Chemical Compatibility of Depacon® with Medications Frequently Administered by Intravenous Y-Site Delivery in Patients with Epilepsy or Head Trauma

Abstract

Intravenous Y-site administration of more than one medication through the same in-line catheter is a common practice used in the management of acute seizures. The objective of this study was to determine the compatibility of valproate sodium (Depacon(®); 2 or 20 mg/mL) with 13 medications that are frequently administered to manage seizures or are given to patients with an acute head injury who are at risk for developing post-traumatic epilepsy. The study medications included atracurium, dexamethasone, diazepam, fosphenytoin, lorazepam, magnesium sulfate, mannitol, methyl-prednisolone, midazolam, pentobarbital, phenytoin, ranitidine, and thiopental. Equal volumes of valproate and each of the study drugs were admixed and immediately examined using several physiochemical criteria: Tyndall effect, color and pH change, gas evolution, and particle formation (HIAC/Royco liquid particle counter). Samples were also evaluated using HPLC analysis (C(18) column; methanol/tetrahydrofuran/ phosphate buffer; 44/1/55% v/v, at 1.5 mL/min; 50°C) with UV (190-400 nm) photodiode detection. The valproate peak (220 nm) was quantified by both peak area and height. Samples were analyzed within 5 minutes of admixture and were reassessed at 15 and 30 minutes. With the exception of diazepam, midazolam, and phenytoin, all of the remaining drugs were chemically compatible with valproate, both in 5% Dextrose Injection, USP(D5W) and in 0.9% Sodium Chloride Injection, USP (Normal Saline -NS). None of the compatible medications produced a significant pH change, discernible gas, particle formation, reduced valproate titer by HPLC analysis (coefficient of variability < 1.5%), or the temporal formation of unidentified UV absorbing (190-400 nm) peaks. Intravenous valproate is compatible with most agents employed in seizure management or used in patients at risk for seizures following head injury and is safe for concurrent Y-site drug administration.