Smoking and smoking cessation: clinically significant interactions with commonly used medicines

Doses of theophylline, fluvoxamine, caffeine, coumarins including warfarin and the antipsychotics clozapine and olanzapine may have to be altered.

Article date: October 2009

Pharmacokinetic interactions

Polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke are potent inducers of the hepatic cytochrome P450 (CYP) isoforms 1A1, 1A2, and possibly 2E1. Of these, 1A2 is the most important. Enzyme induction results in increased metabolism of substrates. Thus larger doses of CYP1A2 substrates may be required to ensure efficacy in people who smoke, and a reduction in dose may be needed during smoking cessation to prevent side effects.

Many commonly used medicines are substrates for CYP1A2: theophylline; fluvoxamine; caffeine; coumarins, including warfarin; and the antipsychotics clozapine and olanzapine. However, not all possible drug-smoking interactions are clinically significant. Important factors that determine the clinical significance of an interaction in smokers are:

  • The extent to which the medicine is metabolised by CYP1A2—ie, the fractional clearance. The interaction will be most significant when CYP1A2 is the main elimination pathway
  • The therapeutic index of the medicine metabolised for CYP1A2. For example, for a narrow therapeutic index drug such as theophylline, small changes in drug concentration may have significant clinical effects

It is also important to remember that it takes about 1 week for the effect of the induction of CYP1A2 to wear off after smoking cessation, and thus dose adjustment is not usually necessary in situations where there is temporary smoking cessation (eg, during acute hospital stay).

Further information on the most clinically significant pharmacokinetic drug interactions with smoking can be found in: Kroon LA. Drug interactions with smoking. Am J Health Syst Pharm 2007; 64: 1917–21. See also Baxter K. Stockleys Drug Interactions (Pharmaceutical Press, 2007).

Pharmacodynamic interactions

Pharmacodynamic interactions between medicines and smoking or smoking cessation are attributable to the effects of tobacco smoke, including nicotine. The most clinically significant pharmacodynamic interactions with smoking include: hormonal contraceptives (increased risk of cardiovascular disease); inhaled corticosteroids (efficacy may be reduced in smokers with asthma); and beta-blockers (nicotine activation of sympathetic nervous system may counteract effect).

Furthermore, stopping smoking, with or without the aid of drug treatment, may be associated with psychiatric symptoms, and stopping smoking may also exacerbate an underlying psychiatric condition.

Advice for healthcare professionals:

Clear guidelines for clinical practice are not available. We would thus suggest the following general approach should be taken:

• On starting CYP1A2 substrates:

  • Obtain smoking status
  • Determine clinical significance of any potential interaction
  • Monitor efficacy and side effects
  • Adjust dose if necessary
  • Monitor smoking status and advise patients to seek advice from doctor if smoking status is to change

• During smoking cessation:

  • Find out what medicines the patient is taking
  • Determine clinical significance of any potential interaction
  • Monitor for side effects
  • Adjust dose if necessary

The most important medicines to consider in those who smoke, or who are trying to quit, include theophylline, olanzapine, clozapine, caffeine, and warfarin.

Remember that you can report suspected interactions on a Yellow Card at


Article citation: Drug Safety Update Oct 2009, vol 3 issue 3: 9.

Updates to this page

Published 11 December 2014