Download Over-the-Counter Medications

NCC Pediatrics Continuity Clinic Curriculum
Over-The-Counter Cough & Cold Medications
Goals & Objectives
1. Be able to recite the science on the use of over-the-counter cough
& cold medications in children.
2. Compare and contrast the science & FDA policy on OTC pediatric
cough & cold medications.
3. Know that branding alone is not a reliable indicator of the OTC
medications present in a cough & cold preparation.
4. Identify risks related to multiple ingredient products and multiple
caregiver administration of OTC cough & cold medication
5. State five non-pharmacologic interventions parents can implement
to provide symptom relief for cough and cold symptoms.
Pre-Meeting Preparation
• Read the 2-page Perspectives on OTC Medications from the 2007
NEJM
• Read the labels of the 3 included pediatric cough & cold
formulations
Conference Agenda
• Review quiz on OTC cough & cold medication
• Discuss the case
Extra Credit
- Read the AAP recommendations for treating the symptoms of the
common cold http://www.healthychildren.org/English/health-issues/conditions/ear-nose-throat/Pages/Children-andColds.aspx
- Text your Program Director if you know who said that “the only
way to treat the common cold is with contempt.
The
NEW ENGLA ND JOURNAL
of
MEDICINE
Perspective
december 6, 2007
Over the Counter but No Longer under the Radar —
Pediatric Cough and Cold Medications
Joshua M. Sharfstein, M.D., Marisa North, B.A., and Janet R. Serwint, M.D.
I
n recent weeks, over-the-counter cough and cold
medications for children have received unprecedented attention from regulators, physicians, the
media, and parents. This scrutiny represents a
long-overdue reassessment of products that were purchased by 39%
of U.S. households during the past
3 years.1 It also reflects an important evolution in the standard
of evidence for medications used
in children.
Over-the-counter cough and
cold preparations include various
combinations of antihistamines,
decongestants, antitussives, and
expectorants. There is no standard
for describing these products; two
products marketed similarly may
have different types of ingredients
(see table). Consumers purchase
about 95 million packages of such
medication for use in children each
year.1 Within the pediatric com-
munity, however, concern over the
effectiveness and safety of such
drugs has been growing for more
than two decades.
Since 1985, all six randomized,
placebo-controlled studies of the
use of cough and cold preparations
in children under 12 years of age
have not shown any meaningful
differences between the active
drugs and placebo. In 1997, the
American Academy of Pediatrics
noted in a policy statement on
cough medications that “indications for their use in children have
not been established.” In 2006,
the American College of Chest
Physicians found that “literature
regarding over-the-counter cough
n engl j med 357;23
www.nejm.org
medications does not support the
efficacy of such products in the
pediatric age group.”
Meanwhile, poison-control centers have reported more than
750,000 calls of concern related
to cough and cold products since
January 2000.2 A recent report
from the Centers for Disease Control and Prevention identified more
than 1500 emergency room visits
in 2004 and 2005 for children under 2 years of age who had been
given cough or cold products.3
Among other concerns are findings in children under six linking
decongestants to cardiac arrhythmias and other cardiovascular
events, antihistamines to hallucinations, and antitussives to dede
pressed levels of consciousness
and encephalopathy. A review by
the Food and Drug Administration (FDA) identified 123 deaths
related to the use of such prod-
december 6, 2007
The New England Journal of Medicine
Downloaded from nejm.org on May 24, 2015. For personal use only. No other uses without permission.
Copyright © 2007 Massachusetts Medical Society. All rights reserved.
2321
PE R S P E C T I V E
Over the counter but no longer under the radar
Ingredients and Marketing of Some
of the Available Pediatric Cough and Cold Products.*
Ingredients
Brand Name
Marketed Use
Pediacare
Nighttime cough
Triaminic
Cough and runny nose
Antitussive
Robitussin
Long-acting cough
Decongestant
Dimetapp
Decongestant
Antihistamine and antitussive
Robitussin
Long-acting cough and cold
Tylenol Plus
Cough and runny nose
Antihistamine
Antihistamine and decongestant
Antitussive and decongestant
Decongestant and expectorant
Antihistamine, antitussive,
and decongestant
Antitussive, decongestant,
and expectorant
Dimetapp
Cold and allergy
Pediacare
Nighttime multisymptom cold
Triaminic
Nighttime cough and cold
Dimetapp
Decongestant plus cough
Pediacare
Multisymptom cold
Triaminic
Daytime cough and cold
Dimetapp
Cold and chest congestion
Triaminic
Chest and nasal congestion
Dimetapp
Cold and chest congestion
Tylenol Plus
Flu
Tylenol Plus
Multisymptom cold
Robitussin
Cough and cold
* The antihistamines include brompheniramine, chlorpheniramine, and diphenhydramine; the antitussive is dextromethorphan, the decongestant is phenylephrine,
and the expectorant is guaifensin. All formulas of Tylenol Plus also contain acetaminophen.
ucts in children under six during
the past several decades.4 Serious
adverse effects have been associated with accidental overdose, inadvertent misuse, and drug–drug
or drug–host interactions in children given standard doses.
The marketing of these preparations for young children does
not reflect the risks or the lack of
evidence of efficacy. The Federal
Trade Commission, which oversees
advertising for over-the-counter
products, does not have the FDA’s
scientific expertise for evaluating
2322
marketing materials and does not
require that advertisements show
a “fair balance” between risks and
benefits. Direct-to-consumer advertisements assert that preparations are safe and effective, and
many state that ingredients are
“pediatrician-recommended.” A frequent theme is that giving children
these products allows parents to
relax. In fiscal year 2007, according to data provided by the Prescription Project (a policy-advocacy organization), companies spent
more than $50 million marketing
n engl j med 357;23
www.nejm.org
pediatric over-the-counter cough
and cold preparations to parents.
The fact that these medications are widely marketed and
used despite the lack of evidence
of efficacy can be explained in
part by their regulatory history.
This class of drugs was first marketed well before 1972, the year
that the FDA began a comprehensive review of hundreds of overthe-counter cough and cold preparations. It obtained input from
an expert advisory panel, solicited public comment on proposed
rules, and prepared a monograph
outlining conditions of use. In
1976, the advisory panel endorsed
the use of some over-the-counter
ingredients for cough or cold
symptoms in adults but, in the
face of “negligible or nonexistent”
data on pediatric use, recommended against their marketing
for children under two. For older children, it endorsed the ex
extrapolation of doses from those
recommended for adults, using
a crude formula: half the adult
dose for children between 6 and
11 years of age and a quarter of
the adult dose for children between 2 and 5 years. Dose rec
recommendations were calculated
for children as young as 6 years
for antihistamines and as young
as 2 years for all other categories of cough or cold drugs. The
FDA adopted these guidelines in
its monograph but permitted manufacturers to market the drugs
for children below these ages if
labeling instructed parents to consult a doctor before use.
In the ensuing 30 years, the
FDA never returned to review the
effects of these preparations in
young children. In March 2007,
we, along with 13 other signatories, filed a petition urging the
december 6, 2007
The New England Journal of Medicine
Downloaded from nejm.org on May 24, 2015. For personal use only. No other uses without permission.
Copyright © 2007 Massachusetts Medical Society. All rights reserved.
P E R S P E CTIV E
Over the counter but no longer under the radar
fects, which could not be
eliminated by labeling or
parent education.
More broadly, the committee debated the appropriateness of extrapolating to children data
No
Yes to both
demonstrating modest efficacy in adults. TestifyReasonable to assume that concentration–
ing for the petitioners,
response will be similar in children and adults?
Wayne Snodgrass of the
University of Texas Medical Branch argued against
No
Yes
extrapolation — describing differences between
Is there a pharmacodynamic
Conduct pharmacokinetic studies
measurement that can be
to achieve levels similar to
adults and children in
used to predict efficacy?
those in adults
the relevant disease proConduct safety trials
cesses and physiology
and citing recent studies,
No
Yes
conducted as a result of
the Best Pharmaceuticals
Conduct pharmacokinetic studies
Conduct pharmacokinetic and
for Children Act and the
Conduct safety and efficacy trials
pharmacodynamic studies
to determine concentration–
Pediatric Research Equity
response for pharmacoAct, that indicate that
dynamic measurement
Conduct pharmacokinetic studies
drugs approved for adult
to achieve target concentrations
use may be ineffective,
based on concentration–
response
incorrectly administered,
Conduct safety trials
or toxic in children. Examples of prescription
FDA’s Decision Tree for Determining Whether Pediatric Efficacy Studies of a Drug Are Needed.
drugs include sumatripModified from FDA presentation, “Guidance for Industry: Exposure–Response Relationships —
tan, gabapentin, and
Study Design, Data Analysis, and Regulatory Applications,” April 2003.
pimecrolimus. The American Academy of Pediatagency to do so. We asked the two and proposed adding the rics concurred, testifying that the
FDA to issue a public statement warning “Do not use to sedate results of pediatric drug studies
explaining that the products have children” to the label for anti- “humble us on a regular basis.”
not been shown to be safe and histamines subject to the mono
monoThe FDA presented an algoeffective for children under six, graph.
rithm (see flow chart) that, in
to take action against misleadAt the meeting, there was lit- keeping with the current legal
ing marketing, and to revise its tle dispute about the lack of evi- standard, permits extrapolation
monograph accordingly. The FDA dence from pediatric efficacy when there is a “similar disease
responded by convening a joint studies. As for safety, the manu- progression” in children and
meeting of the Pediatric Com- facturers claimed that virtually all adults and a “similar response
mittee and the Nonprescription cases of serious injury or death to intervention,” when it is “reaDrug Advisory Committee on Oc- resulted from overdose, which sonable to assume similar contober 18 and 19, 2007. Ten days could be prevented through pa- centration–response,” when safety
before the meeting, major man- tient education. The petitioners trials have been conducted, and
ufacturers voluntarily recalled argued that some serious ad- when pharmacokinetic studies
over-the-counter cough and cold verse events have resulted from show that appropriate adminispreparations for children under confusion and unanticipated ef- tration of the drug will achieve
Reasonable to assume that
Disease progression is similar
in children and adults?
Response to intervention will be
similar in children and adults?
n engl j med 357;23
www.nejm.org
december 6, 2007
The New England Journal of Medicine
Downloaded from nejm.org on May 24, 2015. For personal use only. No other uses without permission.
Copyright © 2007 Massachusetts Medical Society. All rights reserved.
2323
PE R S P E C T I V E
Over the counter but no longer under the radar
“levels similar to [those in]
adults.” Agency scientists, however, stated that pharmacokinetic
data were inadequate to support
extrapolation for cough and cold
preparations. The manufacturers’
trade association promised to conduct additional pharmacokinetic
studies and said it would consider conducting efficacy studies
in consultation with the FDA.
Advisory committee members
expressed concern that these medications have been marketed for
decades without good pediatric
data, when it has long been feasible to conduct additional studies.
The committee rejected the idea
that pharmacokinetic data alone
would be sufficient. All 22 members agreed that it was unaccept
unacceptable to extrapolate data for the
use of these medications in children under 2, and all but 1 member rejected extrapolation for children between 2 and 11. Instead,
the group voted unanimously that
pediatric clinical efficacy studies
should be required. The commit
committee voted 13 to 9 in favor of immediate action against the use of
cough and cold medications in
children under six.
After the meeting, the major
manufacturers of these products
announced that they disagreed
with the committee and would
continue to market these preparations for children between 2 and
5 years of age. Because the monograph is still in effect, the products and their “toddler” formu-
2324
lations are still being widely
advertised to parents in ways
that suggest that they are known
to be safe, effective, and recommended by most pediatricians.
Despite their own proposal that
the use of these products for sedation be stopped, companies are
to the broader implications of
the committee’s objection to extrapolating efficacy from adults
to children. When it is questionable whether a drug’s benefits
outweigh its risks, the drug
should be studied in children if
at all possible. The adoption of
this standard would bring benefits far beyond relief of the common cold.
Dr. Sharfstein is the commissioner of health
for Baltimore; Ms. North is a medical student at the Johns Hopkins School of Medicine, Baltimore; and Dr. Serwint is a professor of pediatrics at the Johns Hopkins
School of Medicine, Baltimore. The authors
are the lead signers of the petition to the
FDA on over-the-counter cough and cold
medications.
still marketing “nighttime” preparations containing sedating antihistamines. Although the FDA
does not need to follow the recommendations of its advisory
committees, we believe that it
should immediately ask companies to remove these products
from store shelves and begin legal proceedings to require them
to do so. Rep. Henry A. Waxman
(D-CA) and Sen. Edward Kennedy (D-MA) have recently introduced legislation to expedite this
process by strengthening the FDA’s
oversight of the marketing and
advertising of over-the-counter
medications.
The agency must also respond
n engl j med 357;23
www.nejm.org
1. Consumer Healthcare Products Association. Briefing information for the Food and
Drug Administration joint meeting of the
Nonprescription Drugs Advisory Committee
& the Pediatric Advisory Committee. (Accessed November 14, 2007, at http://www.
fda.gov/ohrms/dockets/ac/07/briefing/
2007-4323b1-01-CHPA.pdf.)
2. Consumer Healthcare Products Association testimony before the Food and Drug
Administration (October 18, 2007). Washington, DC: American Association of Poison
Control Centers, 2007.
3. Infant deaths associated with cough and
cold medications — two states, 2005.
MMWR Morb Mortal Wkly Rep 2007;56:
1-4.
4. Food and Drug Administration, Division
of Drug Risk Evaluation. Nonprescription
Drug Advisory Committee meeting: cold,
cough, allergy, bronchodilator, antiasthmatic
drug products for over-the-counter human
use. 2007:29. memorandum. (Accessed November 14, 2007, at http://www.fda.gov/
ohrms/dockets/ac/07/briefing/2007-4323b102-FDA.pdf.)
Copyright © 2007 Massachusetts Medical Society.
december 6, 2007
The New England Journal of Medicine
Downloaded from nejm.org on May 24, 2015. For personal use only. No other uses without permission.
Copyright © 2007 Massachusetts Medical Society. All rights reserved.
Department
www.jpedhc.org
Pharmacology Continuing Education
Section Editors
Teri Woo, MS, RN, CPNP
University of Portland
School of Nursing, Kaiser
Permanente, Portland,
Oregon
Elizabeth Farrington,
PharmD, FCCP, BCPS
University of North Carolina,
School of Pharmacy and
North Carolina Children’s
Hospital
Pharmacology of
Cough and Cold
Medicines
CE
Teri Woo, MS, RN, CPNP
OBJECTIVES
After reading this manuscript, the reader should be able to:
1. Describe the mechanism of action for commonly prescribed decongestants,
cough suppressants, expectorants, antihistamines, and antipyretics.
2. State FDA dosing recommendations for the use of cough and cold medications
for children less than 2 years of age.
3. List five infant cough and cold products that have been voluntarily withdrawn
from the market.
4. State five non-pharmacologic interventions parents can implement to provide
symptom relief for cough and cold symptoms.
5. Identify risks related to multiple ingredient products and multiple caregiver
administration.
Teri Woo is Instructor, University of
Portland School of Nursing, and
Pediatric Nurse Practitioner, Kaiser
Permanente, Portland, Ore.
Correspondence: Teri Woo, MS, RN,
CPNP, University of Portland School of
Nursing, 5000 N Willamette Blvd,
Portland, OR; e-mail: [email protected].
J Pediatr Health Care. (2008). 22, 73-79.
0891-5245/$34.00
Copyright © 2008 by the National Association of Pediatric Nurse Practitioners.
doi:10.1016/j.pedhc.2007.12.007
Journal of Pediatric Health Care
A New York Times headline
reads, “F.D.A. Panel Urges Ban on
Medicine for Child Colds” (Harris,
2007). Suddenly the use of cough
and cold medicines in children is
the lead story on every news channel. This month’s column will focus on the pharmacology, safety,
and effectiveness of common overthe-counter (OTC) cough and cold
medications in infants and children.
Commonly
available
OTC
cough and cold medications contain either singly or in combination
a decongestant, cough suppressant, antihistamine, expectorant,
and antipyretic. Parents administer
cough and cold medications to
provide temporary relief from the
symptoms of upper respiratory infections in children, including
runny nose, congestion, cough,
and fever.
DECONGESTANTS
The decongestants found in children’s OTC cold medication are either pseudoephedrine or phenylephrine. Systemic decongestants are
adrenergic receptor agonists (sympathomimetics) that produce vasoconstriction within the mucosa of
the respiratory tract, temporarily reducing the swelling associated with
inflammation of the mucous membranes. Sympathomimetic drugs
work on the ␣ receptors in the vascular smooth muscle causing vasoconstriction and pressor effects and
on the ␤-adrenergic receptors in the
heart causing increased heart rate
and force of contraction. Because of
March/April 2008
73
The use of isotonic saline nose drops and gentle
aspiration can be effective in the temporary
relief of nasal obstruction in infants.
the cardiac effects, these agents
should be used with caution in children with congenital heart disease,
hypertension, or cardiac arrhythmias without consulting the patient’s
pediatric cardiologist. Pseudoephedrine (Sudafed) and phenylephrine (Sudafed PE) may have
mild central nervous system (CNS)
stimulant effects in patients sensitive
to sympathomimetics. Oral decongestants also should be used with
caution in patients with hyperthyroidism and diabetes mellitus.
Topical decongestant products
are applied topically to the nasal
tissues via spray or drops. Topical
decongestants stimulate the ␣-adrenergic receptors in the arterioles
of the nasal mucosa, leading to vasoconstriction and shrinkage of nasal tissues. There is minimal systemic absorption if used as
directed. Therapy should not exceed 3 to 5 days because of the
development of rebound congestion with ␣-adrenergic receptor
agents. If congestion persist, normal saline nose drops may be substituted for the vasoactive drugs for
3 to 5 days, then another trial of
active drug may be attempted if
necessary. Two topical decongestants currently are available OTC in
the United States: phenylephrine
(Neo-Synephrine) and oxymetazoline (Afrin).
The use of isotonic saline nose
drops and gentle aspiration can be
effective in the temporary relief of
nasal obstruction in infants. Also
useful is the general humidification
of room air. Moisture tends to dilute tenacious nasal mucus so that
it is easier to remove.
COUGH SUPPRESSANTS
Dextromethorphan is the cough
suppressant found in OTC cough
74
Volume 22 • Number 2
medications, and it often is combined with the expectorant guaifenesin. Dextromethorphan, the D
isomer of the codeine analogue
levorphanol, acts centrally in the
cough center in the medulla to
suppress cough. Drowsiness, dizziness, nausea, and gastrointestinal
upset also may be seen with dextromethorphan use.
Diphenhydramine, an antihistamine, also is marketed as a cough
suppressant for children (PediaCare Children’s Long-Acting Cough).
The exact mechanism of action of
first-generation antihistamines antitussive effects is unknown, although it is thought that the CNS
depression effects of first-generation antihistamines may depress
respiratory reflexes, thus suppressing cough (McLeod et al., 1998).
EXPECTORANTS
Guaifenesin is the most commonly prescribed oral mucolytic
agent as an expectorant in the
United States. Its mechanism of action is to reduce the surface tension and viscosity of the mucus,
which increases the ease of expectoration. Respiratory mucus removal is facilitated by increased
flow of the thinned secretions via
ciliary action. Studies on the efficacy of guaifenesin have failed to
demonstrate either improved pul-
monary function or decreased sputum viscosity. Hence, its clinical
usefulness is questionable.
ANTIHISTAMINES
Diphenhydramine, chlorpheniramine, and brompheniramine
are the antihistamines found in
children’s cold and allergy formulas. Antihistamines, also known as
H1 receptor antagonists, compete
for and block the action of histamine at the H1 receptor site on
cells in the respiratory tract, gastrointestinal tract, and blood vessels.
In the respiratory tract, antihistamines decrease congestion related
to allergies.
Naclerio and colleagues (1988)
studied the response of inflammatory mediators to induced viral infections. All variables except histamine grew stronger in direct
relationship with the symptoms as
the cold increased in severity. This
finding indicates that antihistamines
have no role in the treatment of the
common cold; they will not shorten
the period of symptoms. They are
helpful, however, in the treatment of
the symptoms of allergic rhinitis.
Lastly, in young infants, sympathomimetic-antihistamine mixtures are
particularly dangerous because they
may cause respiratory depression.
ANTIPYRETICS
Some multi-symptom cold formulas contain acetaminophen or
ibuprofen as an antipyretic and
analgesic. Acetaminophen acts centrally to inhibit the synthesis prostaglandins in the CNS and peripherally
to block pain impulse generation.
Antipyretic activity is due to its ac-
Studies on the efficacy of guaifenesin have
failed to demonstrate either improved
pulmonary function or decreased sputum
viscosity. Hence, its clinical usefulness is
questionable.
Journal of Pediatric Health Care
tion against prostaglandin E2 in the
CNS, which increases in fever
(Aronoff & Neilson, 2001). Ibuprofen is a cyclo-oxygenase (COX) enzyme inhibitor. COX is needed for
prostaglandin synthesis, and inhibiting COX leads to antipyretic activity
because of decreased prostaglandin
E synthesis in the CNS.
LACK OF EVIDENCE FOR
EFFECTIVENESS OF COUGH
AND COLD MEDICATIONS IN
CHILDREN
Evidence is lacking for the effectiveness of cough and cold
medications in children. A recent
Cochrane review of the use of decongestants to treat nasal congestion associated with the common
cold found a small (6%) but statistically significant improvement in
congestion in adults (Taverner &
Latte, 2007). The review found insufficient evidence in the literature
regarding the effectiveness of decongestants to treat the common
cold in children and recommended that decongestants not be
used in children younger than 12
years (Taverner & Latte). A Cochrane review of the use of cough
medications for acute cough in
children found a lack of evidence
for the use of OTC cough medications in children, including antitussives, expectorants, and antihistamines (Schroeder & Fahey, 2004).
The American College of Chest
Physicians evidence-based practice guidelines note limited efficacy of cough suppressants in patients with cough due to the
common cold and do not recommend the use of cough suppressants for upper respiratory infections (Bolser, 2006). This guideline
is consistent with the American
Academy of Pediatrics (AAP) policy, which states there are no wellcontrolled scientific studies regarding the efficacy and safety of
antitussives in children (AAP Committee on Drugs, 1997).
Journal of Pediatric Health Care
SAFETY OF OTC COUGH
AND COLD MEDICATIONS IN
INFANTS AND CHILDREN
Concerns regarding the safety
of cough and cold medications can
be found in the scientific literature
for at least 15 years. Case reports of
infants presenting to the emergency department with OTC cold
medication toxicity appear in Pediatrics as early as 1992, with the
authors noting that in 1990, 1 in 15
calls to the Maryland Poison Center were regarding cough and cold
medications (Gadomski & Horton,
1992). During 2004 and 2005, an
estimated 1519 children younger
than 2 years were treated in emergency departments for either overdose or other adverse event associated with cough and cold
medications (Centers for Disease
Control and Prevention [CDC],
2007).
In the past 5 years, multiple
studies pointing to OTC cold medications as the cause of death in
infants have been published. The
Montgomery County Ohio Coroner reported a series of 10 infant
deaths in 8 months with toxicology
findings confirming the presence
of ingredients found in OTC cold
medications (Marinetti et al., 2005).
The authors note toxicology reports confirm that combination
cold products were administered
by parents or caregivers in nine of
the 10 infant deaths (Marinetti et
al.). The Philadelphia Medical Examiners Office reported on a series
of 15 deaths of infants and toddlers
between February 1999 and June
2005 in which pseudoephedrine
was present in the blood or tissues
of all the cases (Wingert, Mundy,
Collins, & Chmara, 2007). Pseudoephedrine was confirmed to have
contributed to or caused the death
in eight of the 15 infants, with high
levels of pseudoephedrine present
in two other cases, with the primary cause of death listed as pneumonia in one case and undetermined cause in the second
(Wingert et al.). A survey of 15
medical examiners from 12 states
by the National Association of
Medical Examiners identified three
infant deaths in 2005 associated
with cold medications, specifically
pseudoephedrine that was found
in high levels on postmortem toxicology reports of all three infants
(CDC, 2007).
A consistent finding in the reports of infant deaths is the high
levels of medication found during
postmortem toxicology reports.
Several possible reasons for this
finding are suggested in the literature, including lack of dosing
guidelines for infants and toddlers,
product labeling that is confusing
to parents, multiple active ingredients in products that lead to accidental overdosing, and multiple
caregivers administering medication to children, leading to accidental overdose.
Lack of FDA Dosing
Guidelines for Children
Younger Than 2 Years
There are no Food and Drug Administration (FDA) approved dosing
recommendations for the use of
cough and cold medications in children younger than 2 years (CDC,
2007). Safety and efficacy studies
have not been conducted in this age
group; therefore, the dosages in
which cough and cold medications
cause illness and death in children
younger than 2 years is not known.
In a recent CDC study of three infant
deaths, pseudoephedrine levels
were nine to 14 times what should
have been found with recommended dosing based on children
age 2 to 12 years (CDC). Cough and
cold product labeling clearly states
that parents should consult their pediatric provider prior to administering the medication to young infants,
yet when a product is labeled for
“infants,” parents may disregard the
product labeling. Box 1 lists products that have been voluntarily withdrawn from the market with confusing labeling messages.
The wide variety of product
forms available confuse parents,
with drops, elixirs, chewable tabMarch/April 2008
75
BOX 1. Infant cough and cold medications voluntarily withdrawn from the market
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Dimetapp Decongestant Plus Cough Infant Drops
Dimetapp Decongestant Infant Drops
Little Colds Decongestant Plus Cough
Little Colds Multi-Symptom Cold Formula
Pediacare Infant Drops Decongestant (containing pseudoephedrine)
Pediacare Infant Drops Decongestant & Cough (containing pseudoephedrine)
Pediacare Infant Dropper Decongestant (containing phenylephrine)
Pediacare Infant Dropper Long-Acting Cough
Pediacare Infant Dropper Decongestant & Cough (containing phenylephrine)
Robitussin Infant Cough DM Drops
Triaminic Infant & Toddler Thin Strips Decongestant
Triaminic Infant & Toddler Thin Strips Decongestant Plus Cough
Tylenol Concentrated Infants’ Drops Plus Cold
Tylenol Concentrated Infants’ Drops Plus Cold & Cough
Data from Consumer Healthcare Products Association, 2007.
lets, and medicated strips available. Adding to the misunderstanding is the graphic on labels,
which may depict a toddler-aged
child, even though the labeling
states not to give the product to
children younger than 2 years.
Medication-impregnated strips that
dissolve when placed on the
tongue are marketed to parents to
make medication administration
easier. The concern for these products is that they are dosed for children age 6 to 12 years, yet developmentally, it is usually children
younger than 6 years who refuse to
take medication. Night Time Triaminic Thin Strips Cough and Cold
packaging depicts a child who appears to be significantly younger
than age 6 years, yet the product
dosing information fine print states
parents should consult their provider for dosing in children
younger than 6 years (Novartis
Consumer Health, 2007). Similar
graphics and dosing information is
found on Triaminic Softchews
Cough and Runny Nose (Novartis
Consumer Health). Sudafed PE
Quick Dissolve Strips are labeled
for use in children 12 years or
older and adults (McNeil-PPC,
2007). The Sudafed PE strips label
depicts an ageless head with sinuses highlighted, which is less
misleading for parents, yet the
product can easily be inappropri76
Volume 22 • Number 2
ately used in children by parents
seeking an easier method of administering decongestants.
Multiple Ingredient Products
Parents may be confused by
product labeling and not understand
that many cough and cold products
contain multiple ingredients. They
may give a “cough” formula and a
“runny nose” formula based on the
symptoms their child is experiencing, not understanding that they
may be doubling the dose of the
active ingredients. This is a concern
not only for cough and cold medications but also for antipyretics, because many products labeled
“cough and cold” also contain either
acetaminophen or ibuprofen. Acetaminophen above therapeutic levels
was documented in one infant death
reported by the Philadelphia Medical Examiners Office (Wingert et al.,
2007). As noted previously, combination cold products were administered by parents or caregivers in
nine of the 10 infant deaths in the
Montgomery County study (Marinetti et al., 2005).
Multiple Caregivers
Administering Medication
A problem unique to young
pediatric patients is that their
medication is administered by a
caregiver. Working parents and
multiple caregivers increase the
risk of accidental overdose if
caregivers do not communicate
with each other when medications are administered.
RECOMMENDATIONS FOR
USE OF COUGH AND COLD
MEDICATIONS
Pediatric nurse practitioners
(PNPs) need to be familiar with the
safety and efficacy of cold medications in children, including appropriate dosing for different aged children. Parents need to be educated
regarding the appropriate use of
cough and cold medications in children. Establishing a culture of safety
around the use of OTC cough and
Parents may be confused by product labeling
and not understand that many cough and cold
products contain multiple ingredients.
Journal of Pediatric Health Care
TABLE 1. Dosing of common cough and cold medications
Drug
Oral decongestants
Pseudoephedrine
Phenylephrine (Sudafed PE)
Topical decongestants
Phenylephrine (Neo-Synephrine)
Age of child
Expectorants
Guaifenesin
Maximum/24 h
⬍2 y
2-5 y
6-12 y
⬎12 y
⬍2 y
2-5 y
6-12 y
⬎12 y
Not recommended
15 mg q 6 hⴱ
30 mg q 6 h
60 mg q 6 h
Not recommended
5 mg q 4 hⴱ
10 mg q 4 h
10-20 mg q 4 h
6-12 y
⬎6 y
2-3 drops each nostril or 1-2 sprays of 0.25%
solution q 4 h
2-3 drops each nostril or 1-2 sprays of 0.25%
or 0.5% solution q 4 h
2 sprays each nostril q 12 h
⬍2 y
⬎2-6 y
7-12 y
⬎12 y
Not recommended
2.5 to 7.5 mg q 4 to 8 hrs*
5-10 mg q 4 h or 15 mg q 6 to 8 h
10-30 mg q 4 to 8 h
30mg/24h
60mg/24h
120mg/24h
⬍2 y
2-5 y
6-11 y
⬎12 y
Not recommended
50-100 mg q 4 h
100-200 mg q 4 h
200-400 mg q 4 h
600mg/24h
1.2gm/24h
2.4gm/24
⬎12 y
Oxymetazoline (Afrin)
Cough suppressants
Dextromethorphan
Dosing
60mg/24h
120mg/24h
240mg/24h
q, Every.
*Cough and cold medications should be used with caution in children younger than age 6 years.
cold medications will encourage appropriate use and decrease the likelihood of accidental overdose.
Prescribing Cough and Cold
Medications
Evidence is lacking regarding
the effectiveness of cough and
cold medications in children;
therefore, PNPs need to rethink
their prescribing practice if they
currently recommend these products. Understanding the rationale
for following FDA labeling recommendations is crucial for patient
safety. An understanding of the
risks and benefits of prescribing
these medications and providing
parents with the correct dose for
their child will improve safety
when cough and cold medications
are prescribed.
Off-label prescribing. Off-label prescribing is the practice of
prescribing medications outside of
the FDA-approved label recommendations. To pass through the
FDA labeling process, drug manufacturers need to provide pharmaJournal of Pediatric Health Care
cokinetic, safety, and efficacy data
for all populations they want the
product label to reflect. Historically, a large number of pediatric
medications have been prescribed
off-label in children because studies were never done in this population. Adult data were extrapolated to determine pediatric dosing
with little attention to the developmental pharmacokinetic differences in children. The FDA Modernization Act of 1997 and the Best
Pharmaceuticals for Children Act
of 2003 encourages pharmaceutical companies to perform pediatric
studies on medications, awarding
a 6-month extension on the patent
if pediatric studies are done. These
acts allowed the FDA to issue a
request to pharmaceutical companies for medications that may be
used in children. As a result, 138
medications have had pediatric
pharmacokinetic, safety, and efficacy data updated and have been
relabeled. The first medication to
have labeling changes to add pre-
scribing information for 2- to
6-year-olds was ibuprofen suspension (Advil, Motrin) in 1998. The
only cough or cold products that
have gone through this relabeling
process as of November 2007 are
Advil Cold and Motrin Cold suspensions (ibuprofen/pseudoephedrine).
Off-label prescribing is not illegal because the FDA only approves drugs to enter the market
and relabels when drug manufactures submit additional data.
When choosing to prescribe outside the FDA approved label,
providers need to reflect on
whether there is strong evidence
in the literature supporting offlabel use of medications. Using
current prescribing references
such as The Harriet Lane Handbook, Micromedex, or Lexicomp’s
Pediatric Dosage Handbook will
determine the community standard of practice regarding off-label prescribing of specific medications, recognizing that even in
the Harriett Lane Handbook,
March/April 2008
77
BOX 2. Parent education regarding cough and cold medications
Pathophysiology of cough and upper respiratory infections
Symptomatic treatment for cough
● Warm fluids for coughing spasms
● Children aged 1 to 4 years: Corn syrup, ½ to 1 tsp for coughing spasms
● Children ⬎4 years: cough drops or hard candy to coat and sooth irritated throat and calm cough
Cough suppressants
Generally not recommended for coughs in children
● If dry, hacky cough interferes with sleep, cough suppressants may be used in children ⬎2 years with clear guidelines for
use
● Cough suppressants are not to be used for wet, productive coughs
● Symptomatic treatment of congestion from upper respiratory infections
● Clear secretions from infant and toddler’s nose with a bulb syringe as needed
● Use saline drops to loosen dried nasal secretions for children of all ages at least four times a day and whenever children
cannot breathe through nose because of congestion
● Encourage fluid intake to keep secretions loose
●
Decongestants
Systemic decongestants not recommended in children younger than 2 years
● Use with caution in children age 2 to 6 years
● Avoid multi-symptom products
● Provide parents with accurate dosing information
● Educate regarding use of topical decongestants
● Discourage use of sibling’s medications for younger children
●
Recording medication administered
Encourage parents to make a written note of when medication was administered
● Parents and other caregivers need to communicate regarding what medications are administered and when to prevent
accidental overdose
●
more than 25% of the medications in the formulary lack FDA
labeling recommendations (Novak & Allen, 2007). In the case of
children’s cough and cold medications, the literature is clear regarding lack of evidence regarding efficacy of these medications,
BOX 3. Adverse event
reporting
Report adverse events that may be
related to the use of cough or cold
medicines in children younger than
2 years to the FDA Med Watch
program.
Online:
http://www.fda.gov/medwatch
Phone:
1-800-FDA-1088
Mail:
FDA Med Watch 5600 Fishers
Lane, Rockville, MD 20852-9787
78
Volume 22 • Number 2
with clear recommendations
from the FDA and national organizations against use of cough
and cold medications in infants
and young children.
Appropriate dosing in pediatric patients. With the myriad of
cough and cold formulas available,
if a provider chooses to prescribe
them for children, it is critical to
accurately dose the medication,
whether writing a prescription or
educating parents about medications. I recommend that PNPs follow the FDA and AAP recommendations that cough and cold
medications not be prescribed to
children younger than 2 years.
There is some concern by pediatric
experts regarding the safety of
these medications in children
younger than 6 years, and while
It is clear from the literature that the use of
cough and cold medications in infants and
young children is not recommended. Evidence
is lacking for effectiveness in the treatment of
cough and congestion due to the common cold,
with real concerns for the safety of using these
medications in children younger than 2 years.
Journal of Pediatric Health Care
official statements have not been
issued, caution should be taken
when prescribing for children ages
2 to 6 years. Table 1 provides dosing information for commonly
used cough and cold products. If
making recommendations to parents, a dose in milligrams (mg)
with clear instructions regarding
dosing interval will decrease the
likelihood of accidental overdose.
The differences between formulations such as infant drops, elixirs
or suspensions, chewable tablets,
and quick dissolve strips should be
discussed, and it should be recommended that parents look at the
strength of each medication before
administering it. To encourage safe
use of medications, it is important to
encourage parents to contact the
provider (or advise nurse) before
administering any new OTC medication to their child.
Educating Parents
Parent education should begin
with the underlying pathophysiology
of cough and colds. Education regarding the natural progression of a viral
upper respiratory illness (URI) and the
expected duration of illness is essential. Parents often do not understand
that cough and cold medications are
for symptom relief, mistakenly thinking the medication is going to shorten
the duration of or cure the cold. A trip
to the drugstore with many feet of
shelf space dedicated to cough and
cold medicine may imply that these
medications are the expected treatment for a URI. Educating parents regarding nonpharmacologic symptomatic care for colds, such as removing
secretions with a bulb syringe in infants and toddlers, the use of saline
nose drops, and the use of a humidifier will give them tools to use when
their child is uncomfortable because
of URI symptoms. Offering a “homemade” cough syrup of corn syrup to
children older than 12 months gives
parents an alternative to OTC cough
medication when their child is coughing (use of corn syrup in children
Journal of Pediatric Health Care
younger than 12 months is discouraged because of botulism concerns).
Encouraging parents to contact the
provider before administering any
OTC products to their child will decrease the likelihood of inappropriate
use. Box 2 discusses key parent education that should occur regarding
cough and cold medication use in
children.
SUMMARY
It is clear from the literature that
the use of cough and cold medications in infants and young children
is not recommended. Evidence is
lacking for effectiveness in the
treatment of cough and congestion
due to the common cold, with real
concerns for the safety of using
these medications in children
younger than 2 years. PNPs should
review their practice regarding recommending OTC cough and cold
medications to determine if their
practice aligns with the standard of
practice set by the AAP. PNPs
should report suspected overdose
or adverse events from cough and
cold medications to the FDA Med
Watch program (Box 3). Proactively educating parents regarding
the safety and efficacy of these
products in infants and young children will counter pharmaceutical
advertising to parents. Offering
nonpharmacologic symptom control techniques will encourage parents to hold off on reaching for
cough and cold medications, yet
still provide them with “something
to do” for URI symptoms. These
steps will ensure that OTC cough
and cold medications are used appropriately in pediatric patients.
REFERENCES
American Academy of Pediatrics Committee on
Drugs. (1997). Use of codeine- and dextromethorphan-containing cough remedies in
children. Pediatrics, 99, 918-920.
Aronoff, D. M., & Neilson, E. G. (2001). Antipyretics: Mechanisms of action and clinical
use in fever suppression. The American
Journal of Medicine, 111, 304-315.
Bolser, D. C. (2006). Cough suppressant and
pharmacologic protussive therapy:
ACCP evidence-based clinical practice
guidelines. Chest, 129(Suppl. 1),
238S-249S.
Centers for Disease Control and Prevention
(2007). Infant deaths associated with
cough and cold medications—two
states, 2005. MMWR: Morbidity & Mortality Weekly Report, 56, 1-4.
Gadomski, A., & Horton, L. (1992). The
need for rational therapeutics in the use
of cough and cold medicine in infants.
Pediatrics, 89, 774-776.
Harris, G. (2007, October 20). F.D.A panel
urges ban on medicines for child colds.
Retrieved January 16, 2008, from
http://www.nytimes.com/2007/10/20/
washington/20fda.html?_r⫽1&scp⫽
4 & sq ⫽ cold ⫹ medications ⫹ and ⫹
children&oref⫽slogin.
Marinetti, L., Lehman, L., Casto, B., Harshbarger, K., Kubiczek, P., & Davis, J. (2005).
Over-the-counter cold medications-postmortem findings in infants and the relationship to cause of death. Journal Of Analytical
Toxicology, 29, 738-743.
McLeod, R. L., Mingo, G., O’Reilly, S.,
Ruck, L. A., Bolser, D. C., & Hey, J. A.
(1998). Antitussive action of antihistamines is independent of sedative and
ventilation activity in the guinea pig.
Pharmacology, 57, 57-64.
McNeil-PPC. (2007). Sudafed PE Quick Dissolve Strips. Retrieved November 25,
2007, from http://www.sudafed.com/
products/pe_quickstrips.html
Naclerio, R. M., Proud, D., Kagey-Sobotka,
A. Lichtenstein, L. M., Hendley, J. O.,
Gwaltney, J. M., et al. (1988) Is histamine responsible for the symptoms of
rhinovirus colds? A look at inflammatory
mediators following infection. Pediatric
Infectious Disease Journal, 7, 215-242.
Novak, E., & Allen, P. J. (2007). Prescribing
medications in pediatrics: Concerns regarding FDA approval and pharmacokinetics. Pediatric Nursing, 33, 64-70.
Novartis Consumer Health. (2007). Triaminic: The medicine of motherhood.
Retrieved November 26, 2007, from
http://www.triaminic.com/us_en/
product_all.shtml
Schroeder, K., & Fahey, T. (2004). Over-thecounter medications for acute cough in
children and adults in ambulatory settings. Cochrane Database Of Systematic Reviews (Online), 4, 1-21.
Taverner, D., & Latte, J. (2007). Nasal decongestants for the common cold. Cochrane Database Of Systematic Reviews (Online)(1), CD001953.
Wingert, W. E., Mundy, L. A., Collins, G. L.,
& Chmara, E. S. (2007). Possible role of
pseudoephedrine and other over-thecounter cold medications in the deaths
of very young children. Journal of Forensic Sciences, 52, 487-490.
March/April 2008
79
NCC Pediatrics Continuity Clinic Curriculum
Over-The-Counter Cough & Cold Medications
Quick Quiz – Do it in 5 minutes
Match the OTC cough & cold medications with their characteristics
A. Expectorant
B. Decongestant
C. Antihistamine
Brompheniramine __________________
D. Cough-suppressant
Gauifenisin
Phenylephrine
__________________
__________________
E. CNS stimulant when used alone; added CNS-depressant
effects with anti-histamines
Diphenhydramine __________________
F. Sympathomimetic on a and beta adrenergic receptors
Dextromethorphan __________________
G. Centrally active opioid derivative
Chlorpheniramine __________________
H. Linked to hallucinations in kids < 6 years old
I. Linked to CNS depression in kids < 6 years old
J. Linked to arrhythmias in kids < 6 years old
K. Acts centrally in the medulla to suppress cough
L. Reduces surface tension & viscosity of mucus
Fill in the Blank
New OTC anti-histamine labeling specifically advises that ___________________ is not an indication.
The OTC cough & cold medication ______________ is the one linked to the most infant deaths.
What are risk factors for adverse effects of OTC cough & cold medication use in children?
Misleading marketing / Multiple ingredient products / Multiple caregivers giving medication
Quote you can use in the exam room….
“Since 1985, there have been ____ RCTs of pediatric cough & cold medications in children under __ years of age
that showed no benefit over placebo.”
NCC Pediatrics Continuity Clinic Curriculum
Over-The-Counter Cough & Cold Medications
NCC Pediatrics Continuity Clinic Curriculum
Over-The-Counter Cough & Cold Medications
Case
You’ve just got back from the ED during a night shift and the mommy pager beeps. You call
back and Mrs. Santos answers. She reports that her 23 month old girl, Angela, has a bad cold.
Gather a history from a faculty-member who will play the part of the parent.
What physical exam maneuvers can you accomplish over the phone to help
triage this patient?
The parent divulges that she gave a dose of Triaminic and one dose of Mucinex.
What specific medications did Angela receive when her mother gave her
Mucinex and Triaminic? Why do you think the mother used the OTC
Medications?
How would you triage this patient?
The next morning, Angela is your 0945 appointment. On exam, she is clinging to mother and has
loud noisy breathing with no stridor or wheezing. Her weight is higher than her 18 month
appointment weight and on the same percentile. Her respiratory rate is 21, heart rate 98,
temperature 99.7 ° F, and O2 saturation is 98% on room air. Sclera white with dried mucus in
her medial canthi. No nasal flaring. Nose has moist yellow mucus in each nose, TMs are mobile
and without effusion. Moist mucous membranes; no oral lesions. Heart is RR with a normal S1
and S2. Lungs have equal air movement throughout with transmitted upper airway sounds. No
retractions. Cap refill is normal and skin turgor is normal with warm extremities. No rash.
What are useful cough & cold interventions that are safe to use? Ask the
experienced pediatricians to recite their instructions to parents of young
children with colds.