Pharmacokinetic and pharmacodynamic evidence of adrenaline administered via auto‐injector for anaphylactic reactions: A review of literature

Abstract

Anaphylaxis is a severe allergic reaction that can lead to death if not treated quickly. Adrenaline (epinephrine) is the first‐line treatment for anaphylaxis and its prompt administration is vital to reduce mortality. Following a number of high‐profile cases, serious concerns have been raised, both about the optimal dose of intramuscular adrenaline via an auto‐injector and the correct needle length to ensure maximal penetration every time. To date, the public data are sparse on the pharmacokinetics–pharmacodynamics of adrenaline administered via an auto‐injector. The limited available literature showed a huge variation in the plasma concentrations of adrenaline administered through an auto‐injector, as well as variations in the auto‐injector needle length. Hence, delivering an effective dose during an anaphylaxis remains a challenge for both patients and healthcare professionals. Collaborative work between pharmacokinetics–pharmacodynamics experts, clinical triallists and licence holders is imperative to address this gap in evidence so that we can improve outcomes of anaphylaxis. In addition, we advise inclusion of expertise of human factors in usability studies given the necessity of carer or self‐administration in the uniquely stressful nature of anaphylaxis.

Adrenaline auto injectors pharmacokinetic/pharmacodynamic studies and potential consequences for clinical practice

“…24 The PK/PD profile of adrenaline depends on the AAI used for its delivery. 32 This paper is an attempt to better understand the impact of the devices' functional properties on systemic adrenaline…”

“…Over the last 4 decades, autoinjector technology has been widely used to deliver life–saving adrenaline during an episode of anaphylaxis 24 . The PK/PD profile of adrenaline depends on the AAI used for its delivery 32 . This paper is an attempt to better understand the impact of the devices' functional properties on systemic adrenaline delivery and its subsequent CV response due to the PK/PD profile.…”

“… 24 The PK/PD profile of adrenaline depends on the AAI used for its delivery. 32 This paper is an attempt to better understand the impact of the devices' functional properties on systemic adrenaline delivery and its subsequent CV response due to the PK/PD profile. Throughout the studies, a syringe‐based delivery was a common comparator to the AAIs as adrenaline administered via a syringe and needle is the standard clinical practice.…”

International recommendations on epinephrine auto-injector doses often differ from standard weight-based guidance: a review and clinical proposals

“…For ethical reasons, it is nearly impossible to perform double-blind placebo-controlled studies on the effect of different doses of epinephrine used during anaphylaxis. Recently, Moss et al [ 10 ] proposed that a method to further investigate optimal dosing could involve documentation of serum epinephrine levels in patients reacting during oral provocation challenges. However, patients react to different degrees with different symptoms to different amounts of ingested or injected allergen and there is also variability in the time from exposure to reaction.…”