More on the Fabled “Epinephrine Allergy”

Ever since I posted Dental MythBuster #10 – I’m Allergic to Epinephrine back in November 2013, I have observed its growing popularity. But much to my surprise, the “epinephrine allergy” post generated a tremendous number of comments and emails which attempted to refute my assertions and/or attack me personally. In fact, one email even threatened physical harm!

photo of epinephrine where people believe they are allergic

Many believe they are allergic to this.

I had no idea that I would strike such a nerve. Apparently, there are many individuals out there who are convinced they are allergic to a substance that has been running through their bloodstream since before they left their mother’s uterus. And they will stop at nothing to attack, ridicule, or even threaten anyone who might suggest otherwise.

While I generally attempt to stay away from the more controversial dental topics out there (like public water fluoridation or amalgam fillings containing mercury), I do feel compelled to publish additional facts and data to support the fact that an epinephrine allergy does not exist!

You Could be Reacting to Sulfites or Latex

Many individuals who claim to have an epinephrine allergy learn, either through an allergist or through my blog, that their post-injection symptoms were caused by either sensitivity or allergies to two components found in most dental injections: sulfite preservatives and/or latex.

Sulfites found in local anesthetics and red wine can give you allergic reactions.

Sulfites are found in most red wine and in local anesthetics containing epinephrine.

Sulfites are used to preserve epinephrine in dental anesthetics. Sulfites can provoke severe sensitivity reactions in certain individuals. If you receive a dental injection with sulfites and you are sensitive to it, the reaction can closely resemble an allergic type response (for in depth details on sulfites and dental local anesthetics, see this post I published).

On the tip of every dental local anesthetic carpule is a tiny piece of latex. Studies have shown that the latex allergen can enter into the local anesthetic solution when that latex is pierced for an injection. But those same studies also show no reports of an allergic reaction due to the latex. (Study info: Shojaei AR, Haas DA. Local anesthetic cartridges and latex allergy: a literature review. J Can Dent Assoc. 2002;68:622-626.)

I mention all this to demonstrate that there are at least two chemicals in the injection which could potentially cause an allergic type response. But it’s not the epinephrine!

It’s Documented in Textbooks and Articles

Many readers of my first post simply attacked me personally and stated that I was wrong. Others wanted proof. Here is a screen shot from an online article:

Article proving that an allergy to epinephrine does not exist

This screen shot is from this article in the magazine Dentistry Today. It says “allergy to epinephrine cannot occur.” It can’t get any more clear cut than with that statement!

Need more proof? In the book a Handbook of Local Anesthesia by Dr. Stanley Malamed, he writes:

Allergy to epinephrine cannot occur in a living person.

This is on page 320 from the 5th edition.

Why isn’t an Epinephrine Allergy Listed on the Drug Insert or Prescribing Information?

After tobacco companies, pharmaceutical firms are probably the biggest litigation targets out there. Haven’t we all seen ads on TV looking for plaintiffs to sue drug companies? Ever hear of the website

Naturally, drug companies list all the known adverse effects on the drug sheet. If they don’t list something, and then an event occurs, the attorneys will have a field day! So if an allergy to epinephrine existed, wouldn’t it be listed on the drug sheet?

penicillin lists an allergic reaction as a  risk

Unlike epinephrine, the insert for penicillin mentions the risk of allergy.

Look at the drug inserts for these common medications: Zithromax (Z-Pak), Penicillin, Bactrim

On all of these, you will see mentions of allergic reactions. This indicates that known allergies can occur after taking the medications.

Now look at the prescribing information for all these forms of epinephrine: Epinephrine Auto Injector, Epi-Pen, Epinephrine Injection.

None of them mention an allergy to epinephrine (note that some mention a reaction to the sulfite).

So I’ll pose the question again: if an allergy to epinephrine existed, wouldn’t it be listed on the drug sheet? Why would the drug companies fail to include it knowing they could potentially be sued over its exclusion?

Note that I’ve used the terms Drug Insert and Prescribing Information quite liberally here. There are many variations depending upon who it is for (consumer vs. prescriber), but it is the FDA-required document that pharmaceutical companies must publish.

Show us a Mechanism

If you’ve made it this far, and you’ve already read my first post, you’ve hopefully learned that an allergy to epinephrine is not possible. But for those determined skeptics, I’ll make this request:

Please provide a plausible mechanism for how you can be allergic to a chemical that has been in your bloodstream since before birth and is currently being synthesized and released in your body as you read this.

Should you wish to post comments on this article, I will ask politely that you refrain from profanity and/or personal attacks. And if you read this and your heart starts to race (either because you’re angry at me or you’re excited with what you learned), that’s because of the adrenaline being released into your bloodstream… to which you are not allergic!


  1. Stella Wells says

    Dr. Calcaterra,
    Of course you are correct, but you already know that. The following is for the skeptics: When I had a reaction to Carbocaine 2% (mepivacaine), I saw an allergist. He assured me that there was no recorded allergies to these ‘caines, nor to epinephrine. He said there could be a possible allergy to sulfites (10% of the population). So I will simply ensure that my future shots have no preservatives. In fact, due to sensory issues, & a history of hypersensitivity vasculitis, next wk I’m trying Prilocaine 4% (Citanest Plain). Thanks for your excellent information provided & for your time & dedication to this site.

    • Stella,
      Thank you for posting your experiences on this subject in an objective manner. I hope these articles along with your comment convince people that allergic reactions to epinephrine simply not possible.

  2. Well, I guess now I’ll have to stop telling people I’m allergic to the world and everything in it. But that does sort of give me a little happy that there’s at least one thing my body won’t/can’t freak out and get all weird over. Thanks for sharing!

  3. Interesting thoughts here. It’s amazing how allergies and chemicals work – how it can seem like you’re allergic to epinephrine but you’re not. Thanks for sharing your insight here!

  4. As a former Dental Assistant, and now a Nurse…. I would like to suggest that some patients can, and do have *hypersensitive* to epinephrine. — Having been a dental Assistant, and also having a former husband in the dental field….. I have NO fear of having dental work done on myself, however IF epinephrine is given to me I can developed tachycardia. — And to better prove my hypersensitive case…. I was given epinephrine while UNDER anesthesia for a medical procedure, and my heart went cRaZy. My attending doc stated that he had never seen a reaction like that before. (*Hypersensitive* to Epinephrine)

    • Sharon,

      Your comment is proving the intent of my original post on the mythical epinephrine allergy (

      Epinephrine, broadly speaking, is released as part of the fight or flight response. IT IS SUPPOSED TO CAUSE TACHYCARDIA. If you’re about to face a dangerous situation, you want your heart beating fast and hard.

      So a racing heart after an injection means your body is reacting NORMALLY to epinephrine. In your case, your response was exaggerated.

      If someone drank half a beer and then got horribly drunk, you wouldn’t say they’re allergic to alcohol?

  5. Lou Murray, PhD says

    The tiny amount of epinephrine in an injection of local anesthetic is NOT supposed to cause hypertension and tachycardia, and does not in the average person. If it does, then that patient has a hypersensitivity to ephinephrine and it should not be used on that patient. If a patient tells you that they have an allergy to epinephrine, leave it out. Doesn’t matter if they call it an allergy or a hypersensitivity, there are some patients who cannot tolerate it in a local anesthetic because of that adverse reaction. The reason is because those patients have way too many receptors for epinephrine. I am one of those patients. If a doctor mistakenly uses anesthetic with epi on me, I am headed straight to the emergency room with blood pressure of 220/110 and a resting pulse of 125. That isn’t normal. But that is how I react to epi.

    • Lou,

      Thank you for the insightful comment.

      The tone of your post is suggestive that I – and perhaps other dentists – would simply ignore a patient’s requests and inject with a local anesthetic that contained epinephrine. That couldn’t be farther from the truth (at least with me that is).

      The point of this post – and the one that preceded it – was to educate individuals on the difference between a true allergy and an unexpected drug reaction. All too often, the word allergy is thrown around incorrectly, either intentionally or unintentionally. Approximately 1 month ago, I was at a restaurant, and a woman told the wait staff she did not want onions because she was “allergic to them.” After the waiter left, she told her companion that she just didn’t like the taste of onions. See the rough similarity?

      Your point that unexpected hypertension and tachycardia occur only in individuals with a hypersensitivity to epinephrine is overly simplified. Many factors affect this – which include the concentration of epinephrine, the type of local anesthetic (some are vasodilatory), the amount injected, the location of the injection and proximity to major vascular beds, the rate of injection, whether the operator aspirates or not, the patient’s pre-injection anxiety level, medications the patient may be on (example: non-selective beta blockers make the patient’s alpha adrenergic receptors more sensitive to epi), and of course the patient’s OWN EPINEPRHINE which they release at the stress of the injection. A person with a “normal” number of receptors can experience transient tachycardia and/or hypertension in any of the above cases.

      Having said all that, I’m glad that you acknowledge that an epinephrine allergy does not exist, and you put forth a very plausible mechanism for why you – and others – are more sensitive to the effects of epinephrine than others. You’re the first poster who has done this – and I appreciate your contribution.

      • Lou Murray, PhD says

        You are welcome. I did not mean to imply that I think you would use epi if a patient says not to. In fact, you stated earlier that you respect their wishes, even if they call it an allergy. So I beleive that you do listen to patients who tell you that they can’t have epi, whether they call it an allegy or hypersensitivity.

        Most doctors and dentists do listen to me when I tell them that I can’t have epinephrine, but when I was having surgery to remove a squamous cell carcinoma on my face, the plastic surgeon didn’t listen to me, didn’t believe me, even argued with me about it, and then used anesthetic with epi in it. The tachycardia was fairly transiet, about 20 minues before my pulse was back to normal. But my blood pressure skyrocketed and stayed up for HOURS while I was in the ER. My blood pressure remained out of control for days afterwards. Not exactly what I call transient. That episode has caused me post traumatic stress disorder in regard to medical or dental procedures, esp with anyone new that I don’t trust yet. I absolutely freak out with panic and fear. I am having major abdominal surgery tomorrow and the surgeon told me that he injects the incision sites with local anesthetic with epi in it at the end of surgery (for greater patient comfort upon awakening). I told him about my bad reaction to epi and he didn’t believe me! Did the same thing the plastic surgeon did, tried to argue me out of the bad reaction that I know from experience that I have to epi. I plan to write NO EPI on my abdomen with Sharpie in case he “forgets,” because I will be unconcsious and can’t remind him. The nurses say to call it an allergy, even though it isn’t, and I will have a temporay bracelet on that says Allergic to Epinephrine, even though allergy is not the correct term. I don’t think that they have a bracelet that says “Hypersensitive to Epinephrine.” And for sure they don’t have one that says “this patient has way too many receptors for stress hormones, and is already producing an overabundance of adrenaline/epinephrine because of the fear of surgery, so no epi.”

        • Lou,
          Thanks for your new comments. We in the medical profession are often guilty of propagating incorrect information. Your point about the nurse telling you to call it an allergy is a prime example. I’m sure he/she knows that she/he is doing. It is just easier to call it an allergy.

          On a related note, I will make it a point to spend some time seeing if there is a reason why you have more receptors. Sometimes, certain medications can cause the over-expression of certain receptors. If I can find a peer-reviewed article, that will form the basis of a new blog post. Good luck with your surgery (although I realize you’ve had it already).

        • William R Watson says

          Your blood pressure was not out of control for days due to the epi in the surgeon’s local anesthetic. The HBP from the epi are very transient.

  6. Kathy McCartney says

    I had an almost immediate reaction in 1981 from an injection of Parke Davis epinephrine in an ER. This was NOT from a dental procedure; it was in response to a case of hives. I have a medical background and am very familiar with signs/symptoms of anaphylaxis. I did not have an anaphylactic reaction, however, within the hour I had systemic ANE. I was immediately hospitalized and a battery of testing and retesting begun. At the end of the week swelling had reduced enough to allow joint movement, and I was released from the hospital. My diagnosis was listed as a severe allergic reaction; the cause (as they explained it) was the Parke Davis brand epinephrine. Not the epi itself, but a chemical used as the stabilizer for the drug or possibly a chemical used in the synthesis…they were unable to nail down the specific ingredient. It was suggested that an aquaeous form or other brands may not have the same chemical and reaction. However, for safety, it was determined that attempting to identify the specific ingredient would be too risky.

    For this reason, I am always very specific when saying I have an epi allergy, and always include it was to a chemical in that specific brand name. So, while it is impossible to have an allergy to epi specifically, it is not impossible to have a true allergy to chemicals commonly included in synthetic forms of the drug. Just because an epi allergy is reported, does not mean that it should be dismissed as “impossible”.

    Whether or not epi preparations should be used in dental procedures with this type of diagnosis is an individual decision between what both the dentist and patient is comfortable with. I have had dental procedures in the past without incident, however I do not know if the epi preparations were used. ……Just saying…..

    • Kathy,

      I can’t speak to formulations in 1981. What I know for sure is that epinephrine in a vial is very unstable – it breaks down very quickly – so preservatives are added to prevent this. The most common preservatives used in the dental field are sulfite derivatives. You probably know that already. People can develop severe reactions to the sulfite. I wrote about it here:

      You are certainly correct that a by-product used in the synthesis of the epinephrine could potentially provoke a reaction. You also imply that perhaps that formulation came as a solid? In all those cases, unexpected reactions could occur. You can call me naive, but I do believe that now, in 2016, that local with epi (along with epi-pens and other forms of epi – like the 1:10,000 forms I have for medical emergencies) have been purified to the point where possible allergens are not present.

      • In 1980, I was planning on having a rhinoplasty. As a pre-anesthetic, the doctor injected my nose with an epinephrine solution that was mixed with Lidocaine. I had an incredibly adverse reaction — pulmonary edema— and came close to dying. I was 16 at the time, and I was told that I had an epinephrine allergy. I remember that an article came out saying that there was a problem with some formulation of epinephrine at the time, and now I am wondering if it was the Parke Davis formulation. I cannot believe that I’m allergic to this medicine and think it’s terrible to have to go through life thinking I can never have it when it was probably a bad batch!

  7. I have a question… I had a hypersensitive reaction to epihephrin at the dentist. Now I am looking at getting an epipen, because I had a mild reaction to a bee sting. How do folks with this hypersensitivity balance a potential need for an epipen? thanks.

    • Nina,
      I can’t give you specific medical advice because I am not your health care provider. However, allergic reactions can be quite serious, and fatal in some cases. In fact, the prescribing information for an Epi-pen – at least when I checked a year ago – said that in the case of anaphylaxis, even if you are allergic/sensitive to the sulfite preservative in the Epi-pen, you should still use it.
      You should bring this up with your allergist and she what he/she says.

  8. Thank you for this explanation. Was wondering if epinephrine-free anesthetic is available in all medical procedures? I have fainted a total of three times – once at the dentist, at the eye doctor getting my eyes dialated, and once receiving an injection in my leg. Each reaction was well after the fact of receiving the local anesthetic. Would I be able to receive local anesthetic in future surgical procedures without epinephrine? Also, as I plan on starting a family, if needed, would I be able to get an epidural? Is there a way to control these reactions?

    • Kelsey,

      I can’t speak with certainty about other areas of medicine but in dentistry, an epinehphrine-free local anesthetic is always available. I would caution you against generalizing and making the assumption that the epinephrine is what caused the fainting episode. Also, many individuals assume that the medication used to dilate eyes is epinephrine, but most of the time it is not. Typically an anti-cholinergic medication such as tropicamide is used. Regarding an epidural, I would rely on the anesthesiologist to answer this. Epinephrine will likely be the least of your concerns during childbirth.

  9. I have one side effect of novacaine with epinephrine that I can’t find documented. I used to describe it as an allergic reaction; I promise I won’t, ever again! I am still puzzled why something that, as you point out, is always in my bloodstream, makes me drunk when I get a Novacaine shot or take Sudafed.

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