Tylenol PM and other widely used acetaminophen pain drugs that include a sleep aid, failed to show any significant benefit in a key study, U.S. health regulators have told drugmakers 15 years after industry submitted the data.
Patients taking the drugs, most commonly sold as Johnson & Johnson's Tylenol PM and Novartis AG's Excedrin PM, did not fall asleep significantly faster than those who took only acetaminophen or the sedative, known as diphenhydramine citrate, the FDA said in a letter to the industry earlier this year.
"There is an insufficient basis to support the combination of acetaminophen and diphenhydramine as a nighttime sleep aid for relief of occasional sleeplessness when associated with minor aches and pains," Dr. Charles Ganley, head of the FDA's Office of Nonprescription Products, wrote in a Feb. 16 letter to the Consumer Health Products Association, or CHPA, which represents makers of nonprescription medicines.
The letter, obtained this week by Reuters, comes amid closer scrutiny of dozens of other Tylenol products for children recalled last Friday after FDA inspection turned up contaminated ingredients and unsanitary conditions.
While the agency's letter does not raise any safety question with such acetaminophen nighttime drugs, it does call into question data backing up their effectiveness.
"The concern ... is that we need an additional study demonstrating that the combination product is more effective than acetaminophen alone, and more effective than diphenhydramine alone," FDA spokeswoman Shelly Burgess said.
"There has to be a statistically significant increase in effectiveness of the combination product over either active ingredient alone," she told Reuters.
It is not immediately clear what impact the agency's decision could have on the combination products, for which the industry initially sought FDA backing in 1995.
Such nonprescription products are not big moneymakers for the drugmakers, but carry significant brand recognition and are widely used.
While they have been sold on the U.S. market for years, winning the FDA's formal backing offers companies stronger ground with which to market their products.
"We know then that the ingredients have been accepted as safe and effective, we know the final labeling, we know the final dosages ... there's much more certainty," said an industry source familiar with the letters who did not want her name used given the ongoing industry negotiations with FDA.
Despite the FDA's concerns that the initial study does not support the drug, the agency has not raised any safety concerns over the years, and the drugs remain on the U.S. market.
Tylenol PM is the top-selling nighttime painkiller, ahead of Excedrin PM and Pfizer's Advil PM, which combines the same sleep aid with ibuprofen.
J&J's version had sales of $94.5 million over a yearlong period through mid-April, ranking it as the fifth largest-selling analgesic brand tablet, according to market research firm SymphonyIRI Group. Excedrin brought in $14.7 million in sales.
Advil PM saw $48.6 million over the same period, according to the Chicago-based group, which tracks most drugstores, supermarkets, and mass market retailers.
In March, J&J's McNeil Consumer Healthcare unit, which makes Tylenol PM, submitted additional data after working with the FDA in 2006, company spokeswoman Caroline Almeida told Reuters. The two J&J studies looked at several hundred people and were completed last year.
"These data indicate that the combination of an analgesic and sleep-aid provides significantly more benefit for the relief of pain and sleeplessness than either ingredient alone," McNeil wrote in a March 31 letter to the agency.
It was not immediately clear if other makers of nighttime acetaminophen products conducted similar studies. Novartis referred questions to the CHPA, which could not be immediately reached for comment.
The FDA's Burgess said the agency would consider any new industry data.
Unlike prescription medications, those sold over the counter can be marketed without going through a formal approval process, as long as their main ingredients are on the FDA's approved list, called a monograph.
But if a nonprescription drug does not meet the list's standards, it must win formal approval before it can be sold on U.S. shelves.
Still, the FDA's 15-year gap comes somewhat as a surprise even at an agency where actions can take years.
Burgess cited the agency's "significant workload in regulating over-the-counter drug products," and the need to prioritize based on available agency resources.
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