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Epinephrine for Anaphylaxis


In the recent times, anaphylaxis frequency is increasing and management is difficult. Epipen is not available in India. Adrenalin Injection self-administration is difficult.

Alternate routes of administration of Adrenalin 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.


The sublingual route of administration is indeed a promising alternative route for adrenaline administration for several reasons. Drugs that are absorbed sublingually bypass metabolic conversion, and reach the systemic circulation in a pharmacologically active form (7, 8).  Drugs with a low molecular weight such as epinephrine are absorbed across the sublingual mucosa into the venous circulation by transcellular diffusion (9), a mechanism driven by the concentration gradient. Sublingual epinephrine tablets should be less expensive to produce than the currently available autoinjectors are. They are unobtrusive to carry and to self-administer, and repeat dosing is practical. They can be formulated in a range of epinephrine doses to provide accurate dosing for individuals with a wide range of body weights.

Although first pharmacokinetic data from rats published in 2006 (10) showed promising data, studies in humans using this route of application have not been published in detail yet. More recent publications indicated an improvement of the epinephrine tablet formulation resulting in promising data in preclinical models. This opens possibilities to further establish this route of application in clinical practice. As no clinical studies in humans have been performed yet the tablet is in a developmental stage currently and therefore not available as a licensed drug (11, 12).


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Mullins RJ, Dear KB, Tang ML (2015). Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012. J Allergy Clin Immunol 136(2):367-375.

Dyer AA, Lau CH, Smith TL, Smith BM, Gupta RS (2015). Pediatric emergency department visits and hospitalizations due to food-induced anaphylaxis in Illinois. Ann Allergy Asthma Immunol 115(1):56-62.

Simons FE, Ebisawa M, Sanchez-Borges M, Thong BY, Worm M, Tanno LK, Lockey RF, El-Gamal YM, Brown SG, Park HS, Sheikh A (2015). World Allergy Organ J 28;8(1):32.

Muraro A1, Roberts G, Worm M, Bilò MB, Brockow K, Fernández Rivas M, Santos AF, Zolkipli ZQ, Bellou A, Beyer K, Bindslev-Jensen C, Cardona V, Clark AT, Demoly P, Dubois AE, DunnGalvin A, Eigenmann P, Halken S, Harada L, Lack G, Jutel M, Niggemann B, Ruëff F, Timmermans F, Vlieg-Boerstra BJ, Werfel T, Dhami S, Panesar S, Akdis CA, Sheikh A; EAACI Food Allergy and Anaphylaxis Guidelines Group (2014). Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy 69(8):1026-45.

Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Bernstein J, Ellis A, Golden DB, Greenberger P, Kemp S, Khan D, Ledford D, Lieberman J, Metcalfe D, Nowak-Wegrzyn A, Sicherer S, Wallace D, Blessing-Moore J, Lang D, Portnoy JM, Schuller D, Spector S, Tilles SA (2015). Anaphylaxis--a practice parameter update 2015. Ann Allergy Asthma Immunol 115(5):341-84.

Rachid O, Rawas-Qalaji M, Simons FER, Simons KJ (2012). Rapidlydisintegrating sublingual tablets of epinephrine: role of nonmedicinal ingredients in formulation development. Eur J Pharm Biopharm. 82(3):598–604.

Rachid O, Simons FE, Rawas-Qalaji M, Simons KJ (2010). An electronic tongue: evaluation of the masking efficacy of sweetening and/or flavoring agents on the bitter taste of epinephrine. AAPS PharmSciTech 11(2):550–7.

Muller RH, Gohla S, Keck CM (2011). State of the art of nanocrystals—special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm 78(1):1–9.

Rawas-Qalaji MM1, Simons FE, Simons KJ (2006). Sublingual epinephrine tablets versus intramuscular injection of epinephrine: dose equivalence for potential treatment of anaphylaxis. J Allergy Clin Immunol 117(2):398-403.

Rawas-Qalaji MM, Werdy S, Rachid O, Simons FE, Simons KJ. Sublingual Diffusion of Epinephrine Microcrystals from Rapidly Disintegrating Tablets for the Potential First-Aid Treatment of Anaphylaxis: In Vitro and Ex Vivo Study. AAPS PharmSciTech. 2015 Oct;16(5):1203-12.

Rawas-Qalaji M1, Rachid O, Mendez BA, Losada A, Simons FE, Simons KJ (2015). Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model. J Pharm Pharmacol 2015 Jan;67(1):20-5.

Margitta Worm, Prof. Dr. med.
Klinik Für Dermatologie
Venerologie Und Allergologie
Charité - Universitätsmedizin Berlin
Berlin, Germany