Clozapine Interactions

Polycyclic aromatic hydrocarbons in tobacco smoke (not nicotine) strongly induce CYP1A2, the liver enzyme that handles most clozapine metabolism, so smokers tend to have lower clozapine levels and need higher doses. The greater danger is stopping smoking: levels can climb sharply over a few days as the enzyme returns to baseline, risking sedation, seizures, and toxicity unless the dose is reviewed.

Caffeine and clozapine are both broken down by the liver enzyme CYP1A2, and caffeine competitively inhibits it. Large changes in caffeine intake - especially starting or stacking energy drinks - can raise clozapine to toxic levels, with a documented case report of severe toxicity and multiorgan failure.