Rethinking Stop-SmokingMedications:
myths and facts
Ontario Medical Association, June 1999

The OMA wishes to express its gratitude to the many individuals and representatives of groups for their valued comments during the development of this position paper, notably:

• OMA Committees and Clinical Sections
• Outside reviewers including clinical, research, and policy experts in smoking cessation and tobacco control in Canada and the United States.

Please Note:
This paper may be reproduced providing authorship is acknowledged

As with other drug dependencies, tobacco dependence is a progressive, chronic, relapsing disorder.¹ Unlike other drug dependencies, however, tobacco dependence is normalized in society. Survey data indicate that almost 6.8 million Canadians aged 15+ smoke (29 percent of the 15+ population), and that the vast majority (86 percent of all smokers) smoke on a daily basis.²

Tobacco dependence can be treated successfully,³ and sustained tobacco abstinence has numerous and significant health benefits.⁴ Physicians, particularly family physicians, are in the best position to assist smokers in making these health gains, and counselling smokers to quit is recommended during periodic health examinations.⁵ Clinicians can choose from a number of strategies to help patients achieve tobacco abstinence. A discussion of these strategies is beyond the scope of this paper. Rather, the reader is encouraged to consult published clinical US⁶,⁷ and UK⁸ guidelines for helping patients quit smoking. These are based on thorough reviews of the literature and expert opinions of advisory panels.

This paper will address one important and frequently misunderstood component of treating tobacco dependence: the use of stop-smoking medications.

Nicotine replacement therapies and bupropion hydrochloride are two effective stop-smoking medications which have been approved by Health Canada. Ideally, use of these medications should be accompanied by counselling, which some drug manufacturers provide by means of a toll-free line. Nicotine replacement therapy (NRT) is considered a cornerstone in clinical guidelines for smoking cessation in the US^6,7 and the UK⁸. NRT makes it easier to avoid smoking by replacing some (but not all) of the nicotine obtained from tobacco.⁹ Thus, it reduces withdrawal symptoms (e.g. cravings) from tobacco abstinence by supplying nicotine in a safe manner, without the harmful constituents contained in tobacco smoke. NRT is available in Canada in the form of nicotine gum and nicotine patches. Other forms of NRT (such as the nicotine inhaler and nicotine nasal spray) are available in the US. As of April 23, 1999, nicotine gum and patch are available over-the-counter in Ontario.

Bupropion hydrochloride, also marketed as an antidepressant, was approved for use as a stop-smoking medication by Health Canada in 1998 in the form of a sustained-release (SR) tablet. Bupropion SR is the first government-approved, non-nicotine-based medication for quitting smoking. It is also the only government-approved stop-smoking aid available in pill form. Because it is a new stop-smoking medication in Canada and the US, it has not been included in previous clinical guidelines on quitting smoking. However, bupropion has recently been positioned along with NRT as first-line therapy for treating tobacco dependence.¹⁰ Bupropion's efficacy does not appear to be due to its antidepressant effects.¹¹ The exact mechanism by which bupropion works is not known, but it is presumed to alleviate cravings associated with nicotine deprivation by affecting noradrenaline and dopamine, two chemicals in the brain that may be key components of the nicotine addiction pathway.¹¹ Bupropion should not be used for patients with seizure disorders, or those with a current or prior diagnosis of bulimia or anorexia nervosa.¹² Furthermore, it should not be used in patients treated with other medications that contain bupropion, or in individuals concurrently receiving monoamine oxidase inhibitors. The risk of seizures associated with bupropion use, although low, increases with higher doses of bupropion.¹²

Unfortunately, for a number of reasons, stop-smoking medications have had little uptake among smokers. The vast majority of smokers attempt to quit smoking on their own,¹³ even though unaided quitting has very high failure rates compared to other strategies.¹⁴ In Canada, no method of quitting other than "cold turkey" was used by more than 2 percent of former smokers. (Other methods included nicotine gum or the patch, but not bupropion as it was not available at the time of the survey).¹⁵

Medications are likely to play a more central role in the future treatment of tobacco dependence as smokers appear to become more highly dependent.^16,17 Across Canada, almost 25 percent of daily smokers aged 15+ said they smoke their first cigarette within 5 minutes of waking² (part of a measure indicating very high nicotine dependence¹⁸) and 60 percent within 30 minutes of waking. When asked, without prompting, what would make them quit, 17 percent of smokers in Canada said that nothing, or only their own death, would make them quit.¹⁹

The OMA would like to help smokers, especially highly dependent smokers, overcome their tobacco dependence, and believes that increasing the use of NRT and bupropion will assist in achieving this goal. This paper will address common misconceptions regarding stop-smoking medications, particularly NRT, as there is a great need for clarification in this area.

Recommendations in this paper broaden the therapeutic potential of NRT and bupropion. They also call for regulatory and policy changes to increase recognition of, and access to, these stop-smoking medications. Included are recommended changes to Health Canada's labelling requirements for NRT products, which are based on evidence (mainly from drug manufacturers) available at the time of review, as well as changes to the regulatory status of nicotine gum and patches in Ontario.

This position paper is based on up-to-date scientific and clinical evidence and experience. Its development is consistent with the OMA's role in contributing to community programs and policies aimed at the prevention of tobacco use and treatment of tobacco dependence over the past 30 years.

Myth #1:

Nicotine is the harmful substance in cigarettes. Fact: It is not nicotine, but the thousands of toxins present in tobacco and its combustion products, that are responsible for the vast majority of tobacco-caused disease.

Cigarettes are a well-known cause of cancer, chronic respiratory illnesses, and heart disease.²⁰ There are over 4,000 compounds in tobacco and tobacco smoke and over 40 of these substances including benzopyrene, nitrosamines, vinyl chloride, arsenic, chromium, and nickel are known to be cancer-causing.²⁰ Nicotine has long been believed to be one of the major toxins that contributes to tobacco-caused disease. However, it is the myriad of other toxins in cigarette smoke that is responsible for the majority of these harmful effects.²¹ Nicotine has not been shown to cause cancer.²¹ It is not implicated in the development of chronic respiratory disorders due to smoking. Heart disease caused by smoking is largely due to tobacco combustion products, not nicotine.²¹ It is the delivery system, not the drug, which is responsible for the vast majority of tobacco-caused disease.
 
 

Myth #2:

Nicotine's addictive potential is the same regardless of whether nicotine is obtained through nicotine gum, the patch, or cigarettes.

Fact:

Cigarettes are far more addictive than nicotine gum or the patch primarily because of the way in which they deliver nicotine.

Nicotine can be a highly addictive drug, as addictive as heroin or cocaine.³ Its addictive potential differs primarily by the rate and route of nicotine dosing.²² Inhalation of nicotine through cigarettes is the most addictive method of nicotine delivery.²² Because nicotine from cigarettes is absorbed through the lungs, it takes only 10-19 seconds for the drug to reach the brain; faster than an intravenous injection of nicotine.²² Nicotine levels in the blood reach a peak within seconds then decline rapidly, and this pattern is repeated and reinforced with every inhalation. The quick delivery of nicotine to the brain results in a faster and more intense response which leads to addiction.²³

Currently available nicotine replacement products, although so-named, do not actually "replace" all of the nicotine that is obtained from cigarettes.⁹ These products do not produce the high nicotine levels in the blood obtained from cigarette smoking. The patch delivers nicotine through the skin much more slowly, in lower doses, and more evenly than cigarettes.²³ With the patch, nicotine levels in the blood rise over hours, which results in a very slow onset of effects.²⁴ Because of the rate and route of drug delivery, the nicotine patch has almost no addictive potential.²⁴

Chewing releases nicotine from the gum and it is absorbed through the mucous membranes into the bloodstream over 20-30 minutes.²³ Nicotine is absorbed more rapidly from the gum than from the patch, but much more slowly than from cigarettes. Because of the rate and route of drug delivery, nicotine gum has little addictive potential.²⁴

The behavioural aspect of drug administration is also an important factor associated with addiction. With cigarette smoking, it is very easy for a user to reinforce his/her tobacco addiction. Assuming 10 puffs per cigarette, a pack-a-day smoker can repeat the regular "hand-to-mouth" motion 250 times a day, or over 90,000 times a year.²⁵ The smoker is also able to self-titrate the nicotine dose on a puff-by-puff basis to meet his/her needs. By inhaling more deeply or at a faster rate, or by blocking filter holes in the cigarette (that are present to dilute the inhaled substances with air), the smoker is able to increase the amount of nicotine that is obtained through the cigarette.²² Use of nicotine gum, on the other hand, has some behavioural reinforcing effects (chewing is required to release the nicotine), but far fewer than those of cigarette smoking.²³ Use of the nicotine patch involves little or no behavioural component, as it need only be applied and left on the skin.²³

The cigarette has become a highly engineered and carefully designed nicotine delivery system. It is far more addictive than nicotine gum and the patch. Essentially, the cigarette does for nicotine what crack does for cocaine: it makes a highly addictive form of the drug more readily available and convenient to repeatedly self-administer, resulting in higher rates of morbidity and mortality.¹
 

Myth #3:

Nicotine replacement therapy is hazardous for smokers.

Fact:

Nicotine replacement therapy is safe for smokers.

NRT provides nicotine to the smoker without the dangerous toxins that are present in cigarettes and cigarette smoke. These toxins, not nicotine, are responsible for the vast majority of smoking-caused disease. NRT is considered a "clean" nicotine delivery system and is safe for smokers. Major adverse effects from using nicotine gum or the nicotine patch are very rare.²⁶ In addition, the nicotine gum and patch have little or no addictive potential, whereas cigarettes are the most addictive and toxic form of nicotine delivery. As a general rule, nicotine administered as a medication is safer than nicotine obtained by cigarette smoking.²⁷
 

Myth #4:

Smoking while on the patch increases the risk of a heart attack.

Fact:

Use of NRT while smoking does not increase the smoker's cardiovascular risk.

Smokers are already at high risk for cardiovascular events. Smoking causes serious cardiovascular effects such as atherosclerosis, acute myocardial infarction, stroke, and sudden death.²⁰ These health hazards are caused primarily by cigarette combustion components, not nicotine.²¹ Nicotine affects the cardiovascular system by acting as a stimulant, e.g. by increasing heart rate and heart contractility.²⁸ These effects do not increase with higher nicotine intake, which may occur when nicotine is obtained from two sources at once, such as smoking while using NRT.²⁹ Thus, the cardiovascular risk of smoking while using NRT does not appear to be greater than the risk from smoking alone.²⁹

A widespread misconception exists among physicians and the public that smoking while using the nicotine patch poses additional dangers to a smoker's cardiovascular system. This myth likely originated from 6 highly publicized case reports in the media in 1992 about individuals who had suffered heart attacks while smoking and using the patch.³⁰ A subsequent investigation found no evidence of increased toxicity among smokers using the patch.³¹

The Lung Health Study, the largest study on the safety of NRT, and the only study to date investigating long-term NRT use (up to 5 years), found no statistical increase of cardiovascular risk among those who used tobacco and NRT together.³² In another study, smokers on high-dose patch therapy (up to 63 mg/24 hr nicotine patches) did not experience any short-term adverse effects on their cardiovascular system.³³

Health Canada's labelling requirements do not permit the use of NRT and tobacco products together. Since this warning perpetuates the widespread myth that smoking while using NRT is dangerous, a clearer message should be communicated to consumers. In fact, for some people, reduced smoking while using NRT has been a successful antecedent to abstinence, and it is a pathway that may be more achievable for some individuals than an abrupt transition (see Myth #13).
 

Recommendation #1: Health Canada should change its labelling requirements regarding smoking while using NRT to reflect current evidence-based knowledge. Smoking while using NRT should not be prohibited.

Myth #5:

Patients with heart disease should not use the nicotine patch or gum.

Fact:

It is more dangerous for patients with heart disease to continue to smoke than to use NRT. Given the seriousness of their medical condition, cardiac patients who cannot quit should be among those first considered for NRT.

It is extremely dangerous for patients with heart disease to continue to smoke. Smoking causes the activation of coagulation pathways and the promotion of thrombosis, which can cause heart attacks.³⁴ A cardiac patient who smokes also exposes himself/herself to significant heart toxins such as carbon monoxide and oxidant gases which reduce oxygen delivery to the heart.³⁴ As mentioned earlier, tobacco-caused heart disease is caused primarily by toxins other than nicotine. However, nicotine may aggravate cardiovascular disease though its stimulant effects.³⁴

Nonetheless, studies consistently show that the nicotine patch is safe among patients with cardiovascular disease.³¹,³⁵ Cardiac patients who used the nicotine patch were not found to have greater rates of death, heart attacks, or cardiac-related hospitalizations compared to those who did not use NRT.³⁶ NRT should be considered for cardiac patients who cannot quit; however, NRT dosage should be closely monitored by the physician.

Bupropion SR is not prohibited for patients with heart disease,¹² but there is no clinical experience with bupropion among patients with a recent history of heart attack or unstable heart disease.¹² The use of bupropion in this population should be based upon an assessment of the potential risks and benefits of treatment during consultation between an individual patient and his/her physician.
 

Recommendation #2: NRT should be made available to cardiac patients who cannot quit. The physician should closely monitor nicotine dosage. Recommendation #3: As with other drugs, NRT dosage should be modified to suit the smoker's needs.

Myth #6:

Pregnant women should not use nicotine gum or the patch.

Fact:

The nicotine patch and gum are safer than smoking for the pregnant woman and her fetus. 58 percent of female smokers continue to smoke during pregnancy. Pregnant women who cannot quit should be considered for NRT.

The risks of cigarette smoking during pregnancy are well-known: cigarettes substantially increase the risk of spontaneous abortion, prematurity, low birthweight, and perinatal mortality, and these hazards increase with higher cigarette consumption.³⁷ The mechanisms behind these effects are not clear, however, nicotine is suspected to cause some of these effects through its reduction in uterine blood flow.³⁸ There is no safe dose of nicotine during pregnancy³⁸ and ideally, pregnant women should be both tobacco-free and nicotine-free. This is especially important during the third trimester, when the fetus responds most adversely to nicotine administration.³⁸

Unfortunately, most female smokers continue to smoke during pregnancy,³⁹ although they may reduce their daily cigarette consumption. 58 percent of female smokers in Canada report smoking during their most recent pregnancy⁴⁰ even though pregnancy has been cited as one of the top three motivators to quit among women.⁴⁰ Furthermore, among women who quit upon learning of their pregnancy, an estimated 21-35 percent relapse before the end of their term.³⁹

Physicians face a serious ethical dilemma when treating pregnant women who smoke. NRT, although potentially harmful to the fetus, is far safer than cigarette smoking, which exposes the woman and her fetus to a myriad of dangerous toxins and more dangerous levels of nicotine. Most importantly, NRT may help pregnant women stop smoking altogether and reap the substantial health benefits of tobacco abstinence that arise from quitting any time during pregnancy.⁴ Health Canada does not approve of the use of NRT among pregnant women. However, the OMA recommends that NRT should be considered for pregnant women who are unable to quit using non-pharmacologic means. Physicians must inform pregnant women of the risks and benefits of NRT in relation to cigarette smoking. As with all drugs used by pregnant women, NRT use during pregnancy should be closely monitored by the physician.

Bupropion SR is not prohibited in pregnant women.¹² There is no evidence of fetal or reproductive harm due to bupropion;¹² however, bupropion has not been studied in this population.¹² The use of bupropion among pregnant women should be based upon an assessment of the potential risks and benefits of treatment during consultation between an individual patient and her physician.

It is also important to note that exposure of the pregnant mother to second-hand smoke causes low birthweight and sudden infant death syndrome, and may cause spontaneous abortion, as well as have an adverse impact on fetal cognition and behaviour.⁴¹ Partners who smoke should not smoke around pregnant women; they should be encouraged to quit, and consider using NRT or bupropion.
 

Recommendation #4: NRT should be made available to pregnant women who are unable to quit using non-pharmacologic methods. Physicians should closely monitor nicotine dosage. As with other drugs, NRT dosage should be matched to suit the smoker's needs. Recommendation #5: Health Canada's labelling requirements should be modified to include consideration of NRT use among pregnant women. Recommendation #6: Partners who smoke should not smoke around pregnant women; they should be encouraged to quit, and should also consider using NRT or bupropion.

Myth #7:

Smokers under 18 should not use NRT.

Fact:

Most daily smokers begin smoking before age 18. The nicotine patch and gum are far safer than smoking. NRT should be considered for all smokers who need NRT to quit, including those under 18.

Cigarette smoking is an addictive behaviour that is most likely to become established during adolescence.⁴² The developmental process from initiation of cigarette smoking to addiction is estimated to take only 3 years, although this may vary among individuals.⁴² In Ontario, almost two-thirds of daily smokers report smoking daily before age 18, 8 percent before age 13.⁴³ It is not surprising, then, that many adolescent smokers are already addicted to nicotine and report suffering withdrawal symptoms similar to those reported by adult smokers.⁴²,⁴⁴ In one study, over half of youth smokers in Ontario had attempted to quit smoking in the past year.⁴⁵ Over 40 percent of these youth were not able to remain abstinent for longer than a week, and almost 60 percent of the youth who had attempted to quit reported that quitting was very or fairly difficult for them.⁴⁵

There is no evidence that nicotine replacement is harmful to children and adolescents,⁶ yet Health Canada recommends NRT not be used among individuals under 18. Children and adolescents who need NRT to quit should not be denied this treatment. NRT provides them with a safer delivery form of nicotine than cigarette smoking, helps them control their withdrawal symptoms, and most importantly, may help them quit. Clinical guidelines on smoking cessation in the US⁶ and the UK⁸ indicate that youth are a legitimate population in which to consider NRT. A recent trial concluded that the nicotine patch is a safe component to a smoking cessation program for youth.⁴⁶

Bupropion SR is not prohibited in individuals under age 18.¹² However, the safety and efficacy of bupropion have not been established for children and youth.¹² The use of bupropion among smokers under 18 should be based upon an assessment of the potential risks and benefits of treatment during consultation between an individual patient and his/her physician.
 

Recommendation #7: NRT should be made available for smokers under 18 who want to quit. As with other drugs, NRT dosage should be modified to suit the smoker's needs. Recommendation #8: Health Canada's labelling requirements should not prohibit the use of NRT among smokers under 18.

Myth #8:

Stop-smoking medications are not effective in helping people quit.

Fact:

NRT and bupropion are effective, government-approved medications available to help smokers. NRT and bupropion have each been found to approximately double quitting rates compared to placebo.

NRT and bupropion are the two effective, government-approved medications that are available to treat tobacco dependence. Both can help alleviate withdrawal symptoms resulting from nicotine deprivation. Smoking cessation guidelines in the US indicate that pharmacotherapy should be considered in all initial discussions.¹⁰ Nicotine patch therapy approximately doubles 6 to 12 month abstinence rates compared to placebo.⁶ Nicotine gum improves quit rates by approximately 40-60 percent over 12 months of follow-up.⁶ With over 50 published studies on its effectiveness, nicotine gum is by far the most extensively studied pharmacologic treatment for smoking cessation.⁶ NRT has been shown to be effective independent of the intensity of additional support provided or the setting in which NRT was offered;⁴⁷ however, it works best when combined with counselling.⁶ Bupropion has also been shown to double quit rates over 12 months,⁴⁸ however it has not been assessed in a wide variety of clinical contexts (e.g. from minimal to high intensity counselling).
 
 

Myth #9:

The nicotine patch and gum should not be used at the same time and/or in combination with bupropion.

Fact:

The nicotine patch and gum may be used at the same time and/or in combination with bupropion.

Combining nicotine gum with patch therapy has been found to provide superior quit rates than the gum or patch alone, without an increase in adverse effects.^7,10 For some people, this dual therapy is better than nicotine gum or the patch alone at reducing nicotine withdrawal symptoms.⁴⁹ The combined use of gum and the patch is a convenient therapeutic option as it gives the user a steady intake of nicotine (with the patch) that can be supplemented with nicotine gum to respond to momentary smoking urges.⁹ Use of the gum with the patch has been recommended in clinical guidelines on smoking cessation in the US,⁷ and in a 1999 update of the pharmacotherapy of smoking by a group of prominent US smoking cessation experts.¹⁰ Despite the acceptance of this form of treatment, Health Canada does not approve of using nicotine gum and the patch together.

NRT can be used with bupropion,¹² but Health Canada's labelling requirements on NRT products do not reflect that this combination is permitted. For some people, combined use of bupropion with NRT may be an effective strategy,⁵⁰ particularly if single therapy is inadequate. Patients using this combination should be closely monitored by their physicians for treatment emergent hypertension.¹²

Various combinations of stop-smoking medications have been presented: nicotine gum alone, nicotine patch alone, nicotine gum and patch, bupropion alone, or bupropion with NRT. As patient beliefs are strongly associated with the efficacy of therapy, patient preference should be the primary basis for treatment choice.¹⁰
 

Recommendation #9: Smokers should be encouraged to consider use of the gum and patch concurrently, in combination with bupropion as needed, to control their withdrawal symptoms.   Recommendation #10: Health Canada's labelling requirements on NRT products should be modified to include consideration of dual NRT use or NRT with bupropion if single medication therapy is not adequate.

Myth #10:

NRT should only be taken in recommended doses.

Fact:

Smokers should be in control of how they use NRT and should vary the dose according to their own needs. Like smoking, it takes time to learn how best to use NRT in a manner that maximizes its benefits.

Smokers develop a pattern of behaviour that provides them with pleasurable effects, as well as relief from withdrawal symptoms. Cigarette smoking is a very easy and effective means of achieving both of these, and the smoker has learned over time to do this with finesse and flexibility.

Without cigarettes, a smoker may suffer withdrawal symptoms such as depressed mood, irritability, difficulty concentrating, and anxiety.⁵¹ At times, these withdrawal symptoms can be quite severe and extremely difficult to manage. Thus, the treatment should be flexible enough to put more control in the hands of the smoker in order for the medications to suit his/her needs. NRT dosage, as outlined in the labelling, are only guidelines, and should be individualized. Like smoking, it takes time to learn to use NRT in a manner that maximizes its benefits.
 

Recommendation #11: Smokers should be encouraged to individualize their NRT dosage to meet their nicotine needs.

Myth #11:

Enforced smoking abstinence during hospitalization often results in quitting.

Fact:

Enforced smoking abstinence during hospitalization is unlikely to result in quitting. Smokers should be routinely offered stop-smoking medications prior to or during their hospital stay.

For smokers, abstinence from smoking is stressful in its own right. Hospitalization, regardless of the reason, induces a high level of anxiety and stress in both smokers and non-smokers alike. The combination of the two factors compounds stress on the hospitalized smoker. This may lead the smoker to reach for cigarettes at the first available opportunity. Smoke-free ordinances in hospitals are necessary as they work in the best interests of all patients. However, enforced smoking abstinence without the provision of additional assistance does not appropriately serve the health care needs of tobacco-dependent patients.

Smoking cessation guidelines in the US recommend that all hospitalized smokers should be provided assistance with their tobacco dependence.⁶ This may include the use of NRT,⁶ which has been shown to be safe among inpatients with a wide range of diagnoses.⁵² Hospitalization presents a unique opportunity for smokers to learn how to alleviate their withdrawal symptoms during their stay and beyond discharge. It is a time when smokers have increased contact with health professionals who can provide detailed and personalized advice on abstaining from tobacco.⁵² For already hospitalized smokers, the nicotine patch may be especially suitable because of its ease of application and dosing schedule.⁵² For smokers who know of their hospitalization in advance, the family physician should offer assistance in gaining the skills to abstain from tobacco. This may include NRT.

Bupropion may also be used to help hospitalized smokers cope; however, because it takes about one week to achieve effective levels of bupropion in the blood,¹² the earlier bupropion is administered before hospital admission, the more likely it is to be effective.
 

Recommendation #12: Hospitals should include NRT in their drug formularies.   Recommendation #13: The most responsible physician should routinely offer NRT to hospitalized patients who smoke.   Recommendation #14: When smokers know of their hospitalization in advance, family physicians should offer these patients assistance in gaining skills to abstain from tobacco. This may be in the form of NRT and/or include bupropion. Because of the nature of the drug, however, bupropion therapy is best initiated as early as possible prior to hospital admission.

 

Myth #12:

Use of the nicotine patch and gum should not exceed 3 months.

Fact:

The nicotine patch and gum should be used as long as needed to maintain or prolong tobacco abstinence.

Long-term use of NRT has been reported in studies and in clinical observations.⁵³ This appears to be a strategy to maintain or prolong tobacco abstinence, not a sign of dependence.⁵³ The safety of long-term use of nicotine gum has been demonstrated in the Lung Health Study.³² This investigation found no evidence of adverse effects with extended nicotine gum use, based on the experience of over 3,000 users over a period of up to 5 years. In addition, no association between adverse events and prolonged use of the gum and patch has been found, based on postmarket surveillance of these drug products.⁵⁴

Health Canada does not endorse long-term use of NRT and requires manufacturers to indicate that these products are short-term aids to quitting smoking. However, long-term use of these nicotine medications is far preferable to long-term tobacco use. Use of these safer alternative nicotine delivery systems can be part of a long-term harm reduction strategy.⁵⁵
 

Recommendation #15: Smokers should be encouraged to use nicotine gum and the patch for as long as needed to maintain or prolong tobacco abstinence.   Recommendation #16: Health Canada's labelling requirements should be modified to permit long-term use of nicotine gum or the patch if needed.

Myth #13:

Nicotine gum or the patch should only be used to quit smoking.

Fact:

Nicotine gum or the patch can be used by people who are not yet ready or able to quit as, for some individuals, being tobacco-free is not a foreseeable goal. NRT may help these smokers take a "cigarette holiday" or, in some cases, substantially reduce their smoking as an interim, achievable step toward tobacco abstinence.

For some smokers, abstinence from tobacco is not a foreseeable goal.¹⁹ These smokers may not be able to imagine being without cigarettes for a day, or even a few hours. NRT may be useful for these individuals who are not yet ready, or able, to quit by helping them abstain from cigarettes for a short period of time, even during a day at work or during a long plane trip. This "cigarette holiday" may introduce the option of eventually becoming tobacco-free. Individuals who use this strategy should attempt to gradually extend the duration of these cigarette-free periods.

There is no safe level of smoking. The risks of smoking-caused diseases such as cancers, chronic respiratory diseases, and cardiovascular disease increase with higher cigarette consumption.⁵⁶ Therefore, theoretically, smokers can reduce their tobacco-related health risks by substantially reducing their cigarette consumption. But this may not always lead to a reduction in exposure to tobacco toxins since smokers can change their smoking behaviour (e.g. take deeper or longer puffs) in order to proportionately obtain more nicotine from each cigarette.⁵⁷ Since this compensatory response to reduced smoking appears to be driven by nicotine needs, NRT may help smokers reduce their tobacco consumption while minimizing compensation behaviour.¹⁴ Studies have shown that NRT can help reduce smoking consumption among smokers not deliberately trying to cut down.^58,59 In one study, smokers using NRT were able to reduce their smoking by over 50 percent while still maintaining a perceived comfortable level of smoking.⁵⁹

Evidence from the Lung Health Study shows that the use of long-term NRT while smoking is not more harmful than smoking alone.³² However, encouraging continued smoking even with NRT may reduce smokers' motivation to quit completely.¹⁴ Thus, this strategy may not be appropriate for all smokers, but may be suitable for the highly nicotine-dependent individuals who are not ready or able to quit completely.⁵⁶ Individuals who employ this strategy should, ideally, replace more and more of the tobacco they use with NRT.
 

Recommendation #17: Smokers who cannot imagine being without their cigarettes should try using NRT to take a "cigarette holiday". Over time, these smokers should attempt to gradually extend the duration of these cigarette-free periods.   Recommendation #18: Highly dependent smokers who cannot or will not quit completely should use NRT to help them substantially reduce their cigarette consumption. Over time, these smokers should, ideally, replace more and more of the tobacco they use with NRT.

The nicotine-dependent individual currently has two options for obtaining nicotine: NRT, manufactured by the pharmaceutical industry, or tobacco products, manufactured by the tobacco industry. These nicotine delivery systems, however, are fundamentally different in their effects on tobacco dependence and in their ability to cause harm.⁵⁵ Cigarettes are manufactured and marketed with the intention of sustaining tobacco dependence. The aim of NRT, on the other hand, is to end tobacco dependence. Cigarettes deliver nicotine in a manner that maximizes its addictive potential. Cigarettes are a "dirty" drug delivery system which delivers not only nicotine, but also a myriad of toxins that is responsible for the greatest burden of tobacco-caused disease. NRT delivers nicotine in its pure form in a manner that has low addictive potential. Whereas cigarettes have an established record of death and disease, NRT has an established record of safety and effectiveness.

From a regulatory perspective, NRT products are far more restricted than cigarettes, the most hazardous nicotine delivery system available to consumers. Differences in the regulatory status of nicotine in tobacco products, compared to nicotine in non-tobacco products, lie at the root of this paradox.⁶⁰ Tobacco products are governed by the Tobacco Act⁶¹ and the Tobacco Control Act⁶² at the federal and Ontario levels, respectively. These are regulatory frameworks which presume the products to be legal unless specifically restricted by law.⁶³ NRT products, on the other hand, are governed by the Food and Drugs Act⁶⁴ and the Drug and Pharmacies Regulation Act⁶⁵ at the federal and Ontario levels, respectively. These are regulatory frameworks which assume products to be illegal unless specifically permitted by law.⁶³

Consequently, the legislation which governs tobacco sets fewer restrictions on access to, and development of, tobacco products than does the legislation which governs NRT products. For example, tobacco manufacturers are relatively free to manipulate taste and other sensory characteristics to enhance the appeal and continued use of their products. In contrast, making minor changes to such aspects of NRT products (e.g. to increase their palatability and acceptance among smokers) may require years of testing and regulatory review in order to get approval by Health Canada.

Compared to tobacco products, NRT products are less accessible and less widely available to consumers. This leaves nicotine-dependent individuals at a great disadvantage. These individuals have less access to nicotine products that can help prevent illness, but far greater access to nicotine products that can cause disease.

Cost is another barrier to the access of NRT. Although the unit costs of NRT and cigarettes can be similar, a one-time purchase cost of NRT (about $30 for a week's supply) is much higher than a one-time purchase cost of cigarettes (under $4 for a pack). This larger single expenditure is especially problematic for low-income individuals, who tend to have higher smoking rates and lower quitting rates.⁶⁶ The cost at the consumer level can be reduced in a variety of ways. British Columbia, for example, eliminated the provincial sales tax on NRT products in August 1998.
 

Recommendation #19: The provincial government and the pharmaceutical industry should work to closely match the package quantity and cost of nicotine replacement therapies to the package quantity and cost of tobacco products.

Myth #14:

The nicotine patch and gum should be sold only in pharmacies.

Fact:

In addition to pharmacies, the nicotine patch and gum should be available in all outlets where cigarettes are sold. Every opportunity to obtain cigarettes should be an opportunity to obtain the nicotine patch and gum.

There exists a great disparity in smokers' access to cigarettes compared to nicotine gum and the patch. Cigarettes, the most harmful nicotine delivery system on the market, are available in a wide variety of venues, including gas stations, grocery stores, and some doughnut shops (in Ontario, cigarettes are not permitted for sale in pharmacies). Nicotine gum and the patch, on the other hand, can be obtained only in pharmacies. Until recently, this disparity was even greater for smokers in Ontario. Ontario was the last province in Canada to require a prescription for nicotine gum or the patch. As of April 23, 1999, nicotine gum and the patch are available over-the-counter (OTC) in Ontario. Nicotine gum and the patch are also available without a prescription in over 30 countries around the world, including the US, the UK, and Sweden.

Nicotine gum and the patch are considered appropriate for OTC sales because they are safe, effective, and require minimal instructions for proper use.⁶⁶ Early OTC experience in the US has found no evidence of abuse of these products.⁶⁶ Furthermore, although the provision of counselling with NRT is ideal, NRT's effectiveness is largely independent of the intensity of counselling or the setting in which NRT is offered,⁴⁷ thus making it suitable for OTC sales. Some drug manufacturers provide counselling for consumers by means of a toll-free line and/or through educational materials.

In addition to pharmacies, nicotine gum and patches should be available in all outlets where cigarettes are sold. Smokers should have increased opportunity to obtain a safe form of nicotine that has therapeutic benefits over a nicotine delivery system that causes extensive harm. Smokers should also have the opportunity to replenish their NRT supply "after-hours", e.g., on evenings and weekends, rather than turn to tobacco. An opportunity to obtain cigarettes should be an opportunity to obtain NRT.

It must be noted that the availability of NRT products over-the-counter does not diminish the role of the physician in helping patients quit smoking. Physicians are still in the best position to educate patients on how to quit smoking and to provide ongoing advice and care.
 

Recommendation #20: The Ontario government should make nicotine gum and the patch available not only in pharmacies, but in all outlets where cigarettes are sold.

Myth #15:

It is not cost-effective to cover stop-smoking medications under health insurance plans.

Fact:

The use of stop-smoking medications is a cost-effective strategy. NRT and bupropion should be covered under health insurance plans.

The costs associated with smoking to the health care system and to employers are staggering. In 1991 in Canada, health care costs associated with smoking were estimated to be $2.5 billion and smoking-related costs due to worker absenteeism were estimated to be $2 billion.⁶⁷ On the other hand, strategies to help smokers quit, including the use of stop-smoking medications, have been found to be extremely cost-effective.⁶⁸ Greater spending on such interventions produces greater net benefits.⁶⁸

Currently, bupropion and NRT are not covered by the Ontario Drug Benefit Plan. Coverage of these medications under the provincial health insurance plan is a tremendous opportunity for the government to implement a strategy that makes sense from a fiscal, social, and health point of view.

Bupropion and NRT should also be covered under private health insurance plans. Current coverage of smoking cessation products under such plans varies, as these arrangements are made between the employer and the insurer. For instance, these plans may provide some coverage for prescription products, but not necessarily for OTC products. In addition, reimbursement under these plans may be without restrictions, or limited to a maximum expenditure over a lifetime, or a specific number or duration of courses of therapy. Ideally, reimbursement should be based on the treatment that is needed by the smoker.
 

Recommendation #21: NRT and bupropion should be covered under both public and private health insurance plans. Ideally, reimbursement should be based on the treatment that is needed by the smoker.

This paper is based on the most recent expert opinions, medical experience, and scientific evidence. Currently, access to safe medications is restricted, myths regarding the dangers of these medications are perpetuated, and drug plans do not always cover stop-smoking medications. Regrettably, the smoker is often left with the option that is the cheapest, most readily-available, and most harmful source of nicotine that exists: cigarettes. Clinicians and policy-makers should use this document to help make sound, evidence-based decisions that work in the best interests of smokers and society-at-large. It is time to provide smokers with access to the assistance they need.

2. Health Canada. National Population Health Survey highlights: smoking behaviour of Canadians. Cycle 2, 1996/97. Fact sheet 1.2 : Overview of results. Ottawa (ON): Health Canada; 1999 Jan.

3. U.S. Department of Health and Human Services. The health consequences of smoking: nicotine addiction: a report of the Surgeon General. Rockville (MD): U.S. Dept. of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Health Promotion and Education, Office on Smoking and Health; 1988.

4. U.S. Department of Health and Human Services. The health benefits of smoking cessation: a report of the Surgeon General. Rockville (MD): U.S. Dept. of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 1990.

5. Taylor MC, Dingle JL. Prevention of tobacco-caused disease. In: The Canadian Task Force on the Periodic Health Examination, editor. The Canadian guide to clinical preventive health care. Ottawa (ON): Minister of Supply and Services Canada; 1994. p. 500-511.

6. Fiore MC, Bailey WC, Cohen SJ, Dorfman SF, Goldstein MG, Gritz ER, et al. Smoking cessation: clinical practice guideline number 18. Rockville (MD): U.S. Dept. of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; 1996 April.

7. American Psychiatric Association. Practice guidelines for the treatment of patients with nicotine dependence. Am J Psychiatry 1996 Oct;153(10 Suppl):1-31.

8. Raw M, McNeill A, West R. Smoking cessation guidelines for health professionals: a guide to effective smoking cessation interventions for the health care system. Thorax 1998 Dec;53(Suppl 5 part 1):S1-S19.

9. Henningfield JE. Nicotine medications for smoking cessation. N Engl J Med 1995 Nov 2;333(18):1196-1203.

10. Hughes JR, Goldstein MG, Hurt RD, Shiffman S. Recent advances in the pharmacotherapy of smoking. JAMA 1999 Jan 6;281(1):72-76.

11. Goldstein MG. Bupropion sustained release and smoking cessation. J Clin Psychiatry 1998;59(suppl 4):66-71.

12. Product Monograph of Zyban®, Glaxo Wellcome Inc., Jul 1998.

13. Fiore MC, Novotny TE, Pierce JP, Giovino GA, Hatziandreu EJ, Newcomb PA, et al. Methods used to quit smoking in the United States: do cessation programs help? JAMA 1990 May 23/30;263(20):2760-2765.

14. Shiffman S, Mason KM, Henningfield JE. Tobacco dependence treatments: review and prospectus. Annu Rev Public Health 1998;19:335-358.

15. Health Canada. Survey on Smoking in Canada. Cycle 3. Fact sheet 1. Summary highlights - Nov 1994. Ottawa (ON): Health Canada; 1995 Feb.

16. Hughes JR. The future of smoking cessation therapy in the United States. Addiction 1996 Dec;91(12):1797-1802.

17. Fagerstrom K-O, Kunze M, Schoberberger R, Breslau N, Hughes JR, Hurt RD, et al. Nicotine dependence versus smoking prevalence: comparisons among countries and categories of smokers. Tob Control 1996 Spring;5(1):52-56.

18. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom K-O. The Fagerstrom test for nicotine dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 1991 Sep;86(9):1119-27.

19. Health Canada. Survey on smoking in Canada. Cycle 3. Fact sheet 5. Starting and quitting smoking - Nov 1994. Ottawa (ON): Health Canada; 1995 Feb.

20. U.S. Department of Health and Human Services. Reducing the health consequences of smoking: 25 years of progress: a report of the Surgeon General. Rockville (MD): U.S. Dept. of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion, Office of Smoking and Health; 1989.

21. Benowitz NL. Summary: risks and benefits of nicotine. In: Benowitz NL, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 185-195.

22. Benowitz NL. Nicotine pharmacology and addiction. In: Benowitz NL, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 3-16.

23. Benowitz NL. Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol 1996;36:597-613.

24. Stitzer ML, De Wit H. Abuse liability of nicotine. In: Benowitz NL, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 119-131.

25. Canadian Council on Smoking and Health. Your guide to a smoke-free future. Ottawa (ON): Canadian Council on Smoking and Health; 1996.

26. Hughes JR. Risk-benefit assessment of nicotine preparations in smoking cessation. Drug Saf 1993 Jan;8(1):49-56.

27. Benowitz NL. In: Benowitz NL, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 183.

28. Benowitz NL. The role of nicotine in smoking-related cardiovascular disease. Prev Med 1997;26:412-417.

29. Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol 1997 Jun;29(7):1422-1431.

30. Hwang SL, Waldholz M. Heart attacks reported in patch users still smoking. Wall St J 1992 Jun 19;Sect. B1.

31. Rennard SI, Daughton D, Windle J. Toxicity of nicotine replacement in patients with coronary artery disease. In: Benowitz NL, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 49-53.

32. Murray RP, Daniels K. Long-term nicotine therapy. In: Benowitz NL, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 173-182.

33. Zevin S, Jacob P, Benowitz NL. Dose-related cardiovascular and endocrine effects of transdermal nicotine. Clin Pharmacol Ther 1998 Jul;64(1):87-95.

34. Benowitz NL. Cardiovascular toxicity of nicotine: pharmacokinetic and pharmacodynamic considerations. In: Benowitz NL, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 19-27.

35. Tzivoni D, Keren A, Meyler S, Khoury Z, Lerer T, Brunel P. Cardiovascular safety of transdermal nicotine patches in patients with coronary artery disease who try to quit smoking. Cardiovasc Drugs and Ther 1998 Jul;12(3):239-244.

36. Joseph AM, Norman SM, Ferry LH, Prochazka AV, Westman EC, Steele BG, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996 Dec 12;335(24):1792-1798.

37. Benowitz NL. Nicotine replacement therapy during pregnancy. JAMA 1991 Dec 11;266(22):3174-3177.

38. Oncken CA, Hardardottir H, Smeltzer JS. Human studies of nicotine replacement during pregnancy. In: Benowitz NL, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 107-116.

39. Floyd RL, Rimer BK, Giovino GA, Mullen PS, Sullivan SE. A review of smoking in pregnancy: effects on pregnancy outcomes and cessation efforts. Annu Rev Public Health 1993;14:379-411.

40. Health Canada. Survey on smoking in Canada. Cycle 3. Fact sheet 4. Smoking behaviour of women - Nov 1994. Ottawa (ON): Health Canada; 1995 Feb.

41. California Environmental Protection Agency, Office of Environmental Health Hazard Assessment. Health effects of exposure to environmental tobacco smoke: final report. Sacramento (CA): California Environmental Protection Agency. Office of Environmental Health Hazard Assessment; 1997 Sep.

42. U.S. Department of Health and Human Services. Preventing tobacco use among young people: a report of the Surgeon General. Atlanta (GA): U.S. Dept. of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 1994.

43. Ashley MJ, Cohen J, Bull S, Poland B, Gao J, Stockton L, et al. Smoking in Ontario: analysis of data from the "Q&Q" study. Toronto (ON): Ontario Tobacco Research Unit; 1997 Mar. 31.

44. Rojas NL, Killen JD, Haydel KF, Robinson TN. Nicotine dependence among adolescent smokers. Arch Pediatr Adolesc Med 1998 Feb;152(2):151-156.

45. Adlaf EM, Ivis FJ, Smart RG. Ontario student drug use survey: 1977-1997. Toronto (ON): Addiction Research Foundation; 1997.

46. Smith TA, House RF, Croghan IT, Gauvin TR, Colligan RC, Offord KP, et al. Nicotine patch therapy in adolescent smokers. Pediatrics 1996 Oct;98(4 Pt 1):659-667.

47. Silagy C, Mant D, Fowler G, Lodge M. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet 1994 Jan 15;343(8890):139-142.

48. Hurt RD, Sachs DPL, Glover ED, Offord KP, Johnston JA, Dale LC, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997 Oct 23;337(17):1195-1202.

49. Fagerstrom K-O, Schneider NG, Lunell E. Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology 1993;111(3):271-277.

50. Jorenby DR, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999 Mar 4;340(9):685-691.

51. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington (DC): American Psychiatric Association; 1994.

52. Lewis SF, Piasecki TM, Fiore MC, Anderson JE, Baker TB. Transdermal nicotine replacement for hospitalized patients: a randomized clinical trial. Prev Med 1998 Mar-Apr;27(2):296-303.

53. Hughes JR. Dependence on and abuse of nicotine replacement medications: an update. In: Benowitz N, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 147-157.

54. Spyker DA, Alderfer RJ, Goetsch RA, Longmire AW, Kramer ED. Adverse events and prolonged use of nicotine gum and patch. In: Benowtiz N, editor. Nicotine safety and toxicity. New York (NY): Oxford University Press; 1998. p. 167-172.

55. Warner KE, Slade J, Sweanor DT. The emerging market for long-term nicotine maintenance. JAMA 1997 Oct 1;278(13):1087-1092.

56. Jimenez-Ruiz C, Kunze M, Fagerstrom K-O. Nicotine replacement: a new approach to reducing tobacco-related harm. Eur Respir J 1998 Feb;11(2):473-479.

57. Slade J, Henningfield JE. Tobacco product regulation: context and issues. Food Drug Law J 1998;53(Suppl 1):43-74.

58. Benowitz NL, Zevin S, Jacob P. Suppression of nicotine intake during ad libitum cigarette smoking by high-dose transdermal nicotine. J Pharmaco Exp Ther 1998 Dec;287(3):958-962.

59. Fagerstrom K-O, Tejding R, Westin A, Lunell E. Aiding reduction of smoking with nicotine replacement medications: hope for the recalcitrant smoker? Tob Control 1997 Winter;6(4):311-316.

60. Sweanor DT. The regulation of tobacco and nicotine: the creation, and potential for resolution, of a public health disaster. Drugs: Educ Prev Policy 1998;5(2):135-140.

61. Tobacco Act, S.C. 1997, c.13.

62. Tobacco Control Act, S.O. 1994, c.10.

63. Canadian Council on Smoking and Health, National Clearinghouse on Tobacco and Health. Regulatory options for tobacco control in Canada. Ottawa (ON): Canadian Council on Smoking and Health. National Clearinghouse on Tobacco and Health; 1995 Nov.

64. Food and Drugs Act, R.S.C. 1985, c. F-27.

65. Drugs and Pharmacies Regulation Act, R.S.O. 1990, C.H.4.

66. Shiffman S, Gitchell J, Pinney JM, Burton SL, Kemper KI, Lara EA. Public health benefit of over-the-counter nicotine medications. Tob Control 1997 Winter;6(4):306-310.

67. Kaiserman MJ. The cost of smoking in Canada, 1991. Chronic Dis Can 1997;18(1):13-19.

68. Cromwell J, Bartosch WJ, Fiore MC, Hasselblad V, Baker T. Cost-effectiveness of the clinical practice recommendations in the AHCPR Guideline for Smoking Cessation. JAMA 1997 Dec 3;278(21):1759-1766.