Skip to main content
Consumer site
French version coming soon
KenvuePro Logo

Order samples

Drug interactions: how tobacco smoke impacts the cytochrome P450 system

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.1,2

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.2,3,4

Did you know?

  • Smoking increases caffeine clearance by ~50%.2,3,5

  • Smoking can increase the metabolism of clozapine and reduce serum levels.3-5

  • The effect of clopidogrel is enhanced in individuals who smoke 10 or more cigarettes a day.5

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.2

Clinically important effects of smoking on drug metabolism have been observed with as few as 7-12 cigarettes per day.6 But importantly, this is an effect due to polyaromatic hydrocarbons and not nicotine itself.2,3,4 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.2 When this happens, there is a risk of drug toxicity and adverse effects.4

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.

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 blockers: Increased clearance which may lower serum levels. Pharmacodynamic interactions may result in less effective antihypertensive and heart rate control.3,5

  • Clopidogrel: 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.4,5

  • Flecainide: Smoking increases clearance. Individuals who smoke may require higher dosages.5

  • Heparin: Individuals who smoke may require increased dosages. Prothrombin time may increase with smoking cessation which can increase the risk of bleeding.3-5

  • Mexiletine: Smoking may increase clearance. Potential increase in levels with smoking cessation.3,5

  • Pirfenidone: Metabolism increased by smoking. Decreased exposure in individuals who smoke might alter efficacy profile.5

  • Propranolol: Clearance is increased by smoking. Serum levels may rise and effects enhanced upon smoking cessation.5

  • Riociguat: Smoking may reduce exposure to riociguat. Potential for increase in levels with smoking cessation.7

  • Warfarin: Smoking may decrease the serum concentration of warfarin. Monitoring of INR is advised with smoking cessation.4,5,8

  • Insulin (subcutaneous): Individuals who smoke may have increased insulin resistance and may require higher dosages. Insulin resistance may decrease with smoking cessation.3-5

  • Quinine: Clearance is increased by smoking. Plasma levels may rise with smoking cessation.9

  • Ropinirole: Smoking may increase metabolism. Potential for increase in levels with smoking cessation.5

  • Tacrine: Smoking may increase metabolism. Individuals who smoke may require higher dosages. Potential for increase in levels with smoking cessation.10

  • Tizanidine: Males who smoke may have lower blood levels. Plasma levels may rise with smoking cessation.5

  • Bendamustine: Smoking may decrease bendamustine concentrations, with an increase in concentrations of its two active metabolites. With cessation, a change in concentration of both bendamustine and its active metabolites may occur.5

  • Erlotinib: Smoking increases clearance. Individuals who smoke may require higher dosages. Potential increase in levels with smoking cessation.5,11

  • Irinotecan: Exposure and efficacy may be reduced with smoking. Potential increase in levels with smoking cessation; however, dosages are not usually adjusted in presence of smoking.5

  • Nintedanib: Exposure is reduced by smoking. Potential increase in level with smoking cessation; however, dosages are not usually adjusted in presence of smoking.5

  • Methadone: Smoking may increase methadone metabolism. Potential reduction in metabolism with smoking cessation. The patient should be monitored for signed of methadone toxicity.3,7

  • Opioids: Smoking may increase the metabolism of some opioids. Smoking may decrease the analgesic effect of opioids. Adequate pain control may be experienced with lower opioid doses upon cessation.8

Chlorpromazine: Smoking can reduce serum levels. Potential increase in levels with smoking cessation. Dose should potentially be increased for smokers.4,5

Clozapine: Smoking can increase metabolism and reduce serum levels. Potential increase in levels with smoking cessation. Dose may need to be reduced by an average of 50%.3-5

Duloxetine: Smoking may lower plasma levels. Potential increase in levels with smoking cessation.3

Fluphenazine: Smoking may lower plasma levels. Potential increase in levels with smoking cessation.3

Fluvoxamine: Smoking may lower plasma levels. Potential increase in levels with smoking cessation. Smokers may need a lower dose.3-5

Haloperidol: Smoking may lower plasma levels. Individuals who smoke may require higher dosages.3,5

Lithium: Smoking increases clearance of caffeine, which indirectly affects lithium levels. Smoking cessation could indirectly change lithium excretion in the absence of a reduction in caffeine intake.3

Mirtazepine: Smoking lowers levels. Potential increase in levels with smoking cessation.3

Olanzapine: Metabolism and clearance increased by smoking. Dosage modifications are not routinely recommended, but individuals who smoke may require higher dosages.3,5

Tricyclic antidepressants: Smoking may decrease blood levels. Serum levels may increase upon quitting.5

Theophylline: Smoking increases metabolism. Maintenance doses are considerably higher in individuals who smoke. Plasma levels rise with smoking cessation.3,5

Benzodiazepine: Stimulation from nicotine may reduce sedative effects. Increased metabolism may result in lower serum levels.3-5

Zolpidem: Smoking may lower plasma levels and reduce hypnotic effect. Individuals who smoke heavily may need higher dosages. Plasma levels may rise with smoking cessation.3

Caffeine: Smoking increases the clearance of caffeine by about 50%. Potential increase in levels with smoking cessation.3-5

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. Bjorngaard, et al. Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis. International Journal of Epidemiology, Vol. 46, No. 6; 1958-67.
2. Kroon, L. Drug interactions with smoking. Am J Health-Syst Pharm—Vol 64 Sep 15, 2007:1917-21.
3. 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.
4. 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.
5. 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.
6. 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.
7. NHS. What are the clinically significant drug interactions with tobacco smoking? July 2020. https://www.sps.nhs.uk/wp-content/uploads/2020/03/UKMi_QA_Interactions-with-tobacco_update_Jul-2020.pdf. Accessed March 16, 2022.
8. Zevin S, Benowitz NL. Drug interactions with tobacco smoking. Clin Pharmacokinet 1999;36:425–438.
9. Wanwimolruk S et al. Cigarette smoking enhances the elimination of quinine. Br J Clin Pharmac 1993; 36: 610-614.
10. University of California San Francisco. Drug Interactions with Tobacco Smoke, Rx for Change, 2017. https://rxforchange.ucsf.edu/file_downloads/PA4%20INTRXN.pdf. Accessed March 6, 2023.
11. Roche Canada. Tarceva Product Monograph. https://www.rochecanada.com/PMs/Tarceva/Tarceva_PM_E.pdf. Accessed March 16, 2022.