March 23, 2020 

Important Prescribing Information 



Subject: 

Important Safety Information on the EpiPen¨ and EpiPen Jr¨ Auto-Injectors and 
their authorized generic versions: 

- Risk of device failure due to spontaneous activation. 
- Difficulty removing the device from the carrier tube may also occur. 
- Use errors. 


These issues could delay or prevent emergency treatment when needed. 



 

Dear Healthcare Provider, 

 

The purpose of this letter is to inform you that the administration of EpiPen¨ 0.3 mg and EpiPen Jr¨ 0.15 
mg Auto-Injectors and the authorized generic versions (referenced collectively as EpiPen in the remainder 
of this letter) may be delayed or prevented during an emergency due to: 

 

1. Device failure from spontaneous activation caused by using a sideways force to remove the blue 
safety release. 
2. Device failure from inadvertent or spontaneous activation due to a raised blue safety release 
3. Difficulty removing the device from the carrier tube. 
4. Certain identified use errors. 


 

Additional detail around the identified issues is provided below. 

 

Since EpiPen is administered for severe and potentially life-threatening allergic reactions, anything that 
prevents or delays the administration of the intended dose of epinephrine could result in a high risk to the 
patient, including the risk of death. 

 

Your patients should continue to carry their EpiPen or EpiPen Jr or authorized generic version at all times, 
and we encourage you to review the information below with your patients and their caregivers to ensure its 
appropriate use. Per the instructions for use, we recommend that patients always carry two EpiPen or 
EpiPen Jr auto-injectors or the authorized generic version at all times. Please refer to the important training 
reminders enclosed in this letter and precautionary handling instructions for healthcare providers and 
patients/caregivers, including pictures of the auto-injector, included in Appendix 1. This letter is being 
issued with the knowledge of the FDA. 

 

1. Device Failure from Spontaneous Activation Caused by Using a Sideways Force to 
Remove the Blue Safety Release 


 

¥ Removing the blue safety release using sideways forces has been shown to activate the EpiPen 
prematurely. If spontaneous activation occurs, the device cannot be used to inject epinephrine; a 
new device must be obtained. 
- This can occur if a user tries to hold the EpiPen with only one hand and tries to remove the 
blue safety release with their thumb using a lateral force. As an example, parents who are 
administering EpiPen to their children should first restrain their child, then use both 



hands to hold the EpiPen and remove the blue safety release with the other hand straight 
up without bending, twisting or applying horizontal force. 


 

¥ To prevent this premature activation, patients and their caregivers should be advised of the 
following: 
- Do NOT flip the blue safety release off using a thumb or by pulling it sideways or bending and 
twisting. This may cause the device to spontaneously activate: a ÒclickÓ is heard, the orange 
needle tip is extended, and the window is blocked. An activated device cannot be used for a 
patient. If this occurs, obtain a new EpiPen. 
- Use both hands to remove the blue safety release. Hold the EpiPen auto-injector in one fist 
with the orange end pointing down, while removing the blue safety release with the other hand 
straight up without bending, twisting or applying horizontal force. 
- Healthcare providers should instruct parents who are administering EpiPen to their 
children to first restrain the child and then use both hands to remove the blue safety 
release. 


 

2. Device Failure from Inadvertent or Spontaneous Activation Due to a Raised Blue Safety 
Release 


 

¥ In a very limited number of cases, EpiPen devices may have a blue safety release that is slightly 
raised. 
¥ The function of the blue safety release is to ensure the device does not activate prior to its intended 
use. 


¥ If the blue safety release is raised (see Appendix 1), the device may activate prematurely, which 
could potentially delay or prevent emergency treatment when needed. 
¥ To prevent this spontaneous activation, pharmacists, patients, and their caregivers should be 
advised of the following: 
- When dispensing or receiving an EpiPen or EpiPen Jr Auto-Injector or authorized generic, and 
prior to using the device, visually inspect the auto-injectors to confirm the blue safety release 
is not raised (see Appendix 1, Steps 1 through 5 for more details including pictures). 
- If the blue safety release is raised, the auto-injector should NOT be dispensed or used since 
premature activation may occur. Contact Mylan Customer Relations at 1-800-796-9526 to 
obtain a replacement device(s) at no additional cost. 


 

3. Difficulty Removing the Device from the Carrier Tube 


 

¥ In some (approximately 0.0002% or 2 parts per million units based on the internal manufacturing 
process occurrence rate) cases, EpiPen devices may not slide out of their carrier tube easily or 
potentially at all, which could potentially delay or prevent emergency treatment. 
¥ This issue is related to a slight deformation on the open rim of the plastic carrier tube that may be 
present but may not be visually obvious to patients/caregivers. 
¥ The probability of an auto-injector that may have a deformity that could cause a delay in release 
from the carrier tube is very low. 
¥ This issue may affect any EpiPen auto-injector lot currently on the market in the U.S. with the 
labeled expiry on the device and carton prior to September 2020. 





¥ To ensure the device can be used when needed, pharmacists, patients, and their caregivers 
should be advised of the following: 
- When dispensing or receiving an EpiPen or EpiPen Jr Auto-Injector or authorized generic, and 
prior to using the device: remove both carrier tubes from the S-clip, flip open the caps of the 
carrier tubes, and tip each carrier tube to verify that each auto-injector readily slides out of the 
tube (see Appendix 1, Steps 2, 3 and 4 for more details including pictures). 
- If the auto-injectors do not readily slide from the carrier tubes, they should NOT be dispensed 
or used. Contact Mylan Customer Relations at 1-800-796-9526 to obtain a replacement 
device(s) at no additional cost. 


 

4. Certain Identified Use Errors 


 

Through a study examining use by intended users in expected use environments as well as a thorough 
review of post marketing information, Pfizer, whose subsidiary Meridian Medical Technologies 
manufactures EpiPen, identified that certain use errors have occurred. 

 



Use Errors 

Correct Administration/Important Reminders 



. Failing to remove the device from the 
carrier tube prior to use. 


. EpiPen must be removed from the carrier tube it is 
provided in prior to use. 




. Failing to remove the blue safety 
release prior to use. 


. EpiPen will not activate with the blue safety release in 
place. 




. Activating the auto-injector upside 
down, resulting in hand injections. 


. The needle exits from the orange end of the EpiPen 
which should be in contact with the outer thigh (upper 
leg) at a right angle (perpendicular) to the thigh prior 
to, and during activation. The orange needle tip will 
extend to cover the needle after activation. If the 
needle is still visible, do not attempt to reuse it. 




. Failing to apply sufficient force to 
activate EpiPen. 


. EpiPen should be administered by swinging and 
pushing firmly against the outer thigh until it Òclicks.Ó 
The click signals that injection has started. The correct 
dose has been administered if the orange needle tip is 
extended and the window is blocked. 




. Administering at a site other than the 
outer thigh. 


. Administer EpiPen in the outer thigh only. 




. Failing to hold the auto-injector in 
place for a full three seconds. 


. Hold EpiPen in place for at minimum 3 seconds 
following activation (count slowly 1, 2, 3). 




 

 


Risk 

These use errors could potentially delay or prevent emergency treatment of epinephrine. Since EpiPen is 
administered for severe and potentially life-threatening allergic reactions, anything that prevents or delays 
the administration of the intended dose of epinephrine could result in a high risk to the patient, including 
the risk of death. Additionally, failure to hold EpiPen in the correct orientation could result in inadvertent 
puncture of the hand, which could lead to infection, anaphylactic shock, or death. Failure to administer 
EpiPen in the outer thigh could result in incomplete treatment or a bone strike. Incomplete treatment could 
lead to worsened patient outcomes, including possibly death. Bone strike could lead to infection or nerve 
injury. 

 

Important Training Reminders 

¥ It is important that you review the Patient Information and Instructions for Use with your patients and 
caregivers at the time of prescribing and dispensing of EpiPen, as well as during your regular patient 
interactions. 
¥ It is important that you demonstrate use of the EpiPen with your patients and caregivers. During this 
review and demonstration reinforce the correct administration associated with the use errors in the 
above chart. 
¥ In addition, encourage patients and their caregivers to regularly read and to ensure they understand the 
Patient Information and Instructions for Use. 
¥ Please refer to Appendix 2 of this letter for the Patient Information and Instructions For Use. 
¥ The complete Prescribing Information can be found at https://www.epipen.com/. 
¥ Patients and caregivers should periodically practice using the EpiPen trainer, a needle-less, non-drug 
containing device, referred to as the Trainer in this letter, and included in the EpiPen carton. 
¥ Healthcare providers and consumers should review training resources on EpiPenÕs Instructions For 
Use on a regular basis, which can be found on the product website at https://www.epipen.com/aboutepipen-
and-generic/how-to-use-epipen, as well as the official EpiPen YouTube channel at 
https://www.youtube.com/user/EpiPenOfficial. 


 

AFFECTED PRODUCT 

¥ EpiPen¨ 0.3 mg (EpiPen¨ NDC 49502-500-02) (Authorized Generic NDC 49502-102-02) 
¥ EpiPen Jr¨ 0.15 mg (EpiPen Jr¨ NDC 49502-501-02) (Authorized Generic NDC 49502-101-02) 


 

CONTACT AND REPORTING INFORMATION 

Please contact Mylan Customer Relations at 1-800-796-9526 (Monday-Friday 8 a.m. - 5 p.m. ET) for any 
questions you may have regarding this notification. 

 

To report adverse reactions or quality issues, contact Mylan at 1-877-4-INFO-RX (1-877-446-3679). 

 

Adverse events or quality problems experienced with the use of this product may be reported to the FDAÕs 
MedWatch Adverse Event Reporting Program either online, by regular mail, phone, or by fax: 

 

¥ Complete and submit the report Online: www.fda.gov/medwatch/report.htm 
¥ Regular mail, phone, or Fax: download form www.fda.gov/MedWatch/getforms.htm or call 1-800- 
332-1088 to request a reporting form, then complete and return to the address on the pre-addressed 
form, or submit by fax to 1-800-FDA-0178 (1-800-332-0178) 


 


This letter is not intended as a complete description of the benefits and risks related to the use of EpiPen¨ 
0.3 mg and EpiPen Jr¨ 0.15 mg Auto-Injectors, and the authorized generic versions of these strengths. Full 
Prescribing Information is available at https://www.epipen.com/. 

 

We understand the challenge and inconvenience that the additional actions requested in this letter and in 
Appendix 1 may pose. Thank you for your attention to these important reminders and continued training to 
patients and caregivers to ensure proper use and reporting of any potential concerns or questions regarding 
their EpiPen. 

 

 

Sincerely, 

 

 

 

 

A drawing of a person
Description automatically generated 


_________________________________________ _______________________________________ 

Edward G.M. Power, Ph.D., M.B.A. Rafael Muniz, M.D. 

VP North America Medical Affairs, Hospital Business Head of Global Medical Affairs 

Pfizer, Inc. Mylan, Inc. 


Appendix 1: Precautionary Handling Instructions for Healthcare Providers and Consumers 

Verifying EpiPen¨ Auto-Injectors for Ease of Removal from Carrier Tube and No Raised Blue 
Safety Release 

 

EpiPen¨ 0.3 mg and EpiPen Jr¨ 0.15 mg Auto-Injectors, and the authorized generic versions of these 
strengths, inside the carrier tubes are shown below in Figure 1. 

 

Figure 1. Auto-Injectors in the Carrier Tubes 



 

 

 

 



 

 

 

 



 




1. Before dispensing or administering EpiPen 0.3 mg and EpiPen Jr 0.15 mg Auto-Injectors, and the 
authorized generic versions of these strengths, open the carton and remove both carrier tubes 
containing auto-injectors from the carton. Leave all other contents inside the carton (i.e., package 
inserts and auto-injector trainer). 




2. Remove both carrier tubes from the S-clip. 




3. Per the Instructions for Use, flip open the caps of the carrier tubes. The carrier 
tube caps are: 
a. yellow for EpiPen or Epinephrine 0.3 mg, and 
b. green for EpiPen Jr or Epinephrine 0.15 mg. 




 







4. Tip each carrier tube and verify that each auto-injector readily slides out of the 
tube. 


 

 



5. Visually inspect both auto-injectors to confirm the blue safety release is not raised: 
(Note: Quarter is included for thickness reference only.) 


 

 

 

 Call Mylan to obtain a replacement OK to dispense or use. 

 unit(s) at no additional cost. 

 

If the blue safety release is raised, return EpiPen to the carrier tube, close the carrier tube lid and return 
the unit. Do NOT attempt to push the blue safety release back down. 

 

The blue safety release should be kept on the auto-injector until the time of use. Do NOT remove the 
blue safety release from the auto-injector unless you are ready to use the auto-injector. 







6. If both auto-injectors readily slide from the carrier tube AND the blue safety release is not raised: 
a. place both auto-injectors back into the carrier tubes, 
b. close both carrier tube caps, 
c. connect both carrier tubes to the S-clip, and 
d. place both auto-injectors back into the carton. 




 

Ensure all contents (both carrier tubes each containing an auto-injector, S-clip connecting the carrier 
tubes, package inserts and auto-injector trainer) are placed back inside the carton and close the carton. 
These auto-injectors are ready to be dispensed or used. 



7. If an auto-injector does not readily slide out of the carrier tube OR if the blue safety release is raised, 
the auto-injector should NOT be dispensed or used. Contact Mylan Customer Relations at 1-800-796- 
9526 to obtain a replacement unit(s) at no additional cost. 




 


Appendix 2: Patient Information and Instructions for Use