Sublingual Epinephrine?

Intramuscular administration of epinephrine is considered to be the  treatment of choice in patients experiencing anaphylaxis in community settings.  Considering the skills that are needed to provide IM injections are often unfamiliar to dentists, many keep very expensive epinephrine auto injector devices in their emergency drug kits.  Since aqueous epinephrine degrades quickly in normal storage conditions, including exposure to light, heat, oxygen and neutral or alkaline pH values1, they have a relatively short shelf-life (12-14 months).  Wouldn’t it be great if there was a cheaper, easier to administer, and longer lasting alternative?

Sublingual epinephrine has been under development for at least 20 years, and a recently published study touts a new sublingual matrix, AQST-109, as a promising vehicle by which epinephrine may be administered2.  Results showed nearly equivalent, if not better, loading and peak concentrations, when compared to traditional intramuscular absorption.  

Don’t get too excited yet, as that study was only the first human study, as was performed on only 24 healthy adult volunteers.  While low molecular weight, lipophilic drugs such as epinephrine are likely absorbed across sublingual mucosa into venous circulation by transcellular diffusion3, there still is no evidence that absorption will be effective in the presence of edema in the lingus and other proximal mucosa, when the osmotic gradient favors mass movement to the interstitial space– a common occurrence during anaphylaxis.  In addition, a previous study4 found varied absorption rates of epinephrine delivered through the sublingual route.  To be fair, the epinephrine was in a powered formulation, different than the AQST-109 sublingual matrix, and included only 10 adult men in its dataset.  Another rabbit study5 hypothesized that sublingual absorption occurs in a series of peaks, as alpha effects of epinephrine causes vasoconstriction, limiting the amount of absorption possible after initial exposure.  

So for right now, we are in a holding pattern. 

This might also be a good time to think about the incidence of anaphylaxis in dentistry.  In my hundreds of conversations with dentists, it seems to me that anaphylactic shock is one of the most feared emergencies, yet very few have actually encountered a true anaphylactoid-like reaction in practice or elsewhere.  This inexperience is consistent with estimates that anaphylaxis occurs in 0.004 – 0.015 cases per dentist per year. 6-8  Morbidity occurs only in 0.5% to 1.5% of all anaphylaxis cases.9-11

Please do not get the impression that I am advocating for a dentist to abdicate responsibility to be prepared to manage an anaphylactoid-like scenario.  However, given the above, it seems difficult to justify spending upwards of $1000 every year or so on something you should not use during the off-chance of encountering a case of anaphylaxis.  Instead, you should know how to recognize anaphylactoid-like reactions, administer epinephrine, diphenhydramine and oxygen immediately, position the patient in the trendelenburg position (or as close as possible), and be ready to administer albuterol.  Most importantly, call 9-1-1 as soon as possible, keeping in mind that your emergency medical kit should be designed to keep your patient alive for 15 – 30 minutes.

Erik Zalewski is a Nationally Registered Paramedic and New York State EMS Certified Instructor Coordinator with almost 30 years experience responding to 9-1-1 calls for medical emergencies.  Erik has taught EMTs and paramedics at Stony Brook University and the Suffolk County, NY EMS academy.  He and his team at Have Dummy Will Travel, Inc. are dedicated to helping medical professionals respond to emergencies safely, efficiently and in the most cost-effective manner possible.  Call or text 631-849-4978 for additional information.  


  1. Rawas-Qalaji, M.M. et al (2013). Long term stability of epinehrine sublingual tablets for the potential first-aid treatment of anaphylaxis.  Annals of Allergy and Asthma Immunology. 111:567-579.
  2. Golden, D. et al. (2023). Pharmacokinetics and pharmacodynamics of epinephrine sublingual film versus intramuscular epinephrine.  Journal of Allergy and Clinical Immunology.  AB4.
  3. Birudaraj, R., Berner, Shen, S. & Li, X. (2005).  Buccal permeation of buspirone: mechanistic studies on transport pathways.  Journal of Pharmacological Science.  94:70-78.
  4. Simons, K.J., Gu, X., & Simons, F.E.R. (2004). Sublingual epinephrine administration in humans: A preliminary study. Journal of Allergy and Clinical Immunology.  113(2):S260.
  5. Rawas-Qalaji, M, Simons, F.E.R. & Simons, K.J. (2006). Sublingual epinephrine tablets versus intramuscular injection of epinephrine: Dose equivalence for potential treatment of anaphylaxis.  Journal of Allergy and Clinical Immunology. 117(2): 398-403.
  6. Girdler,  N.M. & Smith, D.G. (1999). Prevalence of emergency events in British dental practice and emergency management skills of British dentists. Resuscitation. 41:159–167. 
  7. Muller, M.P., Cansel, M., Stehr, S.N., Weber, S. & Koch T. (2008).  A statewide survey of medical emergency management in dental practices: incidence of emergencies and training experience. Emergency Medical Journal. 25:296–300. 
  8. Arasti, F., Montalli, V.A., Florio, F.M., et. al. (2010). Brazilian dentists’ attitudes about medical emergencies during dental treatment. Journal of Dental Education. 74:661–666.  
  9. Moneret-Vautrin, D., Morisset, M., Flabbee, J., Beaudouin E., & Kanny, G. (2005). Epidemiology of life-threatening and lethal anaphylaxis: a review. Allergy 60:443–451. 
  10. Helbling, A., Hurni, T., Mueller, U. & Pichler, W. (2004).  Incidence of anaphylaxis with circulatory symptoms: a study over a 3-year period comprising 940,000 inhabitants of the Swiss Canton Bern. Clinical and Experimental Allergy.  34:285–290. 
  11. Sheikh, A. &  Alves, B. (2001).  Age, sex, geographical and socio-economic variations in admissions for anaphylaxis: analysis of four years of English hospital data. Clinical and Experimental Allergy. 31:1571–1576.

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