FDA plans to revise monograph language for over-the-counter pediatric cough/cold products, but the agency is seeking input on some basic data questions first, indicating many steps will be taken before a rule can be finalized.

The agency needs additional data about pediatric cough/cold product ingredients to draft a proposed rule to revise labeling under the current final monograph, according to a notice prepared for the Aug. 25 Federal Register.

FDA will hold an informal public hearing Oct. 2 to gather input from parents, health care practitioners, drug manufacturers and other stakeholders about the safety, efficacy and use by children of ingredients covered in the cough, cold, allergy, bronchodilator and anti-asthmatic drug products monograph.

The proposed questions for the hearing reveal FDA is willing to consider options as strict as making these products prescription only. They also show FDA still needs input on appropriate study design and proposed up-to-date methods for determining appropriate pediatric dosing and other issues (see chart: " ¹ Scope Of FDA Public Hearing On Cough/Cold Monograph ").

The agency is taking "a new look at the assumptions that were used to create the pediatric conditions for cough and cold medicines contained in the CCABADP monograph" in response to concerns about pediatric cough and cold products, including those raised by a March 2007 citizen petition, according to the notice.

The petition, submitted by 16 pediatricians and health care experts, recommends FDA relabel cough/cold products as not safe and effective for children under 6 years old (² Also see "FDA Review Of Children’s Cough/Cold OTCs Has Broader Implications" - Pink Sheet, 5 March, 2007., p. 3).

FDA's planned development of a proposed rule also follows an advisory panel's recommendation in October 2007 that OTC cough/cold medicines should not be used for children under 2 years old. Drug manufacturers voluntarily withdrew these products from store shelves in October due to potential misuse (³ Also see "FDA Panel Narrowly Votes Against Cough/Cold Drugs For Children Up To Age 6" - Pink Sheet, 22 October, 2007., p. 3 and ⁴ Also see "Infant Cold Products Pulled; Waxman Looks For More OTC Risks" - Pink Sheet, 15 October, 2007., p. 6).

The committees also voted 13 to 9 that children under 6 years of age should not use pediatric cough/cold products while rulemaking proceeds, and voted 15 to 7 that children 6 to 12 years old may use the products while new safety and efficacy studies are conducted.

Members of the panel also said more accurate data is needed to directly measure the efficacy of nonprescription cough/cold products in children.

FDA seeks comment on how to gather this safety and efficacy data, including recommendations on how to design and power studies to determine the appropriate dose of cough/cold ingredients for children.

These fundamental questions suggest FDA's planned modernization of pediatric cough/cold regulation is still in an early stage.

The Consumer Healthcare Products Association has already begun pharmacokinetic studies in 2- to 12-year-olds on common cough/cold product ingredients including dextromethorphan, phenylephrine, guaifenesin, brompheniramine, diphenhydramine and doxylamine. The trade group has also taken the first steps towards conducting efficacy studies (⁵ Also see "CHPA Plans Pharmacokinetic Trials On Pediatric OTC Cough/Cold Drugs" - Pink Sheet, 8 October, 2007., p. 8).

FDA has also reviewed safety and efficacy data of cough/cold products, including information from the Adverse Event Reporting database and the Centers for Disease Control and Prevention, the agency says in the notice (⁶ Also see "Child-Resistant Packaging In The Works For More OTC Cold Products – CHPA" - Pink Sheet, 4 February, 2008., p. 8).

Based on this data and a recent report that found one in 10 children use one or more cough/cold products in any given week, FDA concluded that children under 4 years of age are more likely to experience non-allergic adverse events than other children (⁷ Also see "National Survey Shows 1 In 10 Children Use Cough/Cold OTCs Each Week" - Pink Sheet, 11 August, 2008., p. 12).

However, "serious adverse events are relatively rare given the extensive use of the drug products," according to the notice.

Nonetheless, FDA decided to collect additional data about pediatric cough/cold product use, efficacy and safety "using modern standards" to either "support the current dosing or to establish new dosing regimens for children," according to the notice.

Baltimore Commissioner of Health Joshua Sharfstein, who filed the March 2007 citizen petition, lauds FDA's decision to re-open the relevant regulation and to "hold these products to a modern scientific standard of safety and effectiveness."

"It is clear that these products cannot meet such a standard today," Sharfstein adds in an Aug. 22 release. He urges FDA to "move swiftly through this process to protect children."

FDA Asks About Switching OTC Products To Rx

Other questions FDA seeks comment on include whether pediatric cough/cold products should continue to be available OTC or if they should be available by prescription only. If the products are prescription only, what is the risk that consumers would give children smaller doses of adult formulated products, the agency asks in the notice.

CHPA opposes switching OTC cough/cold products to Rx status because it "would make access to these medicines costly and burdensome without directly addressing the primary issues of concern," the trade group said, adding that "these medicines have a long history of being safe and effective for over-the-counter use and have been used for decades."

It adds that its "initiatives - advancing the science, educating parents and utilizing innovative packaging developments - are the right steps to specifically address the questions raised."

Combination Products May Be On The Line

FDA also asks if it should permit combination products for all pediatric age groups and if data should support each combination.

There are approximately 38 active ingredients in the cough/cold monograph and some combination products contain as many as four of these active ingredients in a single dosage form, the agency notes.

- Elizabeth Crawford (e.crawford@elsevier.com)

FDA Call For Pediatric Cough/Cold Input Signals New Rule Is A Long Way Off

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