New Epinephrine Spray and Anaphylaxis Materials

NASAL SPRAY EPINEPHRINE MAY BE USED TO OVERCOME BARRIERS TO TREATING ANAPHYLAXIS

Jennifer Salvon, RPh

Jennifer Salvon is a clinical pharmacist at Mercy Medical Center in Springfield, Massachusetts, and a freelance medical writer at Salvon Scientific.

Topic Overview:

Anaphylaxis can be a life-threatening allergic reaction primarily caused by histamines. It can be mild and self-limiting but can also be fatal. Epinephrine is the primary treatment for anaphylaxis. It first appeared and was administered as an auto-injector. However, there are barriers to its use, which increase the dangers of anaphylaxis. These barriers include trypanophobia, incorrect administration, and limited access to auto-injectors. These barriers can interfere with anaphylaxis treatment. The introduction of an epinephrine nasal spray may help overcome these barriers. This course also reviews the proper use and administration of an epinephrine formulation delivered as a nasal spray.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-24-164-H01-P

Pharmacy Technician  0669-0000-24-165-H01-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation

Release Date: November 23, 2024 Expiration Date: November 23, 2027

Target Audience: This educational activity is for pharmacists and pharmacy technicians.

How to Earn Credit: From November 23, 2024, through November 23, 2027, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “Educational Activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives:

Upon completion of this educational activity, participants should be able to:

Identify triggers, signs, and symptoms of anaphylaxis

Compare available epinephrine products approved for use in anaphylaxis

Recognize barriers to patient adherence with epinephrine auto- injectors

Describe the proper use and administration of nasal epinephrine spray

Disclosures

The following individuals were involved in developing this activity: Jennifer Salvon, RPh, and Pamela Sardo, PharmD, BS. Pamela Sardo and Jennifer Salvon have no conflicts of interest or financial relationships regarding the subject matter discussed. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.

© RxCe.com LLC 2024: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity

Nasal Spray Epinephrine May Be Used to Overcome Barriers to Treating Anaphylaxis

Introduction

Anaphylaxis can be a life-threatening allergic reaction primarily caused by histamines. It can be mild and self-limiting but can also be fatal. The dangers of anaphylaxis are increased because of barriers to treatment. In this activity, participants will learn to identify triggers, signs, and symptoms of anaphylaxis. Clinicians will also learn about the epinephrine products approved for anaphylaxis, including epinephrine auto-injectors and epinephrine delivered by nasal administration. These treatment options can help address trypanophobia.

Overview of Barriers to Treating Anaphylaxis

Epinephrine is the primary treatment for anaphylaxis. It first appeared and was administered as an auto-injector. However, there are barriers to its use. These barriers include trypanophobia, incorrect administration, and limited access to auto-injectors. These barriers can interfere with anaphylaxis treatment. The introduction of an epinephrine nasal spray may help overcome these barriers. Trypanophobia will be discussed next, and the remaining barriers will be reviewed below under the section on epinephrine auto- injectors.

What is Trypanophobia?

Trypanophobia is an extreme fear of needles or injections in a medical setting.1 Some people have a fear of needles, which is so great that it may cause severe anxiety that prevents them from getting life-saving medical care.1 This is called trypanophobia. It is closely related to other phobias involving the fear of needles, pins, and sharp, pointed objects. The fear of needles and pins is known as belonephobia, and the fear of sharp, pointed

objects is known as aichmophobia.1,2 Trypanophobia specifically refers to the fear of injections in a medical setting; it may also include the fear of having blood drawn.1

Trypanophobia is more common in children than in adults, with two out of three children experiencing it and one in four adults.1 It is estimated that between 11.5 to 66 million adults experience some form of trypanophobia.3 Several risk factors are associated with developing trypanophobia, including the following:3,4

History of a negative experience involving needles

Family history of needle phobia

Other fears related to illness or medicine

Generalized anxiety disorder or obsessive-compulsive disorder

Individuals with trypanophobia may experience persistent anxiety and fear in the presence of injections. This may manifest as increased heart rate, increased blood pressure, sweating, dizziness, or nausea.4 Some people may even experience a vasovagal reaction to the sight of needles.4 A vasovagal reaction occurs when a sudden increase in heart rate and blood pressure is followed by an immediate decrease in heart rate and blood pressure, leading to fainting.4 People with trypanophobia tend to avoid situations involving needles and injections, such as vaccinations.4

Several strategies exist to manage trypanophobia. Patient education, including discussion and understanding of the procedure, may help.2 Distraction—by looking away, focusing on something else, or talking to someone—and relaxation techniques, such as deep breathing, meditation, and hypnosis, also help many patients.2,4 Topical stimuli, such as vibration devices that buzz on the skin or provide a cooling sensation, help the brain focus on that sensation rather than the injection. Numbing the area with a topical anesthetic is also beneficial.2,4

POINT TO PONDER:

Have you ever encountered a patient with trypanophobia?

Anaphylaxis

One area where trypanophobia can have a significant impact is the treatment of anaphylaxis. Historically, the first reference to anaphylaxis appeared in 2600 BC. Pharaoh Menes is believed to be Egypt's first pharaoh and is widely credited with unifying Upper and Lower Egypt, establishing Egypt’s first dynasty.5 He is also credited with introducing papyrus and writing, founding cities such as the legendary city of Memphis, and building important dikes.5

There is some debate about how Pharaoh Menes died, but the prevailing theory states that he died after being stung by a wasp in 2600 BC.5 This is believed to be the first description of an anaphylaxis-type reaction.

Despite this first description, it was in the early 1800s that scientists took note of and studied fatal systemic reactions. A French physiologist named Francois Magendie conducted experiments involving the injection of egg albumin in rabbits, resulting in severe, fatal reactions.6 Over the next several decades, other scientists noticed that lab animals developed sudden and severe reactions when injected with foreign substances at doses that the animals had previously tolerated.6

In 1902, two scientists, Charles Richet and Paul Portier, conducted a series of experiments to immunize dogs against the toxins found in sea anemones. Dogs were first injected with a small dose of toxin, the thought being that they would become less sensitive to the toxin. Unfortunately, the opposite proved true, and upon subsequent injection with a larger dose, the dogs experienced fatal reactions. They named the reaction ‘anaphylaxis’ based on two Greek words: ana, meaning absence, and phylaxis, meaning protection – anaphylaxis is the lack of protection.6,7

Anaphylaxis is an acute reaction of the body’s immune system due to exposure to an allergen, commonly called a trigger. Allergic reactions can range from mild and self-limiting to severe and potentially fatal. Mild allergic reactions are usually limited to a single organ system, such as a rash or hives on the skin.6-8

Anaphylaxis typically but does not always involve multiple organ systems: the respiratory, cardiovascular, gastrointestinal, or neurological. Upon exposure to an allergen, the immune system responds by degranulating mast cells, releasing mediators that initiate the systemic manifestations of the reaction. Histamine is one of the primary mediators and affects multiple organ systems.7,8

The true incidence of anaphylaxis is unknown, but the lifetime prevalence of anaphylaxis in the general population from all triggers is estimated to be between 0.05% and 2%.7,9 In children under ten, anaphylaxis occurs more often in males than females, but in children older than ten and adults, it occurs more often in females than males.7 Unfortunately, rates are rising in the U.S., and between 2008 and 2016, there was a 3.2-fold increase in anaphylaxis-related emergency department visits.7

Categorization

Anaphylaxis is categorized based on the triggering mechanism into immunologic, non-immunologic, and idiopathic.10 These are depicted in Figure 1 below.

Immunologic anaphylaxis results from an immune system reaction and is subcategorized into IGE-mediated and non-IGE-mediated reactions. IGE is an immunoglobulin the immune system produces in response to exposure to an antigen. Reactions to food drugs and insect stings are IGE-mediated reactions.10

Less common are non-IGE-mediated reactions, which are either IgG- mediated or complement-mediated. IgG is another immunoglobulin produced by the immune system. Triggers such as iron dextran or monoclonal antibodies, such as infliximab, may result in IgG-mediated reactions. Polyethylene glycol is an example of a trigger causing a complement-mediated reaction.7,10

Non-immunologic anaphylactic reactions result from direct mediator release by mast cells and basophils. One trigger that elicits direct mediator release is allergic reactions to opioid medications such as oxycodone.10 Physical factors can also provoke an anaphylactic reaction, such as intense physical exercise and exposure to extreme heat.10 Reactions to dialysis membranes during dialysis are another example of a non-immunologic anaphylaxis reaction.10

Idiopathic anaphylactic reactions pose significant challenges in diagnosis, prediction, and management. The triggering allergen is unidentified, often resulting in sudden reactions. These episodes can vary in severity from mild to life-threatening and can escalate rapidly.10 Due to the lack of a known allergen, preventing idiopathic anaphylactic reactions is particularly challenging, leading to heightened stress and anxiety for patients, caregivers, and healthcare providers.

Anaphylaxis

Immunologic

Non-

Im gic

munolo

Idiopathic

IgE mediated

Non-IgE mediated

Physical

Other

Figure 1 Categorization of Anaphylaxis10

Triggers and Risk Factors

Food is the leading cause of anaphylactic reactions, and interestingly, the specific foods that trigger these reactions can vary with age.7 Cow milk is the most common trigger for infants, while peanuts are prevalent among children. Shellfish and tree nuts are the usual triggers for young adults and adults.7,11 Other frequent food triggers include eggs, wheat, soy, and sesame. Insect stings—like those from bees, wasps, hornets, yellow jackets, and fire ants—can also cause anaphylactic reactions.7,11 Various medications are linked to these severe reactions, with penicillin and aspirin being the most common offenders.7 Additionally, latex is another well-known trigger.10

Several risk factors can increase the chances of experiencing a severe or life-threatening anaphylactic reaction, including the following:10

Age: Infants are at increased risk because allergies may go underrecognized and underdiagnosed, and there is currently no suitable auto-injector available for them. In teenagers, the heightened risk often stems from denial or a lack of awareness about the allergy's potential severity, leading to not filling or carrying auto-injectors. Furthermore, older adults face a greater risk of anaphylaxis due to insect venom.

Comorbidities: Comorbidities increase the risk of anaphylaxis as well. This includes severe or uncontrolled asthma, patients with cardiovascular disease or taking antihypertensives, and patients with atopic diseases such as eczema.

Allergen: The type of allergen is also a factor with a higher risk associated with certain foods, including nuts, seafood, shellfish, egg, milk, and sesame; with insect stings; with allergies to cat and horse dander or grass pollen; and latex.

Other Risk Factors: These include strenuous exercise, psychological stress, past severe anaphylaxis, sleep deprivation, and alcohol consumption.

Symptoms

Anaphylactic symptoms typically come on quickly, within minutes to a few hours of exposure to the allergen. Symptoms include the following:9,10,12

Generalized erythema with hives, flushing, and itching

Angioedema, or swelling, often around the eyes, lips, throat, hands, or feet

Gastrointestinal symptoms, such as nausea, vomiting, and diarrhea

Patients may sometimes have a feeling of impending doom. They may have difficulty breathing, wheezing, throat tightness, hoarseness, or cough. They may experience hypotension or a weak pulse or become dizzy or faint.9,10,12

Diagnosis

Prompt recognition and diagnosis are critical, along with quick treatment. The most widely accepted diagnostic criteria are the National Institute of Allergy and Infectious Disease or NIAID and the Food Allergy and Anaphylaxis Network or FAAN criteria.7

This consists of three criteria, with only one criterion needing to be met for the clinical diagnosis of anaphylaxis to be highly likely. The criteria include the following:7

Acute onset of signs and symptoms involving the skin and mucous membranes, along with signs and symptoms of respiratory and or cardiovascular involvement, for example, a patient experiencing sudden onset of hives and difficulty breathing, even without a clear trigger.

Sudden onset of signs and symptoms after exposure to an allergen and involving two or more organ systems.

Sudden onset of hypertension after exposure to unknown allergen.

Treatment

This activity does not cover comprehensive anaphylaxis management. Acute anaphylaxis management starts with positioning the patient, reclining, and elevating the legs if feasible. Evaluating a patient’s airway, breathing, and circulation while providing supportive care is critical. It may be necessary to administer oxygen, establish IV access, and provide fluids. Administering epinephrine is universally acknowledged as the primary treatment for anaphylaxis.9,12

Epinephrine

In 1895, two scientists, George Oliver and E.A. Schaeffer, first isolated epinephrine. They extracted it from the adrenal medulla of various animals, such as sheep, guinea pigs, dogs, and cats. Upon injection into laboratory animals, this extract was found to increase heart rate and blood pressure, dilate blood vessels, and slow the respiratory rate.13 This discovery set the stage for its further purification into the active ingredient we use today. While epinephrine received certification in the U.S. in 1939, it was already used for medical purposes as early as 1901. Park Davis patented epinephrine under the name adrenaline in 1903; it later became part of Pfizer.13

Epinephrine is a hormone and an adrenergic agonist, targeting both alpha and beta receptors. Its action on alpha-1 receptors causes an increase in peripheral resistance, beta-1 receptors an increase in cardiac output, and beta-2 receptors a reversal of bronchospasm.12 Epinephrine engages multiple organ systems to address the primary factors of an anaphylactic reaction. Figure 2 shows the chemical structure of epinephrine.

Figure 2

Chemical Structure of Epinephrine

Adverse Effects and Drug Interactions

While the administration of epinephrine has life-saving effects on a person experiencing anaphylaxis, it can also result in adverse effects. Moderate adverse effects include pallor, tremors, nausea, vomiting, anxiety, and heart palpitations. More severe side effects include ventricular arrhythmias, myocardial infarction, hypertensive crisis, and pulmonary edema.14-17

The potential exists for drug interactions between epinephrine and several classes of medications. Potential drug interactions are covered in Table 1.

Table 1

Potential Drug Interactions with Epinephrine14-17,28

Routes of Administration

Epinephrine may be administered by several different routes: intravenous (IV), subcutaneous (SC), intramuscular (IM), and intranasal (IN). IM administration offers a quick onset and rapid absorption into the bloodstream; this is especially important in treating anaphylaxis.18 In contrast, SC administration is less frequent due to its slower absorption rate. IM administration leads to peak plasma concentrations of epinephrine more quickly than SC.18 IV administration is reserved for emergencies, such as cardiac arrest.18 Oral intake is not viable because epinephrine quickly degrades in the gastrointestinal system.12 Intranasal administration is a newer method we will explore further.

Epinephrine Auto-injectors

The first epinephrine auto-injector product to be approved was the EpiPen®, a brand widely recognized in the epinephrine auto-injector market. This product was first patented in 1977 and gained FDA approval in 1987.13 The first generic epinephrine auto-injector was introduced in late 2016 by

Mylan.19 Additional generic epinephrine auto-injectors were introduced from Amneal in 2016, followed by Teva in 2018.19

Auvi-Q® was approved in 2012 with 0.3 and 0.15 mg strengths.20 In 2017, a 0.1 mg strength was approved for infants and children weighing 16.5 to 33 pounds.21 This is the only product available in this strength. Auvi-Q® is slightly different from other auto-injectors; when activated, a voice guides the patient through the proper product administration.14 All available epinephrine auto-injectors have similar storage conditions. Table 2 summarizes available epinephrine auto-injectors.

Table 2

Available Epinephrine Auto-injectors14-17

Administration of Epinephrine Auto-injectors

Administration of epinephrine auto-injectors involves the following steps:14-17

Remove from the case

Remove a safety cap

Position the product on the middle of the outer thigh at a 90° angle

Push down firmly until you hear a click

Hold in place for 10 seconds.

All available products are single-dose and cannot be reused. It is important not to inject into veins, the buttocks, fingers, toes, hands, or feet. They can be injected through clothing; after administration, massaging the injection area for several seconds is recommended.14-17

Access and Utilization

Epinephrine auto-injectors can be expensive. In 2009, the average price was $100, but it rose to $600 by 2016.19 These steep prices accelerated the approval of previously mentioned products. Although insurance often covers the expense, co-pays and coinsurance can be substantial. In some cases, prior authorization is needed, especially if a patient fills two prescriptions—one for home use and another for school. Despite being commonly prescribed, fewer than 50% of individuals consistently carry an epinephrine auto-injector.22

Shortage

Epinephrine auto-injectors have experienced intermittent supply issues since 2017.19 As of September 2024, the generic epinephrine auto-injector from Mylan and the EpiPen brand are also experiencing supply issues. Auvi-Q is currently available, but only through certain suppliers. Currently, the Amneal and Teva generic epinephrine auto-injector products are not experiencing supply issues.23

POINT TO PONDER:

How do drug shortages affect patient care?

Nasal Epinephrine

Nasal epinephrine is a newly approved administration avenue for anaphylaxis. As noted above, less than half of at-risk patients carry epinephrine auto-injectors. Many who do have them delay their use during a reaction. Many do not fill prescriptions due to trypanophobia. Products can be costly based on insurance coverage and may be hard to find due to supply issues. This low utilization creates an unmet need in the treatment of anaphylaxis, prompting the study of novel administration avenues.24

Nasal administration has many advantages, including ease of use, rapid absorption, and lack of needle pain. The nasal mucosa is highly vascular, providing a direct pathway for rapid drug absorption. The nasal cavity has a relatively large surface area, ideal for absorbing small molecules. Drug absorption from nasal mucosa bypasses the liver’s first-pass metabolism, where these drugs might otherwise be broken down. Nasal administration allows for a rapid onset of action.25

Several drugs are available in nasal formulations, including the following:24

Naloxone for use in opioid overdose

Diazepam for the treatment of frequent seizures in adults and children

Ketamine for treatment-resistant depression

Sumatriptan for migraines

The FDA approved the first epinephrine nasal spray in August 2024 and granted the nasal epinephrine application fast-track designation.26 The FDA uses fast-track designation to speed up the review of drugs that treat serious conditions or fill unmet medical needs.27 This new nasal epinephrine product

is manufactured by ARS Pharmaceutical and marketed under the brand name neffy®.28

Nasal epinephrine is approved for emergency treatment of anaphylactic reactions in adults and children 12 years or older and weighing 66 pounds or more.28 It is available as a single-dose spray containing 2 mg of epinephrine in 0.1 ml, offering a promising alternative for those who are hesitant or fearful of needles.

This new nasal epinephrine product is a combination of three FDA- approved components:24

Epinephrine

Intravail, which is also known as dodecyl maltoside (DDM)

The unit-dose spray device is designed to produce a droplet-sized spray pattern to maximize drug delivery to the nasal mucosa.

Most people have not heard of Intravail or DDM. DDM is an alkyl saccharide that enhances the nasal absorption of drugs by altering mucosal viscosity and loosening cell junctions. It is currently used in several FDA- approved products, including a sumatriptan spray for treating migraines and a naloxone spray for treating opioid overdoses.24

The unit-dose spray device used in the nasal epinephrine product has proven effective for over twenty years. It is simple to use and highly reliable, with Published spray device data indicating a failure rate of less than one in 100,000 uses. This device is engineered to expel and deliver more than 80% of the active ingredient, epinephrine, in a droplet size that maximizes drug absorption.24

Clinical Trials

The clinical trials that led to the FDA's approval of intranasal epinephrine did not evaluate its effectiveness in patients experiencing anaphylaxis due to safety concerns if the product was ineffective.24,28 Approval was based on

studies assessing pharmacodynamics and pharmacokinetics in controlled settings that simulated various real-life conditions, including allergic and infectious rhinitis. Blood samples were collected before and at regular intervals after administration to analyze pharmacokinetics and measure plasma levels. Pharmacodynamic measurements, including systolic and diastolic blood pressure and pulse rate, were recorded before and after the administration of epinephrine at specified intervals.24,28

The 1 mg and 2 mg doses of nasal epinephrine were studied. Initial studies evaluated the 1 mg dose. Pharmacokinetic results showed the 1 mg dose of nasal epinephrine was comparable to manual intramuscular epinephrine administration, though it was lower than levels seen with auto- injector use.24

Research with the 2 mg dose of nasal epinephrine revealed that administering nasal epinephrine produced pharmacokinetic profiles consistent with existing epinephrine auto-injectors. The pharmacodynamic effects of inhaled epinephrine were equal to or better than those of currently available auto-injector products.24 These findings were consistently confirmed under varying nasal conditions, including moderate allergic or infectious rhinitis congestion.24 However, individuals with existing structural or anatomical nasal issues, like polyps or a history of nasal fractures or surgeries, were excluded from the study, raising concerns about how absorption might be affected in such cases.24

Similar results were reported in another clinical trial published in 2023.29 This study evaluated the pharmacokinetics and pharmacodynamics of epinephrine after administration by manual IM, auto-injector, and intranasal inhalation. The study found that the intranasal pharmacokinetic profile was similar to approved injection products, and the pharmacodynamic responses were comparable to or better than those of the approved injection products.29

Administration

Proper technique and device training are important in administering nasal epinephrine. Patients and caregivers should thoroughly read the device's instructions before needing it. Table 3 lists the steps for administering nasal epinephrine.

Table 3 Administration of Nasal Epinephrine28

Supply and Storage

Nasal epinephrine is available in a carton containing two blister packs, each with a single-dose nasal spray product. Each spray contains 2 mg of epinephrine in 0.1 ml.28 A handy carrying case is available on the product website for storage. The sprays should be stored at room temperature between 68 and 77°F, and exposure to temperatures up to 122°F is allowed for a few days. It is important not to freeze the product; if it freezes, it will not disperse.28 The product carries a 30-month expiration date.

Adverse Reactions

Adverse reactions with nasal epinephrine include throat irritation, a tingling nose, headache, nasal discomfort, shakiness, fatigue, dizziness, jittery, and having a runny nose or sneezing.28 Elderly patients may be at an increased risk of developing adverse reactions. It should be noted that using nasal epinephrine may alter the nasal mucosa for up to two weeks after administration and increase the systemic absorption of other nasal products.28

Pharmacy Team: Front Line Support

Pharmacists and pharmacy technicians are among the most accessible healthcare professionals. People frequently seek advice on various health issues from their local pharmacies. Anaphylaxis is a serious and potentially

fatal condition, making the pharmacy team's expertise crucial for proactive patient preparation and management.

Educating patients is vital. The pharmacy team can help individuals recognize that anaphylaxis is a severe, life-threatening allergic reaction that can develop rapidly and impact the entire body. Understanding the symptoms of anaphylaxis—such as hives, itching, flushing, lips, tongue, or throat swelling, and shortness of breath—is important for early detection.

Patients must always carry their epinephrine product, particularly when exposure to triggers may happen. Patients should have a clear plan outlining the steps to take if a reaction occurs, including using epinephrine, lying down with elevated feet, and calling emergency services. The pharmacy team is well-equipped to teach patients how to use an epinephrine auto-injector or nasal spray and, if needed, provide practice with a trainer.

Patients have told pharmacy personnel that they carry epinephrine in their vehicles and keep epinephrine in multiple locations, such as at home, school, or work. Pharmacy staff may also see prescriptions written for two injector devices. Prescribers may also write for two containers of nasal epinephrine because the nasal formulation can be repeated, as this module discusses.

Pharmacy staff should be aware that a prescriber may prescribe an auto- injector and the neffy nasal spray formulation together because the nasal formulation is new, and prescribers like to see long-term safety and efficacy data.30 There is no guidance here because the nasal spray product is new. However, in these cases, a prescriber may suggest that a patient carry a nasal spray and auto-injector epinephrine.30 This way, if a patient uses neffy and notices no improvement within the first five minutes or symptoms worsen, the patient can administer a second dose or, on the advice of their physician, use the co-prescribed auto-injector.30 Pharmacy staff should continue researching this issue and learn about new guidelines as they evolve.

Patients should regularly check the expiration dates on their epinephrine products and secure replacements when necessary. If a patient’s copay or coinsurance is substantial, the pharmacy team can assist in locating co-pay assistance programs and contacting insurance companies for proper approvals when products are needed.

The pharmacy team plays a vital role in the healthcare provider network, and collaborating with other team members may be necessary to ensure the effective management of patients experiencing anaphylaxis.

Summary

As you may have gathered from this information, anaphylaxis is a serious, potentially life-threatening allergic reaction that can develop swiftly, usually within minutes of encountering an allergen, such as food, insects, medications, or latex. It produces various symptoms, including breathing difficulties, facial or throat swelling, hives, a sudden drop in blood pressure, and gastrointestinal issues.

Epinephrine is the primary treatment for anaphylaxis. It rapidly alleviates symptoms by relaxing airway muscles, constricting blood vessels, and stabilizing blood pressure. It can be delivered through intramuscular injection or a newly approved intranasal product, which is an effective alternative for individuals with a fear of needles or trypanophobia.

Clinical trials of nasal epinephrine demonstrated a pharmacokinetic and pharmacodynamic profile comparable to that of the standard epinephrine auto-injectors, along with similar side effects. Patients must always seek emergency medical assistance right after using epinephrine, as symptoms may return. The pharmacy team plays a crucial role in ensuring positive patient outcomes.

Course Test

Which list of triggers below most accurately reflects the reasons for the onset of anaphylaxis?

Milk, peanuts, shellfish, stinging insects

Normal saline, peanuts, tree nuts, cocoa butter

Distilled water, shellfish, foot powder, lanolin

Foot powder, stinging insects, saline, tree nuts

Which option below best describes anaphylaxis?

Anaphylaxis is always life-threatening, and a person can go blind in 2 days

Anaphylaxis involves dopamine, which targets multiple organ systems

Anaphylaxis can be mild and self-limiting or can be potentially fatal

Anaphylaxis has a lifetime prevalence from all triggers of 20-40%

A patient comes to the pharmacy and nervously states that a bee stung her arm while she removed weeds in her garden. Which physical appearance suggests she may have anaphylaxis?

She has a cane, walks with a limp, and has a swollen knee

She has erythema on her arm and has difficulty breathing when speaking

She appears obese and has a flaky, scaly, psoriatic rash on her neck

She appears to have a fungal infection on her thumb

Which epinephrine formulation has automated voice instructions?

Teva generic epinephrine auto-injector

Auvi-Q® epinephrine autoinjector

Epipen Jr® epinephrine autoinjector

neffy® nasal epinephrine formulation

Which dose strength below is not an FDA-approved epinephrine formulation?

0.1 mg

0.15 mg

0.3 mg

0.9 mg

Which administration discussion point below is NOT accurate for nasal epinephrine administration?

Each nasal epinephrine device has only one dose for a single use

While lying down, the patient can angle the nozzle of the nasal epinephrine device

The patient may sit, stand, or lie down when administering nasal epinephrine

Right-handed patients should administer nasal epinephrine into the right nostril

The first step for administering an epinephrine auto-injector requires the patient to

hold the autoinjector in place for 10 seconds.

remove the safety cap on the autoinjector.

position the auto-injector on the middle outer thigh.

push down firmly until it clicks.

Which option below likely explains possible barrier(s) to epinephrine use for anaphylaxis?

Less than 50% of anaphylaxis-prone patients regularly carry epinephrine

No insurance covers epinephrine, and patients have a fear of needles

Patients have a fear of needles, and the FDA approval is only for adults

The FDA approval is only for children, but it is not allowed in schools

After opening the packaging and removing the epinephrine nasal spray device, the user should first

insert the device's nozzle into their nostril until their fingers touch your nose.

angle the nozzle into the nose away from their forehead.

press the plunger firmly until it snaps up and sprays liquid.

hold the device with their thumb on the bottom of the plunger and a finger on either side of the nozzle

Which choice below describes epinephrine nasal supply and storage information?

It is a 2-spray pack and is stored at room temperature (68-77°F)

It is stored at room temperature (68-77°F), and it can be frozen

Do not freeze it, and it can be stored up to 122°F for 6 months

Keep it refrigerated, and it has a 36-month expiration date

References

Trypanophobia: Definition, symptoms, causes, and more. Published November 13, 2023. https://www.medicalnewstoday.com/articles/trypanophobia-2. Accessed October 25, 2024.

Duncanson E, Le Leu RK, Shanahan L, et al. The prevalence and evidence-based management of needle fear in adults with chronic disease: A scoping review. PLoS One. 2021;16(6):e0253048. Published 2021 Jun 10. doi:10.1371/journal.pone.0253048

Love AS, Love RJ. Considering Needle Phobia among Adult Patients During Mass COVID-19 Vaccinations. J Prim Care Community Health. 2021;12:21501327211007393. doi:10.1177/21501327211007393

Orenius T, LicPsych, Säilä H, Mikola K, Ristolainen L. Fear of Injections and Needle Phobia Among Children and Adolescents: An Overview of Psychological, Behavioral, and Contextual Factors. SAGE Open Nurs. 2018;4:2377960818759442. Published 2018 Mar 14. doi:10.1177/2377960818759442

Krombach JW, Kampe S, Keller CA, Wright PM. Pharaoh Menes' death after an anaphylactic reaction--the end of a myth. Allergy. 2004;59(11):1234-1235. doi:10.1111/j.1398-9995.2004.00603.x

Boden SR, Wesley Burks A. Anaphylaxis: a history with emphasis on food allergy. Immunol Rev. 2011;242(1):247-257. doi:10.1111/j.1600- 065X.2011.01028.x

Dribin TE, Motosue MS, Campbell RL. Overview of Allergy and Anaphylaxis. Emerg Med Clin North Am. 2022;40(1):1-17. doi:10.1016/j.emc.2021.08.007

Motosue MS, Li JT, Campbell RL. Anaphylaxis: Epidemiology and Differential Diagnosis. Immunol Allergy Clin North Am. 2022;42(1):13-

25. doi:10.1016/j.iac.2021.09.010

Moore LE, Kemp AM, Kemp SF. Recognition, treatment, and prevention of anaphylaxis. Immunol Allergy Clin North Am. 2015;35(2):363-374. doi:10.1016/j.iac.2015.01.006

DuToit G, Smith P, Muraro A, et al. Identifying patients at risk of anaphylaxis. World Allergy Organ J. 2024;17(6):100904. Published 2024 Jun 11. doi:10.1016/j.waojou.2024.100904

Sicherer SH, Simons FER; SECTION ON ALLERGY AND IMMUNOLOGY.

Epinephrine for First-aid Management of Anaphylaxis. Pediatrics. 2017;139(3):e20164006. doi:10.1542/peds.2016-4006

Navalpakam A, Thanaputkaiporn N, Poowuttikul P. Management of Anaphylaxis. Immunol Allergy Clin North Am. 2022;42(1):65-76. doi:10.1016/j.iac.2021.09.005

Coady P, Dretchen KL, Mesa M. Epinephrine Administered in Anaphylaxis: The Evolution of 0.3 mg Dosage. Ther Adv Allergy Rhinol.

2023;14:27534030231161784. Published 2023 Mar 26. doi:10.1177/27534030231161784

Auvi-Q. [package insert]. Richmond, VA: Kaleo, Inc.; 2024. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6180 fb40-7fca-4602-b3da-ce62b8cd2470&type=display. Accessed October 25, 2024.

EpiPen. [package insert]. Morgantown, WV: Mylan Specialty LP. 2023. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?type=displa y&setid=7560c201-9246-487c-a13b-6295db04274a. Accessed October 25, 2024.

Epinephrine. [package insert]. New York, NY: Amneal Pharmaceuticals; 2021.

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e13f05f1- 7d21-49bb-b8d5-24bf9301c3d7&audience=consumer. Accessed October 25, 2024.

Epinephrine. [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2021.

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=04f07f15- 55e2-411b-abb8-07eab37f5664. Accessed October 25, 2024.

Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020;145(4):1082-1123. doi:10.1016/j.jaci.2020.01.017

Westermann-Clark E, Pepper AN, Lockey RF. Anaphylaxis: Access to Epinephrine in Outpatient Setting. Immunol Allergy Clin North Am. 2022;42(1):175-186. doi:10.1016/j.iac.2021.09.004

Press Room - Sanofi US News. Sanofi.us. Published 2024. https://www.news.sanofi.us/press-releases?item=131480. Accessed November 15, 2024.

Kaléo. U.S. FDA Approves Kaléo’s AUVI-Q® (Epinephrine Injection, USP)

0.1 mg Auto-Injector for Life-Threatening Allergic Reactions in Infants and Small Children - Kaléo. Kaléo. Published November 20, 2017. https://kaleo.com/u-s-fda-approves-kaleos-auvi-q-epinephrine- injection-usp-0-1-mg-auto-injector-for-life-threatening-allergic- reactions-in-infants-and-small-children/. Accessed October 15, 2024.

Lin YY, Chang HA, Kao YH, et al. Investigation of the underuse of adrenaline (epinephrine) and prognosis among patients with anaphylaxis at emergency department admission. Front Med (Lausanne). 2023;10:1163817. Published 2023 Jul 7. doi:10.3389/fmed.2023.1163817

American Society of Health-System Pharmacists. Drug shortage detail: Epinephrine Auto-Injectors. ASHP. 2024. https://www.ashp.org/drug- shortages/current-shortages/drug-shortage-

detail.aspx?id=420&loginreturnUrl=SSOCheckOnly. Accessed November 16, 2024.

Ellis AK, Casale TB, Kaliner M, et al. Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions. Pharmaceutics. 2024;16(6):811. Published 2024 Jun 14.

doi:10.3390/pharmaceutics16060811

Grassin-Delyle S, Buenestado A, Naline E, et al. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol Ther. 2012;134(3):366-

379. doi:10.1016/j.pharmthera.2012.03.003

U.S. Food and Drug Administration. FDA Approves First Nasal Spray for Treatment of Anaphylaxis. FDA. Published 2024. Accessed October 15, 2024. https://www.fda.gov/news-events/press-announcements/fda- approves-first-nasal-spray-treatment-anaphylaxis. Accessed October 15, 2024.

U.S. Food and Drug Administration. Fast Track. FDA. Published 2018. https://www.fda.gov/patients/fast-track-breakthrough-therapy- accelerated-approval-priority-review/fast-track. November 16, 2024.

Neffy [package insert]. San Diego, CA: ARS Pharmaceuticals Operations, Inc. https://www.ars-pharma.com/wp- content/uploads/pdf/Prescribing_Information.pdf. Accessed October 28, 2024.

Casale TB, Ellis AK, Nowak-Wegrzyn A, Kaliner M, Lowenthal R, Tanimoto S. Pharmacokinetics/pharmacodynamics of epinephrine after single and repeat administration of neffy, EpiPen, and manual intramuscular injection. J Allergy Clin Immunol. 2023;152(6):1587- 1596. doi:10.1016/j.jaci.2023.08.007

Katella K. 5 things to know about neffy, the new nasal spray for anaphylaxis. Yale Medicine. October 8, 2024. https://www.yalemedicine.org/news/5-things-to-know-about-neffy-the- new-nasal-spray-for-anaphylaxis. Accessed November 8, 2024.

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