Prescriptions to Help Smokers Quit

In the 1950s, smoking was depicted as a sophisticated, enjoyable activity, and advertisements brimmed with smiling, happy people puffing away. Although ads still depict smoking as sophisticated and enjoyable, in the 1990s the health dangers of smoking are widely known--and about 76 percent of the nation's approximately 46 million smokers say that they would like to quit, according to a 1991 Gallup poll.

Smoking cessation is a major goal of the U.S. Public Health Service's Healthy People 2000 Program. Cigarette smoking causes lung cancer, heart attacks, and other serious health problems in smokers. It can cause health problems in nonsmokers exposed to "second-hand" smoke as well. Airlines, restaurants, hospitals, and workplaces are banning smoking or restricting it to designated areas, and pressure to quit is intense.

As former Surgeon General C. Everett Koop, M.D., said, "If you have a spouse who's nagging you at home to quit, children who suggest that you're going to die if you don't, and then your boss says you can't smoke at the worksite, that's a pretty good indication that it's time to try to quit."

But quitting is a lot easier said than done. Each year, about 17 million Americans try to stop smoking, according to the American Cancer Society. Only 1.3 million succeed.

While many people have successfully stopped smoking on their own, many other smokers need help if they're going to succeed in quitting. For a number of years, stop-smoking programs have been available through various organizations such as the American Cancer Society and the American Lung Association.

In recent years, the Food and Drug Administration has approved two types of products to help smokers quit: nicotine chewing gum and the
transdermal nicotine patch. Nicorette chewing gum, containing 2 milligrams (mg) of nicotine, was approved by FDA in 1984. Last June, a 4-mg dosage form of the Marian Merrell Dow product was approved.

The newest stop-smoking tool is the transdermal nicotine patch. It looks like a Band-Aid, is changed daily, and delivers nicotine to the
bloodstream. Four brands of nicotine patch--Nicoderm, Habitrol, Prostep, and Nicotrol--were approved for marketing by FDA in late 1991 and early 1992. Both the chewing gum and the patch are to be used as aids to a comprehensive smoking-cessation program.

Tobacco is regulated by the Bureau of Alcohol, Tobacco and Firearms. Within the U.S. Department of Health and Human Services, the Office on Smoking and Health has the responsibility for educating the public about the health hazards of smoking. FDA, also an HHS agency, regulates nicotine gum and patches as prescription drugs; a doctor's expertise is needed to identify which patients might benefit from these products, and to prescribe the most effective course of treatment for an individual patient.

Targeting Nicotine

Cigarette smoke contains more than 4,000 chemicals and affects many of the body's chemical messengers, such as neurotransmitters and hormones. These chemical messengers mediate a wide range of bodily responses, such as metabolism and heart and respiratory function. In 1988, the Surgeon General's report on "The Health Consequences of Smoking" identified nicotine as the addictive component of tobacco smoke. Its absence triggers the symptoms of withdrawal--irritability, anger, anxiety, restlessness, inability to concentrate, hunger, and nicotine craving.

The idea behind nicotine replacement therapy, which includes the patch and nicotine gum, is that providing nicotine in a form other than a cigarette can minimize the symptoms of withdrawal while a person is weaned from smoking. During this time, with the help of a counselor or doctor in a smoking-cessation program, the patient learns to live without the habits associated with cigarette smoking, such as having something in the hand or mouth, drawing smoke in and puffing it out, or reaching for a cigarette in response to a behavioral cue, such as a cup of coffee or stress.

"The phone rings, you say, 'Just a second,' and grab a cigarette. You smoke after a meal. The gum and patch are different in that they separate the behavioral cues from the nicotine delivery," says Elbert D. Glover, Ph.D., director of the Tobacco Research Center at the West Virginia University School of Medicine in Morgantown.

"A nicotine patch is not a magic bullet."

--Michael Eriksen, Centers for Disease Control

Nicotine Patches

Brand Name Dosage Type

Nicotrol 21 mg 24-hour
Habitrol 14 mg
7 mg

Prostep 22 mg 24-hour
11 mg

Nicotrol 15 mg Worn only while awake
10 mg
5 mg

OTC Stop-Smoking Aids Not Effective

No over-the-counter smoking deterrent products on the market are effective, FDA has concluded. Pills, tablets, lozenges, and chewing gum claiming to eliminate nicotine addiction can be sold until supplies arc exhausted, but new shipments of these products were prohibited after Dec. 1, 1993.

Some manufacturers of these OTC products have suggested conducting clinical trials on lobeline sulfate and silver acetate-two ingredients in current products. Past studies of these and other ingredients have not shown that they are effective to help people stop or reduce smoking.

Marion Merrell Dow has expressed interest in switching its prescription chewing gum product, Nicorette, to nonprescription status. Before allowing a switch, the agency would need to consider carefully Nicorette's own potential for addiction, since it contains nicotine.

FDA informed companies that it will work closely with them to develop new products effective in this area.

A Special Way to Chew

To be most effective, Nicorette must be chewed in a special way. When doctors prescribe nicotine chewing gum, they tell smokers to stop smoking completely and discuss what the maximum number of pieces of gum a day should be.

When the smoker craves a cigarette, he or she places one piece of nicotine gum in the mouth and begins to chew--very slowly. This slowness is important for the proper release of the nicotine and to avoid side effects similar to those experienced when inhaling tobacco for the first time or smoking too fast. These side effects include lightheadedness, nausea, vomiting, throat and mouth soreness, hiccups, and upset stomach.

After about 15 chews, the smoker notes a peppery taste or a tingling in the mouth. This is the signal to "park" the gum by placing it between the cheek and the gums. When the peppery taste or tingling is almost gone, the user starts chewing again. When the taste or tingling returns, the person "parks" the gum in a different place in the mouth. This process continues for about 30 minutes, at which point the nicotine is gone from the gum.

After about two or three months, the smoker should be ready to be weaned from the gum by gradually reducing use. Some ways this can be done are by reducing the number of pieces each day, by chewing some pieces for shorter amounts of time, or by using sugarless gum in place of Nicorette.

Automatic Dosage

A drawback of gum is that, as with smoking itself, the user controls the dose and schedule of nicotine delivery. In contrast, with the 24-hour skin patch, nicotine enters the body automatically, either over a 24-hour period or only while the person is awake, depending on the type of patch used.

All four patch brands come in different dosages so that the amount of nicotine supplied to the patient can be gradually lowered. (See box.) For example, treatment with Nicoderm (marketed by Marion Merrell Dow) or Habitrol (manufactured by Kabi Pharmacia) begins with a 21-mg per day dose, about equal to the nicotine in a pack of cigarettes. Each patch is worn for 24 hours. After four to eight weeks, the patient switches to a 14-mg patch, and then, two to four weeks later, to the final 7-mg patch. ProStep (marketed by Lederle Labs) is also worn around the clock. It comes in two dosage levels, 22 mg and 11 mg. Nicotrol (manufactured by Parke-Davis), the most recently approved patch, is worn only while awake. It comes in dosages of 15 mg, 10 mg, and 5 mg.

Which patch and dosage is best for any particular individual is a medical decision made by a doctor, taking into account the patient's smoking level and lifestyle and other needs. For example, a person who smokes less than a pack a day probably would not be told to use a patch supplying a higher level of nicotine, such as that delivered by patches supplying one-pack equivalent dosage.

All patches deliver nicotine through the skin and prevent withdrawal symptoms from stopping smoking, but the specific design of each patch and a patient's skin type determines how fast the nicotine enters the body. Glover explains that some patches deliver nicotine rapidly into the skin, from which it enters the bloodstream, whereas other patches control the release from the device itself.

Says Michael Eriksen, director of the national Centers for Disease Control 's Office on Smoking and Health in Atlanta, "A nicotine patch is not a magic bullet. It doesn't make you quit--it just replaces the nicotine after a smoker quits. You have to be motivated on your own and then the patch is helpful."

Quit Rates

A typical short-term "quit rate" for 2mg nicotine gum in well-planned studies in smoking-cessation clinics is 30 to 50 percent of participants. Research is ongoing to determine if rates improve with the 4-mg dosage gum.

To see how the gum was being used-and to determine its success outside the research setting--a team led by Richard E. Johnson, Ph.D., at the Center for Health Research in Portland, Ore., evaluated 2mg gum use by 612 smokers over an 18 month period at a health maintenance
organization. The results, published in the January 1992 Journal of Family Practice, showed that many patients chewed sporadically,
claiming, "I use the gum in situations where smoking is prohibited" or "when I have cravings." Only 1 in 20 gum chewers also had behavioral therapy to stop smoking. This emphasizes the importance of doctors taking time to fully explain the correct use of the nicotine substitution products and of patients asking their physicians questions, if in doubt about correct use.

Quit rates with the transdermal nicotine patch began making headlines when a report in the Dec. 11, 1991, Journal of the American Medical Association discussed findings in nine smoking-cessation clinics across the United States. Three doses of nicotine (21 mg, 14 mg, and a placebo delivering less than 1 mg) in 24-hour patches were compared in a double-blind fashion (neither the patients nor the researchers knew which dosage patients received). Altogether, 756 smokers wore the patches for six weeks, and those who were successful were weaned through decreasing doses during a second six weeks.

The higher the dose of nicotine, the higher the percentage of patients who quit smoking completely in three to six weeks. Sixty-one percent given 21-mg patches, 48 percent of those given 14-mg patches, and 27 percent of those on placebo quit. Counseling consisted of weekly 45- to 60- minute group sessions, including a two minute review of individual progress and discussions of behavior modification techniques. Patients kept a daily diary to record cigarette use, and weekly clinic visits assessed their progress.

The nine-center transdermal nicotine patch study group concluded, "All transdermal nicotine doses significantly decreased the severity of nicotine withdrawal symptoms and significantly reduced cigarette use by patients who did not stop smoking. Compliance was excellent, and no serious systemic adverse effects were reported."

Success rates vary from clinic to clinic and study to study because the programs and patients differ. "The patch helps those people who are the most nicotine dependent-those who have tried to quit in the past, but found withdrawal to be so severe that they had to go back," says CDC's Eriksen. By the same token, it may be less effective for low nicotine-dependent smokers.

A nicotine-dependence scale developed by Karl-Olov Fagerstrom, Ph.D., a clinical psychologist at the Smoking Withdrawal Clinic at Ulleraker Hospital in Uppsala, Sweden, can help determine whether a particular smoker has a high or low nicotine dependency, and is used in many smoking studies. "The Fagerstrom scale is a simple set of questions. The hallmark question is, do you have a cigarette in the morning within the first 30 minutes of rising? If yes, you're pretty dependent," says Eriksen. Another telling sign is if a person smokes when sick in bed. Other common characteristics of the nicotine-dependent smoker include inhaling, smoking many cigarettes a day, and preferring a highnicotine brand.

Smoking's Not Smart

The more educated Americans are, the less likely they are to smoke. In 1974, 27.5 percent of college-educated Americans smoked, but in 1990 that figure had declined by nearly half to 14.1 percent. During the same period, among people who hadn't finished high school, smokers dropped only from 43.8 percent to 36.7 percent. This information comes from interviews with 120,000 persons in 55,000 households. (Source: PHS annual report, Health, United States, 1991)

Possible Problems

In addition to effects resembling first smoking experiences when the gum is chewed too fast, as previously discussed, side effects of nicotine chewing gum can include mouth sores, headaches, heart palpitations, and excess saliva. These are most likely to occur during the first few days of use. Less common but more serious side effects have been reported, and these risks should be discussed with a doctor before taking Nicorette.

With the nicotine patch, the most common side effect is skin irritation. In about 14 percent of users, the area where the patch is applied (a hairless, clean dry spot on the upper pan of the body) becomes irritated (red and itchy) in the first few hours after application. But allergic reaction to the patch is rare--many of these people who initially experience itching simply try again in a different spot and are fine. In some clinical trials, 35 percent of patients had short-term itching or burning and 6 percent dropped out due to skin reactions. To help prevent skin irritation, directions advise against using the same spot twice within a week.

The physician labeling for the nicotine patch includes the precaution that patients should be urged to stop smoking completely when using the patch, and be told that if they continue to smoke they may experience adverse effects due to peak nicotine levels being higher than those from smoking alone. The labeling says that if there is a significant increase in cardiovascular or other side effects. treatment with the patch should be reduced or discontinued.

Signs of nicotine overdose include headache. dizziness. abdominal pain, drooling, nausea, vomiting, diarrhea, cold sweat, blurred vision, difficulty hearing, mental confusion, weakness, and fainting. Symptoms of severe overdose include tremor, respiratory failure, low blood pressure, and prostration.

Since the marketing of the first two nicotine patches in December 1991. FDA has received reports of patients suffering heart attacks while using nicotine patches. including five from Sturdy Memorial Hospital in Attleboro, Mass. Most had continued to smoke while using the patc, and most had preexisting heart disease. The possibility of excess nicotine aggravating heart disease has been pointed out by many researchers, and patch labels advise users to inform the doctor if there is a history of heart attack, irregular heartbeat, heart pain (angina pectoris). or high blood pressure. An FDA advisory committee considered the information available on the possible relationship between nicotine patch use and heart attacks last July 14 and found the data did not show an increased risk of heart attack with patch use. The committee, therefore, did not recommend any change in labeling.

Nicotine gums and patches should be kept out of the reach of children and pets. If eaten, the patch can cause severe nausea and vomiting, and can be fatal. Swallowing a piece of the gum usually causes no symptoms in persons for whom it has been prescribed, but if a child chews or swallows one or more pieces, a doctor or poison control center should be contacted.

Cigarette smoking during pregnancy can cause miscarriage or low birth weight, and animal studies show that nicotine alone can harm a fetus. Therefore, although quitting smoking by behavioral methods is encouraged, neither nicotine chewing gum nor transdermal nicotine
patches are advised for use during pregnancy.

However, scientists are considering whether continuing to smoke during pregnancy poses more risks than using nicotine therapy products. In addition to nicotine. cigarette smoking exposes the fetus to other risks, including doses of thousands of other chemicals such as carbon monoxide, which robs the fetus of oxygen.

At least 5 million smokers have tried the patch, and about 2 million smokers a year have tried the gum. Health-care providers, organizations, family members, and smokers themselves are all hoping that these medications will help more people kick nicotine for good and lead longer, healthier lives.

Ricki Lewis is a geneticist and the author of a college biology text. Judith Levine Willis, editor of FDA Consumer, also contributed to this article.

We hope you found this reprint from FDA Consumer magazine useful and informative. FDA Consumer, the magazine of the U.S. Food and Drug Administration, provides a wealth of information on FDA-related health issues: food safety, nutrition, drugs, medical devices, cosmetics, radiation protection, vaccines, blood products, and veterinary medicine. For a sample copy of FDA Consumer and a subscription order form, write to: Food and Drug Administration. HFI-40, Rockville, MD 20857.

* U.S. GOVERNMENT PRINTING OFFICE 1994

A REPRINT FROM FDA CONSUMER MAGAZINE

This reprint contains originally revisions made in May 1994.

This Article originally appeared in the December 1992 FDA Consumer.

PUBLICATION NO. (FDA) 94-3203