News Summary

The Food and Drug Administration is reviewing the risk and benefits of popular cough and cold remedies indicated for young children, a top official was cited as saying by the New York Times.

The official, Dr. Charles J. Ganley, director of the office of nonprescription drug products at the FDA told the Times that “we’re particularly concerned about the use of these drugs in children less than 2 years of age.”

At high doses, the ingredient(s) in cold medicines can affect the heart’s electrical system, leading to arrhythmias. Some medicines affect the blood vessels, potential leading to hypertension and stroke. Children may get injured even at recommended doses.

A recent report by the Centers for Disease Control and Prevention found that between 2004 and 2005 at least 1,519 children under the age of 2 years suffered serious health problems after using common cough and cold medications.   Three died from implications of such drugs.

But the FDA said it could not expect new regulations in response to a petition filed by prominent pediatricians and public health officials that demands that drug makers stop marketing those cough and cold medications to children under age 6.

The petition was said to claim that those cold and cough remedies do not work and can only cause harm to children.   Doctors said many popular medicines such as Toddler’s Dimetapp, Infant Triaminic and Little Colds should not be given to children younger than age 6 although they are marketed to children as young as 2.

Quite shockingly, the Times reports that many of the medicine in those worthless products did not receive thorough safety review by the FDA.

For the full news report by The New York Times, read U.S. Reviewing Safety of Children’s Cough Drugs .

The following is the report published by the CDC regarding the cough and cold medications.

Infant Deaths Associated with Cough and Cold Medications --- Two States, 2005

Cough and cold medications that contain nasal decongestants, antihistamines, cough suppressants, and expectorants commonly are used alone or in combination in attempts to temporarily relieve symptoms of upper respiratory tract infection in children aged <2 years. However, during 2004--2005, an estimated 1,519 children aged <2 years were treated in U.S. emergency departments for adverse events, including overdoses, associated with cough and cold medications.* In response to reports of infant deaths after such events, CDC and the National Association of Medical Examiners (NAME) investigated deaths in U.S. infants aged <12 months associated with cough and cold medications. This report describes the results of that investigation, which identified deaths of three infants aged <6 months in 2005, for which cough and cold medications were determined by medical examiners or coroners to be the underlying cause. The dosages at which cough and cold medications can cause illness or death in children aged <2 years are not known. Food and Drug Administration (FDA)-approved dosing recommendations for clinicians prescribing cough and cold medications do not exist for this age group. Because of the risks for toxicity, absence of dosing recommendations, and limited published evidence of effectiveness of these medications in children aged <2 years, parents and other caregivers should not administer cough and cold medications to children in this age group without first consulting health-care provider and should follow the provider's instructions precisely ( 1). Clinicians should use caution when prescribing cough and cold medications to children aged <2 years. Moreover, clinicians should always ask caregivers about their use of over-the-counter combination medications to avoid overdose in children from multiple medications that contain the same ingredient.

In January 2006, NAME, in collaboration with CDC, initiated an e-mail inquiry, requesting reports of deaths in infants aged <12 months for which cough and cold medications were determined as the underlying cause. To identify additional cases, CDC examined media and medical-journal reports of infant deaths suspected to be linked to cough and cold medications during 2005. A total of 15 local medical examiners in 12 U.S. states and Canada responded to the NAME survey. However, no cases other than those from media and published reports were identified. From these reports, CDC identified three cases of infant deaths in two states during 2005 that were determined by a medical examiner or coroner to have been caused by cough and cold medications (Table 1).

The three infants ranged in age from 1 to 6 months; two were male. All three infants had what appeared to be high levels of pseudoephedrine (a nasal decongestant) in postmortem blood samples. The blood levels of pseudoephedrine ranged from 4,743 ng/mL to 7,100 ng/mL.^† One infant (patient 2) had received both a prescription and an over-the-counter cough and cold combination medication at the same time; both medications contained pseudoephedrine (Table 1). The other two infants also had received pseudoephedrine-containing medications (one prescription and one over the counter). Two of the infants (patients 1 and 2) had been administered prescription medications containing carbinoxamine (an antihistamine), although neither had detectable postmortem blood levels of carbinoxamine. Two of the infants (patients 2 and 3) had detectable blood levels of dextromethorphan (a cough suppressant) and acetaminophen (an antipyretic and analgesic).

All three infants were found dead in their homes. Autopsy and medical investigation records were obtained. A medical examiner or coroner determined that cough and cold medication was the underlying cause of death for each of the three. None of the deaths were determined to be intentional. On autopsy, two of the infants (patients 1 and 2) had evidence of respiratory infection; no abnormalities in cardiac pathology were revealed in any of the infants.

Reported by: Pediatric Toxicology Committee and Data Committee, National Assoc of Medical Examiners. A Srinivasan, MD, D Budnitz, MD, N Shehab, PharmD, Div of Healthcare Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases (proposed); A Cohen, MD, EIS Officer, CDC.

Editorial Note:

Cough and cold medications (Table 2) are in widespread use to treat children, and the overall incidence of reported adverse events has been low. An estimated 1,519 children aged <2 years were treated for adverse events from such medications during 2004--2005; infant deaths, although rare, also have been reported ( 2--4). The cases described in this report suggest that such deaths continue to be reported and underscore the need for clinicians to use caution when prescribing and caregivers to use caution when administering cough and cold medications to children aged <2 years.

In children aged >2 years, FDA approval of the use of over-the-counter cough and cold medications is based on review of safety and efficacy data by an external advisory review panel. However, in children aged <2 years, systematic reviews of controlled trials of over-the-counter cough and cold medications have concluded they are not more effective than placebo in reducing acute cough ( 5) and other symptoms of upper respiratory tract infection ( 6). Because of the unproven efficacy of the cough suppressants codeine and dextromethorphan in young children and the potential for adverse events, in 1997 the American Academy of Pediatrics issued a policy statement advising that parents should be educated regarding the lack of antitussive effects, risk for adverse events, and potential for overdose in children from these medications ( 7). In 2006, the American College of Chest Physicians released clinical practice guidelines for management of cough, advising health-care providers to refrain from recommending cough suppressants and other over-the-counter cough medications for young children because of associated morbidity and mortality ( 8).

In addition to advising caregivers and health-care providers regarding the risks of administering cough and cold medications to children aged <2 years, public health officials have taken steps to improve the safety of these medications. On June 8, 2006, FDA took enforcement action to stop the manufacture of carbinoxamine-containing medications that had not been approved by the agency; FDA noted that many of the medications were inappropriately labeled for use in infants and young children despite safety concerns regarding use of carbinoxamine in children aged <2 years ( 9). Although manufacturers were required to cease production by September 6, 2006, some products might still be in distribution. In another action, the availability of pseudoephedrine-containing medications has been affected by the federal Combat Methamphetamine Epidemic Act, which was signed into law March 9, 2006. This act bans over-the-counter sales (but permits behind-the-counter sales in limited amounts) of cold medications that contain pseudoephedrine, which can be used to make methamphetamine. Because of this act, pseudoephedrine has been removed as an ingredient in many cough and cold medications and replaced with other nasal decongestants. However, some pediatric cough and cold medications containing pseudoephedrine still might be sold behind the counter. As an alternative to pseudoephedrine and other nasal decongestants, caregivers might consider clearing nasal congestion in infants with a rubber suction bulb; secretions can be softened with saline nose drops or a cool-mist humidifier.

Few data exist regarding the therapeutic or toxic levels of cough and cold medications in children aged <2 years ( 2,3,10). Blood levels of cough and cold medications revealed in postmortem studies might not reflect levels in the bloodstream at the time of administration ( 1). However, in this report, the blood levels of pseudoephedrine found in the three patients aged 1--6 months were approximately nine to 14 times the levels resulting from administration of recommended doses to children aged 2--12 years.

The findings in this report are subject to at least two limitations. First, because no universally accepted criteria exist for attributing deaths to cough and cold medications, the cause of death in these cases was based on the report of the medical examiner or coroner. However, the actual cause of death might have been overdose of one drug, interaction of different drugs, an underlying medical condition, or a combination of drugs and underlying medical conditions. Second, the findings are limited by the low response rate and absence of identified cases from the NAME survey, which might underestimate the number of deaths in infants attributed to cough and cold medications.

No FDA-approved dosing recommendations exist for administering over-the-counter cough and cold medications to children aged <2 years, and proper dosing for children in this age group has not been studied. Instructions on over-the-counter medications advise consumers to "consult a doctor" for children in this age group ( 1). Suggested dosing for some cough and cold medications can be found in parenting and prescribing guides, and clinicians commonly extrapolate a dose based on the weight or age of children aged <2 years from dosing guidelines for adults and older children ( 7). Such extrapolation is based on the assumption that the pathophysiology of the disease and the effects of the drug are similar in adult and pediatric patients.

Caregivers and clinicians should be aware of the risk for serious illness or fatal overdose from administration of cough and cold medications to children aged <2 years. Caregivers should only administer cough and cold medications to children in this age group when following the exact advice of a clinician. Clinicians should be certain that caregivers understand 1) the importance of administering cough and cold medications only as directed and 2) the risk for overdose if they administer additional medications that might contain the same ingredient. Caregivers should always inform their health-care providers of all medications they are administering to a child.

Acknowledgment

This report is based, in part, on contributions by the Food and Drug Administration.

References

1. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use. 21 CFR Part 341 (2006).
2. Gunn VL, Taha SH, Liebelt EL, Serwint JR. Toxicity of over-the-counter cough and cold medications. Pediatrics 2001;108:E52.
3. Marinetti L, Lehman L, Casto B, Harshbarger K, Kubiczek P, Davis J. Over-the-counter cold medications---postmortem findings in infants and the relationship to cause of death. J Anal Toxicol 2005;29:738--43.
4. Boland DM, Rein J, Lew EO, Hearn WL. Fatal cold medication intoxication in an infant. J Anal Toxicol 2003;27:523--6.
5. Schroeder K, Fahey T. Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev 2004(4):CD001831.
6. Smith MB, Feldman W. Over-the-counter cold medications. A critical review of clinical trials between 1950 and 1991. JAMA 1993;269: 2258--63.
7. Use of codeine- and dextromethorphan-containing cough remedies in children. American Academy of Pediatrics. Committee on Drugs. Pediatrics 1997;99:918--20.
8. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest 2006 Jan;129(1 Suppl):1S--23S.
9. Food and Drug Administration. Carbinoxamine products; enforcement action dates. Federal Register 2006;71:33462.
10. Hanzlick R. National Association of Medical Examiners Pediatric Toxicology (PedTox) Registry Report 3. Case submission summary and data for acetaminophen, benzene, carboxyhemoglobin, dextromethorphan, ethanol, phenobarbital, and pseudoephedrine. Am J Forensic Med Pathol 1995;16:270--7.