adrenaline soon in the nose or under the tongue?

Source: Follow-up of the 19th French-speaking congress of allergology (Paris) session M7 – April 17; Allergy. 2014 Oct;69(10):1397-404; J Allergy Clin Immunol Glob. 2023 Aug 30;2(4):100165; J Allergy Clin Immunol Pract. 2023 Oct;11(10):3047-3054.

Anaphylaxis is a serious hypersensitivity reaction, occurring immediately, to a food allergen, a drug, hymenoptera venom, etc., that can be fatal. In 55% of cases, it occurs within 10 minutes and in 80% within 30 minutes. Anaphylaxis presents in various ways, sometimes misleading, and progresses very rapidly. When faced with this serious allergic reaction, individuals at risk (or parents of allergic children) are typically trained to react urgently by self-injecting adrenaline intramuscularly (in the middle third of the thigh, slightly outwards).

Adrenaline in Emergency: A Reflex Not Yet Acquired

Adrenaline auto-injector pens should be carried at all times by people at risk of a serious allergic reaction. These devices can save many lives. However, this treatment remains underused, as highlighted by a 2022 study in France, notes Dr. Catherine Neukirch (GHU NUP, Bichat Claude Bernard site, Paris): “Less than 20% of people presenting to emergency departments in Lorraine had used this treatment in 2015, and this figure is even lower among children, at 11%. There is underuse of adrenaline by patients and caregivers, as well as a delay in its administration, which increases the risk of morbidity and mortality. »

Self-Injection of Adrenaline: Many Barriers

Even today, there are many obstacles to using adrenaline in emergencies. In addition to the misleading clinical forms of anaphylaxis (without specific symptoms of an allergic reaction), numerous barriers hinder the optimal use of these auto-injectors:

• technical difficulties with usage;
• incorrect administration;
• the need for appropriate needle sizes for patients with obesity;
• needle phobia;
• fear of adverse effects;
• not carrying two auto-injectors (two injections are sometimes necessary);
• constraints related to shelf life and transport;
• lack of training and practice in proper use.

Intranasal Adrenaline Under Study

To promote the rapid use of adrenaline and overcome reluctance to carry and use injection devices, intranasal, sublingual, and transcutaneous forms are being developed. As of mid-2024, three intranasal forms of adrenaline are well advanced and showing conclusive results in cases of anaphylaxis. One of these is even under review by the American and European health authorities.

Sublingual Adrenaline Film, Needle-Free Auto-Injector… Promising Results

A sublingual film is also well advanced in research. Placed under the tongue, it allows for the rapid delivery of epinephrine-1 (an inactive version of adrenaline that becomes active once in the body). The product, regarding the size of a postage stamp, dissolves upon contact with the tongue. Sublingual adrenaline film might show promise in real-world situations, says Dr. Neukirch, especially in the case of food allergy with recent ingestion of the allergenic food (peanut butter, for example). »

Another promising technique under development is the delivery of adrenaline directly through the skin. A French company, funded by the European Union, is developing a transcutaneous form in the form of a needle-free auto-injector. A gas generator propels the drug at very high speeds through the skin, potentially even through clothing, in a matter of milliseconds.

Anaphylaxis: The Urgent Need for Improved Adrenaline Delivery

Anaphylaxis is a life-threatening allergic reaction that can occur within minutes of exposure to an allergen. It’s crucial to have readily available and effective treatment options for this medical emergency. While adrenaline auto-injectors are the current standard of care, their use remains limited due to various obstacles.

Adrenaline Auto-injectors: A Vital Tool Underutilized

Adrenaline auto-injectors, such as epinephrine pens, are essential for managing anaphylaxis, but their utilization falls short of what’s needed. A 2022 study in France revealed that less than 20% of individuals with anaphylaxis who sought emergency care had used the treatment. This underutilization, particularly among children (just 11%), raises concerns regarding increased morbidity and mortality risks.

Barriers to Adrenaline Auto-injector Use: A Deep Dive

Several factors contribute to the underutilization of adrenaline auto-injectors, making it crucial to address these challenges for better patient outcomes:

• Misleading Symptoms: Anaphylaxis can present with diverse, sometimes atypical symptoms, which can delay recognition and treatment.
• Technical Barriers: Handling and administering the auto-injectors correctly can be challenging for some individuals, especially in stressful situations.
• Needle Concerns: Some individuals experience needle phobia, leading to reluctance in using injection devices.
• Fear of Side Effects: Concerns regarding potential side effects, although rare, can also discourage the use of adrenaline.
• Lack of Access and Availability: Ensuring that individuals at risk have access to the appropriate auto-injector, the correct dosage, and adequate supplies is crucial.
• Insufficient Training and Practice: Proper training and regular practice with adrenaline auto-injectors are critical to developing confidence and competence in their use.

Alternative Delivery Methods: Promising Developments

Recognizing the limitations of auto-injectors, researchers and manufacturers are exploring alternative adrenaline delivery methods that might overcome these barriers and improve patient outcomes.

Intranasal Adrenaline: A Nasal Solution for Anaphylaxis

Intranasal adrenaline holds the potential to revolutionize anaphylaxis management. It offers a needle-free, non-invasive approach, making it more appealing to those who fear injections. Multiple intranasal adrenaline formulations are currently undergoing clinical trials, with promising results. Several are in advanced stages, under review by regulatory authorities in the US and Europe, suggesting their potential for widespread use in the near future.

Sublingual Adrenaline Film: Quick, Easy, and Convenient

Sublingual adrenaline films, resembling a postage stamp, offer a convenient and rapid way to deliver adrenaline. Placed under the tongue, it dissolves quickly, allowing for fast absorption and a potentially quicker response than other methods.

This approach might be particularly advantageous in cases of food allergy, where timely intervention is crucial following accidental ingestion of the allergen.

Transcutaneous Adrenaline: Needle-Free and Painless

Transcutaneous adrenaline delivery, using a needle-free auto-injector, is a cutting-edge approach that’s gaining attention. This technology propels adrenaline into the bloodstream through the skin using a high-speed jet stream, potentially bypassing the need for needles and making it more accessible to those with needle phobia. This method is still under development, but its potential to revolutionize anaphylaxis management is significant.

While adrenaline auto-injectors remain the mainstay for anaphylaxis treatment, ongoing research and development of alternative delivery methods are driving progress towards more user-friendly and effective solutions. These advancements offer hope for overcoming the existing challenges and ensuring timely, effective management of this life-threatening condition.