Smoking and Clozapine Dosing

Effect of Smoking on Clozapine Metabolism

• Smoking induces cytochrome P450 1A2 (CYP1A2) enzyme activity, which is the main metabolic pathway for clozapine, resulting in faster drug clearance and lower blood concentrations 1
• The FDA considers smoking status when managing clozapine therapy, as it affects CYP1A2 enzyme activity 1

Clinical Implications for Dosing

• When initiating clozapine in patients who smoke, anticipate the need for higher doses to achieve therapeutic levels, and consider that smoking status affects clozapine metabolism similarly to how it affects olanzapine 1, 2
• Document smoking status (including amount) at each visit, as even changes in the number of cigarettes smoked can affect clozapine metabolism 1, 2

Additional Considerations

• Other substances that may affect clozapine metabolism include caffeine consumption and recreational drugs, and smoking status has a stronger effect on clozapine metabolism than genetic polymorphisms 1