Skip to main content
Consumer site
Order samples

Drug interactions: how tobacco smoke impacts the cytochrome P450 system

Tobacco smoke impacts the metabolism of many drugs in the liver


When patients quit smoking, their drug levels – and response – may change due to the change in the levels of tobacco smoke they’re exposed to.

This is because polyaromatic hydrocarbons – one of the many chemicals found in tobacco smoke – have been shown to induce multiple forms of cytochrome P450 enzymes in the liver. For those who smoke, this results in more rapid metabolism of drugs metabolized by cytochrome P450, which can lead to a clinically significant reduction in drug level and pharmacological effect in the body for some drugs.15

Clinically important effects of smoking on drug metabolism have been observed with as few as 7-12 cigarettes per day.19 But importantly, this is an effect due to polyaromatic hydrocarbons and not nicotine itself.15,16,17 Symptoms that arise during smoking cessation may, in fact, be due to drug interactions – not nicotine replacement therapy or nicotine withdrawal.

With smoking cessation, the activity of cytochrome P450 enzymes begins to return to ‘normal’, resulting in a slowing of drug metabolism.15 When this happens, there is a risk of drug toxicity and adverse effects.17

The risk of drug toxicity upon smoking cessation is variable, and is related to several factors, both patient and drug-specific. The drug in question, the number of cigarettes smoked each day, and other factors can impact the extent of the interaction.

icon of ask

Ask: Are you taking any prescription or non-prescription medications?

icon of advise

Advise: When you reduce or quit smoking, medication levels in the body can be affected.

icon of act

Act: Consider dose adjustment or increased monitoring for adverse medication reactions when smoking status changes.

Medications and caffeine intake can be affected by smoking

Patients may be living with other heath conditions that require medication that may be affected by a patient’s current smoking status. When helping patients quit, consider how drug levels may change and require monitoring or action.

icon of coffee

Even the body’s response to caffeine is affected by tobacco smoke.
Smokers may find that quitting while consuming their usual amount of caffeine (in coffee, tea, cola, etc.) can cause symptoms of caffeine toxicity, such as sleeplessness or jittery feelings.15,16,17

This is why, prior to a patient’s quit date, caffeine intake should be reduced by half to help reduce the risk of side effects.15,16,17

Did you know?

  • Smoking increases caffeine clearance by ~50%15,16,18.

  • Smoking can increase the metabolism of clozapine and reduce serum levels.16,17,18

  • The effect of clopidogrel is enhanced in individuals who smoke 10 or more cigarettes a day.18

Drug interactions with tobacco smoke

Explore some of the effects that tobacco smoke and quitting can have on these medications.

Download the complete list of medications and recommended actions here:

New Canadian Guide: Drug InterACTIONS with Tobacco Smoke

  • Beta blockers1,2,3,4:  
    PK    : Propranolol clearance may be increased by smoking, which may lower serum levels.
    PD: Smoking may reduce the effects of beta-blockers on blood pressure and heart rate.

  • Clopidogrel1,2,3,4:
    PK: Smoking-related enzyme induction may increase the metabolism of clopidogrel to its active metabolite. Effect of clopidogrel is enhanced in individuals who smoke 10 or more cigarettes a day.

  • Flecainide1,2,4,10:
    PK: Smoking increases clearance and reduces plasma levels of flecainide.

  • Heparin1,2,3,4,9:
    PK & PD: The mechanism of interaction is unclear, but individuals who smoke may require increased dosages of heparin due to PK and PD effects.

  • Mexiletine1,2:
    PK: Smoking may increase clearance and decrease plasma levels of mexiletine.

  • Pirfenidone1,2:
    PK: Smoking increases metabolism of pirfenidone. Decreased exposure in individuals who smoke might alter efficacy profile.

  • Riociguat1,2:
    PK: Smoking reduces plasma levels of riociguat significantly (50% to 60%).

  • Warfarin1,2,3,4,7:
    PK: Smoking may increase clearance and decrease the serum concentration of warfarin.

  • Insulin (subcutaneous)1,3,4 :
    Possibly PK and PD    : Individuals who smoke may have increased insulin resistance and decreased insulin absorption due to vasoconstriction. Higher insulin dosages may be required in individuals who smoke.

  • Ropinirole1,2:
    PK    : Smoking may reduce plasma levels of ropinirole.

  • Bendamustine11,12,13:
    PK    : Cigarette smoking may affect the circulating levels of bendamustine and its active metabolites.

  • Erlotinib1,2,3:
    PK    : Smoking increases clearance and reduces plasma levels of erlotinib.

  • Irinotecan1,3:
    PK    : Systemic exposure and efficacy of irinotecan may be reduced with smoking.

  • Pomalidomide2,8:
    PK    : Smoking may reduce pomalidomide exposure.

  • Methadone1,2,3,4,7:
    Likely PK and PD    : Smoking may increase methadone metabolism (PK); nicotine affects the endogenous opioid system (PD).

  • Clozapine1,2,3,4,5:
    PK: Smoking can increase metabolism and reduce serum levels of clozapine.

  • Duloxetine2,3,5:
    PK: Smoking may lower plasma levels of duloxetine.

  • First generation antipsychotics (i.e., chlorpromazine, fluphenazine, haloperidol)1,2,3,4,9:
    PK: Smoking can reduce antipsychotic serum levels.

  • Fluvoxamine1,2,3,5,9,10:
    PK: Smoking may lower plasma levels of fluvoxamine.

  • Mirtazepine3,5:
    PK: Smoking reduces plasma levels of mirtazapine.

  • Olanzapine1,2,3,4,5,7:
    PK: Smoking increases clearance and reduces plasma levels of olanzapine.

  • Tricyclic Antidepressants (TCAs) (e.g., amitriptyline, imipramine, nortriptyline) 1,2,3,4,5:
    PK: Smoking may reduce plasma levels of TCAs.

  • Theophylline1,2,3,4,7:
    PK: Smoking increases metabolism and reduces plasma levels of theophylline.

  • Benzodiazepines (e.g., alprazolam, diazepam, clonazepam)1,2,3,4,9:
    PK: Possible increased metabolism may result in lower serum levels of benzodiazepines.
    PD: Stimulation from nicotine may reduce sedative effects of benzodiazepines.

  • Caffeine1,3,9:
    PK    : Smoking increases the clearance of caffeine by more than 50%.

Knowing which drugs interact with tobacco smoke can help inform dose adjustments, monitoring and smoking status changes.

Drug InterACTIONS with Tobacco Smoke: A Fireside Chat with Dr. Andrew Pipe and Ron Pohar

Join Dr. Andrew Pipe and pharmacist Ron Pohar, two of Canada’s foremost experts on smoking cessation, as they discuss the new Drug InterACTIONS with Tobacco Smoke tool and how to utilize it to support your patients along their smoking cessation journey.

Content is restricted by privacy settings. Please review your cookie settings to enable access.

References

1. Drug Interactions with Tobacco Smoke, Rx for Change, 2024. https://rxforchange.ucsf.edu/download.php?file=A4+DI+TABLE.pdf (Accessed April 1, 2024).
2. Managing specific interactions with smoking.
Published 31 October 2023. https//www.sps.nhs.uk/articles/managing-specific-interactions-with-smoking/ (Accessed April 1, 2024).
3. Drug interactions with smoking.
https://hnc.org.au/wp-content/uploads/2020/04/drug-interactions-with-smoking.pdf (Accessed April 1, 2024).
4. Quick guide to drug interactions with smoking cessation. New South Wales Government Health.
https://www.health.nsw.gov.au/tobacco/Factsheets/tool-7-guide-dug-interactions.pdf (Accessed April 1, 2024).
5. Medicines & Smoking. https://www.tewv.nhs.uk/content/uploads/2021/11/Medicines-and-Smoking.pdf (Accessed April 1, 2024).
6. Drug Interactions between melatonin and Nicorette.
https://www.drugs.com/drug-interactions/melatonin-with-nicorette-1548-0-1716-1071.html?professional=1 (Accessed April 1, 2024).
7. What are the clinically significant drug interactions with cigarette smoking?
https://www.betterhealthns.co.uk/wp-content/uploads/2022/05/What-are-Drug-interactions-with-smoking-cigarettes_update_Nov-2017.pdf (Accessed April 1, 2024).
8. Pomalyst and Alcohol/Food Interactions.
https://www.drugs.com/food-interactions/pomalidomide,pomalyst.html?professional=1 (Accessed April 1, 2024).
9. Government of Australia Department of Health. Mental health smoking assessment checklist. https://www.healthywa.wa.gov.au/~/media/Files/Corporate/general%20documents/Tobacco/PDF/Mental_Health_Smoking_Checklist.ashx (Accessed November 12, 2024).
10. Oxford Health. Guidance on the effects of smoking and smoking cessation on psychotropic and other medications. https://www.oxfordhealthformulary.nhs.uk/docs/Smoking%20and%20cessation%20effetcs%20on%20psychotropics%20and%20other%20medications_DTG%20approved%20Dec%202023.pdf (Accessed November 24, 2024).
11. https://www.cancercareontario.ca/en/system/files_force/BENDRITU_HEM_NHLLO.pdf?download=1
12. https://www.mayoclinic.org/drugs-supplements/bendamustine-intravenous-route/description/drg-20071660
13. Treanda Product Monograph.
https://pdf.hres.ca/dpd_pm/00043152.PDF. Accessed November 24, 2024
14. Bjorngaard, et al. Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis. International Journal of Epidemiology, Vol. 46, No. 6; 1958-67.
15. Kroon, L. Drug interactions with smoking. Am J Health-Syst Pharm—Vol 64 Sep 15, 2007:1917-21.
16. New South Wales Government Health. Medication interactions with smoking and smoking cessation. https://www.health.nsw.gov.au/tobacco/publications/tool-14-medication-intera.pdf. Accessed March 16, 2022.
17. New South Wales Government. Quick guide to drug interactions with smoking cessation. https://www.health.nsw.gov.au/tobacco/Factsheets/tool-7-guide-dug-interactions.pdf. Accessed March 16, 2022.
18. University of California San Francisco. Drug Interactions with Tobacco Smoke, Rx for Change, 2022. https://smokingcessationleadership.ucsf.edu/factsheets/drug-interactions-tobacco-smoke-rx-change-2019. Accessed March 16, 2022.
19. Haslemo T, Eikeseth PH, Tanum L, Molden E, Refsum H. The effect of variable cigarette consumption on the interaction with clozapine and olanzapine. Eur J Clin Pharmacol 2006;62:1049-53.