Adrenaline auto-injectors - referral

Current status

European Commission final decision

Overview

Better training tools to support patients using adrenaline auto-injectors

Training device and audio-visual material expected to promote appropriate use of auto-injectors

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.

References

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.

Adrenaline auto-injectors Article-31 referral - Better training tools recommended to support patients using adrenaline auto-injectors

Reference Number: EMA/465403/2015 Summary:

Training device and audio-visual material expected to promote appropriate use of auto-injectors

Key facts

About this medicine

• Approved name:
  Adrenaline auto-injectors
• International non-proprietary name (INN) or common name:
  adrenaline (epinephrine)

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-31/1398
• Type:
  Article 31 referrals

  This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Key dates and outcomes

• CHMP opinion date:
  25/06/2015
• EC decision date:
  14/08/2015

All documents

Opinion provided by Committee for Medicinal Products for human Use

Adrenaline auto-injectors Article-31 referral - Review started

Reference Number: EMA/242569/2014 Rev. 1

Adrenaline auto-injectors Article-31 referral - CHMP List of questions

Reference Number: EMA/CHMP/225802/2014

Adrenaline auto-injectors Article-31 referral - Timetable for the procedure

Reference Number: EMA/CHMP/225801/2014

Adrenaline auto-injectors Article-31 referral - Notification

European Commission final decision

Adrenaline auto-injectors Article-31 referral - CHMP assessment report

Adopted Reference Number: EMA/478468/2015

Adrenaline auto-injectors Article-31 referral - Annex II

Adrenaline auto-injectors Article-31 referral - Annex IV

Adrenaline auto-injectors Article-31 referral - Annex III

Adrenaline auto-injectors Article-31 referral - Annex I

Reference Number: EMA/254887/2014

Adrenaline auto-injectors Article-31 referral - Better training tools recommended to support patients using adrenaline auto-injectors

Reference Number: EMA/465403/2015 Summary:

Training device and audio-visual material expected to promote appropriate use of auto-injectors

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.