A systematic review of epinephrine stability and sterility with storage in a syringe

Abstract

Background Epinephrine is a lifesaving medication in the treatment of anaphylaxis. Epinephrine auto-injectors are the preferred method of epinephrine administration, but are not universally available or affordable. Little is known about the effects on epinephrine when it is drawn up in advance and stored as prefilled syringes. Objective To study the stability and sterility of epinephrine when stored in syringes. Methods We searched Embase, Medline, and Web of Science in June 2016 for all studies of epinephrine stored in syringes in concentrations between 0.1 and 1 mg/mL that measured epinephrine stability and/or sterility over time, regardless of date published or language. Results Three studies were included, one testing two concentrations of epinephrine. Only one study tested epinephrine 1 mg/mL, the concentration clinically relevant for intramuscular use during anaphylaxis. Neither this study nor the one study testing 0.7 mg/mL epinephrine found significant degradation after 56 and 90 days, respectively. One of the two studies testing epinephrine at a concentration of 0.1 mg/mL found significant degradation by 14 days; the other found no degradation up to 168 days. Two studies tested for bacterial growth, with none detected after 28 and 90 days, respectively. One study tested for fungal growth, with none detected after 90 days. Conclusions Limited evidence suggests that syringes filled with 1 mg/mL epinephrine are stable and sterile for 90 days. More research is needed testing the duration of stability and sterility of prefilled syringes with the 1 mg/mL concentration most commonly used in anaphylaxis, testing more extensively in different storage conditions and across a wider range of marketed syringe brands.

An Evaluation of the Drone Delivery of Adrenaline Auto-Injectors for Anaphylaxis: Pharmacists’ Perceptions, Acceptance, and Concerns

“…It was noted that supply interruptions have caused manufacturing stability data to be reviewed, where certain brands are advising new extended shelf lives [50]. Supply chain issues have also raised awareness of other available options of adrenaline, i.e., pre-filled syringes (which are often not considered and are of least preference due to their complex application technique) [21].…”

“…There has been an increase in child anaphylaxis (72%) and adult anaphylaxis (34%) hospital admissions over the past 5 years in England, with the largest increase in admissions (167%) occurring in London [20]. Adrenaline (also known as epinephrine) is the only first-line medication for anaphylaxis treatment [21] where prompt injection is crucial to preserve a patient's life. Adrenaline is licensed as a dilute solution for injection in the forms of ampoules, auto-injectors, pre-filled syringes, and inhalers [22], with patient preference residing in the auto-injector subtype [23].…”

“…Patients who have a known risk of anaphylaxis should carry at least one auto-injector [21] with them due to the danger of an unpredictable onset, with the UK government recommending the carrying of two auto-injectors [18]. Manufacturers recommend that, "Adrenaline should be stored in a dark place, protected from light, at room temperature 20-25 °C (where excursions 15-30 °C are permitted).…”

“…However, in the real world, strict adherence to these storage conditions for individuals may not always be possible and may conflict with the idea of ensuring a reliable dose [29]. There are currently universal supply chain issues [30] with EpiPen ® -they are becoming increasingly unavailable and unaffordable [21] as manufacturers are increasing their prices, which impacts greatly on patient safety [31].…”

Prefilled Cyclic Olefin Sterilized Syringes of Norepinephrine Injection Solution Do Not Need to Be Stabilized by Antioxidants

“…A further disadvantage of sodium metabisulfite is the possible adverse events due to sulfite hypersensitivity of patients which can result in symptoms varying from mild discomfort up to life-threatening episodes and even death ( 12 , 13 ). In a recently published systematic review, various results have been found about the stability of epinephrine ( 14 ).…”