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Potentially Harmful Interactions Between Smoking and Prescription Drugs Just One More Reason Not to Smoke

Nov 1, 2007

Tobacco companies denied for years that cigarettes were dangerous. Today, cigarette packages are required to have warning labels about known dangers of smoking – such as lung cancer, emphysema and heart disease. In the United States, cigarettes have small, unobtrusive warning labels that are often ignored by the smoker. But something never mentioned on cigarette warning labels is that smoking can affect the way a number of medications work, in some cases resulting in significant, dangerous adverse outcomes. Smokers should be aware that a number of medications may not work as well because of smoking cigarettes.

How does smoking interact with medications? In addition to delivering a number of cancer-causing substances (carcinogens) into the body, tobacco smoke contains other chemicals that stimulate certain enzymes in the liver – enzymes that break down drugs to facilitate their elimination from the body. In other words, smoking makes your body clean out, or metabolize, the drugs you take faster than normal. This might sound like a good thing, but overactive enzymes can reduce the blood levels of medications to the point that they do not work.

As discussed in “Drug Interactions 101,” this is an example of a metabolic change called enzyme induction. The chemicals that enter your body when you smoke cigarettes cause certain enzymes to go into overdrive, so that the enzymes are “gobbling up” other medications too quickly. Smoking stimulates these “gobbling” enzymes, and a chronic medication that was working fine (Drug X) stops working because it is being cleared out of the body much more rapidly than before. Sometimes this kind of interaction can be circumvented by increasing the dose of Drug X, but other times the enzyme stimulation is so strong that Drug X just stops working completely. This type of drug interaction usually takes place gradually over a week or two, and even longer in some cases.

Medications Impacted by Smoking


 Ramelteon (ROZEREM)

 Clozapine (CLOZARIL)

 Rasagiline (AZILECT)

 Flutamide (EULEXIN)

 Ropinirole (REQUIP)

 Frovatriptan (FROVA)

 Tacrine (COGNEX)



 Mexiletine (MEXITIL)

 Tizanidine (ZANAFLEX)

 Mirtazapine (REMERON)

 Triamterene (DYRENIUM)

 Olanzapine (ZYPREXA)

 Zolmitriptan (ZOMIG)

What enzyme is affected by smoking? The primary drug-metabolizing enzyme in the body that is affected by smoking has the daunting name of cytochrome P-450 1A2, but we will call it by its nickname, “CYP1A2”. This enzyme is involved in the metabolism of an increasing number of medications, so smoking-drug interactions have become more important in recent years. The table that accompanies this article lists some of the medications and substances that are metabolized by CYP1A2.

All of the drugs listed above are affected by the smoking-induced “gobbling” results. Their levels in the body might be too low because they are being metabolized more rapidly than they are intended to be metabolized.

Do all nicotine products have the same interactions with medications? No. Nicotine products such as patches, gum and inhalers, because they do not contain any of the other multiple chemicals contained in cigarette smoke, do not cause the same drug interactions with the enzyme CYP1A2 and other enzymes as smoking does. This is important, because different drug interactions can occur when people stop smoking and start a nicotine product, or when they quit a nicotine product and resume smoking.

What are the negative outcomes of smoking-drug interactions? The primary unwanted outcome of smoking-drug interactions is lack of effectiveness of the medications listed in the table. For instance, it has been known for decades that patients who smoke cigarettes require considerably higher doses of theophylline to achieve the same blood levels as nonsmokers. Of course, theophylline is used for asthma and other lung diseases, so smoking is a particularly bad idea for such people.

Other medications may also be affected by smoking. For example, a number of patients with schizophrenia treated with clozapine (CLOZARIL) or olanzapine (ZYPREXA) have developed dramatic worsening of their schizophrenia after they stopped nicotine (such as inhalers or patches) and went back to smoking. Again, the smoking decreased the blood levels of clozapine or olanzapine, thus making their schizophrenia worse.

There is also recent evidence suggesting that smokers may experience less of an effect from the anti-cancer drug, irinotecan. In one study, smokers had lower blood levels of irinotecan and less effect on the white blood cell count compared to nonsmokers. Both of these findings are consistent with a decreased anticancer effect of irinotecan in smokers; additional studies should shed light on the clinical importance of these findings.

One would also expect smokers to have reduced effects of other drugs that are metabolized by CYP1A2. Smokers, therefore, should be on the lookout for interactions such as reduced antidepressant effect of mirtazapine (REMERON); reduced anti-Parkinson effect of rasagiline (AZILECT) or ropinirole (REQUIP); decreased effect of ramelteon (ROZEREM) on insomnia; decreased muscle relaxation from tizanidine (ZANAFLEX); and possibly impaired anti-migraine effects of frovatriptan (FROVA) and zolmitriptan (ZOMIG).

Can stopping smoking affect medications? The answer is yes, and for this reason it is important to make sure all of your physicians and other prescribers are aware that you are stopping smoking, particularly if you are taking any of the medications listed in the table. If you are a smoker and have figured out drug dosage levels that work, removing the drug-gobbling chemicals (quitting smoking) will change the way your body gets rid of the drug, and the levels of the medications in your body will rise. For example, severe clozapine or olanzapine toxicity with seizures and other neurological toxicity has been reported in patients who stopped smoking because the blood levels of the drugs increased when the smoking-induced drug gobbling stopped.This can be prevented simply by close monitoring and using stepwise reductions in the clozapine (or any other drug) dose as needed.

But adverse outcomes can be easily prevented with appropriate precautions – so don’t use this as an excuse not to stop smoking! Giving up cigarettes dramatically reduces the risk of life-threatening illnesses such as lung cancer and heart attacks. Also, as the person’s CYP1A2 calms down after stopping smoking, they can reduce doses of medications that are metabolized by CYP1A2, saving money and hassle.

Cigarette smoking can alter the actions of many other medications, and in some cases the effects can be severe. Smokers should be aware that a number of medications may not work as well. You may require a higher dose or even an alternative drug. A time of increased risk occurs when a person stops a nicotine product and resumes smoking, or when a person stops smoking. If you are taking medications, notify your prescriber if you start smoking, stop smoking (either “cold turkey” or with the help of smoking cessation treatments) or substantially change the number of cigarettes you smoke per day.

Tobacco remains the most controversial consumer product ever sold. It is known to causes a multitude of debilitating and even deadly illnesses. It carries several different warnings that should frighten away anyone with common sense. It is a killer, plain and simple.

Nevertheless, the tobacco industry continues to lure new (and mostly young and female) smokers with enticing advertising campaigns (“Joe Camel”), tempting products (flavored cigarettes), and misleading claims (“light” and “low tar” cigarettes).

The amazing thing is that the harmful effects of smoking have yet to be fully defined. Thus, it is not surprising that new dangers associated with tobacco use are being discovered on a regular basis.

Earlier this year (August), a study published in the Lancet revealed that tobacco use of any kind greatly increases the risk of myocardial infarction. This includes not only smoking and exposure to secondhand smoke but also other forms of tobacco use such as chewing tobacco and smokeless tobacco.

The authors of the study, Dr. Koon K. Teo, from McMaster University–Hamilton Health Sciences and his colleagues, revealed that their findings indicated that “tobacco is harmful in any form.”  They also found that there was a significant “dose-response” relationship between the amount of cigarettes smoked on a daily basis and the likelihood of myocardial infarction.  This is even true when the amount smoked is only a couple of cigarettes per day.

The authors of the study estimate that the number of worldwide smokers is currently 1.3 billion people. In the 20th century, 100 million people died as a result of tobacco-related diseases.  This number is expected to increase to a staggering 1 billion in the 21st century, with adults losing an average of 22 years from their life expectancy.

This latest trial involved a case-control study of 15,152 cases of first acute myocardial infarction and 14,820 controls recruited from 262 centers in 52 countries in Asia, Europe, the Middle East, Australia, and North and South America. The goal was to compare risks for tobacco exposure and first acute myocardial infarction with different types of tobacco exposure among men and women of different ages.

Dr. Ira S. Ockene, from the University of Massachusetts Medical School, commented on the study for Heartwire and said it really adds a “global perspective” because it looks at the variations on tobacco use in different regions of the world.  For example, the effects of “beedie” cigarettes – small amounts of tobacco wrapped in a dried temburini leaf and tied with a string (common in South Asia) – and sheesha smoking – consuming tobacco through a water pipe (common in the Middle East) - were examined in addition to more commonly known western forms of smoking. Dr. Ockene also added that many cardiologists are not quite aware of how quickly the risk of cardiovascular problems decreases upon quitting smoking as the lung-cancer risk still takes years to improve after a smoker completely quits.

Dr. Teo argues that this study should be helpful in helping and treating patients from diverse backgrounds who may think that their method of tobacco consumption are not as hazardous as smoking or exposure to secondhand smoke from cigarettes.  The new study shows that all forms of tobacco use are harmful and could help convince patients to stop using tobacco in any of its forms. 

In February 2006, just a few months before this study was published, the British American Tobacco (BAT), and ITL (International Tobacco Limited) were criticized for developing and executing a deceptive marketing strategy specifically designed to hide the high level of toxicity of their so-called “low tar” brands.

According to company documents published in a study in the Lancet, the cigarette companies were aware that smokers typically take puffs from these “low tar” brands that are almost double the size of the International Standards Smoking (ISO) testing machine. So in reality, smokers of these “low tar” brands are still receiving potent levels of tar and nicotine in each cigarette.

The report the Lancet indicated that the companies looked to exploit the incongruity between the low machine yields, which is normally considered to be valid information used in marketing campaigns and printed on cigarette packages, and the levels of tar and nicotine actually inhaled by smokers.

The study authors argue that BAT and ITL designed products and a marketing strategy that would deliberately fool smokers and tobacco regulators into thinking these products were somehow “safer, less-hazardous.”

The authors are also advocating for a review of the current ISO standards, claiming that new standards should be drafted to “meet the needs of consumers and regulators, rather than those of the tobacco industry.”

While these reports certainly help to shed light on the continuing hazards of smoking and the attempts made by tobacco companies to hide or “play-down” these hazards, there has been enough information surfacing over the past two decades to enable consumers to understand the real and serious health risks associated with smoking.

The following is a list of some key information about the health risks associated with smoking and the deceptive marketing of cigarettes to both adults and minors. 

I. The Misleading Notion of “Light” and “Low Tar” Cigarettes: The tobacco industry has always led the public to believe that smoking “light” or “low tar” versions of cigarettes is less harmful because health risks are minimized. Recent studies, however, indicate that this is not the case at all. There are a number of factors which show that the information provided by the tobacco industry is indeed misleading.

  • A recent report published by the National Cancer Institute found that people who switched to low-tar cigarettes actually smoked more in order to get the same total amount of nicotine. For the most part, the ratio between tar and nicotine remains the same in all cigarettes and, therefore, the risk for the smoker exposing his or her lungs to the carcinogenic ingredients remains the same. The same report found that smokers of these “mild” brands inhale eight times more nicotine than the amount listed on the packet. “The [report] clearly demonstrates that people who switch to ‘low-tar’ or ‘light’ cigarettes…are likely to inhale the same amount of cancer-causing toxins,” says Scott Leischow, Ph.D., Chief of the NCI Tobacco Control Research Branch. “Scientific research does not show that changes in cigarette design and manufacturing over the last 50 years have benefited public health.”
  • According to an analysis in Tobacco Control, a British Medical Association publication, many tobacco companies recognized that low tar products were as dangerous as regular cigarettes, yet continued to market them as “healthier” alternatives. The industry believed that, with all the evidence linking tobacco with lung cancer, smokers would be encouraged to quit and thus they devised “low tar” and “light” products in order to reassure them that smoking was not as bad as they originally thought.
  • Cigarettes that are branded as “hi-fi” or “high filtration” imply that they are somehow able to reduce health risks associated with smoking. This filtering ploy was recently described in industry documents as “an effective advertising gimmick” which was merely cosmetic, offering “the image of health reassurance.”
  • While test results related to “low tar/light” cigarettes seem to illustrate that they are a healthier alternative to full-flavor cigarettes, the test results themselves are subject to question. The tobacco industry designed cigarettes specifically so that the Federal Trade Commission tests, which have used smoking machines since the 1960s to determine the levels of smoke toxicity, would find that these “light” and “low-tar” cigarettes yield less tar when smoked. In actuality, they still deliver full doses of tar and nicotine to actual smokers.
  • Although low-tar cigarettes are frequently made with porous paper and more loosely packed tobacco in an effort to reduce tar intake, research has shown that smokers will still receive the maximum levels of tar because they will usually take more (and deeper) puffs or smoke more total cigarettes per day. Some of these cigarettes also have small holes in the filters designed to dilute the tar and nicotine with air. Reports show, however, that many people will consciously or unconsciously cover these holes with their mouths while smoking thus receiving the same amounts of tar and nicotine as in regular cigarettes.
  • In a study conducted last year by the American Journal of Preventative Medicine, less than 10% of smokers nationwide knew that one light cigarette could deliver the same amount of tar as one regular cigarette.
  • William Farone, a former employee of Phillip Morris, the nation’s largest cigarette manufacturer, has testified that the company increased the tar in one “low-tar” brand, Cambridge Lights, from 0 to 12 mg. over a seven-year period. The company never told consumers that the tar content had gradually been increased. Smokers of the aforementioned brand as well as smokers who bought Marlboro Lights subsequently sued Phillip Morris on the grounds that the label “lights” was deceptive regarding tar and nicotine levels. (The lawsuit was for the refund of money they paid for the cigarettes as opposed to one for personal injuries). A spokesman for Phillip Morris said that the company does not want the terms “light” and “low-tar” banned from cigarette packs but would support greater regulation of their use.

II. Second-Hand Smoke: Just as Dangerous. There is no longer any real doubt that second-hand smoke is indeed harmful and that increased and prolonged exposure to it can result in the very same health risks as those associated with first-hand smoke. As the following indicates, second-hand smoke should be avoided whenever possible:

  • A Japanese study examined the effects of spending 30 minutes in a hospital’s smoking room on smoking and non-smoking men. The study found that the non-smokers exhibited a reduced ability of heart arteries to dilate which previous research has suggested may be a precursor to the hardening of arteries. It was not determined, however, if these effects were permanent.
  • An international study concluded that exposure to second-hand smoke increases the risk for a person to experience a variety of respiratory ailments such as breathlessness, nighttime chest tightness, nighttime breathlessness, and breathlessness after activities.
  • In June of 2002, the International Agency for Research on Cancer found that second-hand smoke could be classified as carcinogenic to humans. Non-smokers are exposed to the same carcinogens as active smokers. Even typical levels of passive exposure have been shown to cause lung cancer among people who never smoked.

III. Specific Risks for Women and Children: Although the IARC study found that lung cancer risks are similar in women and men and that 90% of lung cancers in both sexes are attributable to cigarette smoking, there are specific health risks for women and children about which the public should be aware.

  • As our previous discussion on this particular issue revealed, since 1950, there has been a 600% increase in women’s death rates from lung cancer. Three million women have died of diseases caused by smoking or in fires ignited by cigarettes since 1980 and, on average, these women died 14 years prematurely. In the 1990s, American women lost a collective 2.1 million years of life because of smoking.
  • According to a study conducted at Massachusetts General Hospital, female smokers are at greater risk than non-smokers for infertility. Cigarette smoke includes a toxin that can trigger ovarian failure by accelerating the destruction of egg cells in ovaries. The process is gradual and cannot be immediately detected. Researchers are now studying the possibility that smoking by pregnant women could damage the ovaries of developing female fetuses and reduce the number of egg cells produced by the female offspring of women who smoke.
  • Additional evidence has reinforced previous reports that pregnant women who smoke are at a greater risk of having: (1) a baby with a low birth weight; (2) a stillborn baby; (3) a neonatal death; or (4) a child with sudden infant death syndrome (SIDS). In addition, the children of smoking women have a greater risk of developing asthma, bronchitis, colds and pneumonia.
  • Female smokers suffer from lower bone density and experience a premature decline in lung function.
  • Women are more easily conned into smoking light cigarettes: 58% of women use lights compared to 50% of men.
  • In addition to lung cancer, women who smoke are at greater risk to develop cancers of the mouth and pharynx, esophagus, larynx, bladder, pancreas, kidney, and cervix. They also have an increased risk of cardiovascular disease, especially when using oral contraceptives.
  • It bears repeating that the children of women who smoke during pregnancy are at greater risk of developing Type II diabetes and obesity. The findings suggest that smoking deprives the fetus of nutrients, resulting in lifelong metabolic abnormalities. Because diabetes and obesity are associated with heart disease, smoking during pregnancy can also risk shortening the child’s life span.
  • A study by the Hong Kong University Faculty of Medicine found that babies who live with two or more smokers are 30% more likely to need hospital treatment that those who grow up in smoke-free homes.
  • Childhood exposure to environmental tobacco smoke (ETS) is associated with an increased prevalence of asthma among adult non-smokers. People exposed to ETS during childhood are also more likely to experience breathing difficulties from exercise and when exposed to cold air.
  • The American Journal of Clinical Nutrition reported that children whose parents smoke may have lower levels of vitamin C, a vital antioxidant, than children of non-smokers. Vitamin C is needed for normal growth and development. Even very low exposure to second-hand smoke was found to be associated with lower levels of vitamin C.

As we previously reported, smoking even causes premature wrinkles and lines according to a study in the Lancet Medical Journal. The study concluded that smoking switches on a gene involved in destroying collagen, the structural protein that gives skin its elasticity. This suggests that smoking produces an effect on skin that is similar to the injury caused by over exposure to the sun.

With all of the evidence that continues to surface regarding the harmful and deadly effects of cigarettes and other tobacco products, the percentage of smokers has still not seen a significant overall decline. People continue to perpetuate this deadly habit despite major health risks and adolescents are still beginning to smoke regardless of the warnings they receive from their parents, in school, and from other sources.

The enormous financial wealth of the tobacco industry allows it to flood underdeveloped nations with its products. In most of these countries there is not even an attempt to educate consumers as to the enormous health risks they are being exposed to. There is only minimal regulation of advertising (if any) and a high percentage of the products being sold are the most dangerous since they are unfiltered and carry no warnings. It is also common for children to smoke since the practice is not discouraged nor is the sale of tobacco to minors illegal.

There are also few restrictions on smoking in public places such as restaurants, workplaces, and transportation facilities. Many smokers in these poorer countries also tend to be heavy or “chain” smokers who expose their families, co-workers, and others to dangerously high levels of second-hand smoke.

“Big Tobacco” has no conscience and it will exploit consumers wherever a market presents itself. Thus, as awareness of the dangers posed by smoking increases in countries like the United States, Canada, and England, cigarette sales are being pushed harder in countries with fewer governmental regulations and restrictions.   

We caution our readers not to be taken in by the tobacco industry’s misleading advertising campaigns. Don’t be fooled by the hype surrounding “light” and “low-tar” cigarettes. Avoid exposure to as much second-hand smoke as possible. Do everything you can to discourage your children from smoking and guard against their exposure to second-hand smoke.

The experts agree that the only way to reduce health risks associated with smoking is to quit completely. (Many states operate free services to help people quit smoking). To avoid those same risks altogether, however, a person should neither start smoking nor use any form of tobacco in the first place. 

If you or a loved one has suffered an injury (or death) that is suspected to be tobacco-related, do not hesitate to contact Parker & Waichman at for a free consultation.



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