On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10. The FDA has provided the following information for patients, family members, and caregivers at http:///Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/.
Levetiracetam at concentrations of up to 10 µM did not demonstrate binding affinity for a variety of known receptors, such as those associated with benzodiazepines, GABA (gamma-aminobutyric acid), glycine, NMDA (N-methyl-D-aspartate), re-uptake sites, and second messenger systems. Furthermore, in vitro studies have failed to find an effect of levetiracetam on neuronal voltage-gated sodium or T-type calcium currents and levetiracetam does not appear to directly facilitate GABAergic neurotransmission. However, in vitro studies have demonstrated that levetiracetam opposes the activity of negative modulators of GABA- and glycine-gated currents and partially inhibits N-type calcium currents in neuronal cells.
Status Epilepticus: Loading Dose:
Infants, Children: 15 to 20 mg/kg IV in a single or divided doses
Anticonvulsant: Loading Dose:
All ages: 15 to 20 mg/kg orally (based on phenytoin serum concentrations and recent dosing history). The oral loading dose should be given in 3 divided doses administered every 2 to 4 hours.
Anticonvulsant: Maintenance Dose:
(IV or oral) (Note: May initially divided daily dose into 3 doses/day, then adjust to suit individual requirements.)
Less than or equal to 4 weeks: Initial: 5 mg/kg/day in 2 divided doses
Usual: 5 to 8 mg/kg/day IV in 2 divided doses (may require dosing every 8 hours).
Greater than or equal to 4 weeks: Initial: 5 mg/kg/day in 2 to 3 divided doses
Usual: (may require up to every 8 hour dosing)
6 months to 3 years: 8 to 10 mg/kg/day
4 to 6 years: to 9 mg/kg/day
7 to 9 years: 7 to 8 mg/kg/day
10 to 16 years: 6 to 7 mg/kg/day