
authors.affiliation: Division of Pharmacy, Chiba Cancer Centre, Chiba, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Division of Neurological Surgery, Chiba Cancer Centre, Chiba, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawasaki
authors.affiliation: Division of Neurological Surgery, Chiba Cancer Centre, Chiba, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Division of Neurological Surgery, Chiba Cancer Centre, Chiba, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakaida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000150:complications / Q000601:surgery*; D015331:Cohort Studies; D003399:Craniotomy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D010672:Phenytoin / Q000009:adverse effects / Q000627:therapeutic use*; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control*; D011446:Prospective Studies; D012640:Seizures / Q000517:prevention & control*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010672:Phenytoin; D010889:Piracetam
keywords: EPILEPSY; NEUROONCOLOGY; NEUROSURGERY