Why Does Anaphylm (Oral Epinephrine Film) Work So Fast?
A study of Anaphylm, oral epinephrine film, in which persons were presented with food allergens found quick symptom resolution of issues like inflammation. Data shows that it prompts a fast increase in blood pressure in the first few minutes after administration. This is what you want to see in an epinephrine rescue medication where an allergic reaction can prompt a dangerous crash in blood pressure.
When someone has a severe allergic reaction (anaphylaxis), there is a release of histamine and bradykinin which prompts blood vessels, particularly small ones, to widen or dilate. Fluid can leak out of vessels and into surrounding tissues causing swelling. These events can cause a life-threatening loss in blood pressure and result in loss of consciousness.
The studies of epinephrine rescue medications we posses that use exposure to an allergen are limited to Neffy (nasal spray) and Anaphylm (oral film). That means we lack this data on popular autoinjectors like the EpiPen. There is some data from non-allergen studies that suggests many of these autoinjectors appear to prompt faster absorption than manual injections using a standard syringe and vial of medication. This may be a product of the length of the needle, compression of tissue, and the force at which the medication is emitted. In manual IM injections, epinephrine tends to pool at the end of the needle. With autoinjectors, it is typically delivered deeper and distributed over a larger area.
There are individual factors that impact where a medication is delivered and subsequently the speed of absorption. For example, obesity can result in a subcutaneous injection (SC), an injection into the fat tissue between the skin and muscle. SC injections result in much slower absorption. With very young children, autoinjectors have the potential to inject into bone which can also impair absorption. One strategy to avoid this is for an adult to squeeze the thigh muscle of the child so that it does not compress during the injection. Yet, this places the adult at greater risk of accidently injecting themselves.
Now, let us return to more conventional impacts of IM injections. When an injection is given in the thigh, the medication is going into muscle tissue. Muscles have an extensive network of blood vessels. These include capillaries, which are tiny blood vessels with thin walls. The medication is absorbed into these capillaries. Eventually, it reaches the heart and is pumped throughout the body.
With most oral medications, it takes some time for them to be metabolized in the liver and intestine before they can reach the bloodstream. Anaphylm dissolves in seconds under the tongue into a dense network of blood vessels that drain directly into the internal jugular vein. The internal jugular vein functions as a superhighway to the heart.
Anaphylm’s speed of symptom resolution is also likely due in part to administration occurring in the mouth where many allergic reaction symptoms occur. It also uses what is called a prodrug to administer the medication. This is a medication that only turns into epinephrine when it reaches the bloodstream. Aquestive Therapeutics has data showing that there is quickly no trace of the prodrug in the bloodstream because the conversion to epinephrine works efficiently.
If you just placed epinephrine in the mouth, it would not absorb well because it is a strong vasoconstrictor. In fact, dentists use it in combination with Lidocaine because it reduces bleeding and keeps the lidocaine trapped at the application location by limiting absorption into the bloodstream. Autoinjectors include a warning about seeking medical attention if you accidentally inject epinephrine in your hands or feet because this can result in a dangerous loss of blood flow in that location. Anaphylm’s prodrug formulation overcomes those properties so that there is fast absorption without vasoconstriction at the administration site.
The makers of Neffy epinephrine nasal spray use transmucosal absorption enhancement technology they licensed from Neurelis. It opens up space between epithelial cells in the nose for the medication to pass into the bloodstream. They did find that nasal inflammation in response to allergies appeared to increase absorption. Yet, a runny nose seemed to move medication out of the nose reducing blood concentrations after about 10 minutes.
There is one other factor that may be impacting the efficacy of IM injections. With an injection in the thigh, it has been asserted that vasodilation increases blood flow in the thigh muscle and causes a decrease in blood pressure. With more blood located in the thigh, there is a decrease in blood in system circulation. Scientists representing Neffy expressed this view during a hearing as they were seeking FDA approval of the drug.
This could explain why some of the Anaphylm studies under no allergen conditions found that manual IM injections resulted in an initial reduction in blood pressure which is the opposite of what you want to treat allergic reactions. Blood pressure values for many of the autoinjectors like EpiPen did not drop, but rose far less than Anaphylm.
With a second IM injection, concern has been expressed that if a second injection is given in the same place it might not absorb well due to local vascular constriction of tissue. Some doctors direct patients that a second injection should be given in the opposite thigh to avoid this problem. If there is actually vasodilation in the muscle, this is not needed and more blood will be taken out of the circulation system with an injection in the opposite thigh. It seems this vascular constriction versus vasodilation issue might not be the same when autoinjectors that give a deeper and more diffuse application of medication are compared to manual injections which result in more shallow pooling of medication. Clearly, more research would be prudent.
In real world use, there should be additional efficacy for Anaphylm because it is likely to be administered quickly without the hesitation associated with many of the device-based epinephrine rescue medications. The fact that Anaphylm is so easy to transport because it can fit on the back of a phone has profound real word impact on fast symptom relief. Many persons will change the practice of only taking their medication when they think they are likely to need it and embrace the new approach of having their medication at their side wherever they go.
(The graphs below compare systolic blood pressure values with different products. The first graph includes Anaphylm under an oral allergen challenge, Anaphylm without an allergen, and manual IM injection without an allergen. The other graphs compare Neffy to other approaches.)
Posted Oct 10, 2025, 7:30 PM UTC