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Tolerability and efficacy of oral loading of levetiracetam

From the Department of Neurology (M.Z.K., S.A., I.P., M.A.W.), Case Western Reserve University, Cleveland, OH; and the Department of Neurology (M.Z.K., G.K.B.), Johns Hopkins University, Baltimore, MD.

Address correspondence and reprint requests to Dr. Mohamad Z. Koubeissi, Department of Neurology, University Hospitals Case Medical Center, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5040 mohamad.koubeissi{at}uhhospitals.org

Objective: Nonsedating antiepileptic drugs (AEDs) that can be initiated rapidly are desirable in a variety of clinical situations. Levetiracetam (LEV) is a newer AED, with a recently approved parenteral formulation, that can be initiated at doses effective in controlling seizures. We investigated whether oral loading of levetiracetam is well tolerated and facilitates stabilization and discharge of patients in epilepsy monitoring units (EMU).

Methods: Adult patients in the EMU at two centers were identified who received 1,500 mg of LEV in a single dose. This was an observational study of these patients where LEV was thought to be an appropriate component of the therapeutic regimen. Patients were either LEV naïve or had been off all LEV for at least 3 days. LEV maintenance was begun 12 hours later at doses of 500 to 1,000 mg twice a day.

Results: A total of 37 adult patients (20 female) were identified. There were no spontaneous complaints of side effects. Upon questioning, 33 patients (89%) denied side effects. The remaining 4 patients (11%) reported transient irritability, imbalance, tiredness, or lightheadedness. Eleven patients (mean weight = 85.0 Kg) had mean LEV serum concentration of 31.5 µg/mL after 1 hour, 23 (mean weight 85.7 Kg) had mean concentration of 30.77 µg/mL after 2 hours, five (mean weight 84.3 Kg) had mean concentration of 12.1 µg/mL after 12 hours, and two (mean weight 94 Kg) had mean concentration of 7.4 µg/mL after 14 hours. No seizures occurred within 24 hours of loading. All patients were able to be discharged 3 to 30 hours after loading.

Conclusions: In the population surveyed, oral loading with levetiracetam was well-tolerated and rapidly yielded serum concentrations thought to decrease seizure frequency. This regimen facilitated discharge from the epilepsy monitoring units.

GLOSSARY: AEDs = antiepileptic drugs; CBZ = carbamazepine; CZP = clonazepam; EMU = epilepsy monitoring units; GPN = gabapentin; LEV = levetiracetam; LTG = lamotrigine; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; TPM = topiramate; VPA = valproic acid; ZNS = zonisamide.

Received February 20, 2007. Accepted in final form February 20, 2008.

Disclosure: Dr. Gregory K. Bergey is on speakers' bureau and has been consultant for UCB Pharma. Dr. MaryAnn Werz has received research support from UCB Pharma for research projects different from the current study. The remaining authors report no conflicts of interest.

Presented in part at the American Epilepsy Society meeting, San Diego, December 2006, and at the 59th annual meeting of the American Academy of Neurology, Boston, May 2007.