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Limited data on cold medicines for kids

An FDA panel last month recommended against using these medications in children younger than age 6.

by Edward A. Bell, PharmD, BCPS
Special to Infectious Diseases in Children


November 2007


Edward A. Bell, PharmD, BCPS
Edward A. Bell

It has been an interesting year for pediatric over-the-counter cough and cold medications.

In March 2007, a Citizen Petition was submitted to the FDA, signed by 14 physicians and one academic pharmacist. This petition requested the FDA to do the following: 1) provide a public statement explaining that OTC antitussive, expectorant, nasal decongestant, antihistamine, and combination cough/cold products are not safe and effective for children younger than 6 years; 2) explain that use of “infant” or “baby” on OTC cough/cold products is not supported by scientific evidence; and 3) change pediatric OTC product labeling to state that these products are not safe or effective in children younger than 6 years.

On Aug. 15, 2007, the FDA issued a Public Health Advisory (published in the September issue of Infectious Diseases in Children). This advisory primarily discussed the use of OTC cough/cold medications in children younger than age 2 and, among other recommendations, stated not to use cough/cold products in these children unless specifically instructed to by a health care provider.

On Oct. 11, the Consumer Healthcare Products Association, on behalf of manufacturers of OTC cough/cold medications, voluntarily withdrew 14 pediatric cough/cold products intended for use in children younger than 2 years. This represents all oral cough/cold products labeled for “infants” or for use in these children. These products included some of the PediaCare, Dimetapp, Robitussin, and Tylenol products (not plain single ingredient Tylenol {acetaminophen} products). The specific products can be viewed at

Less than a week later, an FDA advisory panel recommended these medicines should not be given to children younger than age 6 without additional clinical trials. The panel stopped short, however, of recommending against use in children aged 6 to 12.

OTC drug products have been a frequent topic for discussion in this column. Pediatric OTC products are commonly used by parents and caregivers, namely those products used for treatment of fever and discomfort, like acetaminophen and ibuprofen, or symptoms resulting from the common cold. Numerous pediatric OTC products are available to caregivers in pharmacies, and these products are manufactured in various dosage forms, like liquids, chewable tablets and easily dissolved tablets to allow ease of use to infants and young children. Many of these OTC products are heavily.

History of cold products

Regulatory issues pertinent to this discussion of OTC products used to treat cough/cold symptoms in infants and young children date back over 30 years.

The active ingredients found in current OTC cough/cold products have been “generally recognized as safe and effective.”

They were granted FDA approval through the OTC monograph process (Cold, Cough, Allergy, Bronchodilator and Antiasthmatic Drug Products for Over-the-Counter Human Use, 21 CFR 341). However, in the early-mid 1970s the FDA was aware that scientific evidence describing the safety and effectiveness of cough/cold product ingredients in young children was significantly limited or nonexistent. Several factors affected cough/cold product use in young children including the difficulty of conducting clinical trials of the common cold in children. Because young children comprise a large portion of the population which may potentially use cough/cold products, a potential need was present for use of these products.

As no data were available for scientifically based dosage recommendations, in 1974 a panel of seven physicians recommended the following doses for cough/cold products: if the child was younger than 2 years of age, the dose should be established by the physician, if the child was 2 to 5 years of age, one-quarter of the adult dose was recommended, and for those children 6 to 11 years of age, one half of the adult dose was recommended. Body weights used for this dosing rationale included an average adult weight of 60 kg, average weight of 17 kg for ages 2 to 5 years, and average weight of 30 kg for children aged 6 to 11 years. Efficacy studies had not been required for pediatric OTC products, as ingredient efficacy was extrapolated from the adult population, and because of the perceived difficulty of subjective symptom measurement in young children.

Many experts have disagreed with the philosophy that the pathophysiology of the common cold is similar in young children as in adults. Alterations in sinus development and function, airway size, respiratory muscle and chest wall structure, and clinical presentation are some of the differences that may exist between the pediatric and adult populations. This may discount the justification that clinical efficacy studies for cough/cold products are not necessary in children.


Doses for children younger than 6 years found on package labeling for pediatric OTC cough/cold products has been extrapolated from adult data. Labeling on many products for children aged younger than 2 years includes “consult your doctor.” This implies that physicians have access to recommendations based upon pediatric safety and efficacy data. However, this is not true. Physicians may have access to dosing sources not available to the general public, including manufacturer supplied dosing information, or drug dosing handbooks. Lack of OTC product dosing recommendations for children younger than 2 years of age also establishes an incongruity in product use, as the products are available easily (without a physician’s prescription), yet cause the caregiver to consult a physician.

The dosing rationale for pediatric cough/cold products, based solely upon bodyweight (as a fraction of adult weight), does not account for myriad pharmacokinetic alterations and differences of drug disposition in infants and young children, as compared with adults. Using the pharmacokinetic characteristics of absorption, distribution, metabolism, and excretion, numerous physiologic factors exist which may affect a drug’s pharmacokinetic profile (e.g., GI transit time, body water content, hepatic drug metabolizing enzyme maturity) in an infant or child. For example, pharmacokinetic data available from the FDA demonstrates that body clearance of pseudoephedrine and chlorpheniramine are both greater in children as compared to adults. This has implications for determining safe and effective doses, in that dose extrapolation from adults and body weight is not accurate, nor appropriate.

Efficacy and safety studies

As described above, pediatric OTC cough/cold product labeling and approval has been based upon extrapolation from adult data. A review of the published medical literature of pediatric studies finds essentially no data supporting the effectiveness of cough/cold product ingredients in children (see references). While more favorable efficacy data are available for adults, controlled trials of cough/cold ingredients in children have failed to demonstrate efficacy. Differences may relate to drug dosing and pharmacokinetics (i.e., pediatric doses used in trials have been too small), disease pathophysiology, or symptom measurement. This lack of demonstrated efficacy in children formed the basis for the Citizen Petition.

The published literature also includes data on the potential for adversity when OTC cough/cold products are used in the young pediatric population (see references). Deaths have been reported, which are often believed to be due to inappropriate use of OTC cough/cold products in infants and young children. This has included administration of excessive doses, use of inappropriate dose measurement devices, simultaneous use of several products, or use of adult product formulations. The administration of small doses, the potential for lack of efficacy (i.e., more is better), and OTC product availability without health care provider consultation contributes to the potential for adverse effects. Safety data available from the FDA on adverse effects from cough/cold ingredient use in children younger than 6 years of age over a 37-year period (1969-2006) includes 54 fatal cases potentially attributable to decongestant ingredients and 69 fatal cases potentially attributable to an antihistamine. The majority of these cases occurred in children younger than 2 years of age, and many cases resulted from excessive dosing. These numbers, however, maybe low, as adverse effect reporting for these drugs is not required.

The AAP recently submitted an opinion to the FDA on the use of cough/cold products in children younger than 6 years of age. The AAP opinion statement describes the lack of evidence in the published literature for use of these products, the potential for adversity (attributable to dosing errors), and a lack of evidence-based dosing guidelines. Recommendations are given for product labeling changes to reflect these safety, efficacy, and dosing concerns. The AAP has previously commented on cough products, stating that data supporting cough ingredient safety and efficacy in children from controlled trials do not exist.

Manufacturers of commonly used pediatric cough/cold products have defended their use. The Consumer Healthcare Products Association has stated that pediatric cough/cold products are safe and effective when used as directed. The Association states “rare patterns of misuse leading to overdose…particularly in infants” as the basis for the recent voluntary product withdrawal.


Viral upper respiratory tract infections commonly occur in infants and young children. Numerous OTC products are available to caregivers to treat symptoms from URIs in their children.

Despite their widespread availability, scientific data supporting the safety and efficacy of pediatric OTC cough/cold products are limited. Regulation of pediatric OTC cough/cold products has been based, in part, upon adult data extrapolation and imprecise dosing recommendations. These products are likely frequently given by caregivers without adverse effects. However, the potential for serious adverse effects and toxicity exists. Dosing errors, unknown doses for children younger than 2 years of age, and product formulation contribute to this potential for adverse effects.

It is possible that additional pediatric pharmacokinetic data dose-ranging studies may demonstrate product effectiveness in the young age group. A recent petition on the use of pediatric OTC cough/cold products, a withdrawal of several products, and renewed discussion by the FDA may dramatically alter the future for pediatric OTC cough/cold products. In the mean time, pediatric clinicians should consider this information, as the respiratory season is approaching.

For more information:
  • Edward A. Bell, PharmD, BCPS, is a professor of pharmacy practice at Drake University College of Pharmacy and a clinical specialist at Blank Children’s Hospital, Des Moines, Iowa.
  • FDA. Nonprescription drug advisory committee meeting – cold, cough, allergy, bronchodilator, antiasthmatic drug products for over-the-counter human use. Oct. 18-19, 2007.
  • FDA. Public health advisory – nonprescription cough and cold medicine use in children. Aug. 15, 2007.
  • Smith MBH. Over-the-counter cold medications: a critical review of clinical trials between 1950 and 1991. JAMA. 1993;269:2258-63.
  • Clemens CJ. Is an antihistamine-decongestant combination effective in temporarily relieving symptoms of the common cold in preschool children? Journal Pediatr. 1997;130:463-6.
  • Gadomski A. The need for rational therapeutics in the use of cough and cold medicine in infants. Pediatrics. 1992;89:774-6.
  • Committee on Drugs, American Academy of Pediatrics. Use of codeine- and dextromethorphan-containing cough remedies in children. Pediatrics. 1999;99:918-20.
  • CDC. Infant deaths associated with cough and cold medications – two states, 2005. MMWR. 2007;56(01):1-4.
  • Paul IM. Effect of dextromethorphan, diphenhydramine and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics. 2004;114:e85-e90.

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