Abstracts

Rationale: Levetiracetam became available as an intravenous formulation in 2006. Early safety and pharmacokinetic studies of intravenous levetiracetam were conducted before its pediatric indication and involved patients over 16 years of age and oral formulations. The current package insert suggest diluting the medication in 100 ccs of saline and administering the drug over at least 15 minutes. Safety information is needed on the use of intravenous levetiracetam in children. Additionally, many patients require rapid achievement of high therapeutic concentrations, with smaller infusion volumes. The objective of this study was to evaluate the safety of intravenous levetiracetam in children, adolescents, and young adults when given as a rapid infusion and in smaller fluid amounts. Methods: After obtaining IRB approval, an open label, prospective single centered analysis of the safety of intravenous levetiracetam was performed in patients with epilepsy, ages 3-32 years. The safety and tolerability of a rapid loading dose of IV levetiracetam with minimal dilution was assessed. Safety reviews were conducted by an independent data safety monitoring board (DSMB) after each infusion group was complete, before going to the next higher infusion dose and rate. IV levetiracetam was initially given to 15 patients at a dose of 20 mg/kg (maximum dose of 1 gm), then a second group was enrolled with a dose of 40 mg/kg (maximum single dose 2,000 mg), and then a third group was enrolled at 60 mg/kg per dose (maximum dose 3 gms). The drug was diluted 1-1 with normal saline and given as a five-minute infusion for the first two groups, and a six minute infusion for the third group. Vital signs and inspection of the infusion site was monitored prior to the infusion, during the infusion and after the infusion up to 24 hours. Results: To date, 37 patients have received a single dose of IV levetiracetam with the minimal dilution at rapid infusion. Total levetiracetam doses ramged from 280 mg - 3000 mg. Therapeutic levetiracetam levels were obtained at the end of the infusion (range 13.5 - 188.6 mcg/ml). Fifteen patients have received a dose of 20 mg/kg (or a maximum of 1 gm), and a second group of 15 patients received a loading dose of 40 mg/kg (maximum dose of 2 Gm) with no peripheral side effects and no changes in hemodynamic parameters. To date seven patients have received a single dose of 60 mg/kg (maximum dose 3,000 mgs) with no change in peripheral infusion site or hemodynamic side effects. However, two complained of mild pain during the infusion, one of which required the infusion to be stopped. Conclusions: This study supports the safety of rapid infusion of intravenous levetiracetam with minimal dilution, at doses from 20 to 60 mgs/kgs per dose (maximum 1 - 3 gms per dose) in children, adolescents and young adults ages three to 32 years. Mild pain at the infusion site may be seen with the highest dose, but stops at the end of the infusion. The study has important implications for the treatment of seizure emergencies. Research supported by the Shainberg Foundation