Question: Should levetiracetam be used first line for posttraumatic seizure prophylaxis?
Yoadys Fernandez, PharmD LECOM
Seizures are a recognized complication in
patients with acute traumatic brain injury. Within the first week or two after injury, post
traumatic seizure incidence is about 6-10 % but may be as high as 30 % in severe patients. Seizure
prophylaxis during the first seven days post-trauma has been shown to reduce the incidence of early
seizures; however it does not necessarily prevent the later development of epilepsy. Phenytoin (Dilantin) has been the agent of choice for many
years, but due to its potential for drug interaction, numerous side effects and need for close
serum drug monitoring, many clinicians substitute it with levetiracetam (Keppra).
cohort conducted by Carter and colleagues evaluated the use of phenytoin and levetiracetam in
patients with traumatic brain injury who received early post-traumatic seizure prophylaxis between
January 2007 and August 2008. A total of 101 patients met the inclusion criteria: 36 patients were
in the levetiracetam group and 65 patients in the phenytoin group. The study concluded that the
incidence of seizure and adverse effects were not significantly different between the groups
(seizures-10.9% in the phenytoin group versus 16.2% in the levetiracetam; adverse effects-6.3% in
the phenytoin group versus 8.1% in the levetiracetam group).
A cost minimization analysis comparing both agents indicated
equal effectiveness between them in the prevention of seizures; however, the mean institutional
cost per patient was approximately $151 for phenytoin versus $ 411 for levetiracetam. They also
analyzed the mean charge per patient and it was approximately $ 2,300 vs. $3,500 in favor of
Levetiracetam became the dominant strategy only in the
presence of marked mental status deterioration associated with phenytoin therapy.
A cost utility analysis conducted by Cotton and colleagues
also favored phenytoin for posttraumatic seizure prophylaxis unless levetiracetam prevented 100 %
of seizures and cost less than $ 400 for a 7 day course. The cost/effectiveness ratio were
$1.58/QALY for phenytoin versus $ 20.72/QALY for levetiracetam. This led to the conclusion that
phenytoin was more cost effective than levetiracetam at all reasonable prices.
Further analysis would be required to
reassess this recommendation once levetiracetam becomes more affordable and more robust clinical
trials are available demonstrating a significant clinical advantage over phenytoin for the
prevention of seizures in patients with posttraumatic brain injury.
Carter D., Askari R., Frawley B., Rogers
S . Evaluation of the use of phenytoin
and levetiracetam for seizure prophylaxis in patients with traumatic brain injury. Conference Abstract. 2009,
Cotton, Kao, Kozar, Holcomb. Cost-utility analysis of
levetiracetam and phenytoin for postraumattic seizure prophylaxis. Trauma. 2011, 71
Jones, Puccio, Harshman. Levetiracetam versus phenytoin
for seizure prophylaxis in severe traumatic brain injury. Neurosurgery focus. 2008,
Moore, Beauchamp. Acost-minimization analysis of phenytoin versus levetiracetam for early seizure
pharmacoprophylaxis after traumatic brain injury. Trauma. 2011, 72