Harmful Interactions Between Smoking and Prescription Drugs

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

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.