US Pharm. 2011;36(3):12-15.
Pharmacists advising patients about the appropriate use of nonprescription products have often fielded a difficult type of question. Parents ask the pharmacist what dose of a nonprescription product to give their child. Upon questioning, the pharmacist discovers that the child’s age is below the youngest labeled age on the product. Pharmacists have several options, but patients may become angry if the pharmacist refuses to use guesswork to create a dose. If the pharmacist does guess at a dose, however, significant liability can be incurred if the child is harmed.
FDA-Established Doses
In its ground-breaking review of nonprescription products, the FDA solicited expert input and conducted numerous investigations to determine doses for children that would ensure safe and effective therapy.1 For common cold-related ingredients (e.g., nasal decongestants, cough products, antihistamines), the final rules of the FDA OTC review process were mostly published more than a decade ago, establishing those safe and effective doses.1 For Rx-to-OTC switched ingredients, ages and corresponding dosages are decided upon through collaboration of the manufacturers and the FDA.
Manufacturer’s Pediatric Dosage Charts
As early as the 1980s, manufacturers began to distribute “Professional Dosing Charts” with dosing of antidiarrheals, analgesics, antihistamines, and cough/cold products clearly below the ages known to be safe and effective.1 They were in the form of rigid charts with adhesive on the back, booklets of stickers to be filled out by the pharmacist, paper charts, and refrigerator magnets, among others. Companies providing these dosing charts and products promoted in this way included Burroughs Wellcome (Sudafed), Whitehall-Robins/Wyeth (Robitussin, Dimetapp), Bristol-Myers Squibb (Naldecon), Sandoz (Triaminic), and McNeil (Tylenol, PediaCare, Imodium A-D). In 1992, this author (Steve Pray) reported the practice to a congressional committee investigating poor OTC labeling, and the correspondence was published in the official record of its proceedings.2 However, nothing was done, and the practice continued until at least 2004. To this date, the charts seem to have escaped FDA criticism or scrutiny.
Manufacturers Market Infant Products
In spite of the fact that infant dosing was prohibited by the FDA, manufacturers had begun to market products targeting those under the age of 2 years. The packages clearly depicted infants under the age of 2 years, and often even included the word “infant” as part of the trade name. Examples included Dimetapp Infant, PediaCare Infant, Robitussin Infant, Triaminic Infant, and Tylenol Infant. The manufacturers were careful to omit the doses to be given to infants, a nonsensical decision that forced consumers to make dangerous guesses at appropriate baby doses in the absence of a physician recommendation. Of course, placing doses on the package would have required them to conduct actual safety and efficacy studies in infants, which they presumably were loathe to do. Apparently, the manufacturers intended pharmacists to use their dosing charts to create unapproved doses for these products.
A Citizen’s Petition to the FDA
On March 1, 2007, the FDA received a petition signed by a group of well-respected physicians and pediatricians (e.g., the commissioner of health for Baltimore).3 It asked the FDA to notify the public that antitussives, expectorants, decongestants, antihistamines, and cough/cold combinations are not known to be safe and effective in children under the age of 6 years. It also asked the FDA to notify manufacturers that the practice of using the terms “infant” or “baby” and showing photos of children under the age of 6 years is not backed by scientific evidence. The authors of the petition cited 900 cases of unintentional overdosing in children, and four deaths in Baltimore of children under the age of 4 years, as well as three additional deaths reported by the CDC. The physicians questioned the efficacy of these products in the lower doses generally given to babies (e.g., in the dosing charts).
The FDA’s 2007 Advisory
In August 2007, the FDA issued a Public Health Advisory.4 The FDA warned parents that cough/cold products should not be used in those under the age of 2 years unless the parents had been given specific directions to do so by a health care provider, and that overdoses could cause serious and life-threatening side effects, especially in those under 2 years. The FDA also provided measurement instructions and stressed that all directions must be followed exactly. Finally, the agency announced that the Nonprescription Drugs Advisory Committee (NDAC) would meet in October 2007 to decide whether the benefits justified any potential risk to children, especially those under the age of 2 years.5
CHPA Defends the Products
The Consumer Healthcare Products Association (CHPA) is a group composed of OTC and dietary supplement manufacturers’ representatives that closely examines any new laws, rules, or regulations that would affect nonprescription products, in addition to its other activities. In response to the FDA’s advisory, the CHPA issued a lengthy document meant to influence the NDAC members in their deliberatons.6 The CHPA recommended that cough/cold product labels henceforth include a statement clearly stating “Do Not Use” in children from 0 to under 2 years of age. The CHPA did not, however, recommend recall or destruction of the unapproved pediatric dosing charts.
Recall of Infant Products
Manufacturers announced on October 11, 2007 (one week before the NDAC meeting), a “voluntary” recall of the infant products.7 The president of the American Pharmacists Association (APhA) issued a “Special Alert” stating, “Infants younger than 9 months with symptoms of the common cold should always be referred to their physician, according to the APhA’s Handbook of Nonprescription Drugs.”8 The alert inexplicably failed to warn pharmacists that the doses down to the age of 9 months provided in the APhA OTC textbook were the subject of an FDA advisory, and not known to be safe or effective in babies, further confusing the issue.
The 2007 NDAC Meeting
The NDAC meeting held on October 18-19, 2007, confirmed all of the charges in the citizen petition, with the committee expressing concern that the products had been marketed for decades without pediatric data, when it would have long been feasible to have carried out the relevant studies.9 The committee clearly spoke against the common practice of making up pediatric doses by simply extrapolating from approved doses for older children. With this statement, the pediatric dosing charts marketed for decades were declared invalid, although they were still not recalled. The committee voted 13 to 9 to take immediate action against the use of cough and cold medicines in children under the age of 6 years.
FDA’s 2008 Advisory Warning and 2008 Public Hearing
On January 17, 2008, the FDA issued an advisory and several explanatory documents warning Americans not to use cough and cold products in children under the age of 2 years due to the risks of serious and potentially life-threatening side effects.10-12 The FDA held a public hearing on October 2, 2008, to consider a full ban of cold and cough medications in children under the age of 6 years.13,14 The FDA had expressed concern that a sudden ban would cause parents to administer adult medications to children. This author (Steve Pray) assisted Joshua M. Sharfstein, MD, who was then the commissioner of health for Baltimore (former principal deputy commissioner of the FDA, now Maryland’s secretary of health and mental hygiene) in preparation for discussing the latter question at the meeting by providing information on the low risk to public health a few years earlier when bismuth subsalicylate products underwent an abrupt change in the labeled ages from 3 years to 12 years. During the hearing, the FDA decided against an outright ban, and stated that it needed additional data regarding safety and efficacy in those aged between 2 and 6 years before it would take any action.
Voluntary Changes in Age Labeling
On October 7, 2008, pharmacists and the public were all taken aback by a statement from the CHPA.15 The organization’s president began by asserting that children’s nonprescription cough/cold medicines are safe and effective, although she offered no new studies to prove that assertion. The CHPA also stated, “Research shows that dosing errors and accidental ingestions—not the safety of the ingredients themselves when properly dosed—are the leading causes of rare adverse events in young children.” This was perhaps an attempt to divert the issue away from lack of safety and efficacy studies.
The CHPA also stated that, following FDA consultations, leading manufacturers agreed to a voluntary transition of labels to eventually read not to use them in children under the age of 4 years. Further, manufacturers would place a warning on sedating antihistamines not to use them to sedate children or to make them sleepy. The transition would occur during the 2008-2009 cough and cold season. The FDA did not require a recall of products with the older labeling down to the age of 2 years.
The story behind this surprise move demonstrated the complicated interactions between manufacturers and the FDA. News reports on October 11, 2008, revealed that the FDA conducted a review of data and carried out a vigorous debate regarding pediatric dosing.16 The FDA personnel then held private discussions with industry. The label changes represented a compromise that the manufacturers would accept. The FDA perhaps feared that trying to force a ban under the age of 6 years would cause a lengthy period of public comment and investigation, during which the 2-year age labeled products would continue to be marketed, an unsafe proposition. In an effort to prevent that scenario, the FDA apparently decided to make the best of a bad situation by splitting the difference and offering a compromise age of 4 years.
Manufacturers agreeing to the proposal and the companies/brands affected included McNeil (Tylenol, PediaCare, Sudafed), Novartis (Triaminic), Procter & Gamble (NyQuil, Vicks), Reckitt Benckiser (Delsym, Mucinex), and Wyeth (Dimetapp, Robitussin). Eventually, the label change was to extend to all products, a move endorsed by the FDA.17
A leading public interest organization criticized the move, characterizing it as a self-serving gesture of self-regulation, offering doses for those aged 4 to 6 years without proof of safety.18 As such, the group opined that this arose solely from a political compromise.
PATIENT INFORMATION
You may have recognized that those labels have been drastically revised. The allowed age limit is now 4 years. When the labels were changed, it signaled parents that cough and cold products should not be used in infants and children under the age of 4 years without the supervision and approval of a prescriber.
Why Did the Labels Change?
A growing number of children had been harmed by cough and cold products, and younger children were more at risk. For this reason, the FDA began an examination of whether those products were safe and effective down to the age of 2 years. During this process, manufacturers voluntarily agreed to raise the age limit to 4 years.
Can Those Selling the Products Make a Recommendation?
It is tempting to turn to the seller of the product to ask his or her opinion. Pharmacists are a logical choice for such a question. The highly professional training of pharmacists allows them to provide considerable advice as to when a physician should be consulted and when you can use nonprescription products. However, assessing a child in depth, creating a dose for a child, and monitoring the child are all considered only to be within the realm of a prescriber. Community pharmacists are not prescribers, and creating doses in these situations is an area for which they lack the resources. Typical community pharmacies do not have the basic tools or an appropriate area to assess patients by examining their throats and ears. Pharmacies also cannot provide monitoring.
As an example, suppose a 1-year-old child suffered an acute reaction or injury from a pharmacist-recommended, nonlabeled dose, and the parent called the pharmacy for help, assuming the pharmacy was even open. Pharmacists lack the ability to carry out such obvious interventions as ordering lab tests and admitting the child to a hospital.
A more precarious situation arises if you buy the product from a nonpharmacy outlet. In this situation, clerks and sales personnel are not trained to provide medical advice of any sort, such as when to see a physician or what dose to administer. Asking them to do so or heeding their advice would be a very bad idea.
Under no circumstances should you guess at a dose of your own. It is tempting to assume that the label dose for a 4-year-old can be cut in half for a 2-year-old. This is false and can bring about serious injury. Never guess at a dose. Always call the child’s physician for medical advice and measure the doses very carefully to ensure that the correct dose is given.
REFERENCES
1. Pray WS. Nonprescription Product Therapeutics. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006.
2. Joint Hearing Before the Subcommittee on Regulation, Business Opportunities and Energy of the Committee on Small Business and the Subcommittee on Housing and Consumer Interests of the Select Committee on Aging of the House of Representatives, 102nd Congress, 2nd session. Washington, DC. April 28, 1992;319-322. Small Business Serial No. 102-75.
3. Sharfstein JM, Serwint J, North ML, et al. Citizens petition. March 1, 2007. www.baltimorehealth.org/press/
4. FDA public health advisory. Nonprescription cough and cold medicine use in children. August 15, 2007. www.fda.gov/Drugs/DrugSafety/
5. Use caution with cough and cold medicines for children. FDA. www.fda.gov/ForConsumers/
6. Untitled document. www.fda.gov/ohrms/dockets/ac/
7. Infant cold medicines pulled for overdose risk. MSNBC. www.msnbc.msn.com/id/21247580/
8. Gans JA. Special alert (letter). American Pharmacists Association. October 11, 2007. www.pharmacist.com/AM/
9. FDA proceedings. Joint Meeting of the Nonprescription Drugs Advisory Committee on Safety and Efficacy of Over-the-Counter Cough and Cold Products Marketed for Pediatric Use. Parts 1-4. October 18-19, 2007. www.fda.gov/ohrms/dockets/ac/
10. Public health advisory: FDA recommends that over-the-counter (OTC) cough and cold products not be used for infants and children under 2 years of age. www.fda.gov/Drugs/DrugSafety/
11. OTC cough and cold products: not for infants and children under 2 years of age. FDA. www.fda.gov/ForConsumers/
12. FDA releases recommendations regarding use of over-the-counter cough and cold products. FDA news release. January 17, 2008. www.fda.gov/NewsEvents/
13. Public hearing for over-the-counter cough and cold medications. Beltsville, Maryland: FDA; October 2, 2008. www.fda.gov/cder/meeting/
14. FDA wants more time to study cold meds for kids. HealthDay News. October 2, 2008. http://asthma-allergy-news.
15. Statement from CHPA on the voluntary label updates to oral OTC children’s cough and cold medicines. Consumer Healthcare Products Association (CHPA). October 7, 2008. www.chpa-info.org/10_07_08_
16. Associated Press. Child remedy plan led by FDA. The Oklahoman. October 11, 2008:3A.
17. FDA statement following CHPA’s announcement on nonprescription over-the-counter cough and cold medicines in children. FDA. October 8, 2008. www.fda.gov/NewsEvents/
18. Lurie P. Drug industry proposal for cough and cold medications will not protect children. Public Citizen. October 7, 2008. www.citizen.org/pressroom/
19. Hyland’s teething tablets: recall—risk of harm to children. FDA. October 23, 2010. www.fda.gov/Safety/MedWatch/
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