FDA Will Mull OTC Smoking Cessation Long-Term Use As Support Builds

Participants at an FDA workshop will consider issues that could influence whether the agency extends the use of nicotine-replacement therapies beyond the current 12-week indication.

Meanwhile, more voices join the chorus calling for regulatory changes to encourage expanded use and indications for smoking-cessation products.

In a Sept. 2 Federal Register notice, the Center for Drug Evaluation and Research lists eight questions concerning the risks and benefits of long-term NRT use to be explored at the workshop Oct. 26-27 in Arlington, Va.

The agency seeks input on evidence that long-term NRT use helps people abstain from or reduce smoking. FDA also asks how NRT use compares to complete abstinence in smoking cessation.

The questions also address the long-term safety of nicotine in human and animal studies; dependence and addiction to NRTs; the drug administration type's effect on addiction; and mitigating against NRT addiction and against use by people who are not tobacco users.

As a scientific workshop, the meeting "should not be expected to yield any conclusions or recommendations from" participants, as would be expected from an advisory committee meeting, a CDER spokeswoman noted.

The center emphasizes the workshop is organized to present and discuss data about the risks and benefits of long-term nicotine use.

Nonprescription NRTs currently are available as transdermal patches, gum and lozenges. Labeling for the OTCs, as well as Rx versions, indicates the products should be used "for a short time only (up to 12 weeks) to relieve the acute withdrawal symptoms experienced when quitting smoking," CDER says in the meeting notice.

Experts Back Longer Indication

To Michael Steinberg, director of the Tobacco Dependence Program at the University of Medicine and Dentistry of New Jersey, there is no reason for FDA not to change the indication.

Since more consumers use OTC than Rx smoking- cessation products, the only medical guidance they receive is from labeling, making it even more crucial that the labels include accurate information, he said.

"If the FDA makes their decisions based on clinical practice guidelines, it should be a clear decision to change these labelings," Steinberg said in an interview.

"From a scientific standpoint, it's a no-brainer," he added.

Like Steinberg, consultant and researcher Saul Shiffman says science supports use of NRTs beyond the 12-week indication.

Shiffman, of Bethesda, Md.-based Pinney Associates and a psychology and pharmaceutical science professor at the University of Pittsburgh, said before any NRTs switched from Rx to OTC, labeling indicated six months of use, and encouraged consumers to keep a small dose available after that period.

"That was very sensible labeling," he said, adding that no clinical data produced since then supports a 12-week limit.

A variety of groups and interests support expanded indications for NRTs.

On Aug. 26, the American Cancer Society Cancer Action Network, American Lung Association, Campaign for Tobacco-Free Kids and the American Legacy Foundation filed a citizen ¹ petition asking FDA to re-evaluate the way it reviews smoking cessation products and the conditions it places on their sale and distribution.

"Because the health risks of continued tobacco use are so serious, this new approach should provide an opportunity and an incentive for the development and approval of more effective smoking-cessation products and beneficial revisions to current labeling requirements," the public health groups says in the petition.

The groups "believe that many of FDA's decisions were the result of not considering the risks of the use of these products versus the risk of continued tobacco use," they add.

Department of Health and Human Services guidelines, the groups say, show that long-term use of NRTs is effective.

"These guidelines recognize that continued use of such medicines is preferable to a return to smoking because they do not contain the non-nicotine toxins that are found in cigarettes."

The Association for the Treatment of Tobacco Use and Dependence and the Society for Research on Nicotine and Tobacco Use jointly filed a citizen petition in February asking CDER to take a more flexible approach to NRT regulation, including extending the 12-week cutoff on labels. Research shows the product is effective beyond this time frame, the petitioners said (² (Also see "NRT Petition Calls On FDA To Greatly Expand Indications, Availability" - Pink Sheet, 1 Mar, 2010.)).

The move also has industry support. In December 2009, GlaxoSmithKline - manufacturer of NRTs including Nicorette gum and lozenges and NicoDerm CQ patch - submitted comments to FDA requesting the agency consider several provisions to expand NRT availability, including lengthening the 12-week indication (³ (Also see "GSK Asks FDA To Mull Expansion Of NRT Indications" - Pink Sheet, 7 Dec, 2009.)).

In December 2009, the U.K. approved an indication for GSK's NRT Nicorette Inhalator with no limit on treatment duration, an action experts said could influence FDA to move in a similar direction (⁴ (Also see "U.K. NRT Harm Reduction Indication Could Be Model For U.S." - Pink Sheet, 15 Feb, 2010.)).

"Maybe it's time to re-examine these issues," Schiffman said.

Additional NRT Regs Unaddressed

The February NRT petition also asked FDA to consider approving smaller pack sizes that could be sold at a greater variety of retailers and to modify label warnings about the dangers of continued smoking while using the products and about using combinations of NRTs, such as patches and gum.

Steinberg said product labeling on using combinations of NRTs was particularly "antiquated." Modifying warnings about using combinations could be significant because multiple clinical trials show people are more successful at quitting when they use combinations of products.

The public health groups also urge FDA to consider changing the labeling standards that currently warn against combining products.

Re-examining the 12-week limit is a good first step, Shiffman said, but other regulations also are important, particularly in expanding access to the products.

"In a sense, allowing longer use is a big benefit, but only to the people who've already adopted the medication," he said.

Many smokers do not try NRTs because they think the products are dangerous, Shiffman added. He pointed out labels on cigarettes are fewer than 20 words, while labels on NRTs may be 200 or 300 words.

"It's no wonder people are afraid of these medications," he said.

FDA has planned the meeting since the topic emerged at a joint meeting of CDER and the Center for Tobacco Products in March (⁵ (Also see "CDER-Tobacco Center Joint Meeting Could Signal Talks On NRT Indications" - Pink Sheet, 8 Mar, 2010.)).

The Family Smoking Prevention and Tobacco Control Act of 2009, which gave FDA regulatory control over tobacco products, directed the agency to consider expanding indications and approved duration of NRTs (⁶ (Also see "Tobacco Law Means Drug Sponsor Opportunities May Not Stop At Cessation" - Pink Sheet, 7 Sep, 2009.)).

FDA says it will release the agenda and other materials, including the roster of participants, approximately five days before the workshop. Public comment on the issue will be open through Dec. 27. FDA will decide following the workshop whether additional meetings will be needed to discuss NRTs.

- Carolyn B. Phenicie ( ⁷ [email protected] )