Epinephrine for Anaphylaxis

November 19, 2020
Epinephrine for Anaphylaxis

Question
In the recent times, anaphylaxis frequency is increasing and management is difficult and epinephrine auto-injectors are not available in some countries, while adrenaline injection self-administration is difficult. What are some alternate routes of administration of adrenaline by sublingual route; 40 mgs appears promising, do you recommend for routine use in our patients? Please let us know its efficacy in the management of anaphylaxis.

Answer
Anaphylaxis is an acute, potentially life-threatening hypersensitivity reaction, involving the release of mediators from mast cells, basophils and recruited inflammatory cells. Most cases are mild but any anaphylactic reaction has the potential to become fatal. Although reported cases of anaphylaxis have increased in recent years, adequate diagnosis and management remains a challenge (1,2).

As a first-line international indication, people with a history of anaphylaxis should always carry an epinephrine auto-injector for urgent intramuscular administration (3-5). Despite the lifesaving role of auto-injectors, several factors hinder their accessibility and proper use, such as high cost, lack of local availability, fear of injections, training failure, and diagnostic delay (6,7).

Consequently, sublingual administration of epinephrine was proposed. High vascularity of the sublingual mucosa and epinephrine low molecular weight allow rapid drug absorption through the sublingual veins into the bloodstream (8). Rapidly-disintegrating sublingual tablets (RDSTs) of epinephrine, which can deliver medication in less than 30 seconds, have two major advantages: easier administration and prolonged life time (at least 7 years) in solid state, compared to the limited shelf-life (18 months) of epinephrine (8). Furthermore, RDSTs are hard enough to withstand cutting and handling (8).

Now, the principal matter is whether the sublingual route achieves the same anti-anaphylaxis activity as the intramuscular one. A recent study showed a similar plasma concentration after epinephrine administration using either 40 mg RDSTs or 0.3 mg intramuscular injections (9).

Finally, it is essential to improve awareness of anaphylaxis worldwide, educate the general community on epinephrine use, and guarantee epinephrine availability to all people with an increased risk of anaphylaxis (10).

References

1. Wang Y, Allen KJ, Suaini NHA, McWilliam V, Peters RL, Koplin JJ. The global incidence and prevalence of anaphylaxis in children in the general population: A systematic review. Allergy. junio de 2019;74(6):1063-80.
2. de Silva D, Singh C, Muraro A, Worm M, Alviani C, Cardona V, et al. Diagnosing, managing and preventing anaphylaxis: Systematic review. Allergy. 2 de septiembre de 2020;
3. Song TT, Lieberman P. Who needs to carry an epinephrine autoinjector? Cleve Clin J Med. enero de 2019;86(1):66-72.
4. Alviani C, Burrell S, Macleod A, Edees S, Roberts G, Turner P, et al. Anaphylaxis Refractory to intra‐muscular adrenaline during in‐hospital food challenges: a case series and proposed management. Clin Exp Allergy [Internet]. 30 de septiembre de 2020 [citado 4 de octubre de 2020]; Disponible en: https://onlinelibrary.wiley.com/doi/10.1111/cea.13749
5. Burrell S, Patel N, Vazquez-Ortiz M, Campbell DE, DunnGalvin A, Turner PJ. Self-administration of adrenaline for anaphylaxis during in-hospital food challenges improves health-related quality of life. Arch Dis Child. 18 de septiembre de 2020;archdischild-2020-319906.
6. Lieberman JA, Wang J. Epinephrine in anaphylaxis: too little, too late. Curr Opin Allergy Clin Immunol. octubre de 2020;20(5):452-8.
7. Glassberg B, Nowak-Wegrzyn A, Wang J. Factors Contributing to Underuse of Epinephrine Autoinjectors in Pediatric Patients with Food Allergy. Ann Allergy Asthma Immunol [Internet]. septiembre de 2020 [citado 4 de octubre de 2020]; Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S1081120620310115
8. Rachid O, Simons KJ, Rawas-Qalaji M. In Vivo Evaluation of Taste-Masked Fast-Disintegrating Sublingual Tablets of Epinephrine Microcrystals. AAPS PharmSciTech. noviembre de 2018;19(8):3886-94.
9. Rachid O, Rawas-Qalaji M, Simons K. Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use. Pharmaceutics. 11 de febrero de 2018;10(1):24.
10. Yuenyongviwat A, Wirodwanich T, Jessadapakorn W, Sangsupawanich P. Utility of an educational video on epinephrine prefilled syringe usage for anaphylaxis: a randomized control trial. Asia Pac Allergy [Internet]. 2020 [citado 4 de octubre de 2020];10(3). Disponible en: https://apallergy.org/DOIx.php?id=10.5415/apallergy.2020.10.e32

Author
Marie Angelique Lazo-Betetta, MD

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