Rapid increases in epinephrine concentration following presumed intra-blood vessel administration via epinephrine...

While epinephrine autoinjectors have been the standard of care for the out-of-hospital treatment of anaphylaxis, their use has been associated with potential cardiovascular risks including intravascular injection, resulting in rapid increases in blood pressure and pulse rate. ARS Pharmaceuticals, Inc conducted a clinical trial designed to assess the pharmacokinetics and pharmacodynamics of ARS-1, an intranasal epinephrine spray in development, compared to EpiPen in subjects with a documented history of seasonal allergies. During the conduct of this study, a presumed intrablood vessel injection following EpiPen administration by a medical professional was observed in a female subject. The subject reported palpitations within 1 minute of receiving EpiPen injection; at 4 minutes postinjection, blood pressure was 221/128 mmHg (baseline 118/79), and pulse rate was 71 (baseline 56). In contrast, across all subjects (N = 36) the mean maximum increases in systolic blood pressure, diastolic blood pressure, and pulse rate were 12.0 mmHg, 2.8 mmHg, and 16.3 bpm, respectively. When this subject was removed from the pharmacokinetic analysis, the mean epinephrine C_max of the remaining subjects was 801.1 pg/mL after administration of EpiPen; however, at 4 minutes postinjection this subject had a plasma epinephrine level of 4390 pg/mL, a >6.3-fold increase, illustrating the risks that may be associated with out-of-hospital epinephrine injections that are included as warnings in the product labeling. Despite the potential risks associated with accidental intravessel injection, it is important to note that intramuscular administration of epinephrine is currently the best currently available out-of-hospital treatment for severe allergic reactions and anaphylaxis.