Potential Dangers of Cough and Cold Medications in Children

William T. Basco, Jr., MD, FAAP


January 22, 2009


Recently, there were a host of articles on the potential dangers of cough and cold medications (CCMs) and the rate of use of these medications in children. The reviewer comments for the following 3 articles are combined.

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

Vernacchio L, Kelly JP, Kaufman DW, Mitchell AA
Pediatrics. 2008;122:e323-329


The study by Vernacchio and colleagues was conducted to provide estimates of over-the-counter (OTC) CCM use in children. The data were collected by a random-digit dialing method between 1998 and 2007. For children < 14 years old, parents provided information about medication use, both OTC and prescription, in the 1 week prior to the phone interview. Subjects between the ages of 14 and 18 years provided their own reports of OTC CCM use.

The survey enrolled over 4200 individuals who were 0-17 years old, and the response rate was 62%. The median age of the child subjects was 9 years. Just over 10% (439/4267) of the subjects had taken a CCM in the week prior to survey. Decongestant preparations and antihistamines were the most prevalent (both at 6.3%), followed by antitussives (4.1%) and expectorants (1.5%). Approximately two thirds of the medications taken were multi-ingredient combination preparations.

The exposure rates were highest for children 2-5 years of age, but the 0- to 2-year-old group experienced the second highest exposure rate, with approximately 5.8% of children 0-2 years of age being exposed to antitussives, 9% to decongestants, and 7.7% to antihistamines. From 1999-2000 to 2005-2006, the overall use of OTC CCMs declined approximately 30%. Vernacchio and colleagues concluded that OTC CCMs are used by many children, even children < 2 years old.



Accidental and Nonaccidental Poisonings as a Cause of Apparent Life-Threatening Events in Infants


Pitetti RD, Whitman E, Zaylor A
Pediatrics. 2008;122:e359-362


Pitetti and colleagues wished to evaluate the role of medications in causing apparent life-threatening events (ALTEs) in infants. The subjects were infants < 24 months old presenting to a single pediatric emergency department with ALTEs, defined by strict and accepted criteria. The data were collected prospectively over an approximately 9.5-year period. In the emergency department, the subjects with ALTE all underwent a standardized evaluation that included a urine sample for toxicology testing. These subjects were all admitted to the hospital after presentation for their ALTEs.

Characteristics of the event, findings on exam in the emergency department, and discharge diagnoses were collected for each patient. A urine sample with any drug identified in the urine was considered a "positive urine toxicology screen," and testing for drug identification was completed with gas chromatography/mass spectrometry. A true positive was any drug identified that the subject was not supposed to be taking (eg, routine daily medications), and these were divided into "clinically insignificant" and "clinically significant" true positives on the basis of whether the drug was thought to be one that might lead to ALTEs. CCMs, specifically, were considered clinically significant when identified.

Almost 600 children < 24 months presented with ALTEs during the study period. Of these, 274 had urine toxicology performed, and these subjects had a mean age of 2.5 months. Patients with a significant past medical problem were less likely to get urine toxicology testing, as were former premature infants, and had less obvious potential causes for their ALTEs. Of the 18.2% of toxicology screens considered true positives, 46% of these (8.4% of total) were considered to have clinical significance (4.7% of the total positive for OTC cough and cold preparations).

The most frequently identified drug was ephedrine/pseudoephedrine. The subjects with a clinically significant drug screen were older by 1.4 months than those with a positive screen that was not clinically significant, and they were more than twice as likely to have a viral prodrome illness. Children with OTC CCMs in their urine had a 4 times greater incidence of having an ALTE in a family member compared with those with negative urine screens (25% vs 6%). No parent reported giving an OTC cold medication at enrollment. The study authors concluded that notable proportions of infants presenting with ALTEs have positive urine toxicology screens, and half of those screens are positive for OTC CCMs.



Unexpected Infant Deaths Associated With Use of Cough and Cold Medications


Rimza ME, Newberry S
Pediatrics. 2008;122:e318-322

The study authors noted that concerns about the safety and lack of efficacy of OTC CCMs prompted the US Food and Drug Administration to issue warnings about use of these drugs in children under 2 years of age. In 2007, multiple companies voluntarily withdrew infant OTC CCMs from the market. The study authors reviewed 1 year (2006) of data from the Arizona Child Fatality Review Program to determine the rate of OTC CCM use in children who died unexpectedly.

The review provided by this program involves a comprehensive evaluation of potential causes of death, including initial law enforcement and medical evaluations, followed by a review of the entire case by a team of individuals representing the program. Infant blood, bile, gastric contents, and urine were tested for medications by gas chromatography. Testing was considered positive if any medication commonly used in OTC CCMs was isolated, other than antipyretics. There were 90 unexpected infant deaths reviewed by the program, and 31% of these were classified as sudden infant death syndrome (SIDS). Another 25% of deaths were classified as suffocation, with 21% by "other injury." Twelve percent had respiratory infections as the likely cause of death.

Of the 48 deaths not classified as suffocation or injury, toxicology testing was completed on 21 children (44%). Of the 21 children with toxicology testing, 10 (48%) were positive for OTC CCMs. The oldest of these 10 children was 10 months old, with all others being ≤ 6 months old. All 10 had reported cough and cold symptoms at the times of death. Antihistamines were present in 6 of these infants, dextromethorphan in 5, and pseudoephedrine in 3. Eight of the infants were minority children. Many of the children also had "social risk factors," such as young parents, poverty, limited proficiency in English, and one in foster care.

The study authors concluded that their findings should raise concern about the contribution of OTC CCMs in unexpected infant deaths and that the findings reinforce concerns about the safety of these products in infants. The study authors also noted that exposure to OTC CCMs should be a routine part of the history collected by first responders in unexpected infant deaths.



These studies provide interesting insight into the whole issue of OTC CCM use. The first study has the take-home message that use of these drugs is likely more common than many clinicians consider on any given day. A 10% prevalence rate (the study estimated that 10% of subjects had taken an OTC CCM in the week prior) has implications for so many issues, including office blood pressure measurements (eg, whether they are accurate if the patient is on OTC CCMs) and the potential for interaction with the drugs that we prescribe. On the positive side, the relatively common use of these medications means that almost any visit can serve as a "teaching moment" with regard to proper use or avoidance of OTC CCMs.

The second study by Pitetti and colleagues makes a very good argument that a detailed history about OTC CCM use should be part of any ALTE evaluation, especially given that most centers won't routinely conduct gas chromatography testing for these drugs when patients are admitted. I am particularly struck by the association between use of OTC CCMs in the index case and "family history" of ALTEs. It raises the possibility that some families are "OTC CCM users," and this shows up as multiple ALTE cases in those families.

Finally, the study by Rimza and Newberry is chilling and makes a strong case for considering OTC CCM use as a potential cause in unexplained infant death. If this represents a true association, with 50% of unexplained death infants having OTC CCMs detected in their systems, then these drugs may have a greater "risk" than previously appreciated. All articles review the recent history of restriction of use of these medications that have occurred so far in 2007-2008 (see, and there may very well be more to come.


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