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Cough and Cold Medication Use by US Children, 1999–2006: Results From the Slone Survey

Slone Epidemiology Center, Boston University, Boston, Massachusetts

	ABSTRACT

TOP ABSTRACT METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
OBJECTIVE. Pediatric cough and cold medications are widely marketed in the United States, but the precise patterns of use among children are not known. Such information is especially important given recent reports suggesting that these medications are responsible for previously underappreciated serious adverse events and deaths among children. We sought to describe the prevalence and patterns of pediatric use of cough and cold medications, with particular attention to use among young children.

METHODS. We analyzed data on the use of cough and cold medications, defined as any oral medication that contains 1 antitussive, decongestant, expectorant, and/or first-generation antihistamine active ingredients, among 4267 US children who were younger than 18 years and enrolled during 1999–2006 in the Slone Survey, a national random-digit-dial telephone survey of medication use by the US population.

RESULTS. In a given week, a cough and cold medication was used by 10.1% of US children. Exposure was highest to decongestants (6.3%; mostly pseudoephedrine) and first-generation antihistamines (6.3%; most common were chlorpheniramine, diphenhydramine, and brompheniramine), followed by antitussives (4.1%; mostly dextromethorphan) and expectorants (1.5%; almost exclusively guaifenesin). Multiple-ingredient products accounted for 64.2% of all cough and cold medications used. Exposure to antitussives, decongestants, and first-generation antihistamines was highest among 2- to 5-year-olds (7.0%, 9.9%, and 10.1%, respectively) followed by children who were younger than 2 years (5.9%, 9.4%, and 7.6%, respectively); expectorant use was low in all age groups. The use of cough and cold medications declined from 1999 through 2006.

CONCLUSIONS. Approximately 1 in 10 US children uses a cough and cold medication in a given week. The especially high prevalence of use among children of young age is noteworthy, given concerns about potential adverse effects and the lack of data on the efficacy of cough and cold medications in this age group.

Key Words: cough and cold medications • over-the-counter medications

Abbreviations: CCM—cough and cold medication • OTC—over-the-counter • FDA—Food and Drug Administration • CI—confidence interval

Pediatric cough and cold medications (CCMs), which typically include antitussives, decongestants, expectorants, and/or first-generation antihistamines, are readily available over the counter (OTC) in the United States and are widely promoted for the treatment of children's upper respiratory tract infections. Many of these medications are also approved for the treatment of allergic diseases and may be used for those conditions as well. Reports of adverse effects that are associated with these products (particularly inadvertent overdose) have increased in recent years, especially among very young children. For example, the Toxic Exposure Surveillance System documented nearly 90000 calls and 3 accidental deaths associated with CCM among US children in 2004,¹ and >7000 annual emergency department visits were attributed to CCM in a recent study.² Among children who were younger than 2 years, the Centers for Disease Control and Prevention linked CCMs to >1500 emergency department visits in 2004–2005 and 3 additional deaths in 2005.³ The US Food and Drug Administration (FDA) recently enforced measures against unapproved marketing of the antihistamine carbinoxamine to young children because of reports of 21 deaths that were associated with use of this drug in children who were younger than 2 years.⁴ In a number of case series, CCM overdoses have been linked to neurologic impairment, cardiovascular instability, and death among young children.^5–9

Concerns about these toxicities, especially in light of data that CCMs have not been proved effective in treating symptoms of cough and the common cold in young children,^10–16 led to the filing of a citizen petition with the FDA on March 1, 2007,¹⁷ which prompted an FDA review of the safety and efficacy of CCMs for children. In October 2007, the Consumer Healthcare Products Association announced a voluntary withdrawal of "infant" cough and cold preparations targeted to children who are younger than 2 years.¹⁸ In the meantime, the FDA's Nonprescription Drugs and Pediatric Advisory committees voted to ban OTC CCMs that are intended for children who are younger than 6 years,¹⁹ and the FDA is currently considering the committees' advice.

Although the potential for harm has been documented, understanding the risks of CCMs to children requires information on the prevalence and patterns of use of these medications. It is difficult, however, to identify usage patterns for what are primarily OTC products. Unlike prescription drugs, purchases of OTC medications are not captured in insurance and pharmacy claims data; in addition, data on patterns of exposure can be obtained only directly from patients or their parents. As a result, very few data exist on the prevalence and patterns of CCM use among children. One US study from 1994, relying on interview data from the Longitudinal Follow-up to the National Maternal and Infant Health Survey, found that approximately one third of 3-year-old children had used an OTC CCM within the previous 30 days,²⁰ and a 2007 study from England based on mail survey data from the Avon Longitudinal Study of Parents and Children identified use of CCMs in the previous year by two thirds of children 3.0 to 4.5 years of age and by approximately half of children 5.5 to 7.5 years of age.²¹ A national telephone survey conducted in November 2007 reported that 56% of parents of children who were younger than 2 and 79% of parents of children who were aged 2 to 6 years had ever given their children a CCM, but no additional information on types of products or patterns of use was collected²²; therefore, to characterize the current prevalence and patterns of use of CCMs by US children and to provide a baseline against which to measure any changes in use that occur as a result of marketing and regulatory actions, we analyzed data from the Slone Survey, a random-digit-dial telephone survey of medication use among the US population.

	METHODS

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Detailed methods of the Slone Survey have been published.²³ Briefly, this random-digit-dial telephone survey targeted households in the 48 contiguous states and the District of Columbia and was conducted continuously between February 1998 and April 2007. Once a household was successfully contacted, 1 individual from the household was randomly selected for interview and informed consent was obtained. All medication use (including prescription and OTC products, vitamins/minerals, and herbals/supplements) by the selected individual within the past week was ascertained by structured interview. Medications were linked to their active ingredients through the Slone Epidemiology Center's Drug Dictionary.²⁴ Details of use were obtained, including drug form (eg, tablet, liquid), duration and frequency of use, and reason for use. For children who were younger than 14 years, a parent/guardian was interviewed; for children who were 14 to 17 years of age, either the child or a parent/guardian was interviewed (82.2% of interviews in this age range were completed by a parent/guardian). The study was approved by the Boston University Medical Campus Institutional Review Board.

This analysis used data derived from all individuals who were younger than 18 years for the complete years 1999–2006. We included in the analysis all oral medications, both OTC and prescription, that contained 1 antitussive, decongestant, expectorant, or first-generation antihistamine active ingredients (we excluded first-generation antihistamines such as dimenhydrinate and cyproheptadine that do not carry an indication for the common cold). Response rates were calculated according to the American Association for Public Opinion Research RR3 definition.²⁵ Estimates of the weekly prevalences of use were weighted by household size to adjust for the probability of selection. Prevalence comparisons were performed by ² analysis. SAS 9.1 (SAS Institute, Cary, NC) was used for all analyses.

	RESULTS

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The response rate to the survey during the period 1999–2006 was 61.9%, and 4267 individuals who were aged 0 to 17 years were enrolled. The median age was 9 years (25th, 75th percentiles: 4, 13), and 48.9% were female (both similar to the 2000 US census²⁶). In terms of race/ethnicity, 65.2% were white non-Hispanic (69.1%, census); 14.3% were Hispanic (12.5%, census); 11.7% were black non-Hispanic (12.1%, census); 1.9% were Asian non-Hispanic (3.6%, census); and 7.0% were of other, mixed, or unknown race/ethnicity (2.7%, census). According to US census regions, 19.4% were from the Northeast (18.0%, census), 25.9% from the South (35.4%, census), 25.0% from the Midwest (23.1%, census), and 29.8% from the West (23.5%, census).

Of the 4267 children surveyed, 439 had used a CCM in the previous week, for a weighted prevalence of use of 10.1% (95% confidence interval [CI]: 9.2–11.0). The 1-week prevalences of exposure to specific CCM active ingredients are shown in Table 1; 4.1% of individuals were exposed to antitussives (primarily dextromethorphan), 6.3% to decongestants (primarily pseudoephedrine), 1.5% to expectorants (nearly all guaifenesin), and 6.3% to a variety of first-generation antihistamines.

View larger version (13K): [in this window] [in a new window]   FIGURE 1 Form of cough and cold products used by children, stratified according to age group.

View larger version (19K): [in this window] [in a new window]   FIGURE 2 Prevalence of exposure to antitussive, decongestant, expectorant, and first-generation antihistamine active ingredients according to age group. Bars represent 95% CIs.

View larger version (9K): [in this window] [in a new window]   FIGURE 3 Prevalence of exposure to any CCM and specific active ingredients according to 2-year intervals.

We also examined the duration of use of CCMs on at least 1 day per week among study subjects. As shown in Fig 4, the majority of CCM use was for 1 week. For antitussives and expectorants, 15% of use was for 1 to 4 weeks, with virtually no use lasting >4 weeks. In contrast, 22.9% of first-generation antihistamine use was for >1 week (including 12.2% for >4 weeks), and 22.5% of decongestant use was for >1 week (including 10.4% for >4 weeks). Of the 56 individuals who used a CCM for >4 weeks, 22 used a first-generation antihistamine alone, 14 used a decongestant plus a second-generation antihistamine, and 9 used a decongestant plus a first-generation antihistamine; the majority took them on a daily basis. The reasons for using a CCM for >4 weeks included allergies in 37 (66.1%), sleep in 4 (7.1%), cough in 2 (3.6%), cold in 1 (1.8%), and other reasons in 12 (21.4%). Among those who took a CCM for >4 weeks, there were 11 children who were younger than 6 years. Four of them used a first-generation antihistamine alone; 4 used a decongestant plus first-generation antihistamine; and 1 each used a decongestant alone, a decongestant plus a second-generation antihistamine, and a first-generation antihistamine plus an analgesic.

View larger version (14K): [in this window] [in a new window]   FIGURE 4 Duration of use on at least 1 day per week for antitussive (A), decongestant (B), expectorant (C), and first-generation antihistamine (D) active ingredients.

	DISCUSSION

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In addition to lack of evidence of efficacy for cough and the common cold, CCM use in young children is fraught with the potential for dosing errors. First, because of the lack of clinical and pharmacologic studies of children, most pediatric dosages are extrapolated from adult data, and many CCMs lack formal dosing recommendations for young children.^27,28 Second, concentrations and dosages for young children are not standardized across products, dosage delivery devices differ from product to product, and products with different ingredients can have similar names. Finally, as our data point out, well over half of pediatric CCM use involves multiple-ingredient products (with as many as 5 separate active ingredients), a situation that increases the risk for a child inadvertently receiving >1 product with the same active ingredient.

The prevalence of use of any CCM among children declined somewhat over the years of the study, with the decline most notable for decongestants and first-generation antihistamines. The decline in decongestant use seems largely attributable to the removal of phenylpropanolamine from the market in 2000–2001 because of its association with hemorrhagic stroke in adults.²⁹ We speculate that pseudoephedrine use may likewise decline in the coming years as a result of the 2005 Combat Methamphetamine Act, which requires pseudoephedrine-containing products to be kept behind pharmacy counters.³⁰ More broad, the prevalence and patterns of pediatric CCM use are likely to change substantially given the media attention being paid to the issue of CCM safety, the Consumer Healthcare Products Association's voluntary recall of CCMs that are marketed for children who are younger than 2 years,¹⁸ and any regulatory changes that the FDA may make in response to its advisory panel's recommendations. It will be important to track secular trends in pediatric CCM use as these changes take effect.

Not surprising, we found that the duration of use of CCMs varies substantially by components. Antitussives and expectorants are used almost exclusively for brief periods of time, whereas decongestants and first-generation antihistamines are more commonly used for extended durations. Most long-term use is for allergic diseases, and the predominant products used long-term are antihistamines or decongestant-antihistamine combinations, which are indicated for allergies as well as the common cold. Still, we identified a small number of children, including a few who were younger than 6 years, who were given other combination CCMs regularly for extended periods of time, and the risks that are associated with such long-term exposure are unknown.

Our data suggest that CCM use is not strongly associated with personal and demographic factors such as gender, race/ethnicity, region, parental education, household income, or household size. That use is so widespread among US children suggests that efforts focused on educating the public about safe use of CCMs should be broadly targeted.

Our study has several potential imitations. First, there is the possibility of response bias. Although our response rate was relatively high for a random telephone survey and our distributions of age, gender, and race/ethnicity approximate the 2000 US census data, our sample somewhat underrepresents children from the South and overrepresents those from the West. We cannot determine whether CCM exposure among nonresponders or undersampled populations differs from that of survey participants. A second potential limitation is the accuracy of the drug exposure information collected in the survey. We relied on parent (or patient) reports of products used, but we made significant efforts to ensure that such information was compete and accurate. Individuals were asked to gather all relevant bottles and packages and to read medication names directly from the label; these were matched in real time to drug codes from the Slone Epidemiology Center Drug Dictionary, an electronic compendium of prescription, OTC, vitamin, and herbal/supplement medications.²⁴ Because only very recent use (within the previous 7 days) was elicited, the possibility of recall errors was reduced. In most cases, parents acted as reporters of their children's medication use, which may have led to underreporting of use in adolescents who may have obtained and used CCMs independently. Finally, our survey was not designed to capture illicit drug use or intentional misuse.

	CONCLUSIONS

TOP ABSTRACT METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
This study demonstrates that CCM use is common among US children despite a lack of demonstrated efficacy for treatment of cough and the common cold. Of particular concern are high rates of exposure among young children, for whom dosing recommendations are largely extrapolated from adults and the risk for adverse events is greatest. Regulatory changes (which are currently under consideration by the FDA) as well as efforts aimed at educating parents and caregivers about the safe use of CCMs may be needed to reduce inappropriate exposure to these medications and thereby minimize risks to children.

	ACKNOWLEDGMENTS

 
We greatly appreciate the contributions of Theresa Anderson, study coordinator; Marie Berarducci and Marilyn Wasti, study supervisors; Gene Sun, information systems; and the interviewing staff.

	FOOTNOTES

 
Accepted Apr 16, 2008.

Address correspondence to Louis Vernacchio, MD, Slone Epidemiology Center at Boston University, 1010 Commonwealth Ave, Boston, MA 02115. E-mail: lvernacchio{at}slone.bu.edu

Financial Disclosure: The analyses presented in this article were funded internally by the Slone Epidemiology Center at Boston University; the center has received funding from McNeil Consumer Healthcare for other analyses related to the pediatric use of cough and cold medications.

What's Known on This Subject Pediatric OTC CCMs are readily available in the United States and are widely promoted for the treatment of children's upper respiratory tract infections. Recent reports have linked these products to serious adverse effects and deaths among children.

 

What This Study Adds This study documents the prevalence and patterns of use of CCMs among US children and provides a baseline against which to measure any changes in use that occur as a result of marketing or regulatory actions.

 

	REFERENCES

TOP ABSTRACT METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 

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