Evaluation of the Safety of Rapid Administration of Undiluted High-Dose Intravenous Levetiracetam

Abstract

Background Intravenous (IV) levetiracetam (LEV) is an antiseizure medication traditionally given as an intermittent infusion to mitigate potential adverse effects given its acidic formulation. The process of compounding may lead to delays in treating status epilepticus, which is why administration of undiluted doses is of interest. Prior studies have shown safety of IV doses from 1000 mg to 4500 mg; however, assessments of adverse side effects outside IV site reactions have not been studied. Methods A retrospective analysis was completed with patients who received 1500 mg doses of undiluted IV LEV. We included patients ≥ 18 years old that received at least 1 dose of IV LEV 1500 mg from January 2018 to February 2021. Study end points included assessment of hemodynamic disturbance (bradycardia [HR less than 50 beats per minute] or hypotension [SBP less than 90 mmHg] within 1 hour or documented infusion reaction within 12 hours of LEV. Descriptive statistics were utilized. Results A total 213 doses of 1500 mg of IV LEV were administered to 107 patients. Peripheral lines were used for 85.9% of doses. Approximately half of doses (57) were administered to patients on the general wards, with the remainder in the intensive care unit or emergency department. Two patients (1.9%) experienced bradycardia; however, 1 patient had pre-existing bradycardia. Three patients (3.8%) experienced hypotension; however, those patients were receiving vasopressors prior to the dose. There were no cases of infusion reaction. Conclusion Undiluted, rapid administration of IV LEV 1500 mg was well tolerated and safe.

The safety of rapid infusion levetiracetam: A systematic review

“…14 The third trial showed a few cases of hypotension and bradycardia that were explained by other patient factors and no infusion-related reactions. 16 The results discussed in this review article support the safe administration of levetiracetam as a rapid intravenous bolus given over 5 min. This method of administration would be beneficial in all areas of the hospital especially in times of nursing shortages.…”

“…The remaining three retrospective studies evaluated the use of undiluted levetiracetam given as a rapid intravenous infusion and are detailed in Tables 1 and 2 13,14,16 . One study looked specifically at doses of less than or equal to 1000 mg 13 .…”

“…Another study had very few infusion reactions that were not convincingly related to the administration of levetiracetam 14 . The third trial showed a few cases of hypotension and bradycardia that were explained by other patient factors and no infusion‐related reactions 16 …”

“…18 Another three trials looked at administration of undiluted levetiracetam given as an infusion completed in 5 min or less with one trial including doses up to 4500 mg. 14 These trials also showed very few adverse drug reactions. 13,14,16 One trial showed no concentration-related side effects with undiluted levetiracetam administered over 2-5 min. 13 Another study had very few infusion reactions that were not convincingly related to the administration of levetiracetam.…”

“…Many of these studies also showed that giving levetiracetam as a rapid administration could be done through a peripheral line. 10,13,14,16,18 An open-label, prospective, single-center study in which a 100mg/ml solution of levetiracetam was diluted 1:1 with either normal saline or dextrose 5% in water and given peripherally showed that doses up to 3000 mg could be given safely as an infusion over 5 min. There were two infusion site reactions out of 45 patients and one of these resolved with a new infusion site.…”