Tobacco smoke contains polycyclic aromatic hydrocarbons that increase the activity of certain hepatic enzymes especially CYP1A2.
Smoking increases the metabolism of clozapine and consequently reduces the plasma levels.
The effect of smoking is dose related i.e. the more cigarettes smoked, the greater the enzyme induction.
Any reduction in the number of cigarettes smoked per day may result in increased clozapine plasma levels. This is worth bearing in mind should a patient begin to reduce their smoking in preparation for a quit attempt.
Plasma clozapine may rise substantially within 3-5 days of smoking cessation but enzyme activity may take weeks to return to baseline.
The interaction between smoking and clozapine is unrelated to nicotine, and therefore the use of nicotine replacement therapy or e-cigarettes does not affect plasma clozapine at constant clozapine dose.
The impact of smoking on clozapine treatment should be explained to the patient and any change in smoking status must be discussed with someone responsible for their care as careful monitoring is required.
Patient should be monitored for signs of dose related side effects: