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Published: 12 December 2013

Smoking Can Interact with Medicines

Prescriber Update 34(4): 41-42
December 2013

Key Messages

  • The doses of clozapine, olanzapine, theophylline, and warfarin may need to be reduced when a patient quits smoking.
  • Consider reducing the doses of other medicines metabolised by CYP1A2 when a smoker quits.
  • A dose increase may be required for some medicines if a patient starts smoking.
  • Patients exposed to second-hand smoke may also metabolise medicines faster than non-smokers and this may need to be considered in their treatment plan.
  • Nicotine replacement therapy does not induce CYP P450 activity.


Christmas and the New Year are the most popular time for smokers to try to quit. Similarly some patients may stop smoking if they are admitted to a hospital with a no smoking policy. Smoking has important effects on the metabolism of some medicines. Quitting smoking can increase the risk of patients experiencing adverse reactions to medicines.

The polycyclic aromatic hydrocarbons found in cigarette smoke induce hepatic cytochrome P450 (CYP) isoenzymes: 1A1, 1A2, 2A6, 2B6 and 2E11,2,3. Smoking may also influence the glucuronidation of medicines4.

The net effect of this is to increase the speed by which some medicines are removed from the body. Therefore, smokers may require higher doses of medicines that are metabolised by these induced cytochrome P450s.

Importantly, on quitting smoking the metabolic activity of CYP enzymes reduces. This means that the patient may now be exposed to a relative overdose of the medicine. Predicting the required dose after quitting is difficult and therapeutic medicine monitoring should be used when possible.

A number of medicines metabolised by CYP1A2 also have narrow therapeutic ranges further increasing the risk of toxicity. Medicines that have a narrow therapeutic range have a less than two fold difference between the median lethal and median effective dose, or a less than two-fold difference between the minimum toxic and minimum effective concentration in the blood.

Nicotine does not have the same effects on CYP P450s. Patients using nicotine replacement to help quit smoking will require changes to their medicines as for smokers quitting without assistance2.

Clozapine

Clozapine is metabolised by CYP1A2. It has been estimated that the average plasma levels of clozapine in smokers are approximately 80% those of non-smokers1. Dose reduction is highly recommended in patients who quit or who are hospitalised and unable to smoke. Recommendations are to reduce the dose by about 36% within one week of quitting smoking2. A dose increase may be required for patients starting smoking.

Olanzapine

Smokers have been found to have approximately five-fold lower dose-corrected steady state plasma concentrations of olanzapine compared to non-smokers1. Olanzapine is also metabolised by CYP1A2. After quitting smoking doses should be reduced by 36% over the first week2. Similar to clozapine a dose increase may be required in patients who start smoking whilst taking olanzapine.

Theophylline

The clearance of theophylline is increased by 58–100% and the half-life decreased by 63% in smokers compared to non-smokers1. Theophylline clearance has been estimated to be increased by 50% in children exposed to the second-hand smoke of parents who smoked at least 20 cigarettes daily1. After quitting smoking the clearance of theophylline decreases and the dose should be reduced1.

Warfarin

It was been reported that patients taking warfarin who stopped smoking required a dose reduction of 14–23%2. The INR should be closely monitored when there is a change in the patient’s smoking status2.

Clopidogrel

An enhanced response to clopidogrel has been seen in smokers who are CYP1A2 (163CA) A-allele carriers3.

Caffeine

Caffeine is a component of some analgesics and is almost entirely metabolised by CYP1A2. Caffeine clearance is increased by more than 50% in smokers1. When a patient quits smoking they should reduce their consumption of caffeine by half to avoid toxicity. Symptoms of caffeine overdose include irritability and insomnia which can be mistaken for nicotine withdrawal symptoms1.

Other medicines may also be affected such as: verapamil, propranolol, diazepam, naratriptan, fluvoxamine, lamotrigine1,2,4. Patients taking these medicines should be monitored for overdose effects and dose adjustments made if necessary.

Smoking may also cause pharmacodynamic interactions such as:

References
  1. Kroon LA. 2007. Drug interactions with smoking. American Journal Health-System Pharmacy 64: 1917–1921.
  2. Schaffer SD, Yoon S, Zadezensky I. 2009. A review of smoking cessation: potentially risky effects on prescribed medications. Journal of Clinical Nursing 18: 1533–1540.
  3. Lucas C, Martin J. 2013. Smoking and drug interactions. Australian Prescriber 36: 102–104.
  4. Reinsberger C, Dorn T, Kraemer G. 2008. Smoking reduces serum levels of lamotrigine. Seizure 17: 651–653.
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