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EPINEPHrine for Anaphylaxis: Autoinjector or 1 mg Vial or Ampul?

Anaphylaxis is a medical emergency that requires immediate treatment with EPINEPHrine injection. The condition is becoming more common outside of the hospital due to increases in food allergies and the use of contrast media, chemotherapy, and monoclonal antibodies in outpatient clinics. Cases of anaphylaxis will likely increase along with growth in the use of monoclonal antibodies and biosimilars.

EPINEPHrine autoinjectors

For anaphylactic reactions that occur in community settings, EPINEPHrine autoinjectors provide patients and families with greater availability and access to the drug. Those at risk should be prescribed an autoinjector and be properly trained to use it. Autoinjectors can also be found in office practices, clinics, and other locations outside of the hospital. Some hospitals also provide autoinjectors to treat anaphylaxis for inpatients, so they can sometimes be found in the emergency department or other clinical areas in unit stock or automated dispensing cabinets (ADCs) in hospitals.

An intramuscular (IM) dose of 0.3 to 0.5 mg of EPINEPHrine is recommended for anaphylaxis in adults, but no comparative trials have been conducted to determine which dose is most clinically effective. Autoinjectors of 0.3 mg are available for adult use, and repeat doses are recommended at 5 to 15 minute intervals until symptoms improve. Products are available in 2-packs in case a second dose is needed in outpatient settings before treatment is available from emergency personnel. A 0.01 mg/kg dose is recommended for infants and children. A 0.15 mg autoinjector is available, but that dose is above the recommended dose for children weighing less than 15 kg.

Errors with EPINEPHrine 1 mg ampuls or vials

Last fall, the National Comprehensive Cancer Network (NCCN) sent a letter to member hospitals, calling for deployment of EPINEPHrine autoinjectors as a way to avoid wrong dose and wrong route errors (intravenous [IV] instead of IM) when ampuls or vials are used for severe allergic reactions or anaphylaxis. The concern with 1 mg ampuls or vials of EPINEPHrine is that the contents must be drawn into a syringe. Unfortunately, during a stressful emergency situation, this has sometimes led to the erroneous administration of the full 1 mg dose IV, which could prove harmful to some patients. In a review of more than 600 cases reported to the Pennsylvania Patient Safety Reporting System, wrong route errors involving IV administration instead of IM or subcutaneous injection were responsible for 25.4% of all EPINEPHrine adverse events and 63.3% of the harmful events.1

Errors with EPINEPHrine autoinjectors

There are three brands of autoinjectors available in the US, but they are not interchangeable with respect to training and the way they are used. Given that anaphylaxis may not occur very often at any one location, remembering how to use different devices is difficult. Patients often forget how to use them within 3 months,2 and many health professionals have never been trained to use them at all.

EPIPEN is the most commonly used device, although it has been plagued by occasional misuse when people hold it upside down, press, and inject their thumb, or when a child gains access to the device and presses the wrong end. Both situations have been reported to ISMP, most recently a thumb injection by a nurse. AUVI-Q is another brand of autoinjector, which may be easier to use than the EpiPen since it provides digital voice instructions, and the needle retracts to lessen the risk of a needlestick injury. A generic autoinjector from Lineage Pharmaceuticals, which costs about 20% less than the other brands, is more difficult to use. The product won’t be familiar to those who currently know how to use one of the other autoinjectors. Also, we recently informed Lineage Pharmaceuticals that its pen lacks a barcode, which the company promised to address.

Needle length and cost of EPINEPHrine autoinjectors

There are other drawbacks that have blocked full implementation of autoinjectors in clinical areas. For one, although giving EPINEPHrine by the IM route is most effective, there is no consensus about available autoinjector needle length. People worry that the relatively short needle length (16.5 mm) on pens might not ensure that the drug reaches into the muscle when injected into the lateral thigh, especially in women.3 On the other hand, autoinjectors have proved effective in treating anaphylaxis, and there is at least some evidence that the pressure exerted during the forceful injection is adequate enough to drive EPINEPHrine past the depth of the needle into the muscle.4,5

Although we believe that safety trumps cost, it’s hard not to notice that the cost of an autoinjector has doubled in 3 years and is now about $400 for a 2-pack. This is unfortunate because it may impact a patient’s accessibility to autoinjectors. Fortunately, insurance generally covers the cost of autoinjectors for consumers, but there is an associated copay.6  

For health systems that use these and store them in numerous locations throughout their organization, hundreds of thousands of dollars may be needed annually to stock these devices, which can significantly affect the budget. In addition, staff training and inventory needs have to be considerable when determining the cost. EPINEPHrine autoinjectors have a shelf life of only 12-18 months. Thus, they may not be used prior to expiration, resulting in wasted inventory and increases in cost. Special attention is also needed for organizations that may stock the autoinjectors in ADCs. The expiration date should be closely monitored and stock rotated on a regular basis. Our attention was drawn recently to an emergency medical service in Kings County, Washington, that did away with autoinjectors due to the high cost, replacing them with an anaphylaxis kit. They reasoned that an ampul or vial of EPINEPHrine 1 mg would cost about $1.25. Add in a syringe, alcohol wipe, needle, and so on, the savings are still significant. Some hospitals have taken the same course of action.

Autoinjector or 1 mg vial or ampul?

Deciding between the autoinjector or 1 mg vial or ampul remains a tough choice. Some hospitals have decided that autoinjector manufacturers have priced themselves out of the market, making it difficult to allow use in all areas of the hospital. Instead, they have decided to stock 1 mg ampuls or vials, or for safety, they have prepared kits containing a 1 mg EPINEPHrine ampul or vial along with a syringe, needle, label with proper dose for IM injection, a warning not to administer the entire vial, and any other essential components. Still, we agree with NCCN that the presence of a vial or ampul of EPINEPHrine in the wrong hands invites accidental IV injection when the patient has an IV line established. So, an EPINEPHrine autoinjector is appealing as a properly labeled unit dose that can be employed within seconds to treat the emergency, and the contents cannot be administered IV.

To us, an autoinjector certainly makes sense in outpatient clinics and office practices. Examples would include outpatient areas where chemotherapy or contrast media is administered. If more than one ADC is available, the autoinjectors should be stocked in only one of them with visual aids available on the others to guide staff to the correct ADC when it is needed. If you choose to use an autoinjector, we favor the Auvi-Q device because it provides digital voice instructions to “talk” users through the injection process and is easy to use, even for those not completely familiar with it. However, staff training as well as periodic retraining about proper use of the autoinjector is still a requirement.


  1. Pennsylvania Patient Safety Authority. An update in the “Epi”demic: events involving EPINEPHrine. Pa Patient Safe Advis. 2009;6(3):102-3.
  2. Lowry F. Patients forget how to use EpiPen after 3 months. November 20, 2012. Medscape Medical News. From Abstract 59, presented November 12, 2012, at the American College of Allergy, Asthma & Immunology 2012 Annual Scientific Meeting.
  3. Bhalla MC, Gable BD Frey JA, Reichenbach MR, Wilber ST. Predictors of epinephrine autoinjector needle length inadequacy. Am J Emerg Med. 2013;31(12):1671-6.
  4. Baker TW, Webber CM, Stolfi A, Gonzalez-Reyes E. The TEN study: time epinephrine needs to reach muscle. Ann Allergy Asthma Immunol. 2011;107(3):235–8.
  5. Lieberman P. The 10-second rule and other myths about epinephrine and autoinjectors. Ann Allergy Asthma Immunol. 2011;107(3):189-90.
  6. Kids with Food Allergies Foundation Community. What to do if you can’t afford epinephrine auto-injectors. January 22, 2015.