A newsletter from the Institute for Safe Medication Practices (ISMP) suggests lorazepam injection vial is both physically and chemically stable for up to 60 days at room temperature. However, ISMP does not make recommendations regarding the extension of beyond-use dates outside of manufacturer-approved recommendations. [1], [2]
Communication with Wyeth Pharmaceuticals (a subsidiary of Pfizer, Inc.), the original manufacturer of Ativan (lorazepam) provided unpublished data that found unopened vials remained stable for up to 6 weeks at room temperature (25°C). Although the product remained within specification, the manufacturer does not advocate the use of these products past expiration. [3]
A study evaluated lorazepam 2 mg/mL injectable solutions in clear glass syringes under refrigeration (4-10 °C), at ambient temperatures (15-30 °C), and at oven-heated temperatures (38 °C) for up to 210 days (see Table 2). Results showed lorazepam retained 90% of its original concentration for 150 days at ambient temperature. A similar study measured the stability of lorazepam 4 mg/mL for emergency use under refrigeration, at room temperature, and in a helicopter (mean 11.8 °C) for up to 4 months (see Table 4). At room temperature, the lorazepam solution lost ~22% of its original concentration after 4 months, but the samples under refrigeration and in the helicopter were still stable. This data suggest temperature is the main cause of degradation and the effect of vibrations is negligible. [4], [5]
Prefilled disposable single-use glass syringes with lorazepam 2 mg/mL were studied in instrumented boxes in an emergency medicine environment (variations in ambient temperature). After 60 days, lorazepam maintained a clinically acceptable concentration. This study (See Table 3) had a large variability in temperatures and the authors failed to report the amount (percentage) of degradation observed. [6]
A 2020 study evaluated the long-term stability of lorazepam in sodium chloride 0.9% in polypropylene syringes stored at 5 ± 3°C and room temperature compared to glass bottles at 5 ± 3°C and at room temperature. Eight polypropylene Becton Dickinson (BD) syringes and 6 glass bottles were prepared under aseptic conditions by diluting 1 mL of lorazepam solution 4 mg/mL in 23 mL of sodium chloride solution to a final concentration of 167 mcg/mL. One mL of solution was withdrawn from each syringe and bottle on day 0 (day of preparation) and after 1, 2, 3, 4, and 7 days to perform physical stability testing. An additional 20 microliters were frozen at 80°C for chemical stability testing. Samples were tested for particle, haze, precipitation, and color change. Optical densities (ODs) were measured with a spectrophotometer to search for subvisible particles and assess turbidity; pH was also measured. After 4 days, crystals were detected in syringes stored at 5 ± 3 °C as well as a decrease in OD at 350 nm. Crystallization was also detected after 7 days in syringes at room temperature, 3 days in bottles at 5 ± 3°C, and 2 days in bottles at room temperature. No samples were found to have altered pH, color, or absorbance at 410 nm at any time point during storage. After 2 days, solutions of lorazepam stored in syringes at 5 ± 3°C were considered to be chemically unstable due to a loss of lorazepam concentration greater than 10%. It was concluded this lack of stability prohibits advance preparation. Storage conditions, including temperature and storage form, did not appear to improve stability. [7]
A 2017 study evaluated the physical stability of injectable lorazepam 0.16 mg/mL prepared in polypropylene syringes and stored at room temperature. Under aseptic conditions, 30-mL syringes were prepared, each containing 4 mg of lorazepam diluted into 23 mL of sodium chloride solution for a total volume of 24 mL (0.16 mg/mL). Syringes were stored at room temperature in order to mimic the clinical conditions of administration in the intensive care unit. Immediately after the preparation (hour 0) and after 1, 4, 8, 24, and 48 hours, 2 mL of each solution were withdrawn from each syringe and placed in glass tubes to proceed with the stability test. The pH of the solutions was measured at each time by a glass electrode pH-meter, and all specimens underwent spectrophotometric measurements at three wavelengths (350, 410, and 550 nm). Measurements of pH at each time showed no significant change during storage. The average pH was 7.30 ± 0.23 (minimum 7.06, maximum 7.54), and average spectrophotometric measurements at 350, 410, and 550 nm were 0.07 ± 0.001, 0.001 ± 0.0007, and 0.00003 ± 0.0001, respectively. Additionally, no color change, turbidity, opacity, or precipitation was observed in the solutions during storage for 48 hours. Microaggregates were not detected by microscope. Based on these results, lorazepam 0.16 mg/mL appears physically stable in 0.9% sodium chloride polypropylene syringes when stored at room temperature for 48 hours. [8]