In this episode, I’ll discuss the optimal dosing of levetiracetam for seizure prophylaxis in critically ill patients.
When used for seizure prophylaxis following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery levetiracetam doses used are often very low. However, critically ill patients typically have higher clearance rates of levetiracetam, and this may contribute to decreased efficacy.
A group of authors recently published a prospective observational study in Critical Care Medicine looking at differences in efficacy for low vs high dose levetiracetam for seizure prophylaxis in the neurocritical patient population.
Low dose levetiracetam was defined as 500 mg twice daily while high dose was defined as 750 to 1000 mg twice daily.
All levels were obtained at steady state and the authors examined both the likelihood of a level in the target range of 12 to 46 mcg/mL and the incidence of seizures.
106 patients received a low dose and 99 patients received a high dose of levetiracetam. 45% in the low dose group vs 64% in the high dose group achieved a steady state level in the target range, a difference that was statistically significant.
After adjustment for several variables, the high dose group was associated with a reduced incidence of seizure with a statistically significant odds ratio of 0.32.
The authors concluded:
Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750–1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid).
This is an excellent study that should help bring clarity to the optimal dose of levetiracetam to use for seizure prophylaxis as previous authors have noted that the wide range of dosing protocols may prevent significant decreases in seizure incidence. When translating this research into practice it will be important to clarify to providers that the “high dose” group did not represent a dose of levetiracetam that was higher than previously studied – rather that the dose given simply needs to be higher than 500 mg twice daily to have the best effect.
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