On 25 June 2015, the European Medicines Agency (EMA) recommended several measures, including the introduction of more effective educational material, to ensure that patients and carers use adrenaline auto-injectors successfully. Adrenaline auto-injectors are potentially life-saving treatments for anaphylaxis (severe allergic reactions) while the patient waits for emergency medical assistance.
EMA carried out a review of adrenaline auto-injectors following concerns that currently available devices may deliver adrenaline under the skin instead of into a muscle, and this may delay response to treatment.
Having assessed all the available data, EMA’s Committee for Medicinal Products for Human Use (CHMP) acknowledged that giving the medicine by injection into the muscle is the preferred way to obtain a rapid response in anaphylaxis. However, the CHMP noted that several factors may affect whether adrenaline is actually delivered into a muscle; these include needle length, the thickness of fat under the skin, the way the auto-injector works (e.g. if it is spring loaded or not), the angle at which the device is placed on the skin and the force used to activate the device as well as how well the user follows the instructions for injection.
The CHMP concluded that training of the user is of paramount importance. The companies that market adrenaline auto-injectors have therefore been asked to develop more effective educational material for patients, as well as for healthcare professionals, to ensure their optimal use. This includes a training device with which patients can practise; audio-visual material to show in detail how the device is to be used; and a checklist for prescribers to ensure that sufficient information is given to the patient before they use the auto-injector. The product information of adrenaline auto-injectors has also been updated with further warnings and precautions, including a recommendation that patients should be prescribed two auto-injectors which they should carry at all times and a recommendation for family members, carers or teachers to be trained on how to use the auto-injector.
The CHMP also concluded that further data should be generated to better understand how adrenaline penetrates body tissues when given with each of the different auto-injectors.
The CHMP recommendation was sent to the European Commission which endorsed it and issued a legally binding decision that is valid throughout the EU.
- Information for patients
- Adrenaline auto-injectors are used to treat severe allergic reactions, while the patient awaits emergency medical assistance. They are designed so that they can be easily used by the patient themselves or a carer.
- The review of adrenaline auto-injectors showed that patients could benefit from further training to use the auto-injector successfully.
- You will receive training from your doctor or nurse on how to use your adrenaline auto-injector. A training device will also be developed so that you can practise with it before you need the auto-injector in an emergency. A training video will be produced to show you in detail how to use the injector properly.
- It is important that you use the auto-injector correctly so that the adrenaline is delivered into your muscle and works as quickly as possible.
- If you have been prescribed an adrenaline auto‑injector because you are at risk of severe allergic reactions, you should ensure you are familiar with it and carry it with you at all times.
- It is likely that your doctor will recommend that you carry 2 injectors, in case a second dose is needed while you wait for emergency assistance.
- Your family members, carers or teachers should also be instructed in the correct use of the auto-injector.
- If you have any question or concern, speak with your doctor or pharmacist.
- Information for healthcare professionals
- The review of adrenaline auto-injectors confirmed that intramuscular injection is the preferred route of administration in the treatment of anaphylaxis in order to obtain a rapid response.
- Several factors may affect whether adrenaline reaches the muscle layer. These include: needle length, the skin-to-muscle depth, the way the auto-injector works (e.g. if it is spring loaded or not), the angle of placement on the skin and the force used to activate the device.
- Because of the uncertainties over drug delivery from adrenaline auto-injectors and the consequent uncertainties around the onset of pharmacodynamic response, it is recommended that healthcare professionals prescribe 2 auto-injectors, which patients should carry at all times.
- Educational material will be developed to ensure that patients or carers use adrenaline auto-injectors successfully. This will include a training device that patients can practise with, audio-visual material and a prescriber checklist.
- A study in 2013 by Brown et al. showed that 15% of the mothers were unable to use the auto-injector successfully in their children. This supports the introduction of proper training and comprehensive educational material for patients and healthcare professionals.
- The companies that market adrenaline auto-injectors have been asked to carry out a pharmacokinetic/pharmacodynamic study to better understand how adrenaline penetrates body tissues when given through an auto-injector.
The review looked at data from several studies including:
- Bhalla, M. C., B. D. Gable, et al. (2013). "Predictors of epinephrine autoinjector needle length inadequacy." Am J Emerg Med 31(12): 1671-1676.
- Brown, J., D. Tuthill, et al. (2013). "A randomized maternal evaluation of epinephrine autoinjection devices." Pediatr Allergy Immunol 24(2): 173-177.
- Simons, F. E., X. Gu, et al. (2001). "Epinephrine absorption in adults: intramuscular versus subcutaneous injection." J Allergy Clin Immunol 108(5): 871-873.
- Simons, F. E., J. R. Roberts, et al. (1998). "Epinephrine absorption in children with a history of anaphylaxis." J Allergy Clin Immunol 101(1 Pt 1): 33-37.
- Song, T. T., M. R. Nelson, et al. (2005). "Adequacy of the epinephrine autoinjector needle length in delivering epinephrine to the intramuscular tissues." Ann Allergy Asthma Immunol 94(5): 539-542.
- Stecher, D., B. Bulloch, et al. (2009). "Epinephrine auto-injectors: is needle length adequate for delivery of epinephrine intramuscularly?" Pediatrics 124(1): 65-70.
- Wang, C., R. Wolf, et al. (2013). Comparison of Needle Penetration Depth Probabilities of Two Epinephrine Auto-Injectors. ALLERGY AND ASTHMA PROCEEDINGS, OCEAN SIDE PUBLICATIONS INC 95 PITMAN ST, PROVIDENCE, RI 02906 USA.
- More about the medicine
Adrenaline (epinephrine) auto-injectors are given to people who are at risk of anaphylaxis (severe allergic reaction) or have had a previous episode of anaphylaxis, to use as a first‑aid measure in case of emergencies while waiting for emergency medical assistance.
Anaphylaxis is a life-threatening reaction that causes a drop in blood pressure and breathing difficulties. An injection of adrenaline helps to relieve the symptoms of anaphylaxis quickly by narrowing the blood vessels (thereby increasing the blood pressure) and opening up the airways to help with the breathing.
Adrenaline auto-injectors have been approved through national procedures in all the EU Member States.
- More about the procedure
The review of adrenaline auto-injectors was initiated at the request of the United Kingdom in April 2014, under Article 31 of Directive 2001/83/EC. This followed a national review of all adrenaline auto-injector products approved in the UK, which concluded that there was no robust evidence that the devices deliver adrenaline into a muscle for all patients.
The review was carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which has adopted the Agency’s final opinion. The CHMP opinion was forwarded to the European Commission, which issued a final legally binding decision applicable in all EU Member States on 14/08/2015.
|Approved name||Adrenaline auto-injectors|
|International non-proprietary name (INN) or common name|
|Type||Article 31 referrals|
This type of referral is triggered when the interest of the Community is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.
|Status||European Commission final decision|
- Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
- Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
- List of the medicines affected by the referral (Annex I)
- Scientific conclusions of the Committee (Annex II)
The following two documents are sometimes available:
- Changes to the summary of product characteristics, labeling or package leaflet (also known as Annex III) - available when changes have been recommended by the Committee
- Conditions of the marketing authorisation (also known as Annex IV) - available when the Committee recommends measures to be taken for the marketing authorisation(s) such as safety measures or extra studies
European Commission final decision
More information on Adrenaline auto injectors
- Better training tools recommended to support patients using adrenaline auto-injectors (26/06/2015)
- Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 June 2015 (26/06/2015)
- Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2014 (25/04/2014)