OBJECTIVE. Pseudoephedrine, a decongestant found in many cough-and-cold and allergy medications, has been associated with deaths and adverse events in young children; however, the absolute risks of pediatric pseudoephedrine use are difficult to assess because the number of children exposed on a population basis and typical patterns of use are unknown. In addition, use may be changing because of the Combat Methamphetamine Epidemic Act of 2005, which limited pseudoephedrine availability. We sought to describe the prevalence and patterns of pseudoephedrine use among US children and to assess any change since the 2005 law took effect.
METHODS. We analyzed data on pseudoephedrine use among 4267 children who were aged 0 to 17 years and enrolled from 1999 to 2006 in the Slone Survey, a national random-digit-dial telephone survey of medication use in the US population.
RESULTS. Overall, 214 children took pseudoephedrine in a given week. Use was highest for children who were younger than 2 years. Sixteen children (7.5% of users) took >1 pseudoephedrine-containing product within the same week, including 6 children who were younger than 2 years. Of the pseudoephedrine products used, most were multiple-ingredient liquids (58.9%) and multiple-ingredient tablets (24.7%). Fifty-two children (25.0% of users) took pseudoephedrine for >1 week, including 7 children who were younger than 2 years. Use in 2006 (2.9%) was significantly lower than in 1999–2005 (5.2%).
CONCLUSIONS. Pseudoephedrine exposure, mostly in the form of multiple-ingredient products, is common among US children, especially children who are younger than 2 years, who are at the highest risk for toxicity and for whom safe dosing recommendations are lacking. Concerning patterns of use include taking >1 pseudoephedrine-containing product concurrently and using pseudoephedrine for extended periods. Pediatric pseudoephedrine use seems to be declining since the institution of the 2005 Combat Methamphetamine Epidemic Act.
Pseudoephedrine is a sympathomimetic decongestant found in many cough-and-cold and allergy medications. Known adverse effects of pseudoephedrine include agitation, tremors, emesis, and tachycardia.1,2 A recent report from the Centers for Disease Control and Prevention linked pseudoephedrine overdose to the deaths of 3 infants in 2005,3 and additional pseudoephedrine-associated deaths have been reported in young children.2,4–6 The number of nonlethal adverse events in children associated with pseudoephedrine use is difficult to determine, but cough-and-cold medications as a whole were responsible for nearly 90 000 calls to poison control centers in 20047 and >1500 emergency department visits among children who were younger than 2 years in 2004–20053; however, to put these reports of adverse events into proper perspective, it is necessary to know the number of children exposed on a population basis (ie, the denominator), data that have not been previously available.
Furthermore, patterns of pediatric pseudoephedrine use may have changed as a result of the Combat Methamphetamine Epidemic Act of 2005, a federal law that was designed to reduce illicit methamphetamine production from pseudoephedrine by requiring all pseudoephedrine-containing products to be kept behind pharmacy counters and to be sold to individuals in limited quantities.8 Although the law fully took effect in September of 2006, many large pharmacy chains began to move pseudoephedrine-containing products behind-the-counter in mid-2005. It is unknown what effect, if any, this law has had on patterns of pseudoephedrine use among children. To define the prevalence and patterns use of pseudoephedrine in US children and to investigate whether the Combat Methamphetamine Epidemic Act has had any effect on pediatric pseudoephedrine exposure, we analyzed data from the Slone Survey, a random-digit-dial telephone survey of medication use among the US population.
Detailed methods of the Slone Survey have been published.9 Briefly, the survey was a random-digit-dial telephone survey of medication use that targeted households in the 48 contiguous states and the District of Columbia and was conducted continuously between February 1998 and April 2007. When a household was successfully contacted, 1 individual from the household was randomly selected for interview and informed consent was obtained. All use within the previous 7 days of prescription and over-the-counter medications, vitamins/minerals, and herbals/supplements was ascertained by structured interview. Medications were linked to their active ingredients through the Slone Epidemiology Center's Drug Dictionary.10 Details of use, including drug form (eg, tablet, liquid) and duration and frequency of use, were obtained. 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 is not designed to detect illicit drug use or intentional misuse. The study was approved by the Boston University Medical Campus Institutional Review Board.
This analysis used data that were derived from all individuals who were younger than 18 years and collected from January 1, 1999, through December 31, 2006. Estimates of the weekly prevalences of use are weighted by household size to adjust for the probability of selection. Comparisons of the prevalence of use according to age group and time were performed by χ2 analysis. All statistical analyses were performed with SAS 9.1 (SAS Institute, Cary, NC).
The response rate to the survey during the period 1999–2006 was 61.9%. During that period, we enrolled 4267 children who were younger than 18 years. The median age of children was 9 years (25th, 75th percentiles: 4, 13), and 48.9% were female (both similar to the 2000 US census11). By region, 19.4% were from the Northeast (census 18.0%), 25.9% from the South (census 35.4%), 25.0% from the Midwest (census 23.1%), and 29.8% from the West (census 23.5%). In terms of race/ethnicity, 65.2% were white non-Hispanic (census 69.1%); 14.3% were Hispanic (census 12.5%); 11.7% were black non-Hispanic (12.1%, census); 1.9% were Asian non-Hispanic (census 3.6%); and 7.0% were of other, mixed, or unknown race/ethnicity (census 2.7%).
Overall, 214 children (weighted prevalence: 4.9% [95% confidence interval (CI): 4.2%–5.6%]) had taken pseudoephedrine in the previous week. Of the 231 pseudoephedrine products used by these children, 136 (58.9%) were multiple-ingredient liquid preparations, 57 (24.7%) were multiple-ingredient tablets, 20 (8.7%) were single-ingredient tablets, 15 (6.5%) were single-ingredient liquid preparations, and 3 (1.3%) were multiple-ingredient but unknown form (Table 1). Of the 214 children who were exposed to pseudoephedrine, 198 (92.5%) used 1 pseudoephedrine-containing product, 15 (7.0%) used 2, and 1 (0.5%) used 3. Characteristics of children who used multiple pseudoephedrine-containing products in the same week and the products that they took are shown in Table 2.
Use of pseudoephedrine decreased with increasing age, from a high of 8.1% (95% CI: 5.5–10.7) for children who were younger than 2 years to a low of 3.6% (95% CI: 2.7–4.5) for children who were aged 12 to 17 years (P < .0001; Fig 1).
Most children took pseudoephedrine for ≤1 week (156 [75.0%] children), but 52 (25.0%) children took it for >1 week (Fig 2; 6 children who used pseudoephedrine for an unknown duration were excluded from this analysis). Of the 52 instances of use for >1 week, 17 (32.7%) were daily, 34 (65.4%) were less than daily, and 1 (1.9%) was of unknown frequency; 8 (15.4%) involved pseudoephedrine alone, 17 (32.7%) a second-generation antihistamine-pseudoephedrine combination, and 27 (51.9%) other combination cough-and-cold products containing pseudoephedrine. Seven of the children who used pseudoephedrine for >1 week were younger than 2 years (4 for 1–2 weeks, 2 for 2–3 weeks, and 1 for 4–5 weeks).
As shown in Fig 3, before the institution of the Combat Methamphetamine Epidemic Act (ie, 1999–2005), the prevalence of pseudoephedrine did not vary significantly by year, ranging from a high of 6.2% (95% CI: 3.8–8.6) in 2001 to a low of 3.9% (95% CI: 2.2–5.5) in 2000 (P = .6), with an overall prevalence of use of 5.2% (95% CI: 4.5–5.9). In the single year of data we have during which the act took effect (ie, 2006), the prevalence of use was 2.9% (95% CI: 1.4–4.4). The prevalence of use in 2006 was significantly lower than the pooled prevalence of use for the years 1999–2005 (P = .03).
Our survey demonstrates that pseudoephedrine use is relatively common among US children; during the period 1999–2006, 1 of 20, or ∼3.5 million, children took pseudoephedrine within any given week. Those who were younger than 2 years had the highest prevalence of use (1 in 12, or ∼650 000 children). This is concerning given the lack of evidence for efficacy of pseudoephedrine among this age group, the absence of consumer dosing recommendations for pseudoephedrine-containing products for children who are younger than 2, and the fact that infants seem to be at the highest risk for toxicity from pseudoephedrine overdose.2–6 The risk may be enhanced by the lack of consumer dosing recommendations, leaving parents to guess at the appropriate dosage for a child who is younger than 2, and by the fact that pseudoephedrine is most often given to young children in the form of multi-ingredient cough-and-cold products, leading to potential confusion among caregivers. Indeed, we identified 16 children in our study population (7.5% of the total users) who took >1 pseudoephedrine-containing product within the same week, including 6 children who were younger than 2 years. Although we cannot determine whether these products were taken concurrently, it is likely that this occurred in some children, placing them at higher risk for overdose.
We found that nearly one quarter of pseudoephedrine-containing products were used for >1 week and approximately one tenth for >1 month. Almost all of the long-term use was in older children, but a few infants were given pseudoephedrine for periods of 2 to 5 weeks. The potential for adverse consequences from such weeks-long use in infants, even at what may be considered therapeutic doses, is unknown.
Although the prevalence of use of pseudoephedrine remained fairly constant from 1999 to 2005, there was a decline in 2006 coincident with the implementation of the Combat Methamphetamine Epidemic Act of 2005.8 This change suggests that the implementation of this act may be having the unintended benefit of reducing pseudoephedrine exposure among children and therefore potential pseudoephedrine-related toxicities, although additional data are needed to confirm this trend. Pharmaceutical manufacturers have largely replaced pseudoephedrine with phenylephrine in pediatric cough-and-cold preparations; it remains to be seen whether phenylephrine poses risks to young children, but monitoring of this issue will be important in the coming years.
There are also likely to be more general regulatory changes regarding pediatric cough-and-cold medications in the near future that may alter patterns of pseudoephedrine use. In response to a citizen petition questioning the efficacy and safety of pediatric cough-and-cold medications,12 the US Food and Drug Administration is reviewing the marketing and labeling of these drugs. In the meantime, pharmaceutical manufacturers have voluntary ceased marketing all cough-and-cold medications to children who are younger than 2 years, including those that contain pseudoephedrine.13
Our study has several potential limitations. First, there is the possibility of response bias. Our response rate was relatively high for a random telephone survey and our subjects' age, gender, and racial/ethnic distributions match the 2000 US census data fairly well, although our sample somewhat overrepresented children from the West and underrepresented children from the South. Telephone surveys such as ours cannot reach households without home telephones, and this tends to undersample individuals of lower socioeconomic status. Differences in pseudoephedrine use among nonresponders or undersampled populations might affect the validity of our estimates. Another potential limitation is the accuracy of the respondents' reports. To minimize recall errors, we collected data about only the previous 7 days of use, and participants were asked to gather all relevant bottles and to read medication names directly from the label. Medication names were then matched to specific active components with the Slone Epidemiology Center Drug Dictionary, an electronic compendium of prescription, over-the-counter, vitamin, and herbal/supplement medications.10 The validity of our exposure estimates among adolescents may also be affected by parents' underreporting pseudoephedrine use by adolescents, who may have obtained and used it without parental knowledge. Finally, our survey was not designed to capture illicit drug use or intentional misuse.
This study found that pseudoephedrine use is quite common among US children, with the highest prevalence of exposure occurring in children who are younger than 2 years. Our data suggest that well over half a million US children who are younger than 2 have been exposed to pseudoephedrine weekly in the past several years, despite the absence of evidence of efficacy and the absence of safe dosing recommendations for this age range. Pediatric pseudoephedrine use seems to be declining, however, probably as a result of the Combat Methamphetamine Epidemic Act of 2005. Additional declines may follow the changes that are now occurring in the marketing and regulation of all pediatric cough-and-cold medications. Meanwhile, intensified efforts to educate health care providers and parents about the proper use of pseudoephedrine and to discourage use in children who are younger than 2 are needed to reduce improper and potentially dangerous use of this medication.
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.
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.
- Accepted March 13, 2008.
- Address correspondence to Louis Vernacchio, MD, MSc, Slone Epidemiology Center at Boston University, 1010 Commonwealth Ave, Boston, MA 02115. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
What's Known on This Subject
Pseudoephedrine, a decongestant found in many cough-and-cold and allergy medications, has been associated with adverse events, including deaths in young children; however, the prevalence and patterns of use of pseudoephedrine among US children are not well described.
What This Study Adds
This study describes the prevalence and patterns of pseudoephedrine use among a sample of 4267 US children by using data from the Slone Survey, a national random-digit-dial telephone survey.
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- ↵Census 2000 Gateway. Available at: www.census.gov/main/www/cen2000.html. Accessed November 30, 2007
- ↵Public Health Advisory: nonprescription cough and cold medicine use in children. Available at: www.fda.gov/cder/drug/advisory/cough_cold.htm. Accessed October 23, 2007
- ↵Consumer Healthcare Products Association. Makers of OTC cough and cold medicines announce voluntary withdrawal of oral infant medicines. Available at: www.chpa-info.org/10_11_07OralInfantMedicine.aspx. Accessed October 28, 2007
- Copyright © 2008 by the American Academy of Pediatrics