Epinephrine autoinjectors for anaphylaxis

August 9, 2019

Epinephrine is essential for treating anaphylaxis in children, and autoinjectors are the preferred method for administering epinephrine in an anaphylactic emergency. There is no one-size-fits-all approach to the optimal dose for all children, so here is expert advice about how to choose what’s best for your patient.

Anaphylaxis is a severe systemic allergic reaction that may be life threatening if not quickly recognized and treated. Anaphylaxis most often results from immunoglobulin (Ig)E-mediated mast cell degranulation leading a combination of respiratory and circulatory compromise, coupled with dermatologic, gastrointestinal, and neurologic symptoms.1 Whereas the prevalence of anaphylaxis varies by location worldwide, it is estimated that 0.05% to 2% of people in the United States will experience anaphylaxis within their lifetime.1

The most frequently identified out-of-hospital causes of anaphylaxis are insect stings and food allergies.2 In children, an allergic reaction to food is the most common reason for anaphylaxis.2-4 Incidence of anaphylaxis among children is increasing, which highlights the need for appropriate and affordable access to epinephrine.5 Prescribing intramuscular (IM) epinephrine for self-administration in the community setting is recommended for any patient who presents with an anaphylactic reaction.1-3

Recently, it was found that when epinephrine was administered to pediatric patients in the prehospital setting prior to emergency medical services (EMS) arrival, patients were more likely to have normal vital signs than those who did not receive epinephrine.5 Prompt epinephrine administration for anaphylaxis is associated with a reduced rate of hospitalization, severe shock, hypoxicischemic encephalopathy, and death.2 This highlights the need for proper access to and prescribing of epinephrine for pediatric patients in the out-of-hospital setting, particularly in light of prior reports that patients are not effectively prepared for episodes of anaphylaxis after a first encounter, mostly due to inadequate prescribing of epinephrine.6

Epinephrine product selection

The preferred formulation of epinephrine for anaphylaxis is an autoinjector formulation3 because autoinjectors provide a premeasured packaged dose that requires no measurement or manipulation for dose accuracy. There are several of these epinephrine autoinjectors (EAIs) on the market and deciding on the optimal formulation for the patient presents its own challenges.

For example, some of the products once activated provide verbal instructions to guide the patient or caregiver in administration, which may be helpful in an emergency. Other products have instructions printed directly on the autoinjector itself, preventing the user from having to keep track of both the medication and the instructions separately. Some formulations also have a training device available so the patient and caregiver can practice and see what the product feels like in their hands before actual use. For details on administration and features of the available autoinjectors and other epinephrine products on the market, see the Figure.

Dose selection of autoinjectors is another problem because the premeasured doses do not allow for manipulation. In children weighing less than 7.5 kg, the recommended dose is 0.01 mg/kg, which cannot be supplied by any of the currently available autoinjector products. The smallest available dose for the autoinjectors is 0.1 mg, which was added to the market in November 2017 for the treatment of anaphylaxis in children between 7.5 kg and 15 kg.7 In addition to the novel dose, this autoinjector also features a shorter needle length, which reduces the likelihood that the needle would unintentionally strike the bone when administered in the preferred location. The historical doses on the market are 0.15 mg and 0.3 mg, approved for patients 15 kg to 30 kg and greater than or equal to 30 kg, respectively.

Prior to the introduction of the 0.1 mg dose, the American Academy of Pediatrics (AAP) recommended the use of the 0.15 mg autoinjector for infants as small as 7.5 kg, given the limitations to prescribing a 1 mg/mL vial and instructing the caregiver to draw up and administer an exact dose intramuscularly (IM).2 The 0.1 mg autoinjector also may not be readily available in many pharmacies, so the 0.15 mg autoinjector continues to be recommended as an alternative in patients between 7.5 kg and 30 kg if the caregiver is unable to obtain the 0.1 mg strength.8

In patients requiring a smaller dose than the autoinjectors provide, the available prescription option is a vial of epinephrine 1 mg/mL with education to the caregiver on drawing up the dose using a syringe and needle. This option requires significant education and, in a controlled scenario, caregivers were found to be significantly slower than trained healthcare professionals, in addition to drawing up an inaccurate dose, regardless of time required to prepare.9 Daycare providers and babysitters were not included in this study, and targeted education by a healthcare professional often does not include these caretakers. In these situations, a child would likely not be provided epinephrine in a timely manner or even before EMS arrival.

Summary

Anaphylaxis is a severe life-threatening condition with increasing incidence and lifetime prevalence. As such, the prescription of outpatient epinephrine, the only treatment known to be lifesaving in this condition, is more important now than ever before. Selection of an epinephrine product must take into account the product and patient-specific factors.

There is not a one-size-fits-all approach to prescribing epinephrine. For children weighing less than 7.5 kg, risks of prescribing an inappropriately high dose of epinephrine when prescribing an autoinjector must be balanced with risks of delay in administration and potential errors in dosing in an emergency situation when prescribing a vial with a syringe and needle. In addition, the costs of EAIs has recently been highlighted due to a large spike in patient out-of-pocket costs and increased charges by the drug manufacturers without a major change to the products.

This is a major limitation to access for many patients. For children who meet the weight criteria for the available autoinjectors, factors such as ease of product use and accessibility, including insurance coverage and out-of-pocket costs, must be evaluated to determine appropriate product selection.

References:

1. Lieberman P, Camargo CA Jr, Bohlke K, et al. Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma, and Immunology Epidemiology of Anaphylaxis Working Group. Ann Allergy Asthma Immunol. 2006;97(5):596-602.

2. Sicherer SH, Simons FER; Section on Allergy and Immunology. Epinephrine for first-aid management of anaphylaxis. Pediatrics. 2017;139(3):e20164006.

3. Simons FE, Ardusso LR, Bilò MB, et al; World Allergy Organization. 2012 update: World Allergy Organization guidelines for the assessment and management of anaphylaxis. Curr Opin Allergy Clin Immunol. 2012;12(4):389-399.

4. Ramsey NB, Guffey D, Coleman NE, Davis CM. Characteristics, morbidity, and mortality of anaphylaxis-associated admissions to North American PICUs, 2010-2015 abstract 470]. Presented at: AAAAI/WAO Joint Congress; Orlando, FL; March 2-5, 2018. J Allergy Clin Immunol. 2018;141(2 suppl):AB148.

5. Andrew E, Nehme Z, Bernard S, Smith K. Pediatric anaphylaxis in the prehospital setting: incidence, characteristics, and management. Prehosp Emerg Care. 2018;22(4):445-451.

6. Wood RA, Camargo Jr CA, Lieberman P, et al. Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467.

7. American Academy of Pediatrics (AAP) Section on Allergy and Immunology Executive Committee. Epinephrine auto-injector for infants, toddlers has lower dose, shorter needle. AAP News. Available at: https://www.aappublications.org/news/2018/06/04/autoinjector060318. Published June 4, 2018. Accessed July 19, 2019.

8. American Academy of Pediatrics (AAP). Allergy and anaphylaxis emergency plan. Available at: https://www.healthychildren.org/SiteCollectionDocuments/AAP_Allergy_and_Anaphylaxis_Emergency_Plan.pdf. Updated March 20, 2019. Accessed July 19, 2019.

9. Simons FE, Chan ES, Gu X, Simons KJ. Epinephrine for the out-of-hospital (first aid) treatment of anaphylaxis in infants: is the ampule/syringe/needle method practical? J Allergy Clin Immunol. 2001;108(6):1040-1044.

10. US National Library of Medicine. Adyphren (epinephrine and isopropyl alcohol) kit. Asclemed USA Inc. DailyMed website. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f895c38e-6020-4f64-9dbc-b7edca40a3c8. Updated June 13, 2017. Accessed July 19. 2019.

11. US National Library of Medicine. EpinephrineSNAP-V (epinephrine convenience kit). Snap Medical Industries. DailyMed website. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=791025c6-5425-c68d-e053-2a91aa0a2bc5. Updated October 25, 2018. Accessed July 19, 2019.

12. US Food and Drug Administration; kaléo Inc. Highlights of prescribing information: Auvi-Q (epinephrine injection solution). Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6180fb40-7fca-4602-b3da-ce62b8cd2470&type=display. Revised October 2018. Accessed July 19, 2019.

13. Amedra Pharmaceuticals LLC. Prescribing information: Adrenaclick (epinephrine injection, USP) auto-injector. Available at: https://www.adrenaclick.com/pdf/Prescribing-Information.pdf. Revised April 2013. Accessed July 19, 2019.

14. US Food and Drug Administration; Mylan Specialty LP. Highlights of prescribing information: EpiPen/EpiPen Jr (epinephrine injection). Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?type=display&setid=7560c201-9246-487c-a13b6295db04274a. Revised August 2018. Accessed July 19, 2019.

15. US National Library of Medicine. Symjepi (epinephrine injection). Sandoz Inc. DailyMed website. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b1c6a201-4f23-489f-9fca-f8c82bb9fa58. Updated May 7, 2019. Accessed July 19, 2019.