AAP Presses FDA To Eliminate OTC Pediatric Combination Products

The American Academy of Pediatrics wants FDA to eliminate OTC combination pediatric cough/cold products.

"To maximize patient safety, all OTC drug products, including acetaminophen, should be single ingredient," Daniel Frattarelli, chair of the AAP Committee on Drugs, told a joint panel of the Pediatric and Nonprescription Drugs advisory committees convened May 17 and 18 to discuss the drug's labeling.

AAP pressed this agenda despite FDA's request to focus discussion only on single-ingredient acetaminophen. FDA already is formally considering the idea, which has come up at previous advisory panels.

But even if the idea gains support, any major change likely would be years – if not decades – in the making.

Despite FDA's requested limit on the topic, several panelists and the AAP representative raised safety concerns about combination pediatric products (Also see "Pediatric Acetaminophen Panel Debates Execution Of Dosing Changes" - Pink Sheet, 23 May, 2011.).

During the public comment period, Frattarelli said AAP "feels strongly that there is no reason why OTC combination products containing acetaminophen should be on the market for children."

"Parents are often unaware that drug products, including prescription products, may also contain acetaminophen," he said. As a result, some caregivers unknowingly give children multiple acetaminophen products simultaneously, creating an overdose risk.

While acetaminophen is safe and effective for children, many of the ingredients with which it is combined in pediatric cough/cold products are not effective, he maintained. Thus, the risk of overdose due to concomitant use outweighs the benefits.

Restricting OTC pediatric products with acetaminophen to single-ingredient products would eliminate these risks, he added.

FDA Mulls Nixing Some Combos

FDA advisory committees previously discussed eliminating some OTC combinations.

A 2007 cough/cold advisory committee discussed eliminating combination cough/cold products for children, and a 2009 panel considered eliminating OTC combination products with acetaminophen.

Following the 2007 meeting, FDA requested comments in a 2008 Federal Register notice on possibly eliminating cough/cold combinations for children. The notice discussed revising the cough/cold monograph, which would take years (Also see "FDA Call For Pediatric Cough/Cold Input Signals New Rule Is A Long Way Off" - Pink Sheet, 25 Aug, 2008.).

The 2009 panel voted 24 to 13 against eliminating OTC combination acetaminophen products as a way to prevent liver damage. Even though the majority favored sparing the products, FDA representatives indicated the agency still could order the change.

At the time, Office of New Drugs Deputy Director Sandra Kweder said the minority of the panel in favor of elimination still represented a recommendation – even if it "wasn't as strong for the OTC products as it was for the other prescription products" (Also see "Acetaminophen OTC Combos Are Not Out Of The Woods, Despite Panel Vote" - Pink Sheet, 6 Jul, 2009.).

At the May 17-18 meeting, Kweder said several times the panel should not discuss combinations because "we can't address the combinations until we focus on single ingredients."

She hinted at potential future discussions about combination products though, when saying, "The only way we can effect change in the combinations is to march through the single ingredients."

Based on how long the agency needed to examine acetaminophen, reviewing all 38 active ingredients in the cough/cold monograph could delay significantly any major action on combination pediatric products.

FDA would not eliminate combinations without "extremely diligent research that proved they were improving consumer safety by doing this," said Joseph McGovern, a consultant with The Atlantis Group.

Considering combination products have worked well for decades and that many self-treatable conditions are multi-symptom, the burden of proof to eliminate combination products would be on showing a single-ingredient system could work and would not have unintended consequences, he said.

Industry: Elimination Not The Answer

Industry representatives and other panelists acknowledged consumers taking multiple acetaminophen products together is a root cause of medication errors and overdose. However, eliminating combination products is not the solution, they argue.

"Even if combination products containing acetaminophen were taken off of the market, a parent or patient could still inadvertently take too much acetaminophen by taking two single-ingredient products that contain acetaminophen, such as Tylenol and Triaminic Fever Reducer," panel member Janet Engle said after the meeting.

"Part of the problem is that patients/consumers don't read the label," said Engle, head of the Department of Pharmacy Practice at the University of Illinois at Chicago College of Pharmacy.

"It is important for consumers to read the label, be sure they have all the symptoms that the product treats, heed the warnings, follow the directions and ask their pharmacist if they have any questions about the product and whether it is the correct remedy for their situation," she said.

With that in mind, she said, "combination products have a place in the OTC marketplace. … [They] can decrease confusion about dosing when a patient needs more than one active ingredient to treat his or her symptoms. Rather than having to read two or more labels and interpret the directions, dosing interval, dose, etc. for multiple products, a combination product has one set of dosing direction and warnings."

Many consumers do not know when a prescription drug also includes acetaminophen, which can lead to overdoses if paired with an OTC acetaminophen product, said Ed Kuffner, VP of medical affairs and clinical research at McNeil Consumer Healthcare.

McGovern notes that combination drugs can cost less than separate ingredients, they ease the burden on the health care infrastructure and the risk/benefit case for each combination was determined at approval.

Engle noted, though, that combinations "are not the best choice when a patient does not need all the ingredients contained in the product."

When muscle ache or fever is absent, consumers should choose a product without a pain reliever, the Consumer Healthcare Products Association notes. A spokeswoman added that roughly a third of the OTC medicines sold for cold, flu or allergy symptoms contain only one active ingredient, but that when people experience a range of symptoms, "having choices that treat them concurrently makes sense."

However, Engle said combination cough/cold products might not make sense for children because many ingredients "used to treat colds … do not have good data to support their use."

This was a main reason for AAP's recommendation to eliminate pediatric combination products with acetaminophen, Frattarelli said in his comments.

AAP's Stealth Complaint

Frattarelli's comments also serve as a backdoor reminder to FDA to act on the previous advisory committee's recommendations.

"In 2007, the AAP stood before this joint committee and acknowledged that although some cough and cold medicines were studied in children prior to their introduction on the market, the trials available at this time do not meet current standards, and that subsequent studies have found the products to be ineffective in children," he said.

He and several panelists called on FDA to act more quickly on this issue.

Frattarelli co-signed a citizen petition with 15 other health leaders, including former FDA Principal Deputy Commissioner Joshua Sharfstein (then Baltimore commissioner of health), asking FDA to relabel cough/cold products as ineffective in children under 6 years.

Since then, industry voluntarily relabeled pediatric cough/cold products to warn against use in children younger than 4.

CHPA and manufacturers also conducted multiple pharmacokinetic studies in children on popular cough and cold ingredients and found these ingredients behave in children as they do in adults. They will study efficacy next (Also see "U.K. To Move Kids’ Cough/Cold Drugs BTC, Redraws Age Recommendation" - Pink Sheet, 9 Mar, 2009.).

By Elizabeth Crawford