Best Evidence Analyses and Commentary

Drug Information Question: Should levetiracetam be used first line for posttraumatic seizure prophylaxis?

Yoadys Fernandez, PharmD LECOM 2012

Response

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 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.



References

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, AN: 70191562

Cotton, Kao, Kozar, Holcomb. Cost-utility analysis of levetiracetam and phenytoin for postraumattic seizure prophylaxis. Trauma. 2011, 71 (375-379).

Jones, Puccio, Harshman. Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury. Neurosurgery focus. 2008, 25

Pieracci, Moore, Beauchamp. Acost-minimization analysis of phenytoin versus levetiracetam for early seizure pharmacoprophylaxis after traumatic brain injury. Trauma. 2011, 72 (276-281)


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