How Smoking Affects Medications


Smoking can cause medications to become subtherapeutic, leading to slower improvement in disease states.

An estimated 40 million US adults smoked cigarettes in 2014.1

Smoking not only has the potential to cause death, but it also decreases the efficacy of many medications. For that reason, it’s important for pharmacists to know which medications are affected by smoking so that appropriate counseling measures and dosage adjustments can be provided to patients.

Tobacco smoke induces many of the CYP450 enzymes in the liver, which play an important role in medication absorption, distribution, metabolism, and elimination. Drug interactions are caused by components of tobacco smoke itself, rather than nicotine.2 This means nicotine replacement therapy (NRT) can be used without concern of drug interactions and medication changes.

Psychiatric medications such as antipsychotics, antidepressants, hypnotics, and anxiolytics are widely affected by cigarette smoking. For these classes, the drug concentration in the blood can be decreased with smoking, and reduction in efficacy may lead to inappropriate higher dosage adjustments. Meanwhile, some nonpsychiatric medications such as insulin, warfarin, and caffeine require higher dosages to reach appropriate efficacy with smoking.2

When a patient is a current smoker and is taking a medication that’s negatively affected by smoking, it’s the pharmacist’s goal to try to initiate a smoking cessation regimen or NRT. With smoking cessation, the risk of harming the patient still exists, as abruptly stopping cigarette smoking can make a patient feel uncomfortable and may even cause additional harm.

Since medications are sometimes dosed with consideration that the patient is a smoker, it’s important to make appropriate dosage adjustments when trying to initiate smoking cessations measures.

A specific CYP450 enzyme induced by smoking is CYP1A2. Common medications that are substrates of this enzyme include3:

1. Duloxetine (Cymbalta)

2. Caffeine

3. Clopidogrel (Plavix)

4. Clozapine (Clozaril)

5. Cyclobenzaprine (Flexeril)

6. Diazepam (Valium)

7. Haloperidol (Hadol)

8. Mirtazapine (Remeron)

9. Naproxen (Aleve)

10. Nortriptyline (Pamelor)

11. Olanzapine (Zyprexa)

12. Ondansetron (Zofran)

13. Propanolol (Inderal)

14. Ropinirole (Requip)

15. Theophylline (Theo-24)

Since these medications are substrates of the enzyme being induced (CYP1A2), smoking will lower the drug concentration of the medication along with its efficacy in most cases. However, clopidogrel therapy has been shown to increase platelet inhibition and decrease aggregation in patients that are smokers, providing an exemption from logical belief.4,5 In that case, the efficacy of the medication is enhanced in a sense since it’s following the appropriate physiological mechanism of action.

When assessing certain therapies for patients, health care professionals must take all risks and benefits into consideration. If the risks tremendously outweigh benefits, the therapy shouldn’t be implemented.

When it comes to trying to initiate smoking cessation regimens, pharmacists still should consider the risks, even though the benefits will prevail in most situations because of the fact that smoking has a negative effect in many disease states, interacts with medications, and can potentially cause cancer.


1. Jamal A, Agaky S, O’Connor E, et al. Current cigarette smoking among adults — United States, 2005—2013. CDC website. Published November 28, 2014. Accessed May 12, 2016.

2. Medication interactions with smoking and smoking cessation. NSW Government Health website. Accessed May 10, 2016.

3. Levien TL, Baker DE. Cytochrome P450 drug interactions. Pharmacist Letter. Updated May 2003. Accessed May 11, 2016.

4. Bliden KP, DiChiara J, Lawal L, et al. The association of cigarette smoking with enhanced platelet inhibition by clopidogrel. J Am Coll Cardiol. 2008;52(7):531-533. doi:10.1016/j.jacc.2008.04.045

5. Thorn CF, Aklillu E, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for CYP1A2. Pharmacogenetics and genomics. Published 2011. Accessed May 11, 2016.

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