New Talking Epinephrine Auto-Injectors: Auvi-Q and Allerject

Anaphylaxis is a life-threatening, allergic reaction to a foreign substance that may ordinarily be harmless for most people. Early administration of epinephrine is crucial to successfully treat anaphylactic reactions. Epinephrine (EpiPen, Twinject [Canada only]) is available by prescription in a self-injectable device. Recently, a new talking auto-injector was released in the U.S. (Auvi-Q) and Canada (Allerject). This document discusses the role of epinephrine in the treatment of acute allergic reactions and the place in therapy for Auvi-Q and Allerject.

Allergic reactions to food, latex, medications, and insect stings are the most common causes of anaphylaxis. Food allergy accounts for 35% to 55% of anaphylactic reactions. Allergic reactions to foods such as peanuts, tree nuts (walnuts, pecans, almonds, and cashews), fish, shellfish, cow’s milk, and eggs account for almost half of food-related reactions. Up to 6.5% of the general population has a latex sensitivity with health care workers, children with spina bifida and genitourinary abnormalities, and workers with occupational exposures to latex at higher risk. Penicillin is the most common cause of drug-induced anaphylaxis followed by aspirin and nonsteroidal anti-inflammatory drugs. Insects known to trigger anaphylaxis include honeybees, yellow jackets, hornets, wasps, and fire ants.¹

Symptoms of anaphylaxis include hives; swelling and flushing; difficulty breathing and wheezing; a swelling of the tongue, throat, and nose; dizziness and a dangerous drop in blood pressure; and nausea and cramping. Symptoms typically can occur within minutes of exposure to the offending allergen but also can develop after 30 minutes or more.¹

While prevention through avoidance is vital, exposures occur and can result in severe reactions. The mainstays of therapy are antihistamines, corticosteroids, and epinephrine.²

Although epinephrine is a vital treatment for anaphylaxis, the rate of prescribing and use is low. For example, in a recent study of anaphylaxis care in pediatric emergency departments, only 63% of children who were treated in an emergency department for anaphylaxis received an outpatient prescription for an epinephrine auto-injector.³ Other studies show even lower rates.⁴ In addition, even in those who have an auto-injector, nearly two-thirds of patients reported a delay in seeking medical attention and not using their epinephrine prior to arriving at the emergency department.⁵ Many of these patients felt that their symptoms would go away without treatment. Patients must be educated about the immediate use of epinephrine in the event of an allergic reaction and the need to get immediate medical care.

There are a number of controversies regarding the appropriate use of epinephrine in the treatment of anaphylaxis.

Retrospective clinical studies have been conducted to determine how many patients require more than one dose of epinephrine during an anaphylactic reaction.^6-11 These trials have shown that some patients require more than one dose of epinephrine. While it is not practical for all patients who carry epinephrine auto-injectors to carry two at a time, there are a number of situations where patients should be counseled to carry two doses. These include patients who live in or will be in remote areas, those with a history of immediate, severe reactions such as difficulty breathing, or those older than ten years. Alternatively, schools and day care centers could keep a back-up unassigned auto-injector, in case a second dose is emergently needed in the school or day care setting.

Another controversy regards the length of the needle that is provided with the currently available epinephrine auto-injectors. These auto-injectors often come with a needle which is not of adequate length to penetrate the thigh muscle to provide an intramuscular dose in some children and adults.¹² This could result in subcutaneous administration and a delay in time to achieve maximum epinephrine plasma concentrations. While the available dosage forms are likely adequate for nonobese patients, in obese patients alternatives may be necessary. In cases of severe allergy, parents or patients could be taught how to draw epinephrine from a vial and administer it with needles of adequate length. However, the extra step of drawing epinephrine from a vial can lead to dosing error and a delay in epinephrine administration, so this option is not recommended. Until the currently available products are revised, patients and their families should be counseled to apply moderate pressure (press device down hard) to the thigh prior to epinephrine administration. All patients should be counseled to hold the auto-injector firmly in place for 5 seconds (Auvi-Q or Allerject) or ten seconds (all other epinephrine auto-injectors) to ensure complete delivery of the dose.

For more information on these controversies, see our PL Detail-Document, Self-injected Epinephrine in the Outpatient Treatment of Anaphylaxis.

Auvi-Q (U.S.) and Allerject (Canada) are the first talking epinephrine auto-injectors.^13,14 These products are identical and made by the same manufacturer, Sanofi-Aventis.

The rate of retention of the proper steps for use of an epinephrine auto-injector is low. In a study of 11 patients, Chaudhry and colleagues assessed retention of correct use of their epinephrine (EpiPen). Patients were asked if they believed they knew how to correctly use their epinephrine and were then asked to demonstrate the use. Patients were supposed to include seven key steps for proper use: remove the cap, use the correct side of the injector, inject into the lateral thigh, hold for ten seconds, rub the site after injection, call 911, and carry a second dose. Overall, 91% of patients thought they knew how to use the injector, yet after three months, only 29% to 57% of the steps were demonstrated correctly. The authors concluded that frequent re-training is necessary to ensure proper use of epinephrine.¹⁵

Auvi-Q and Allerject may improve appropriate use of epinephrine. These injectors are available in two prefilled auto-injector strengths, 0.15 mg for people 33 lbs to 66 lbs (15 to 30 kg) and 0.3 mg for those greater than 66 lbs or 30 kg. Both contain epinephrine 1:1000.^13,14

Both injectors are battery operated and include voice instructions (English only for Auvi-Q and English and French for Allerject). The voice instructions keep up with the user’s actions. If the user does not perform the task, the injector will repeat the instructions for that step three times, until the user performs the steps or replaces the outer case. The battery life is several years, usually longer than the expiration of the drug, but the injector continues to work if the batteries no longer work. As with the other commercially available epinephrine auto-injectors, it should be stored between 68^oF to 77^oF (20^oC to 25^oC), but 59^oF to 86^oF (15^oC to 30^oC) excursions are permissible.^13,14

Patients should be instructed to pull off the outer cap. This step initiates the voice-activated steps. Patients should then firmly pull off the red safety guard, place the black end against the outer thigh (through clothing, if necessary) and then press and hold in place for five seconds (as opposed to ten seconds with other epinephrine auto-injectors). Patients should then be counseled to seek medical attention immediately. These steps are all included in the verbal instructions. Once the auto-injector has been used, the injector will state that the injector has been used and an LED light will blink red.^13,14

The cost of two Auvi-Q injectors (in a single box with a training device which contains no drug or needle) is approximately $250, similar to the cost of two EpiPen auto-injectors. In Canada, the cost of Allerject is $87.48, similar to the price of EpiPen and Twinject.

With Auvi-Q there are e-mail notices and an app for iPhones, etc. to remind patients when their auto-injector expires (http://www.auvi-q.com). For EpiPen, patients can register on the product website for an e-mail reminder when their medication will expire (http://www.epipen.com [U.S.] and http://www.epipen.ca [Canada]). The same is true for Allerject (http://www.allerject.ca) andTwinject in Canada (http://www.twinject.ca).

Auvi-Q and Allerject are the first talking epinephrine auto-injectors. Because they are comparably priced with EpiPen and appear to be more convenient to store or carry, these new auto-injectors may be beneficial for some patients. In addition, because many patients forget how to appropriately administer epinephrine, verbal step-by-step instructions during use may be of value.

Project Leader in preparation of this PL Detail-Document: Neeta Bahal O’Mara, Pharm.D., BCPS, Drug Information Consultant

References

1. Anon. What is anaphylaxis? Arm yourself with these facts. American College of Allergy, Asthma and Immunology. http://www.acaai.org/patients/resources/anaphylaxis/Pages/anaphylaxis-facts.aspx. (Accessed February 13, 2013).
2. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma, and Immunology American College of Allergy, Asthma, and Immunology; Joint Council of Allergy, Asthma, and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allerg Clin Immunol 2005:115(3 Suppl 2):S483-523.
3. Russell S, Monroe K, Losek JD. Anaphylaxis management in the pediatric emergency department: opportunities for improvement. Pediatr Emerg Care 2010;26:71-6.
4. Campbell RL, Luke A, Weaver AL, et al. Prescriptions for self-injectable epinephrine and follow-up referral in emergency department patients presenting with anaphylaxis. Ann Allergy Asthma Immunol 2008;101:631-6.
5. Beals JK. More than half of patients with anaphylaxis delay seeking medical attention. December 8, 2009. Medscape. http://www.medscape.com/viewarticle/713534?src=rss. (Accessed February 9, 2013).
6. Korenblat P, Lundie MJ, Dankner RE, Day JH. A retrospective study of epinephrine administration for anaphylaxis: how many doses are needed? Allergy Asthma Proc 1999;20:383-6.
7. Uguz A, Lack G, Pumphrey R, et al. Allergic reactions in the community: a questionnaire survey of members of the anaphylaxis campaign. Clin Exp Allergy 2005;35:746-50.
8. Oren E, Banerji A, Clark S, Camargo CA Jr. Food-induced anaphylaxis and repeated epinephrine treatments. Ann Allergy Asthma Immunol 2007;99:429-32.
9. Kelso JM. A second dose of epinephrine for anaphylaxis: how often needed and how to carry. J Allergy Clin Immunol 2006;117:464-5.
10. Jarvinen KM, Sicherer SH, Sampson HA, Nowak-Wegrzyn A. Use of multiple doses of epinephrine in food-induced anaphylaxis in children. J Allergy Clin Immunol 2008;122:133-8.
11. Rudders SA, Banerji A, Corel B, et al. Multicenter study of repeat epinephrine treatments for food-related anaphylaxis. Pediatrics 2010;125:e711-8.
12. Stecher D, Bulloch B, Sales J, et al. Epinephrine auto-injectors: is needle length adequate for delivery of epinephrine intramuscularly? Pediatrics 2009;124:65-70.
13. Product information for Auvi-Q. Sanofi-Aventis U.S. Bridgewater, NJ 08807. August 2012.
14. Product monograph for Allerject. Sanofi-Aventis Canada, Inc. Laval, QC H7L 4A8. August 2012.
15. Chaudhary RQ, Wolff A. Efficacy and retention of epinephrine auto-injector training. Presented at the Food and Allergy Conference, Anaheim Convention Center, November 8, 2012. Abstract 59.

Cite this document as follows: PL Detail-Document, New Talking Epinephrine Auto-Injectors: Auvi-Q and Allerject. Pharmacist’s Letter/Prescriber’s Letter. March 2013.