SmithKline Beecham to conduct Phase IV Nicotrol safety/efficacy study in adolescents.

NICOTROL PATCH PHASE IV COMMITMENTS INCLUDE SURVEILLANCE OF SALES TO MINORS and a study of the safety and efficacy of Nicotrol use in adolescents, FDA reminded McNeil in its recent approval letter for the Rx-to-OTC switch nicotine patch therapy. The requirements are nearly identical to those for the other smoking cessation aid recently switched to OTC status -- SmithKline Beecham's Nicorette nicotine replacement chewing gum ("The Tan Sheet" Feb. 19, p. 5).

McNeil outlined the Phase IV commitments in May 17 and June 26 submissions to FDA. Nicotrol became the first nicotine patch to be approved for OTC marketing on July 3 and is expected to be on shelves by July 18 ("The Tan Sheet" July 8, p. 1). New York City-based DDB Needham is handling the advertising campaign for OTC Nicotrol. A teaser ad announcing the pending launch was aired July 9 during the Major League Baseball All-Star Game.

The surveillance study, which will be designed to "identify and report on sales to or use of Nicotrol by people less than 18 years of age," must include three components, FDA noted. The first will be "media tracking by McNeil Information Center staff of news on the LEXIS/NEXIS service including scanning national and international wire services and major U.S. newspapers."

The second component will be "a consumer tracking/national survey of Drug Free Schools Coordinators," for which a protocol must be submitted to the agency "prior to implementation of the survey," by early October. The final component will be the "monitoring of misuse/abuse in primary care settings by an advisory panel of independent clinicians, epidemiologists, and smoking cessation experts from different geologic regions."

Surveillance data will be submitted to FDA by McNeil on a quarterly basis for the three years following Nicotrol's introduction to the OTC market, the agency stated, adding that "at the end of this three-year period, an integrated report will be submitted to FDA for review and evaluation to determine the need for continuation of or change to all or parts of the surveillance study." Nicotrol is labeled as not for sale to minors.

FDA will assist McNeil in determining parameters and design for the study in adolescents, which will assess the safety and efficacy of Nicotrol use by adolescents as an aid in smoking cessation. The agency expects to meet with the company regarding the development of the study within six months of Nicotrol's approval (i.e. by early January).

FDA's letter also reminds McNeil of commitments made in its marketing plan for Nicotrol. According to the agency, these commitments include: "targeting any advertising of this product to adult smokers in a variety of ethnic audiences"; "providing Spanish language labeling on request"; and "making available a free smoking cessation program" through a toll-free number on the product label.

In addition, FDA noted, the marketing plan specifies that McNeil will: package patches in child-resistant pouches; not offer trial or sample sizes; work to ensure that Nicotrol is sold with other OTC products and in venues in which proof of age can be obtained; train retailers regarding age restrictions; educate health care professionals about nicotine replacement therapy; and take measures to bring into compliance retailers who violate the conditions of sale for Nicotrol.

The letter also specifies that Nicotrol's final printed label "must be identical" to draft labeling submitted to the agency.

Bulleted warnings on Nicotrol labeling include: "Keep this and all medication out of the reach of children and pets. Even used patches have enough nicotine in them to poison children and pets. Be sure to fold sticky ends together and throw away out of reach of children and pets. In case of accidental overdose, seek professional help or contact a poison control center immediately. Nicotine can increase your baby's heart rate. First try to stop smoking without the nicotine patch. As with any drug, if you are pregnant or nursing a baby, seek the advice of a health professional before using this product."

Consumers are cautioned not to use Nicotrol if they "continue to smoke, chew tobacco, use snuff, or use a nicotine gum or other nicotine-containing products." Labeling warns, "Do not smoke even when you are not wearing the patch. The nicotine in your skin will still be entering your bloodstream for several hours after you take the patch off. If you forget to remove the patch at bedtime, you may have vivid dreams or other sleep disruptions."

Furthermore, consumers are advised to ask a doctor before using Nicotrol if they "are under 18 years of age; have heart disease, recent heart attack or irregular heartbeat," because "nicotine can increase your heart rate," have high blood pressure not controlled by medication," because "nicotine can increase blood pressure," take prescription medicine for depression or asthma" because the dose "may need to be adjusted"; or are "allergic to adhesive tape or have skin problems, because you are more likely to get rashes."

Finally, users are warned, "Stop use and see your doctor if you have: skin redness caused by the patch that does not go away after four days, or if your skin swells or you get a rash; irregular heartbeat or palpitations; or symptoms of nicotine overdose such as nausea, vomiting, dizziness, weakness and rapid heartbeat."

The Nicotrol starter kit contains seven 15 mg Nicotrol patches, an audiotape, an informational booklet, a toll-free hotline number, several self-scoring quizzes, a quick-reference tips card and a "Personal Quit Guide Survey." Consumers complete the survey and return it in a postage-paid self-mailer. In response, they receive a personal quit guide containing tailored tips on smoking cessation.

The starter kit also includes a $3-off coupon for a Nicotrol refill kit. Refill kits contain seven patches and a "Guide to Staying Smoke Free."