Q&A: Epinephrine nasal spray may overcome autoinjector limitations
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Key takeaways:
- Many patients fail to carry or use their autoinjectors because they are afraid of needles.
- NDS1C epinephrine nasal spray had outcomes comparable with autoinjectors and manual injection.
An intranasal epinephrine spray produced pharmacokinetic and pharmacodynamic results that were comparable or superior to intramuscular injections, according to a study published in The Journal of Allergy and Clinical Immunology: Global.
Researchers tested NDS1C (Bryn Pharmaceutics) administered as two sprays totaling 13.2 mg of epinephrine against 0.3 mg of epinephrine administered via autoinjector (USP Autoinjector) and 0.5 mg administered via manual syringe.
Maximum concentrations included 429.4 pg/mL for NDS1C and 328.6 pg/mL for the autoinjector. Areas under the curve for 0 to 360 minutes included 39,060 pg*min/mL for NDS1C and 17,440 pg*min/mL. The manual syringe yielded similar results.
Times to maximum concentration included 20 minutes for NDS1C, 14.9 minutes for the autoinjector and 45 minutes for the manual syringe.
Also, NDS1C had higher pharmacokinetic parameters than autoinjector and intramuscular administration, with NDS1C and autoinjector administration achieving similar effects on blood pressure and heart rate, researchers wrote, adding that NDS1C was safe and well tolerated as well.
Healio spoke with Erin Malawer, executive director of AllergyStrong and cofounder of the Food Allergy Collaborative, and Amanda Michaud, DMSc, PA-C, AE-C, secretary of the Association of PAs in Allergy, Asthma and Immunology and a member of Healio’s Allergy and Asthma Peer Perspective Board, about the impact that nasal epinephrine may have on anaphylaxis care.
Healio: What kinds of challenges do autoinjectors present people with allergies?
Michaud: Patients with a history of IgE-mediated food allergy, venom hypersensitivity, drug allergy, mast cell disorders or sometimes those receiving allergen immunotherapy should have an epinephrine autoinjector available in case of systemic allergic reaction or anaphylaxis. Despite this strong recommendation by us as allergy clinicians, we routinely discover that patients are not carrying their epinephrine autoinjectors. Further, there are patients who may carry them but are afraid of using them.
Barriers to carrying or using autoinjectors include cost, size of the device, social stigma, inconsistent medical advice, inconvenience or forgetfulness, needle phobia, poor device design, limited patient training, or carrying an expired device, among others. There has long been an unmet need in patients with a history of anaphylaxis or who are at risk for anaphylaxis for alternative epinephrine devices.
Malawer: As someone with a life-threatening allergy, you never truly know when accidental exposure will turn into anaphylaxis. That is why it is critical to always carry a set of two epinephrine autoinjectors with you to counteract these serious symptoms. But autoinjectors come with several challenges for people with allergies.
First, they are difficult to carry, and many people leave them behind out of convenience. They are bulky, making it especially difficult for men and adolescents to carry since they do not always fit comfortably in pockets, and men tend not to carry bags regularly. Something I preach to teens, young adults, and anyone else who will listen: Autoinjectors are life savers. But they cannot help you if they are not with you.
Second, epinephrine autoinjectors contain needles. Because of this, many parents and schools are loath to let younger children self-carry their medication. This makes it complex, as children and young adolescents are gaining independence. The alternative poses a safety risk as children participate in activities away from their parents.
Importantly, the needle itself causes issues. The needle mechanism of the autoinjector, effective at delivering epinephrine quickly, can also cause lacerations, particularly in very young patients. Additionally, a recent survey of patients by the Food Allergy Collaborative demonstrated that many respondents were afraid of the needle. Fear of the needle leads to delays in administration of epinephrine — something that those experiencing anaphylaxis cannot afford. Delaying or failing to use epinephrine, as is often the case, increases a person’s risk for needing hospitalization, worsening of dangerous symptoms, and fatality.
Healio: How would a nasal spray improve upon these challenges?
Malawer: Nasal epinephrine offers an approachable, less invasive emergency treatment to those managing food allergies. Because nasal sprays are already in use for other health conditions, they are a less intimidating product that more people are familiar with. And, due to their smaller size, they should be easier to carry. It is my hope that nasal sprays will reduce or eliminate the fear factor currently associated with epinephrine administration, reducing delays. Epinephrine given at the earliest signs of anaphylaxis is associated with better outcomes.
Healio: Do you think the results of this study are surprising or significant?
Michaud: As the study revealed, intranasal epinephrine achieved superior pharmacokinetic measures over the epinephrine autoinjector and, importantly, had sustained drug concentrations over time. Overall safety and tolerability were similar across all routes.
A natural limitation of the study was that it was performed in healthy adult subjects not experiencing systemic allergic reactions or anaphylaxis. However, the pharmacokinetic profile reveals that intranasal epinephrine may be a promising alternative as a “needle-free” device option for patients. This route would be appealing to patients due to the needle-free option, which will cause some patients to delay or avoid treatment with their autoinjector.
Malawer: The results are exciting. They show that intranasal administration is as effective — or more effective — than intramuscular and intravenous administration. It is reassuring to see the data support NDS1C as a safe way to receive epinephrine, underscoring that nasal administration of epinephrine is reliable.
Happily surprising were findings that indicate that NDS1C may help reduce the number of doses needed to control anaphylaxis symptoms. The study results showed that intranasal delivery of NDS1C got patients to higher plasma concentrations than current administration methods. Sustained plasma concentrations mean epinephrine stays in the system longer, combatting the dangerous symptoms of anaphylaxis. In practice, this may mean that NDS1C may help prevent the need for numerous doses of epinephrine when used at the onset of anaphylaxis.
What should the next step be in this research?
Malawer: Any studies that continue to underscore the safety and reliability of this product will help build public trust in this novel administration method.
The introduction of intranasal epinephrine marks a significant step forward for individuals with food, drug and venom allergies. By overcoming barriers to use epinephrine, nasal epinephrine will save lives. This study clearly shows that Bryn Pharma’s NDS1C is as safe and effective as autoinjectors. Individuals with food allergies, their families and others who care for them will benefit greatly from its availability.
Michaud: There are naturally some concerns with use of intranasal epinephrine. What about patients with significant nasal congestion? A poster presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting in November reported findings discussing this concern. Although intranasal epinephrine demonstrated enhanced absorption vs intramuscular treatments regardless of level of congestion in patients with allergic rhinitis, this may continue to be a concern for patients who may have more severe disease or potentially unknown chronic sinusitis, anatomical defects or polyposis.
Another concern with intranasal epinephrine would be the ability of pediatric patients to adequately inhale the medication. A study completed in 2000 by Simons et al found that despite expert coaching, pediatric patients were generally unable to inhale sufficient epinephrine to increase their plasma concentrations promptly and significantly.
Finally, another concern would be in unconscious patients who would be unable to inhale. Therefore, intramuscular epinephrine would still be required.
The next logical step would be to have real-world data with patients being treated for allergic reactions with the various devices, although this is, of course, a challenging task due to ethical reasons. If the intranasal epinephrine device eventually receives FDA approval, having these data will help secure its spot in anaphylaxis management plans.
Either way, every day we discuss the risks, benefits and alternative medications with our patients and families prior to prescribing several medications, new or old. We know epinephrine is first-line management for systemic allergic reactions and anaphylaxis, yet it is grossly underutilized.
Having alternative epinephrine devices fills a large unmet need in our patient population, and as always, we will discuss the potential pros and cons of these various devices with our patients. Our goal is to improve management of anaphylaxis with prompt recognition as well as treatment with epinephrine, and alternative devices such as intranasal epinephrine may help get us there.
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For more information:
Erin Malawer can be reached at erin@allergystrong.com. Amanda Michaud, DMSc, PA-C, AE-C, can be reached at amandamichaud@gmail.com.