DANGER ZONE
ACCIDENTAL PEDIATRIC EXPOSURE
IMIDAZOLINE DERIVATIVES
Authors: Kellie Taylor, PharmD, MPH, and Yelena Maslov, PharmD, Silver Spring, MD
Section Editor: Susan F. Paparella, RN, MSN
Earn Up to 9.5 CE Hours. See page 109.
hen consumers reach for over-the-counter
W (OTC) eye drop solutions and nasal sprays,
they are usually unaware that the relief they seek
from eye redness or nasal congestion is elicited by the
imidazoline derivatives present in their topical OTC
product of choice. These products that contain imidazo-
lines are marketed under a variety of names, including
popular product brands like Visine and Afrin. Topical
products that contain imidazolines frequently are regarded
as innocuous staples of household medicine cabinets and,
in fact, generally are sold without child-resistant closures.
Nevertheless, when ingested accidentally by children, the
imidazoline agonists contained in these products can cause
a number of adverse events and serious harm. 1-4
Adverse effects from accidental ingestion of these
topical products by small children range in severity and
include nausea, vomiting, diarrhea, dizziness, somnolence,
hypothermia, tremors, blurred vision, muscle flaccidity,
difficulty breathing, hypertension followed by hypotension,
bradycardia, seizures, central nervous system (CNS)
depression, coma, and death (U.S. Food and Drug
Administration [FDA] Reporting System; cases from this
database can be obtained through Freedom of Information
[FOI] request).
Kellie Taylor is Deputy Director, Division of Medication Error Prevention
and Analysis, Food and Drug Administration, Silver Spring, MD.
Yelena Maslov is Team Leader, Division of Medication Error Prevention and
Analysis, Food and Drug Administration, Silver Spring, MD.
The views expressed in this manuscript represent the opinions of the authors
and do not necessarily represent the views of the U.S. Food and Drug
Administration.
For correspondence, write: Kellie Taylor, PharmD, MPH, Division of
Medication Error Prevention and Analysis, Food and Drug Administration,
10903 New Hampshire Ave, Silver Spring, MD 20993; E-mail: Kellie.
Taylor@fda.hhs.gov.
J Emerg Nurs 2013;39:59-60.
0099-1767/$36.00
Copyright © 2013 Emergency Nurses Association. Published by Elsevier Inc.
All rights reserved.
http://dx.doi.org/10.1016/j.jen.2012.10.007
January 2013 VOLUME 39 • ISSUE 1
TO
Literature reports describing accidental pediatric expo-
sure after ingestion of topical OTC products containing
imidazolines were published as early as 1948. 5 A recent FDA
review of the adverse events reported to the Agency between
January 1985 and November 2011 identified 57 cases of
accidental imidazoline ingestion by children (see the case
illustration in the Figure). In addition, the U.S. Consumer
Product Safety Commission (CPSC) published a Notice of
Proposed Rulemaking in which they describe 12 cases from
published literature and 172 cases from the Children and
Poisoning system of accidental pediatric ingestion of
imidazolines reported between 1948 and 2010 (the Children
and Poisoning System represents a subset of National
Electronic Injury Surveillance System: Cooperative Adverse
Event Surveillance System [NEISS-CADES] records regard-
ing pediatric poisoning, chemical burn, or ingestion). 6
The cases reviewed from FDA and CPSC include
children aged 25 days to 5 years who ingested eye or nasal
products containing imidazoline in an amount ranging from
1 to 45 mL. Our analysis of this case series revealed that
accidental ingestion of even relatively small amounts of
imidazoline derivatives (eg, 3 mL of an OTC product) by
children younger than 5 years had the capability to cause
serious adverse events. Considering that the typical volume of
packaged product solution is between 15 and 30 mL (ie, 0.5
and 1 fluid ounce), serious pediatric harm occurred after the
ingestion of only a fraction of the packaged volume. Although
none of the children died after the accidental ingestion of
imidazolines, many were hospitalized as a result of serious
adverse events, including hypothermia, hypotension, hyper-
tension, tachycardia, CNS depression, respiratory depression,
cyanosis, and coma (U.S. FDA Reporting System; cases from
this database can be obtained through FOI request). 6
Further examination of the cases indicates that improper
storage of these products by consumers, along with the lack of
child-resistant closure systems for these products, contributes
to the accidental pediatric ingestion of these products. 7
Parents and caregivers may not realize the risk of poisoning
posed by these OTC medications in non–child resistant
packaging: therefore, it is essential that products containing
imidazoline derivatives be stored and kept at all times beyond
WWW.JENONLINE.ORG 59
DANGER ZONE/Taylor and Maslov

A 20-month-old boy who weighed 12.4 kg found a 15-mL bottle of ophthalmic product
containing tetrahydrozoline at home and ingested 7.5 mL from the bottle. Within 15
minutes, the patient became excessively drowsy and within an hour could no longer be
aroused. The patient was hospitalized because of central nervous system depression,
bradycardia, a depressed respiration rate, and hypertension. The patient subsequently was
intubated and underwent mechanical ventilation for 10 hours; he was released after being
symptom-free for 24 hours.

FIGURE
Case illustration.

the reach of children. Some of the cases reported that
accidental ingestion occurred after young children had played
with the imidazoline-containing product containers they had
found in the trash, between sofa cushions, or in a mother's
jewelry box. Although these products bear the FDA-regulated
warning, “Keep out of reach of children, and if swallowed, get
medical help or contact Poison Control Center Right away,”
it is clear from the information in the reports that consumers
do not always attend to admonition. 1,2,7,8
Because of the number of cases reporting accidental
pediatric ingestion of imidazolines and the resultant severe
adverse events, on January 11, 2012, the CPSC proposed a
rule that would require child-resistant closures for all
products containing a total amount of 0.08 mg or more of
imidazoline derivatives. 6
ED practitioners may be the first health care providers
to see such patients and should be able to recognize the signs
and symptoms of imidazoline poisoning, which include
nausea, vomiting, diarrhea, dizziness, somnolence, hypo-
thermia, tremors, blurred vision, muscle flaccidity, difficulty
breathing, hypertension followed by hypotension, brady-
cardia, seizures, CNS depression, or coma. Because similar
signs and symptoms can occur in a variety of diseases and
poisonings, the ED staff should obtain the affected patient's
medical history and question parents or caregivers regarding
drugs—prescription and OTC—that may have been in the
child's environment (eg, home, car, and child care center).
It is important to keep the risks of products that contain
imidazolines in mind and ask questions about the name of
any product that may have been ingested, the possible time
frame of ingestion, and the amount of the product that may
have been ingested. Unfortunately, no antidote exists for
imidazoline poisoning, and as such, supportive treatment of
signs and symptoms is indicated for persons poisoned with
imidazolines. Consider contacting the Poison Control
Center at 1-800-222-1222 to report the accidental
poisoning and to obtain further treatment instructions.
Parents and caregivers of children treated in the
emergency department as a result of possible drug poisoning
should be advised to store all medications and vitamins
properly, out of the reach of children, especially seemingly
harmless OTC eye drop solutions and nasal sprays. Teach
patients and families to avoid taking medication in front of
young children. Children like to mimic adults, which makes
it incumbent upon adults to teach children about
medication safety. For additional resources and guidance
regarding patient education, we suggest that you visit the
Web site http://www.upandaway.org/ and recommend it to
parents and caregivers. 9
REFERENCES
1. U.S. Food and Drug Administration. Cold, Cough, Allergy, Broncho-
dilator, and Anti-asthmatic Drug Products for Over-The-Counter
Human Use. 21 CFR §341 (2011).
2. U.S. Food and Drug Administration. Ophthalmic Drug Products for
Over-The-Counter Human Use. 21 CFR §349 (2011).
3. Elsevier Clinical Decision Support. Clinical pharmacology. http://www.
clinicalpharmacology-ip.com/Default.aspx. Accessed February 14, 2012.
4. Haenisch B, Walstab J, Herberhold S. Alpha-adrenoceptor agonistic
activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol.
2010;6:729-39.
5. Hainsworth WC. Accidental poisoning with naphazoline (Privine). Am J
Dis Child. 1948;75:76-80.
6. U.S. Consumer Product Safety Commission. Notice of proposed
rulemaking: PPPA rule requiring child-resistant packaging for imidazolines.
http://www.cpsc.gov/library/foia/foia12/brief/imidazolines.pdf. Accessed
February 14, 2012.
7. U.S. Consumer Product Safety Commission. Poison Prevention Packa-
ging. 16 CFR §1700.14(a)(30) (2011).
8. U.S. Food and Drug Administration. Over-The-Counter (OTC) Human
Drugs Which Are Generally Considered as Safe and Effective and Not
Misbranded. 21 CFR §330.1(g) (2011).
9. Centers for Disease Control and Prevention. Up and away. http://www.
upandaway.org. Accessed February 14, 2012.
Submissions to this column are encouraged and may be sent to
Susan F. Paparella, RN, MSN
spaparella@ismp.org

60 JOURNAL OF EMERGENCY NURSING VOLUME 39 • ISSUE 1 January 2013