Rapid administration of undiluted IV push valproic acid

Delays associated with traditional intravenous (IV) infusion of valproic acid (VPA) may lead to delays in emergent seizure treatment and headache management. Undiluted IV push (IVP) administration of VPA may be safe and well tolerated; however, evidence evaluating safety across dosing ranges is limited. This study evaluated the safety and tolerability of IVP administration of undiluted VPA for doses up to 4000 mg.

This was a retrospective, observational, single-center cohort analysis of patients who received at least 3 doses of IVP VPA between January 1, 2020 and May 27, 2025, at a large academic medical center in Phoenix, Arizona. Outcomes of interest include the safety and tolerability associated with rapid administration of undiluted VPA.

We evaluated 570 patients who received 5546 doses of undiluted IVP VPA. Fifty-five loading doses were administered, with 3000 mg administered in 33% of cases. The most common maintenance dose was 500 mg (78.6%). Peripheral IV access was documented in 67.6% of administered doses. Three adverse events were identified, none of which were classified as probable or definite drug-related reactions according to the Naranjo scale.

Undiluted IVP VPA demonstrated a favorable safety and tolerability profile across more than 5500 administered doses, including a cohort of loading doses. These findings provide additional evidence supporting rapid administration of VPA across clinical indications, especially in time-sensitive clinical scenarios.