Stability of Naloxone in Normal Saline for Continuous Infusion

Administration of naloxone by continuous infusion for treatment of respiratory depression associated with long-acting opioids often necessitates extemporaneous preparations at drug concentrations that exceed the manufacturer's recommendation. The purpose of this study was to evaluate the stability of naloxone hydrochloride (N-HCl) in 0.9% sodium chloride at concentrations of 40, 80, and 200 mcg/mL.

The appropriate volume was withdrawn from commercially available vials of N-HCl (400 mcg/mL) and injected into 100 mL 0.9% sodium chloride IV bags, which were then stored at room temperature under ambient laboratory lighting for at least four days. The 80 mcg/mL IV bags were also protected from light and evaluated over eight weeks. Samples were withdrawn over time and analyzed by high performance liquid chromatography to determine drug concentration.

The initial measured drug concentrations, expressed as a percentage of the theoretical values adjusted for overfill volume, ranged from 97.9% to 101.5% and remained above 97.5% of the initial values for four days. Measured drug concentrations in the 80 mcg/mL samples also remained high over the eight-week period, decreasing by about three percentage points. In addition, no significant difference in measured drug concentration was found between IV bags stored in amber sleeves and those exposed to ambient laboratory lighting.

Extemporaneously compounded N-HCl in 0.9% normal saline IV bags at concentrations of up to 200 mcg/mL was stable over a four-day period when stored unprotected from ambient laboratory light at room temperature. Moreover, IV bags prepared at concentrations of 80 mcg/mL were also stable over an eight-week period. Ambient laboratory lighting did not adversely affect drug stability in the timeframe studied.