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).
A retrospective 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 phenytoin.
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
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